The latest signed off version for the GMS is v4.0. The current version, shown here, may differ from the signed-off version.

Primary immunodeficiency or monogenic inflammatory bowel disease (Version 4.125)

Relevant disorders: Primary immunodeficiency disorders, A- or hypo-gammaglobulinaemia, Congenital neutropaenia, Agranulocytosis, Combined B and T cell defect, Inherited complement deficiency, SCID, Primary immune disorder, Primary immunodeficiency, A-gammaglobulinaemia, Agammaglobulinaemia, hypo-gammaglobulinaemia, hypogammaglobulinemia, immune deficiency syndromes, Severe combined immunodeficiency, Congenital neutopenia, Familial haemophagocytic lymphohistiocytic disorders, Familial hemophagocytic lymphohistiocytic disorders, PID, Sepsis, Disseminated non-tuberculous mycobacterial infection, Primary immunodeficiency, R15
Panel types: Rare Disease 100K, GMS Rare Disease Virtual, GMS signed-off
Latest signed off version: v4.0 (22 Mar 2023)
Previously signed off versions: v3.0, v2.1

Description

This panel is used as a virtual panel to analyse genome or exome data in the NHS Genomic Medicine Service; the panel will routinely be applied for clinical indication 'R15 Primary immunodeficiency or monogenic inflammatory bowel disease' but can also be used as part of the analysis for a broader clinical presentation, where relevant.

Further information on the testing criteria and any overlapping clinical indications can be found within (https://www.england.nhs.uk/publication/national-genomic-test-directories/) under 'R15 Primary immunodeficiency or monogenic inflammatory bowel disease'.

CNVs, STRs and genes encoded by the mitochondrial genome may not be routinely included in the analysis where the panel is NOT delivered by WGS. Please contact your Genomic Laboratory Hub for information regarding specific queries.

This panel was originally developed for the 100,000 Genomes Project and is still being used for participants in the project. For the rare disease eligibility criteria refer to: https://www.genomicsengland.co.uk/rarediseasecriteria100K

A version of this panel has been signed off under NHS Genomic Medicine Service governance (see 'Latest signed off version' in the panel header information).

This panel will continue to be curated based on external reviews and Genomics England curation. New changes will be reflected in an increase to the minor version of the panel and details of these can be viewed in the 'Panel Activity' page. Periodically, these changes will be reviewed by a NHS Genomic Medicine Service evaluation process. The content that is agreed for the GMS panels will be reflected in an updated signed off version number.

The panel represents primary immunodeficiency disorders, including:
- Combined immunodeficiency, with or without associated/syndromic features
(includes SCID and patients with syndromic features)
- Predominantly antibody deficiencies
- Diseases of immune dysregulation (includes HLH)
- Congenital defects of phagocyte number, function or both (includes neutropenia)
- Defects in intrinsic and innate immunity
- Autoinflammatory disorders
- Complement deficiencies

This panel includes the following sources, the genes from these sources have all been reviewed based on PanelApp guidelines.

1) Previous Genomics England gene panels merged to form this panel:
A- or hypo-gammaglobulinaemia v1.25; Agranulocytosis v1.3; Combined B and T cell defect v1.12; Congenital neutropaenia v1.22; Inherited complement deficiency v0.11 and SCID v1.6. Indicated on this panel by the source listing the panel name.

2) External expert immunodeficiency diagnostic gene lists:
a) GOSH PID v8.0 : Indicated on this panel by the source GOSH PID v8.0.
This is a list of genes from Great Ormond Street Hospital (GOSH) diagnostic PID panel 28th November 2017 (82 unique genes). http://www.labs.gosh.nhs.uk/media/764830/pid_v8.pdf. GOSH PID panel version 8. MOI and Phenotype was inferred by Genomics England curator using OMIM.
b) GRID V2.0 : Indicated on this panel by the source GRID V2.0.
This is a list of genes from Genomics of Rare Immune Disorders (GRID) platform http://grid.cambridgednadiagnosis.org.uk, which is supported by Cambridge Biomedical Research centre/NHS East England NHS GMC and was developed by Ilenia Simeoni in consultation with clinical immunologists : Siobhan Burns, Kimberly Gilmour, Sophie Hambleton, Taco Kuijpers, Sinisa Savic, Ken Smith, Andrew Thrasher, James Thaventhiran, as well as Karyn Megy and Rutendo Mapeta from the NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust. The GRID platform screens in parallel 279 genes known to be causative of Primary Immune disorders, and includes IUIS genes International Union of Immunological Societies (IUIS) publication (2015) PMID: https://www.ncbi.nlm.nih.gov/pubmed/?term=26445875. Version used in this panel is GRID V2.0, sent 14th March 2018. Assembly used : GRCh37.
c) Victorian Clinical Genetics Services (Australian Genomics Health Alliance) : Indicated on this panel by the source Victorian Clinical Genetics Services. This has been generated from the list of diagnostic genes for Immunological disorders (June 2018) from Victorian Clinical Genetics Services, Australia, provided by Zornitza Stark. Inclusion criteria for VCGS panels are that the genes have been reported as causative in at least two cases from unrelated families.

3) Reference lists:
a) ESID Registry: Indicated on this panel by the source ESID Registry 20171117.
European Society for immunodeficiencies (ESID) https://esid.org produces a Registry https://esid.org/Working-Parties/Registry/New-ESID-Registry/List-of-diseases-and-genes and gives an overview of current phenotypes and genes associated to immunodeficiencies and lists, where known, genes for each disease. It also includes recent discoveries of new phenotypes and genes. This is a reference to the ESID registry and does not confer pertinence. The version of the registry used in this panel is from 17th November 2017, ESID_Disease_tree_2017_11_17.
b) IUIS Classification: Indicated on this panel by the source IUIS Classification February 2018. International Union of Immunological Societies (IUIS) http://www.iuisonline.org is an umbrella organization for many of the regional and national societies of immunology throughout the world and maintains a list of gene defects routinely used as a reference to categorize and predict the pathogenicity of variants identified in patients by NGS. The classification gives an overview and includes disease, gene, T cell level, B cell level, inheritance and associated immunodeficiency features, which are included in the panel Phenotypes. This is a reference to the IUIS registry and does not confer pertinence. The version of the classification used in this panel is from the updated IUIS classification table (February, 2018) downloaded 20180614.

Panel Activity

32 reviewers

Ellen McDonagh (Genomics England Curator)

Group: Other
Workplace: Other
Richard Scott (North Thames GMC/UCL)

Group: NHS Genomic Medicine Centre
Workplace: NHS clinical service
Tracy Briggs (Manchester Genomic Medicine Centre)

Group: NHS Genomic Medicine Centre
Workplace: NHS clinical service
Peter Arkwright (Royal Manchester Foundation Trust)

Group: GeCIP domain
Workplace: NHS clinical service
Kimberly Gilmour (Great Ormond Street Hopsital)

Group: GeCIP domain
Workplace: NHS diagnostic lab
Sophie Hambleton (Newcastle University)

Group: GeCIP domain
Workplace: Research lab
William Rae (University Hospital Southampton NHS Foundation Trust)

Group: NHS Genomic Medicine Centre
Workplace: NHS clinical service
Christopher Duncan (Newcastle University)

Group: GeCIP domain
Workplace: Research lab
emma baple (South West GMC)

Group: NHS Genomic Medicine Centre
Workplace: NHS clinical service
Ellen Thomas (Genomics England Curator)

Group: Other
Workplace: Other
Olivia Niblock (Genomics England Curator)

Group: Other
Workplace: Other
Sarah Leigh (Genomics England Curator)

Group: Other
Workplace: Other
Rebecca Foulger (Genomics England curator)

Group: Other
Workplace: Other
Louise Daugherty (Genomics England Curator)

Group: Other
Workplace: Other
Helen Brittain (Genomics England Curator)

Group: Other
Workplace: Other
Owen Siggs (Flinders University)

Group: Other
Workplace: Research lab
Eleanor Williams (Genomics England Curator)

Group: Other
Workplace: Other
Zornitza Stark (Australian Genomics)

Group: Other
Workplace: Other clinical service
Ivone Leong (Genomics England Curator)

Group: Other
Workplace: Other
Ronnie Wright (North West GLH)

Group: NHS Genomic Medicine Centre
Workplace: NHS diagnostic lab
Dmitrijs Rots (Children's Clinical University Hospital)

Group: Other
Workplace: Research lab
Catherine Snow (Genomics England)

Group: Other
Workplace: Other
Ilenia Simeoni (Addenbrooke's Hospital Cambridge Biomedical Campus)

Group: NHS Genomic Medicine Centre
Workplace: NHS diagnostic lab
Abdelazeem Elhabyan (Arizona State University)

Group: Other
Workplace: Other clinical service
Arina Puzriakova (Genomics England Curator)

Group: Other
Workplace: Other
Boaz Palterer (University of Florence)

Group: Other
Workplace: Research lab
Kelsey Jones (Great Ormond Street Hospital)

Group: Other NHS organisation
Workplace: NHS clinical service
Nikolaos Marinakis (Laboratory of Medical Genetics, St Sophia Children Hospital, National & Kapodistrian University of Athens)

Group: Other
Workplace: Research lab
Matthew Buckland (Great Ormond Street Hospital for Children NHS Foundation Trust)

Group: GeCIP domain
Workplace: NHS diagnostic lab
Inga Nartisa (researcher)

Group: Other
Workplace: NHS diagnostic lab
Achchuthan Shanmugasundram (Genomics England Curator)

Group: Other
Workplace: Other
Hannah Knight (NIHR BioResource - University of Cambridge)

Group: Other
Workplace: Research lab

554 Entities

547 reviewed, 327 green

List	Entity	Reviews	Mode of inheritance	Details
Filter Entities 554 Entitiess
Green Green List (high evidence)	ACD	4 reviews 4 green	BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal	Sources Expert Review Green GRID V2.0 London North GLH NHS GMS North West GLH Phenotypes Dyskeratosis congenita, autosomal dominant 6, OMIM:616553 Dyskeratosis congenita, autosomal recessive 7, OMIM:616553 Tags
Green Green List (high evidence)	ACP5	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Spondyloenchondrodysplasia with immune dysregulation Type 1 interferonopathies Spondyloenchondrodysplasia with immune dysregulation, 607944 Type 1 interferonopathies Short stature, SP, ICC, SLE, thrombocytopenia and autoimmune hemolytic anemia, possibly recurrent bacterial and viral infections Autoinflammatory Disorders Tags
Green Green List (high evidence)	ADA	8 reviews 6 green	BIALLELIC, autosomal or pseudoautosomal	Sources Combined B and T cell defect v1.12 ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other SCID v1.6 Victorian Clinical Genetics Services Phenotypes Severe combined immunodeficiency due to ADA deficiency (some mosiacism noted) Severe combined immunodeficiency due to ADA deficiency, 102700 T-B- SCID T-B+ SCID Adenosine deaminase (ADA) deficiency Atypical Severe Combined Immunodeficiency (Atypical SCID) Omenn syndrome Severe combined immunodeficiency (SCID) Low NK, bone defects, may have pulmonary alveolar proteinosis, cognitive defects Immunodeficiencies affecting cellular and humoral immunity Tags gene-therapy-trial
Green Green List (high evidence)	ADA2	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome, OMIM:615688 Polyarteritis nodosa, childhood-onset, early-onset recurrent ischemic stroke and fever Autoinflammatory Disorders Tags
Green Green List (high evidence)	ADAM17	7 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes inflammatory skin Inflammatory skin and bowel disease, neonatal, 1 Inflammatory skin and bowel disease, neonatal 1, 614328 ADAM17 deficiency Autoinflammatory Disorders IBD-1 Early onset diarrhea and skin lesions Recurrent infections Tags
Green Green List (high evidence)	ADAR	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Aicardi-Goutieres syndrome 6, OMIM:615010 Fever Syndromes and Related Diseases Type 1 interferonopathies Autoinflammatory Disorders Tags
Green Green List (high evidence)	AGR2	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature NHS GMS Phenotypes Cystic fibrosis-like syndrome Tags
Green Green List (high evidence)	AICDA	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources A- or hypo-gammaglobulinaemia v1.25 ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Immunodeficiency with hyper-IgM, type 2 Hyper IgM syndrome with lymphoid hyperplasia Immunodeficiency with hyper-IgM, type 2, 605258 Primary Immune Deficiencies CSR defects and Hyper IgM (HIGM) syndromes Bacterial infections, enlarged lymph nodes and germinal centers Predominantly Antibody Deficiencies Tags
Green Green List (high evidence)	AIRE	5 reviews 4 green	BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Autoimmune polyendocrinopathy syndrome, type I, with or without reversible metaphyseal dysplasia, 240300 Chronic mucocutaneous candidiasis (CMC) Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) Autoimmune hypoparathyroidism chronic candidiasis Addison disease syndrome Hypoparathyroidism Addison disease mucocutaneous candidiasis syndrome Multiple endocrine deficiency Addison disease candidiasis syndrome Autoimmunity: hypoparathyroidism hypothyroidism, adrenal insufficiency, diabetes, gonadal dysfunction and other endocrine abnormalities, chronic mucocutaneous candidiasis, dental enamel hypoplasia, alopecia areata enteropathy, pernicious anemia Diseases of Immune Dysregulation Tags
Green Green List (high evidence)	AK2	7 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other SCID v1.6 Victorian Clinical Genetics Services Phenotypes Reticular dysgenesis with sensorineural deafness Reticular dysgenesis, 267500 Reticular dysgenesis, AK2 deficiency Reticular Dysgenesis AK2 (SCID) Granulocytopenia and deafness Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	ALPI	4 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification December 2019 Phenotypes Intestinal Alkaline Phosphatase deficiency Inflammatory bowel disease Autoinflammatory Disorders ALPI deficiency Tags gene-checked
Green Green List (high evidence)	ALPK1	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature NHS GMS Phenotypes ROSAH syndrome, OMIM:614979 Tags
Green Green List (high evidence)	AP3B1	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Hermansky-Pudlak syndrome 2 HPS2 Hermansky-Pudlak syndrome, 608233 Immunodeficient HPS Hermansky-Pudlak syndrome with neutropenia Partial albinism, recurrent infections, pulmonary fibrosis, increased bleeding, neutropenia, HLH Diseases of Immune Dysregulation Tags
Green Green List (high evidence)	ARPC1B	5 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Phenotypes Immunodeficiency 71 with inflammatory disease and congenital thrombocytopenia, OMIM:617718 Combined immune deficiency with or without thrombocytopenia Inflammatory predisposition Tags
Green Green List (high evidence)	ATM	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Ataxia-telangiectasia, OMIM:208900 Combined immunodeficiencies with associated or syndromic features Ataxia, telangiectasia, pulmonary infections, lymphoreticular and other malignancies, increased alpha fetoprotein, increased radiosensitivity, chromosomal instability and chromosomal translocations Tags
Green Green List (high evidence)	ATP6AP1	4 reviews 4 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Expert Review Green IUIS Classification February 2018 London North GLH NHS GMS North West GLH Phenotypes Immunodeficiency 47, 300972 Hepatopathy, leukopenia, low copper Predominantly Antibody Deficiencies Immunodeficiency and hepatopathy with or without neurologic features Tags
Green Green List (high evidence)	B2M	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Immunodeficiency 43,241600 Immunodeficiency by defective expression of HLA class 1 Sinopulmonary infections, cutaneous granulomas. Absent _2m associated proteins MHC-I, CD1a, CD1b, CD1c Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	BACH2	5 reviews 4 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Phenotypes Lymphocytic colitis, sinopulmonary infections Diseases of Immune Dysregulation infantile onset enterocolitis hypogammaglobulinaemia BACH2-related immunodeficiency and autoimmunity (BRIDA) Tags
Green Green List (high evidence)	BCL10	6 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Other Victorian Clinical Genetics Services Phenotypes ?Immunodeficiency 37, 616098 Combined immunodeficiency with B cell, T cell, and fibroblast defects Recurrent bacterial and viral infections, candidiasis, gastroenteritis Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	BLM	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Bloom syndrome, OMIM:210900 Immunodeficiency Short stature, dysmorphic facies, sun-sensitive erythema, marrow failure, leukemia, lymphoma, chromosomal instability Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	BLNK	7 reviews 6 green	BIALLELIC, autosomal or pseudoautosomal	Sources A- or hypo-gammaglobulinaemia v1.25 ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Agammaglobulinemia 4, 613502 agammaglobulinaemia with absent B cells Agammaglobulinemia 4 Agammaglobulinemia Severe bacterial infections, normal numbers of pro-B cells Predominantly Antibody Deficiencies Tags
Green Green List (high evidence)	BLOC1S6	5 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GRID V2.0 GRID V2.0North West GLH NHS GMS Victorian Clinical Genetics Services, London North GLH Phenotypes Hermansky-pudlak syndrome 9, 614171 HPS9, palladin deficiency (NK cell defect) Immune Dysregulation Tags
Green Green List (high evidence)	BTK	8 reviews 7 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources A- or hypo-gammaglobulinaemia v1.25 ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Agammaglobulinemia and isolated hormone deficiency Agammaglobulinemia, X-linked Agammaglobulinemia, X-linked 1, 300755 Agammaglobulinemia and isolated hormone deficiency, 307200 Agammaglobulinemia, X-linked 1 (XLA) Agammaglobulinemia agammaglobulinaemia CVID Severe bacterial infections, normal numbers of pro-B cells Predominantly Antibody Deficiencies Tags
Green Green List (high evidence)	C17orf62	4 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification December 2019 Phenotypes Chronic granulomatous disease 5, autosomal recessive, OMIM:618935 Autosomal recessive CGD EROS Congenital defects of phagocyte number or function Chronic granulomatous disease Tags gene-checked new-gene-name
Green Green List (high evidence)	C1QA	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes C1q deficiency, 613652 Complement component 1 deficiency Immunodeficiency due to a classical component pathway complement deficiency SLE, infections with encapsulated organisms Complement Deficiencies Tags
Green Green List (high evidence)	C1QB	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 Inherited complement deficiency v0.11 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Immunodeficiency due to an early component of complement deficiency, 613652 C1q deficiency Complement component 1 deficiency SLE lupus-like disease susceptibility to invasive bacterial infection SLE, infections with encapsulated organisms Complement Deficiencies Tags
Green Green List (high evidence)	C1QC	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes C1q deficiency, 613652 Complement component 1 deficiency Immunodeficiency due to a classical component pathway complement deficiency SLE, infections with encapsulated organisms Complement Deficiencies Tags
Green Green List (high evidence)	C1R	4 reviews 3 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes C1r/C1s deficiency, combined, Lupus Complement component 1 deficiency Immunodeficiency due to a classical component pathway complement deficiency SLE pyogenic infections SLE, infections with encapsulated organisms, Ehlers Danlos phenotype Complement Deficiencies Tags early-onset
Green Green List (high evidence)	C1S	4 reviews 3 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes C1s deficiency, 613783 C1s deficiency, Lupus Complement component 1 deficiency SLE pyogenic infections SLE, infections with encapsulated organisms, Ehlers Danlos phenotype Complement Deficiencies Tags
Green Green List (high evidence)	C2	5 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 Inherited complement deficiency v0.11 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Complement Component C2 Deficiency C2 deficiency, 217000 Immunodeficiency due to C1, C4, or C2 component complement deficiency Lupus SLE, infections with encapsulated organisms, atherosclerosis Complement Deficiencies Tags
Green Green List (high evidence)	C2orf69	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature NHS GMS Phenotypes Combined oxidative phosphorylation deficiency 53, OMIM:619423 Tags gene-checked
Green Green List (high evidence)	C3	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes C3 deficiency, 613779 Complement component 3 deficiency Infections, glomerulonephritis, atypical hemolytic-uremic syndrome with GOF mutations Atypical hemolytic-uremic syndrome, dense deposit disease Complement Deficiencies Tags
Green Green List (high evidence)	C4A	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes C4a deficiency, 614380 Complement component 4 deficiency Immunodeficiency due to a classical component pathway complement deficiency SLE predisposition infections with encapsulated organisms SLE, infections with encapsulated organisms , partial deficiency is common (either C4A or C4B) and appears to have a modest effect on host defense Complement Deficiencies Tags
Green Green List (high evidence)	C4B	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes C4B deficiency, 614379 SLE predisposition SLE, infections with encapsulated organisms , partial deficiency is common (either C4A or C4B) and appears to have a modest effect on host defense Complement Deficiencies Tags
Green Green List (high evidence)	C5	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes C5 deficiency, 609536 Complement component 5 deficiency Susceptibility to invasive bacterial infection, especially meningococcal Disseminated neisserial infections Complement Deficiencies Tags
Green Green List (high evidence)	C6	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes C6 deficiency, 612446 Complement component 6 deficiency Susceptibility to invasive bacterial infection, especially meningococcal Disseminated neisserial infections Complement Deficiencies Tags
Green Green List (high evidence)	C7	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes C7 deficiency, 610102 Complement component 7 deficiency Susceptibility to invasive bacterial infection, especially meningococcal Disseminated neisserial infections Complement Deficiencies Tags
Green Green List (high evidence)	C8A	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes C8 deficiency, type I, 613790 Complement component 8 deficiency Susceptibility to invasive bacterial infection, especially meningococcal Disseminated neisserial infections Complement Deficiencies Tags
Green Green List (high evidence)	C8B	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes C8 deficiency, type II, 613789 Complement component 8 deficiency Susceptibility to invasive bacterial infection, especially meningococcal Disseminated neisserial infections Complement Deficiencies Tags
Green Green List (high evidence)	C9	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes C9 deficiency, 613825 Complement component 9 deficiency Susceptibility to invasive bacterial infection, especially meningococcal Mild susceptibility to disseminated neisserial infections Complement Deficiencies Tags
Green Green List (high evidence)	CARD11	5 reviews 3 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Immunodeficiency 11A, 615206 (AR) CARD11 deficiency Predominantly antibody deficiencies Atypical Severe Combined Immunodeficiency (Atypical SCID) Combined immunodeficiency Autoimmune lymphoproliferative syndrome (ALPS) B cell expansion with NFKB and T cell anergy (BENTA) (AD), 616452 immunodeficiency 11B with atopic dermatitis (AD), 617638 Severe atopy, recurrent infections Combined immunodeficiencies with associated or syndromic features Splenomegaly, lymphadenopathy, poor vaccine response Predominantly Antibody Deficiencies Pneumocystis jirovecii pneumonia, bacterial and viral infections Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	CARD14	5 reviews 3 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Pityriasis rubra pilaris, OMIM:173200 Psoriasis 2, OMIM:602723 Autoinflammatory Disorders Tags
Green Green List (high evidence)	CARD9	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Candidiasis, familial, 2 212050 CARD9 deficiency Predisposition to invasive fungal disease due to CARD9 deficiency Invasive candidiasis infection, deep dermatophytoses, other invasive fungal infections Defects in Intrinsic and Innate Immunity Tags
Green Green List (high evidence)	CARMIL2	6 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Phenotypes Combined immunodeficiency warts, molluscum contagiosum, and T‐cell dysfunction EBV+ disseminated smooth muscle tumours Recurrent bacterial, fungal and mycobacterial infections, viral warts, molluscum and EBV lymphoproliferative and other malignancy, atopy Diseases of Immune Dysregulation Tags
Green Green List (high evidence)	CASP10	5 reviews 4 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Autoimmune lymphoproliferative syndrome, type II, 603909 Autoimmune lymphoproliferative syndrome (ALPS) Adenopathies, splenomegaly, autoimmunity Diseases of Immune Dysregulation Tags
Green Green List (high evidence)	CASP8	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Caspase-8 deficiency state CEDS Immunodeficiency due to CASP8 deficiency Caspase 8 deficiency Autoimmune lymphoproliferative syndrome (ALPS) ?Autoimmune lymphoproliferative syndrome, type IIB, 607271 Adenopathies, splenomegaly, bacterial and viral infections, hypogammaglobulinemia Diseases of Immune Dysregulation Tags
Green Green List (high evidence)	CCBE1	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Hennekam lymphangiectasia-lymphedema syndrome 1, 235510 Lymphangiectasia and lymphedema with facial abnormalities and other dysmorphic features Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	CD19	6 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources A- or hypo-gammaglobulinaemia v1.25 ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Immunodeficiency, common variable, 3 613493 hypogammaglobulinemia Immunodeficiency, common variable, 3 Common variable immunodeficiency disorders (CVID) Isolated IgG subclass deficiency Recurrent infections, may have glomerulonephritis Predominantly Antibody Deficiencies Tags
Green Green List (high evidence)	CD247	9 reviews 1 green 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 Other SCID v1.6 Victorian Clinical Genetics Services Phenotypes T-B+ severe combined immunodeficiency due to CD3zeta ?Immunodeficiency 25 T-B+ SCID Immunodeficiency 25, 610163 Atypical Severe Combined Immunodeficiency (Atypical SCID) Severe combined immunodeficiency (SCID) Nl NK, no g/d T cells Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	CD27	6 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Combined B and T cell defect v1.12 ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Lymphoproliferative syndrome 2 Combined immunodeficiency with EBV-associated lymphoproliferation Combined immunodeficiency CD27 deficiency Features triggered by EBV infection, HLH, aplastic anemia, low iNKT cells, lymphoma Diseases of Immune Dysregulation Tags
Green Green List (high evidence)	CD3D	8 reviews 6 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other SCID v1.6 Victorian Clinical Genetics Services Phenotypes Immunodeficiency 19 Severe Combined Immune Deficiency Severe combined immunodeficiency, T cell-negative, B-cell/natural killer-cell positive T-B+ SCID CD3d deficiency Atypical Severe Combined Immunodeficiency (Atypical SCID) Severe combined immunodeficiency (SCID) Nl NK, no g/d T cells Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	CD3E	8 reviews 6 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other SCID v1.6 Victorian Clinical Genetics Services Phenotypes Immunodeficiency 18, SCID variant Severe Combined Immune Deficiency Immunodeficiency due to defect in CD3-epsilon T-B+ SCID CD3e deficiency Atypical Severe Combined Immunodeficiency (Atypical SCID) Severe combined immunodeficiency (SCID) Nl NK, no g/d T cells Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	CD3G	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Immunodeficiency 17, CD3 gamma deficient 615607 CD3z deficiency Combined immunodeficiency N/A Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	CD40	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Phenotypes Immunodeficiency with hyper-IgM, type 3 HIGM3 CD40 deficiency CSR defects and Hyper IgM (HIGM) syndromes Hyper-IgM syndrome due to CD40 deficiency non-X-linked hyper IgM syndrome Neutropenia, opportunistic infections, gastrointestinal and biliary tract and liver disease, Cryptosporidium infections Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	CD40LG	5 reviews 4 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Immunodeficiency, X-linked, with hyper-IgM CD40 ligand deficiency CSR defects and Hyper IgM (HIGM) syndromes Hyper-IGM immunodeficiency, X-linked XHIM Hyper-IGM syndrome HIGM IHIS Immunodeficiency 3 IMD3 Hyper-IgM syndrome due to CD40 ligand deficiency Hyper-IgM syndrome due to CD40L deficiency Hyper-IgM syndrome type 1 HIGM1 Neutropenia, thrombocytopenia, hemolytic anemia, opportunistic infections, biliary tract and liver disease, Cryptosporidium infections Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	CD46	4 reviews 4 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Hemolytic uremic syndrome, atypical, susceptibility to, 2, 612922 Membrane Cofactor Protein (CD46) deficiency atypical HUS Atypical hemolytic-uremic syndrome, infections, preeclampsia Complement Deficiencies Tags
Green Green List (high evidence)	CD55	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green IUIS Classification February 2018 London North GLH NHS GMS North West GLH Phenotypes Decay-accelerating factor for complement deficiency (DAF CD55) protein-losing enteropathy hypogammaglobulinaemia angiopathic thrombosis primary intestinal lymphangiectasia Protein losing enteropathy, thrombosis Complement Deficiencies Tags
Green Green List (high evidence)	CD59	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Hemolytic anemia, CD59-mediated, with or without immune-mediated polyneuropathy, 612300 CD59 antigen P18-20 deficiency (CD59) Membrane Attack Complex Inhibitor (CD59) deficiency Primary CD59 deficiency paroxysmal nocturnal haemoglobinuria chronic hemolysis childhood relapsing immune-mediated polyneuropathy Hemolytic anemia, polyneuropathy Complement Deficiencies Tags
Green Green List (high evidence)	CD70	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Phenotypes Combined immunodeficiency CD70-deficiency EBV-related malignancy EBV susceptibility, Hodgkin lymphoma Diseases of Immune Dysregulation Tags
Green Green List (high evidence)	CD79A	7 reviews 5 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources A- or hypo-gammaglobulinaemia v1.25 ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Agammaglobulinemia 3, 613501 Agammaglobulinemia 3 Agammaglobulinemia CD79A deficiency Agammaglobulinemia with autosomal recessive inheritance (ARA) Severe bacterial infections, normal numbers of pro-B cells Predominantly Antibody Deficiencies Tags
Green Green List (high evidence)	CD79B	6 reviews 4 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources A- or hypo-gammaglobulinaemia v1.25 ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Agammaglobulinemia 6, 612692 Agammaglobulinemia 6 Agammaglobulinemia CD79B deficiency, Agammaglobulinemia with autosomal recessive inheritance (ARA) Severe bacterial infections, normal numbers of pro-B cells Predominantly Antibody Deficiencies Tags
Green Green List (high evidence)	CDC42	3 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Phenotypes Neonatal-onset cytopaenia with dyshaematopoiesis autoinflammation rash HLH Tags
Green Green List (high evidence)	CDCA7	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification February 2018 Literature London North GLH NHS GMS North West GLH Phenotypes Immunodeficiency-centromeric instability-facial anomalies syndrome ICF Immunodeficiency-centromeric instability-facial anomalies syndrome 3, 616910 ICF3 immunodeficiency, centromeric instability, facial anomalies syndrome type 3 recurrent respiratory infections hypogammaglobulinaemia enteropathy Facial dysmorphic features, macroglossia, bacterial/opportunistic infections, malabsorption, cytopenias, malignancies, multiradial configurations of chromosomes 1, 9, 16 Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	CEBPE	5 reviews 5 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Specific granule deficiency, OMIM:245480 CCAAT/enhancer binding protein epsilon deficiency (CEBPE) Recurrent infection due to specific granule deficiency Neutrophil lactoferrin deficiency Neutrophils with bilobed nuclei Congenital defects of phagocyte number or function Tags
Green Green List (high evidence)	CFD	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 Inherited complement deficiency v0.11 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Complement factor D deficiency, 613912 Complement factor D deficiency Factor D deficiency Recurrent Neisseria infections due to factor D deficiency Neisserial infections Complement Deficiencies Tags
Green Green List (high evidence)	CFH	4 reviews 4 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 Inherited complement deficiency v0.11 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Complement factor H deficiency, 609814 Infections, disseminated neisserial infections, atypical Hemolytic-uremic syndrome, preeclampsia, dense deposit disease Complement Deficiencies Tags
Green Green List (high evidence)	CFI	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 Inherited complement deficiency v0.11 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Complement factor I deficiency, 610984 {Hemolytic uremic syndrome, atypical, susceptibility to, 3}, 612923 {Macular degeneration, age-related, 13, susceptibility to}, 615439 Complement factor I deficiency C3b inactivator deficiency Factor I deficiency Immunodeficiency with factor I anomaly Infections, disseminated neisserial infections, atypical Hemolytic-uremic syndrome, preeclampsia Complement Deficiencies Tags
Green Green List (high evidence)	CFP	4 reviews 4 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Properdin deficiency Properdin P factor complement deficiency (PFC) Neisserial infections Complement Deficiencies Tags
Green Green List (high evidence)	CHD7	4 reviews 4 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Charge syndrome CHARGE syndrome, 214800 Immunodeficiency COLOBOMA, HEART ANOMALY, CHOANAL ATRESIA, RETARDATION, GENITAL AND EAR ANOMALIES Coloboma, heart anomaly, choanal atresia, intellectual disability, genital and ear anomalies, CNS malformation, some are SCID-like and have low TRECs Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	CIB1	3 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Phenotypes Epidermodysplasia verruciformis 3 618267 HPV infections and cancer of the skin Tags
Green Green List (high evidence)	CIITA	6 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Combined B and T cell defect v1.12 ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Bare lymphocyte syndrome, type II, complementation group A Combined immunodeficiency (MHC class II deficiency, bare lymphocyte syndrome) HLA class II deficiency Respiratory and gastrointestinal infections, liver/biliary tract disease Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	CLPB	5 reviews 4 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes 3-methylglutaconic aciduria, type VIIB, autosomal recessive, OMIM:616271 3-methylglutaconic aciduria, type VIIA, autosomal dominant, OMIM: 619835 Neutropenia, severe congenital, 9, autosomal dominant, OMIM: 619813 Tags
Green Green List (high evidence)	COL7A1	4 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Green Phenotypes Very Early Onset Inflammatory Bowel Disease Inflammatory Bowel Disease Dystrophic Epidermolysis Bullosa Pruriginosa Tags
Green Green List (high evidence)	COPA	5 reviews 4 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Autoimmune inflammatoy arthritis and interstial lung disease, 616414 Autoimmune interstitial lung disease-arthritis syndrome COPA syndrome Autoimmune inflammatory arthritis and interstitial lung disease with Th17 dysregulation and autoantibody production Autoinflammatory Disorders Tags missense
Green Green List (high evidence)	CORO1A	7 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources Combined B and T cell defect v1.12 ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Immunodeficiency 8 Combined immunodeficiency hypogammaglobulinaemia, combined immunodeficiency Coronin-1A deficiency Atypical Severe Combined Immunodeficiency (Atypical SCID) Severe combined immunodeficiency (SCID) Omenn syndrome Detectable thymus, EBV Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	CSF2RA	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Surfactant metabolism dysfunction, pulmonary 4, 300770 Congenital pulmonary alveolar proteinosis hypersensitivity Pulmonary alveolar proteinosis Alveolar proteinosis Congenital defects of phagocyte number or function Tags Pseudoautosomal region 1
Green Green List (high evidence)	CSF2RB	5 reviews 4 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification February 2018 London North GLH NHS GMS North West GLH Phenotypes Surfactant metabolism dysfunction, pulmonary, 5, 614370 Alveolar proteinosis Congenital defects of phagocyte number or function Tags
Green Green List (high evidence)	CSF3R	6 reviews 4 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Congenital neutropaenia v1.22 ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Neutropenia, severe congenital, 7, autosomal recessive, 617014 Neutropenia, severe congenital 7 Congenital neutropenia N/A Congenital defects of phagocyte number or function Tags
Green Green List (high evidence)	CTLA4	7 reviews 4 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources A- or hypo-gammaglobulinaemia v1.25 ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes CVID hypogammaglobulinaemia lymphadenopathy T cell lymphopenia enteropathy interstitual lung disease autoimmunity Autoimmune lymphoproliferative syndrome, type V 616100 Autoimmune lymphoproliferative syndrome, type V Combined immunodeficiency Early-onset multi-organ autoimmune disease Immune dysregulation a broad range of autoimmune phenomena have been described along with polyclonal lymphocytic infiltrates. Susceptibility to infection and hypogammaglobulinaemia are not usually present in isolation Autoimmune cytopenias, enteropathy, interstitial lung disease, extra-lymphoid lymphocytic infiltration recurrent infections Diseases of Immune Dysregulation Tags
Green Green List (high evidence)	CTPS1	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Immunodeficiency 24, 615897 Severe combined immunodeficiency due to CTPS1 deficiency Patients develop Epstein-Barr Virus (EBV) driven Hemophagocytic Lymphohistiocytosis (HLH ) Recurrent/chronic bacterial and viral infections (EBV, VZV), EBV lymphoproliferation, B-cell non-Hodgkin lymphoma Diseases of Immune Dysregulation Tags founder-effect
Green Green List (high evidence)	CTSC	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Papillon-Lefevre syndrome, 245000 Periodontitis, palmoplantar hyperkeratosis in some patients Congenital defects of phagocyte number or function Severe periodontitis palmoplantar keratoderma Haim-Munk syndrome, 245010 Tags
Green Green List (high evidence)	CXCR4	6 reviews 5 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Congenital neutropaenia v1.22 ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes WHIM syndrome, 193670 Myelokathexis, isolated WHIM syndrome Warts hypogammaglobulinemia infections and myelokathexis (WHIM) Warts (HPV) infection, neutropenia, low B cell number, hypogammaglobulinemia Defects in Intrinsic and Innate Immunity Tags
Green Green List (high evidence)	CYBA	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Chronic granulomatous disease, autosomal, due to deficiency of CYBA,233690 Chronic granulomatous disease (CGD) Infections, autoinflammatory phenotype Congenital defects of phagocyte number or function Tags
Green Green List (high evidence)	CYBB	5 reviews 4 green	X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Immunodeficiency 34, mycobacteriosis, X-linked, 300645 Chronic granulomatous disease, X-linked, 306400 Chronic granulomatous disease (CGD) Defects with susceptibility to mycobacterial infection (MSMD) Infections, autoinflammatory phenotype, IBD, McLeod phenotype in patients with deletions extending into the contiguous Kell locus Congenital defects of phagocyte number or function Isolated susceptibility to mycobacteria Defects in Intrinsic and Innate Immunity Tags gene-therapy-trial
Green Green List (high evidence)	DBR1	3 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification December 2019 Phenotypes DBR1 deficiency Defects in intrinsic and innate immunity HSE of the brainstem. Other viral infections of the brainstem Tags
Green Green List (high evidence)	DCLRE1B	7 reviews 4 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Dyskeratosis congenita, autosomal recessive 8, OMIM:620133 Tags Q3_21_expert_review Q3_21_rating to_be_confirmed_NHSE
Green Green List (high evidence)	DCLRE1C	8 reviews 6 green	BIALLELIC, autosomal or pseudoautosomal	Sources Combined B and T cell defect v1.12 ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other SCID v1.6 Victorian Clinical Genetics Services Phenotypes Severe combined immunodeficiency, Athabascan type Severe combined immunodeficiency, Athabascan type, 602450 T-B- SCID T-B+ SCID Severe Combined Immunodeficiency With Sensitivity To Ionizing Radiation DCLRE1C (Artemis) deficiency Atypical Severe Combined Immunodeficiency (Atypical SCID) Combined immunodeficiency Omenn syndrome Severe combined immunodeficiency (SCID) Nl NK, radiation sensitive Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	DEF6	5 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification December 2019 Phenotypes Immunodeficiency 87 and autoimmunity, OMIM:619573 Enteropathy, hepatosplenomegaly, cardiomyopathy, recurrent infections Tags
Green Green List (high evidence)	DKC1	4 reviews 4 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Dyskeratosis congenita, X-linked 305000 Hoyeraal-Hreidarsson syndrome Intrauterine growth retardation, microcephaly, nail dystrophy, sparse scalp hair and eyelashes, hyperpigmentation of skin, palmar hyperkeratosis, premalignant oral leukoplakia, pancytopenia, myelodysplasia, recurrent infections Severe phenotype with DD and cerebellar hypoplasia Hoyeraal-Hreidarsson Syndrome (HHS) may occur in some DKC patients Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	DNAJC21	4 reviews 3 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification February 2018 London North GLH NHS GMS North West GLH Phenotypes Bone marrow failure syndrome 3, 617052 Shwachman-Diamond syndrome-like Metaphyseal changes, short stature, developmental delay, pancreatic dysfunction, bone marrow failure Congenital defects of phagocyte number or function Tags
Green Green List (high evidence)	DNASE1L3	7 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification December 2019 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Phenotypes Systemic lupus erythematosus 16, 614420 Diseases of Immune Dysregulation Autoinflammatory Disorders Systemic lupus erythematosus, lupus nephritis, hypocomplementemic urticarial vasculitis familial early-onset SLE Tags deletions founder-effect
Green Green List (high evidence)	DNASE2	4 reviews 3 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification February 2018 London North GLH NHS GMS North West GLH Phenotypes Autoinflammatory-pancytopenia syndrome, OMIM:619858 Tags
Green Green List (high evidence)	DNMT3B	6 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources A- or hypo-gammaglobulinaemia v1.25 ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Immunodeficiency-centromeric instability-facial anomalies syndrome 1, 242860 Immunodeficiency-centromeric instability-facial anomalies syndrome 1 Immunodeficiency centromeric instability facial anomalies syndrome (ICF) Facial dysmorphic features, developmental delay, macroglossia, bacterial/opportunistic infections, malabsorption, cytopenias, malignancies, multiradial configurations of chromosomes 1, 9, 16 Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	DOCK2	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Dock 2 deficiency, Immunodeficiency 40 Immunodeficiency 40, 616433 Nl NK cells, but defective function. Poor interferon responses in hematopoietic and non-hematopoietic cells Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	DOCK8	7 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources Combined B and T cell defect v1.12 ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Hyper-IgE recurrent infection syndrome, autosomal recessive, 243700 Hyper-IgE recurrent infection syndrome impaired T cell function, Atopy, cutaneous viral infections Combined immunodeficiency Hyper IgE syndrome (HIES) Low NK cells with poor function, eosinophilia, recurrent infections, cutaneous viral, fungal and staphylococcal infections, severe atopy, cancer diathesis Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	EFL1	3 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Phenotypes Shwachman-Diamond syndrome 2, MIM# 617941 Tags
Green Green List (high evidence)	ELANE	6 reviews 5 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Congenital neutropaenia v1.22 ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Neutropenia, cyclic, 162800 Neutropenia, severe congenital 1, autosomal dominant, 202700 Neutropenia, severe congenital 1 Congenital neutropenia Cyclic neutropenia Susceptibility to MDS/leukemia, Severe congenital neutropenia or cyclic neutropenia Congenital defects of phagocyte number or function Tags
Green Green List (high evidence)	ELF4	7 reviews 2 green 3 red	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources A- or hypo-gammaglobulinaemia v1.25 Expert Review Green Phenotypes Inflammatory bowel disease Mucosal inflammation Fever Ulcers Behcet-like disease X-linked hypogammaglobulinemia with isolated growth hormone deficiency Tags
Green Green List (high evidence)	EPG5	6 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Combined B and T cell defect v1.12 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Vici syndrome, 242840 Immunodeficiency with cleft lip/palate, cataract, hypopigmentation, and absent corpus callosum Vici syndrome syndromic phenotype (immunodeficiency variable) Vici syndrome due to EPG5 deficiency Agenesis of the corpus callosum, cataracts, cardiomyopathy, skin hypopigmentation, intellectual disability, microcephaly, recurrent infections, chronic mucocutaneous candidiasis Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	ERCC6L2	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification February 2018 London North GLH NHS GMS North West GLH Phenotypes Bone marrow failure syndrome 2, 615715 Facial dysmorphism, microcephaly, bone marrow failure Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	EXTL3	6 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources A- or hypo-gammaglobulinaemia v1.25 Expert Review Green IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Phenotypes Immunoskeletal dysplasia with neurodevelopmental abnormalities, OMIM:617425 Tags
Green Green List (high evidence)	F12	4 reviews 4 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green GRID V2.0 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Angioedema, hereditary, 3, OMIM:610618 Tags
Green Green List (high evidence)	FADD	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Infections, recurrent, with encephalopathy, hepatic dysfunction, and cardiovasuclar malformations, 613759 ALPS-like disease functional hyposplenism invasive pneumococcal disease para-infectious encephalopathy and hepatopathy cardiovascular malformations Functional hyposplenism, bacterial and viral infections, recurrent episodes of encephalopathy and liver dysfunction Diseases of Immune Dysregulation Tags
Green Green List (high evidence)	FAS	5 reviews 4 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Autoimmune lymphoproliferative syndrome type IA, 601859 Autoimmune lymphoproliferative syndrome, type IA (ALPS-FAS) Autoimmune lymphoproliferative syndrome (ALPS) Splenomegaly, adenopathies, autoimmune cytopenias, increased lymphoma risk, IgG and A normal or increased, elevated serum FasL and IL-10, vitamin B12 Diseases of Immune Dysregulation Tags
Green Green List (high evidence)	FASLG	6 reviews 4 green	BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Autoimmune lymphoproliferative syndrome, type IB, OMIM:601859 autoimmune lymphoproliferative syndrome type 1, MONDO:0011158 systemic lupus erythematosus (SLE) Tags
Green Green List (high evidence)	FAT4	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Hennekam lymphangiectasia-lymphedema syndrome 2, 616006 Lymphangiectasia and lymphedema with facial abnormalities and other dysmorphic features Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	FCHO1	4 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification December 2019 Phenotypes Recurrent infections, lymphoproliferation, increased activation-induced T-cell death, defective clathrin-mediated endocytosis FCHO1 deficiency Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	FERMT1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification December 2019 Phenotypes Dermatosis characterized by congenital blistering, skin atrophy, photosensitivity, skin fragility, and scaling Kindler syndrome, 173650 Diseases of Immune Dysregulation Kindler syndrome, OMIM:173650 FERMT1 deficiency (Kindler syndrome) Tags
Green Green List (high evidence)	FERMT3	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Leukocyte adhesion deficiency, type III, 612840 LAD LAD type 1 plus bleeding tendency Congenital defects of phagocyte number or function Tags early-onset
Green Green List (high evidence)	FNIP1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Primary Immunodeficiency Agammaglobulinemia Hypertrophic Cardiomyopathy Neutropenia Tags
Green Green List (high evidence)	FOXN1	9 reviews 3 green 1 red	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other SCID v1.6 Victorian Clinical Genetics Services Phenotypes T-cell immunodeficiency, congenital alopecia, and nail dystrophy, OMIM:601705 (AR) T-cell lymphopenia, infantile, with or without nail dystrophy, autosomal dominant, OMIM:618806 (AD) T-B+ SCID Severe infections, abnormal thymic epithelium, immunodeficiency, congenital alopecia, nail dystrophy, neural tube defect Combined immunodeficiencies with associated or syndromic features Tags founder-effect
Green Green List (high evidence)	FOXP3	5 reviews 4 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Immunodysregulation, polyendocrinopathy, and enteropathy, X-linked, 304790 IPEX FOXP3 deficiency (IPEX) Immune dysregulation polyendocrinopathy enteropathy X-linked syndrome Autoimmune enteropathy, early onset diabetes, hyroiditis hemolytic anemia, thrombocytopenia, eczema, elevated IgE, IgA Diseases of Immune Dysregulation Tags
Green Green List (high evidence)	G6PC3	6 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources Congenital neutropaenia v1.22 ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Neutropenia, severe congenital 4, autosomal recessive, 612541 Dursun syndrome, 612541 Severe Congenital Neutropenia Neutropenia, severe congenital 4 Congenital neutropenia Structural heart defects, urogenital abnormalities, inner ear deafness, and venous angiectasias of trunks and limbs Congenital defects of phagocyte number or function Tags
Green Green List (high evidence)	G6PD	4 reviews 4 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources ESID Registry 20171117 Expert Review Green IUIS Classification February 2018 London North GLH NHS GMS North West GLH Phenotypes Glucose-6-phosphate dehydrogenase deficiency (G6PD) haemolytic anaemia chronic granulomatous disease-like susceptibility to infection Infections Congenital defects of phagocyte number or function Tags
Green Green List (high evidence)	GATA1	5 reviews 4 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Congenital neutropaenia v1.22 Expert Review Green London North GLH NHS GMS North West GLH Phenotypes Anemia, X-linked, with/without neutropenia and/or platelet abnormalities, 300835 thrombocytopenia dyserythropoietic anaemia neutropenia Tags
Green Green List (high evidence)	GATA2	4 reviews 4 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Immunodeficiency 21,614172 Monocytopenia and mycobacterial infection (MonoMAC) Congenital neutropenia Combined immunodeficiency with susceptibility to mycobacterial, viral and fungal infections Monocytopenia with susceptibility to infections Susceptibility to mycobacteria, HPV, histoplasmosis, alveolar proteinosis, MDS/AML/CMMoL, lymphedema Congenital defects of phagocyte number or function Tags
Green Green List (high evidence)	GFI1	6 reviews 5 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Congenital neutropaenia v1.22 ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Neutropenia, nonimmune chronic idiopathic, of adults, 607847 Severe congenital 2, autosomal dominant, 613107 Neutropenia, severe congenital 2 Congenital neutropenia Severe congenital neutropenia Chronic non-immune neutropenia of adults B/T lymphopenia Congenital defects of phagocyte number or function Tags
Green Green List (high evidence)	GINS1	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green IUIS Classification February 2018 London North GLH NHS GMS North West GLH Phenotypes GINS1 deficiency intrauterine growth retardation chronic neutropenia NK cell deficiency Immunodeficiency 55, 617827 Neutropenia, IUGR, NK cells very low Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	GUCY2C	5 reviews 1 green 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green GOSH PID v.8.0 London North GLH NHS GMS North West GLH Phenotypes Diarrhea 6, 614616 meconium ileus, 614665 Diarrhea 6, OMIM:614616 Tags
Green Green List (high evidence)	HAVCR2	4 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification December 2019 Phenotypes T-cell lymphoma, subcutaneous panniculitis-like, 618398 Tim-3 deficiency Autoinflammatory Disorders Tags
Green Green List (high evidence)	HAX1	8 reviews 6 green	BIALLELIC, autosomal or pseudoautosomal	Sources Agranulocytosis v1.3 Congenital neutropaenia v1.22 ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Neutropenia, severe congenital 3, autosomal recessive, 610738 Severe congenital neutropenia Neutropenia, severe congenital 3 Congenital neutropenia Cognitive and neurological defects in patients with defects in both HAX1 isoforms, susceptibility to MDS/leukemia Congenital defects of phagocyte number or function Tags
Green Green List (high evidence)	HELLS	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification February 2018 Literature London North GLH NHS GMS North West GLH Phenotypes Immunodeficiency-centromeric instability-facial anomalies syndrome ICF Immunodeficiency-centromeric instability-facial anomalies syndrome 4, 616911 ICF4 Facial dysmorphic features, macroglossia, bacterial/opportunistic infections, malabsorption, cytopenias, malignancies, multiradial configurations of chromosomes 1, 9, 16 Combined immunodeficiencies with associated or syndromic features Tags early-onset
Green Green List (high evidence)	HPS1	4 reviews 2 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GOSH PID v.8.0 London North GLH NHS GMS North West GLH Phenotypes Hermansky-Pudlak syndrome 1 oculocutaneous albinism bleeding inflammatory bowel disease pulmonary fibrosis Tags
Green Green List (high evidence)	HPS4	4 reviews 2 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GOSH PID v.8.0 London North GLH NHS GMS North West GLH Phenotypes Hermansky-Pudlak syndrome 4, 614073 Tags
Green Green List (high evidence)	HPS6	4 reviews 2 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GOSH PID v.8.0 London North GLH NHS GMS North West GLH Phenotypes Hermansky-Pudlak syndrome 6, 614075 Tags
Green Green List (high evidence)	HTRA2	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Congenital neutropaenia v1.22 Expert Review Green London North GLH NHS GMS North West GLH Phenotypes 3-methylglutaconic aciduria, type VIII, 617248 early onset neurological syndrome neutropenia Tags
Green Green List (high evidence)	ICOS	7 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources A- or hypo-gammaglobulinaemia v1.25 ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Immunodeficiency, common variable, 1 Immunodeficiency, common variable, 1, 607594 Common variable immunodeficiency disorders (CVID) Isolated IgG subclass deficiency hypogammaglobulinaemia gammaglobulinaemia combined immunodeficiency Recurrent infections, autoimmunity, gastroenteritis, granulomas Immunodeficiencies affecting cellular and humoral immunity Tags deletions
Green Green List (high evidence)	IFIH1	4 reviews 4 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Aicardi-Goutieres syndrome 7, OMIM:615846 (AD) Singleton-Merten syndrome 1, OMIM:182250 (AD) Susceptibility to RNA viruses (AR) Tags
Green Green List (high evidence)	IFNAR2	5 reviews 2 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification December 2019 IUIS Classification February 2018 NHS GMS Phenotypes Immunodeficiency 45, OMIM:616669 Tags
Green Green List (high evidence)	IFNGR1	4 reviews 4 green	BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Immunodeficiency 27A, (AR) 209950 Immunodeficiency 27B, (AD) 615978 Mycobacteriosis Defects with susceptibility to mycobacterial infection (MSMD) Susceptibility to mycobacteria and Salmonella Defects in Intrinsic and Innate Immunity Tags
Green Green List (high evidence)	IFNGR2	4 reviews 4 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Immunodeficiency 28, mycobacteriosis, OMIM:614889 Tags
Green Green List (high evidence)	IGHM	6 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources A- or hypo-gammaglobulinaemia v1.25 ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Phenotypes Agammaglobulinemia 1, 601495 Agammaglobulinemia 1 Agammaglobulinemia Severe bacterial infections, normal numbers of pro-B cells Predominantly Antibody Deficiencies Tags
Green Green List (high evidence)	IGLL1	6 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources A- or hypo-gammaglobulinaemia v1.25 ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Agammaglobulinemia 2, 613500 Agammaglobulinemia 2 Agammaglobulinemia Severe bacterial infections, normal numbers of pro-B cells Predominantly Antibody Deficiencies Tags
Green Green List (high evidence)	IKBKB	8 reviews 4 green	BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Immunodeficiency 15A, OMIM:618204 (AD) Immunodeficiency 15B, OMIM:615592 (AR) Combined immunodeficiency Recurrent bacterial, viral, fungal infections, opportunistic infections Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	IKBKG	5 reviews 4 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Immunodeficiency 33, 300636 Ectodermal dysplasia, hypohidrotic, with immune deficiency 300291 Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency, 300301 Immunodeficiency, isolated, 300584 Invasive pneumococcal disease, recurrent isolated, 2,300640 Defects of TLR/NFkappa-B signalling Anhidrotic ectodermal dysplasia (in some), various infections (bacteria, mycobacteria, viruses and fungi), colitis, conical teeth, variable defects of skin, hair and teeth, monocyte dysfunction Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	IKZF1	6 reviews 3 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources A- or hypo-gammaglobulinaemia v1.25 ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Immunodeficiency, common variable, 13, 616873 Immunodeficiency, common variable 13 IKAROS deficiency Recurrent sinopulmonary infections Predominantly Antibody Deficiencies Tags
Green Green List (high evidence)	IKZF2	4 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green Literature NHS GMS Phenotypes combined immunodeficiency thrush mucosal ulcers chronic lymphoadenopathy reduced MAIT cells Tags gene-checked
Green Green List (high evidence)	IKZF3	2 reviews 1 green 1 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Phenotypes Immunodeficiency 84, OMIM:619437 Tags
Green Green List (high evidence)	IL10	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Early-onset inflammatory bowel disease Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome Inflammatory bowel disease (IBD) Folliculitis, recurrent respiratory diseases, arthritis, Diseases of Immune Dysregulation Tags
Green Green List (high evidence)	IL10RA	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Inflammatory bowel disease 28, early onset, autosomal recessive, 613148 Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome IBD, Folliculitis, recurrent respiratory diseases, arthritis, lymphoma Diseases of Immune Dysregulation Tags early-onset
Green Green List (high evidence)	IL10RB	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Inflammatory bowel disease 25, early onset, autosomal recessive,612567 Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome IBD, folliculitis, recurrent respiratory diseases, arthritis, lymphoma Diseases of Immune Dysregulation Tags early-onset
Green Green List (high evidence)	IL12B	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Immunodeficiency 29, mycobacteriosis, 614890 Defects with susceptibility to mycobacterial infection (MSMD) Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency Susceptibility to mycobacteria and Salmonella Defects in Intrinsic and Innate Immunity Tags
Green Green List (high evidence)	IL12RB1	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Immunodeficiency 30, 614891 Defects with susceptibility to mycobacterial infection (MSMD) Susceptibility to mycobacteria and Salmonella Defects in Intrinsic and Innate Immunity Tags
Green Green List (high evidence)	IL17RA	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Candidiasis, familial, 5 Chronic mucocutaneous candidiasis (CMC) Immunodeficiency 51, 613953 Defects in Intrinsic and Innate Immunity CMC, folliculitis Defects in Intrinsic and Innate Immunity Tags
Green Green List (high evidence)	IL17RC	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Candidiasis, familial, 9 616445 Chronic Mucocutaneous Candidiasis CMC Defects in Intrinsic and Innate Immunity Tags
Green Green List (high evidence)	IL1RN	6 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Interleukin 1 receptor antagonist deficiency, OMIM:612852 Sterile multifocal osteomyelitis, periostitis, and pustulosis DIRA Autoinflammatory Disorders Tags
Green Green List (high evidence)	IL21R	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Immunodeficiency 56, OMIM:615207 Tags
Green Green List (high evidence)	IL2RA	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Interleukin-2 receptor, alpha chain, deficiency of Combined immunodeficiency Omenn syndrome Interleukin 2 receptor alpha deficiency (CD25) (IPEX phenotype) Immunodeficiency 41 with lymphoproliferation and autoimmunity, 606367 Lymphoproliferation, autoimmunity, impaired T cell proliferation Diseases of Immune Dysregulation Tags
Green Green List (high evidence)	IL2RB	4 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification December 2019 Phenotypes CD122 deficiency Lymphoproliferation, lymphadenopathy, hepatosplenomegaly, autoimmune hemolytic anemia, dermatitis, enteropathy, recurrent viral (EBV, CMV) infections Immunodeficiency 63 with lymphoproliferation and autoimmunity, 618495 Tags
Green Green List (high evidence)	IL2RG	8 reviews 6 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other SCID v1.6 Victorian Clinical Genetics Services Phenotypes Combined immunodeficiency, X-linked, moderate Severe combined immunodeficiency, X-linked Severe combined immunodeficiency, X-linked, 300400 Severe Combined Immune Deficiency T-B+ SCID SCID SCID (x-linked) Atypical Severe Combined Immunodeficiency (Atypical SCID) Omenn syndrome Severe combined immunodeficiency (SCID) Low NK Immunodeficiencies affecting cellular and humoral immunity Tags gene-therapy-trial
Green Green List (high evidence)	IL36RN	6 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Psoriasis 14, pustular, OMIM:614204 Autoinflammatory Disorders Tags
Green Green List (high evidence)	IL6R	6 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification December 2019 Literature Phenotypes [Interleukin 6, serum level of, QTL] 614752 [Interleukin-6 receptor, soluble, serum level of, QTL] 614689 Hyper-IgE Eczema Recurrent infections Recurrent pyogenic infections, cold abscesses, high circulating IL-6 levels Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	IL6ST	6 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification December 2019 Literature Phenotypes Hyper-IgE recurrent infection syndrome 4, autosomal recessive 618523 Stuve-Wiedemann-like syndrome: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response. Hyper-IgE syndrome, autosomal dominant Tags
Green Green List (high evidence)	IL7R	8 reviews 6 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other SCID v1.6 Victorian Clinical Genetics Services Phenotypes Severe combined immunodeficiency, T-cell negative, B-cell/natural killer cell-positive type Severe Combined Immune Deficiency Severe combined immunodeficiency, T-cell negative, B-cell/natural killer cell-positive T-B+ SCID IL7Ra deficiency Atypical Severe Combined Immunodeficiency (Atypical SCID) Omenn syndrome Severe combined immunodeficiency (SCID) Nl NK Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	INO80	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes INO80 deficiency, HIGM severe bacterial infections Severe bacterial infections Predominantly Antibody Deficiencies Tags gene-checked
Green Green List (high evidence)	IRAK4	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes IRAK4 deficiency, 610799 Invasive pneumococcal disease, recurrent isolated, 1, 6107 Defects of TLR/NFkappa-B signalling Defects with susceptibility to mycobacterial infection (MSMD) Bacterial infections (pyogens) Defects in Intrinsic and Innate Immunity Tags
Green Green List (high evidence)	IRF7	4 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 NHS GMS Victorian Clinical Genetics Services Phenotypes Immunodeficiency 39 , OMIM:616345 Tags
Green Green List (high evidence)	IRF8	4 reviews 4 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Immunodeficiency 32A, mycobacteriosis, autosomal dominant, 614893 Immunodeficiency 32B, monocyte and dendritic cell deficiency, autosomal recessive, 226990 Defects with susceptibility to mycobacterial infection (MSMD) Susceptibility to mycobacteria Defects in Intrinsic and Innate Immunity Susceptibility to mycobacteria and multiple other infectious agents Tags
Green Green List (high evidence)	22q11.2 recurrent (DGS/VCFS) region (proximal, A-B) (includes TBX1) Loss ISCA-37433-Loss Region	3 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ClinGen Expert Review Green Phenotypes 188400 immune deficiency renal anomalies 22q11.2 deletion syndrome 192430 facial dysmorphic features, high frequency of cardiac defects, including conotruncal defects, prematurity, growth restriction, microcephaly, and mild developmental delay cleft palate, polydactyly polyhydramnios Velocardiofacial syndrome diaphragmatic hernia DiGeorge syndrome congenital heart disease Learning difficulties Tags
Green Green List (high evidence)	22q11.2 recurrent (DGS/VCFS) region (proximal, A-D) (includes TBX1) Loss ISCA-37446-Loss Region	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ClinGen Expert Review Green Phenotypes 188400 neonatal hypocalcemia, which may present as tetany or seizures, due to hypoplasia of the parathyroid glands, and susceptibility to infection due to a deficit of T cells micrognathia clefting Hearing deficits Velocardiofacial syndrome cardiac malformations DiGeorge syndrome Tags
Green Green List (high evidence)	ISG15	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Immunodeficiency 38, 616126 Defects with susceptibility to mycobacterial infection (MSMD) idiopathic basal ganglia calcification Susceptibility to mycobacteria, brain calcifications Defects in Intrinsic and Innate Immunity Tags
Green Green List (high evidence)	ITCH	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Autoimmune disease, multisystem, with facial dysmorphism, 613385 Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) Syndromic multisystem autoimmune disease due to Itch deficiency Early-onset chronic lung disease (interstitial pneumonitis), autoimmunity (thyroiditis, type I diabetes, chronic diarrhea/enteropathy, and hepatitis), failure to thrive, developmental delay, dysmorphic facial features Diseases of Immune Dysregulation Tags founder-effect
Green Green List (high evidence)	ITGB2	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Leukocyte adhesion deficiency, 116920 LAD Leukocyte adhesion deficiency type I Delayed cord separation, skin ulcers, periodontitis, leukocytosis Congenital defects of phagocyte number or function Tags
Green Green List (high evidence)	ITK	7 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources Combined B and T cell defect v1.12 ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Lymphoproliferative syndrome 1 Combined immunodeficiency ITK deficiency (HLH phenotype) EBV viraemia, HLH EBV associated B cell lymphoproliferation, lymphoma, Nl or low IgG Diseases of Immune Dysregulation Tags
Green Green List (high evidence)	JAGN1	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Neutropenia, severe congenital Congenital neutropenia Neutropenia, severe congenital, 6, autosomal recessive,616022 severe congenital neutropenia Myeloid maturation arrest, osteopenia Congenital defects of phagocyte number or function Tags
Green Green List (high evidence)	JAK3	8 reviews 6 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other SCID v1.6 Victorian Clinical Genetics Services Phenotypes SCID, autosomal recessive, T-negative/B-positive type Severe Combined Immune Deficiency T-B+ SCID Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, Nk Cell-Negative JAK3 deficiency Atypical Severe Combined Immunodeficiency (Atypical SCID) Omenn syndrome Severe combined immunodeficiency (SCID) Low NK Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	KDM6A	5 reviews 1 green	X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)	Sources Expert Review Green IUIS Classification December 2019 IUIS Classification February 2018 Other Phenotypes Kabuki syndrome 2, OMIM:300867 Recurrent infections (otitis media, pneumonia) Autoimmunity Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	KMT2A	4 reviews 1 green 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ESID Registry 20171117 Expert Review Green IUIS Classification December 2019 Phenotypes Wiedemann-Steiner syndrome, OMIM:605130 Tags
Green Green List (high evidence)	KMT2D	5 reviews 1 green 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green IUIS Classification December 2019 IUIS Classification February 2018 Other Phenotypes Kabuki syndrome 1, OMIM:147920 Hypogammaglobulinemia Recurrent infections (otitis media, pneumonia) Autoimmunity Tags
Green Green List (high evidence)	LAMTOR2	6 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Immunodeficiency due to defect in MAPBP-interacting protein, 610798 Congenital neutropenia Primary immunodeficiency syndrome due to p14 deficiency Neutropenia, Hypogammaglobulinemia CD8 cytotoxicity, partial albinism, growth failure Congenital defects of phagocyte number or function Tags
Green Green List (high evidence)	LAT	6 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources A- or hypo-gammaglobulinaemia v1.25 Combined B and T cell defect v1.12 Expert Review Green IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other SCID v1.6 Phenotypes Immunodeficiency 52, 617514 Adenopathy, splenomegaly, recurrent infections, autoimmunity Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	LCK	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Immunodeficiency 22, 615758 LCK deficiency Combined immunodeficiency Severe combined immunodeficiency due to LCK deficiency Recurrent infections, immune dysregulation, autoimmunity Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	LIG1	6 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Expert Review Green IUIS Classification December 2019 IUIS Classification February 2018 Literature Other Phenotypes Combined immunodeficiencies with associated or syndromic features Recurrent respiratory infections, growth retardation, sun sensitivity, lymphoma, radiation sensitivity DNA-ligase 1 ATP-dependent deficiency (LIG1) DNA ligase I deficiency Tags
Green Green List (high evidence)	LIG4	8 reviews 6 green	BIALLELIC, autosomal or pseudoautosomal	Sources Combined B and T cell defect v1.12 ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other SCID v1.6 Victorian Clinical Genetics Services Phenotypes LIG4 syndrome, 606593{Multiple myeloma, resistance to}, 254500 Severe combined immunodeficiency with sensitivity to ionizing radiation, 602450 Severe Combined Immunodeficiency with Sensitivity to Ionizing Radiation T-B- SCID T-B+ SCID LIG4 syndrome Combined immunodeficiency Severe combined immunodeficiency (SCID) DNA ligase IV deficiency Nl NK, radiation sensitive, microcephaly Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	LPIN2	6 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Majeed syndrome, OMIM:609628 Chronic recurrent multifocal osteomyelitis, transfusion-dependent anemia, cutaneous inflammatory disorders Autoinflammatory Disorders Tags
Green Green List (high evidence)	LRBA	6 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Immunodeficiency, common variable, 8, with autoimmunity, 614700 Unclassified antibody deficiency Recurrent infections, inflammatory bowel disease, autoimmunity, EBV infections Diseases of Immune Dysregulation Tags
Green Green List (high evidence)	LYST	6 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Chediak-Higashi syndrome 214500 Chediak Higashi syndrome Partial albinism, recurrent infections, fever, HSM, HLH, giant lysosomes, neutropenia, cytopenias, bleeding tendency, progressive neurological dysfunction Diseases of Immune Dysregulation Tags age-specific-variation
Green Green List (high evidence)	MAGT1	7 reviews 5 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Combined B and T cell defect v1.12 ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia 300853 Chronic active EBV, lymphoproliferation, combined immunodeficiency, impaired t cell function XMEN syndrome Immunodeficiency, X-linked, with magnesium defect Epstein-Barr virus infection and neoplasia (XMEN) Combined immunodeficiency EBV infection, lymphoma, viral infections, respiratory and GI infections Diseases of Immune Dysregulation Tags
Green Green List (high evidence)	MALT1	6 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Immunodeficiency 12 615468 Combined immunodeficiency Bacterial, fungal and viral infections Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	MAP3K14	6 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Immunodeficiency 112, OMIM:620449 Tags
Green Green List (high evidence)	MCM4	7 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Immunodeficiency 54, 609981 Natural killer cell and glucocorticoid deficiency with DNA repair defect Predisposition to several viral infection MCM4 deficiency NK cells: low number and function. Viral infections (EBV, HSV, VZV), short stature, B cell lymphoma, adrenal failure Combined immunodeficiencies with associated or syndromic features Tags founder-effect
Green Green List (high evidence)	MEFV	6 reviews 4 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Familial Mediterranean fever, AD, OMIM:134610 Familial Mediterranean fever, AR, OMIM:249100 Neutrophilic dermatosis, acute febrile, OMIM:608068 Recurrent fever, serositis and inflammation responsive to colchicine Predisposes to vasculitis and inflammatory bowel disease Autoinflammatory Disorders Tags
Green Green List (high evidence)	MOGS	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Congenital disorder of glycosylation, type IIb 606056 Bacterial and viral infections, severe neurologic disease, also known as congenital disorder of glycosylation type IIb (CDG-IIb) Predominantly Antibody Deficiencies Tags
Green Green List (high evidence)	MPEG1	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Phenotypes Immunodeficiency 77, OMIM:619223 Tags
Green Green List (high evidence)	MSN	5 reviews 4 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources ESID Registry 20171117 Expert Review Green IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Phenotypes Combined immunodeficiency Immunodeficiency 50, 300988 Recurrent infections with bacteria, varicella, neutropenia Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	MTHFD1	6 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia 617780 Defects of Vitamin B12 and Folate metabolism Recurrent bacterial infection, Pneumocystis jirovecii, megaloblastic anemia, failure to thrive, neutropenia, seizures, intellectual disability, folate-responsive Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	MVK	6 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Hyper-IgD syndrome, OMIM:260920 Mevalonic aciduria, OMIM:610377 Periodic fever and leukocytosis with high IgD levels Autoinflammatory Disorders Tags
Green Green List (high evidence)	MYD88	6 reviews 4 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources A- or hypo-gammaglobulinaemia v1.25 ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Pyogenic bacterial infections, recurrent, due to MYD88 deficiency 612260 Defects of TLR/NFkappa-B signalling recurrent pyogenic bacterial infection Bacterial infections (pyogens) Defects in Intrinsic and Innate Immunity Tags
Green Green List (high evidence)	MYO5B	8 reviews 4 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GOSH PID v.8.0 London North GLH NHS GMS North West GLH Phenotypes Diarrhea 2, with microvillus atrophy, OMIM:251850 Tags age-specific-variation
Green Green List (high evidence)	MYSM1	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Phenotypes MYSM1 deficiency Bone marrow failure neurodevelopmental delay mid-face hypoplasia immunodeficiency Short stature, recurrent infections, congenital bone marrow failure, myelodysplasia, immunodeficiency affecting B-cells and granulocytes, skeletal anomalies, cataracts, developmental delay. Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	NBN	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Phenotypes Nijmegen breakage syndrome 251260 Nijmegen breakage syndrome (NBS1) Aplastic anemia 609135 Microcephaly, dysmorphic facies, lymphomas, solid tumors, increased radiosensitivity, chromosomal instability Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	NCF1	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Chronic granulomatous disease due to deficiency of NCF-1 233700 Chronic granulomatous disease (CGD) Infections, autoinflammatory phenotype Congenital defects of phagocyte number or function Tags
Green Green List (high evidence)	NCF2	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Chronic granulomatous disease due to deficiency of NCF-2 233710 Chronic granulomatous disease (CGD) Infections, autoinflammatory phenotype Congenital defects of phagocyte number or function Tags
Green Green List (high evidence)	NCF4	6 reviews 5 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes ?Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III 613960 Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III Chronic granulomatous disease (CGD) Infections, autoinflammatory phenotype Congenital defects of phagocyte number or function Tags
Green Green List (high evidence)	NCKAP1L	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Immunodeficiency Immune dysregulation Tags
Green Green List (high evidence)	NFE2L2	4 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green IUIS Classification December 2019 Phenotypes white matter cerebral lesions, increased level of homocysteine Recurrent respiratory and skin infections, growth retardation, , developmental delay Immunodeficiency, developmental delay, and hypohomocysteinemia, 617744 NFE2L2 GOF increased expression of stress response genes Combined immunodeficiencies with associated or syndromic features mmunodeficiency, developmental delay, and hypohomocysteinemia, 617744 Recurrent respiratory and skin infection Growth retardation Developmental delay, borderline ID White matter cerebral lesions Tags
Green Green List (high evidence)	NFKB1	5 reviews 4 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Immunodeficiency, common variable, 12 616576 Common variable immunodeficiency disorders (CVID) Unclassified antibody deficiency Recurrent sinopulmonary infections, COPD, EBV proliferation, autoimmune cytopenias, alopecia and autoimmune thyroiditis Predominantly Antibody Deficiencies Tags
Green Green List (high evidence)	NFKB2	7 reviews 5 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources A- or hypo-gammaglobulinaemia v1.25 ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Immunodeficiency, common variable, 10 615577 Hypogammaglobuliaemia immune dysregulation central adrenal insufficiency Common variable immunodeficiency disorders (CVID) Unclassified antibody deficiency Recurrent sinopulmonary infections, alopecia and endorinopathies Predominantly Antibody Deficiencies Tags
Green Green List (high evidence)	NFKBIA	6 reviews 4 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Ectodermal dysplasia, anhidrotic, with T-cell immunodeficiency 612132 Defects of TLR/NFkappa-B signalling Anhidrotic ectodermal dysplasia, various infections (bacteria, mycobacteria, viruses and fungi), colitis, variable defects of skin, hair and teeth, T cell and monocyte dysfunction Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	NHEJ1	9 reviews 7 green	BIALLELIC, autosomal or pseudoautosomal	Sources Combined B and T cell defect v1.12 ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other SCID v1.6 Victorian Clinical Genetics Services Phenotypes Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation Severe combined immunodeficiency with microcephaly, growth retardation and sensitivity to ionizing radiation, 611291 T-B- SCID T-B+ SCID Combined immunodeficiency Cernunnos/XLF deficiency Nl NK, radiation sensitive, microcephaly Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	NHP2	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Dyskeratosis congenita, autosomal recessive 2 613987 Dyskeratosis congenita Hoyeraal-Hreidarsson syndrome Intrauterine growth retardation, microcephaly, nail dystrophy, sparse scalp hair and eyelashes, hyperpigmentation of skin, palmar hyperkeratosis, premalignant oral leukoplakia, pancytopenia, myelodysplasia, +/- recurrent infections. A severe phenotype with developmental delay and cerebellar hypoplasia known as Hoyeraal-Hreidarsson Syndrome (HHS) may occur in some DKC patients Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	NLRC4	6 reviews 4 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Autoinflammation with infantile enterocolitis, OMIM:616050 ?Familial cold autoinflammatory syndrome 4, OMIM:616115 Severe enterocolitis and macrophage activation syndrome Autoinflammatory Disorders Tags
Green Green List (high evidence)	NLRP12	6 reviews 4 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Familial cold autoinflammatory syndrome 2, OMIM:611762 Non-pruritic urticaria, arthritis, chills, fever and leukocytosis after cold exposure Preterm premature rupture of membranes (PPROM) Autoinflammatory Disorders Tags
Green Green List (high evidence)	NLRP3	6 reviews 4 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes CINCA syndrome, OMIM:607115 Deafness, autosomal dominant 34, with or without inflammation, OMIM:617772 Familial cold inflammatory syndrome 1, OMIM:120100 Muckle-Wells syndrome, OMIM:191900 Tags
Green Green List (high evidence)	NOD2	7 reviews 4 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Blau syndrome, OMIM:186580 {Inflammatory bowel disease 1, Crohn disease}, OMIM:266600 {Yao syndrome}, OMIM:617321 Tags
Green Green List (high evidence)	NPC1	3 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Phenotypes Very Early Onset Inflammatory Bowel Disease Tags
Green Green List (high evidence)	NSMCE3	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification February 2018 London North GLH NHS GMS North West GLH Phenotypes Lung disease, immunodeficiency, and chromosome breakage syndrome, 617241 Severe lung disease (possibly viral), thymic hypoplasia, Chromosomal breakage, radiation sensitivity Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	OAS1	5 reviews 3 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green IUIS Classification December 2019 Phenotypes Immunodeficiency 100 with pulmonary alveolar proteinosis and hypogammaglobulinemia, OMIM:618042 Tags
Green Green List (high evidence)	ORAI1	8 reviews 4 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other SCID v1.6 Victorian Clinical Genetics Services Phenotypes Immunodeficiency 9 612782 T-B+ SCID immunodeficiency, ectodermal dysplasia and myopathy Combined immunodeficiency Autoimmunity, EDA, non-progressive myopathy Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	OTULIN	8 reviews 6 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Green IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes {Immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection}, OMIM:619986 Autoinflammation, panniculitis, and dermatosis syndrome, OMIM:617099 Tags Q3_23_MOI
Green Green List (high evidence)	PARN	5 reviews 4 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Dyskeratosis congenita, autosomal recessive 6 616353 Pulmonary fibrosis and/or bone marrow failure,telomere-related, 4 616371 Intrauterine growth retardation, microcephaly, nail dystrophy, sparse scalp hair and eyelashes, hyperpigmentation of skin, palmar hyperkeratosis, premalignant oral leukoplakia, pancytopenia, myelodysplasia, +/- recurrent infections. A severe phenotype with developmental delay and cerebellar hypoplasia known as Hoyeraal-Hreidarsson Syndrome (HHS) may occur in some DKC patients Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	PAX1	3 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Phenotypes Otofaciocervical syndrome 2, 615560 Syndromic SCID dysmorphism ear abnormalities otofaciocervical syndrome Tags
Green Green List (high evidence)	PEPD	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Phenotypes Prolidase deficiency, 170100 Autoantibodies common, chronic skin ulcers, eczema, infections Diseases of Immune Dysregulation Tags
Green Green List (high evidence)	PGM3	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Immunodeficiency 23 615816 Combined immunodeficiency Severe atopy, autoimmunity, bacterial and viral infections, skeletal anomalies dysplasia: short stature, brachydactyly, dysmorphic facial features, and intellectual disability cognitive impairment, hypomyelination Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	PI4KA	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Phenotypes Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, OMIM:616531 Tags
Green Green List (high evidence)	PIK3CD	10 reviews 7 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources A- or hypo-gammaglobulinaemia v1.25 ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Immunodeficiency 14A, autosomal dominant, OMIM:615513 Immunodeficiency 14B, autosomal recessive, OMIM:619281 Combined immunodeficiency Activated PI3K-delta syndrome (APDS) Predominantly Antibody Deficiencies Sinopulmonary infections, dysgammaglobulinaemia, lymphadenopathy, nodular lymphoid hyperplasia and herpesviremia Severe bacterial infections Tags
Green Green List (high evidence)	PIK3CG	3 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Immune dysregulation HLH-like childhood-onset antibody defects cytopenias T lymphocytic pneumonitis and colitis Tags
Green Green List (high evidence)	PIK3R1	8 reviews 7 green	BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal	Sources A- or hypo-gammaglobulinaemia v1.25 ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Immunodeficiency 36 Agammaglobulinemia 7, autosomal recessive, 615214 SHORT syndrome, 269880 Immunodeficiency 36, 616005 Agammaglobulinemia 7 Immunodeficiency 36 Combined immunodeficiency Activated PI3K-delta syndrome (APDS) Agammaglobulinemia immunodeficiency with hypogammaglobulinaemia, lymphoproliferation and inflammatory disease (AD) Severe bacterial infections, decreased or absent pro-B cells Predominantly Antibody Deficiencies Severe bacterial infections, pro-B cells present and low numbers of memory B cells, EBV Tags
Green Green List (high evidence)	PLCG2	9 reviews 5 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources A- or hypo-gammaglobulinaemia v1.25 ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Autoinflammation, antibody deficiency, and immune dysregulation syndrome, OMIM:614878 Familial cold autoinflammatory syndrome 3, OMIM:614468 Hypogammaglobulinaemia, cold induced urticaria, autoinflammatory Tags
Green Green List (high evidence)	PLG	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Phenotypes Angioedema, hereditary, 4, OMIM:619360 Tags
Green Green List (high evidence)	PNP	7 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other SCID v1.6 Victorian Clinical Genetics Services Phenotypes Immunodeficiency due to purine nucleoside phosphorylase deficiency T-B+ SCID Atypical Severe Combined Immunodeficiency (Atypical SCID) Combined immunodeficiency Autoimmune haemolytic anemia, neurological impairment Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	POLA1	5 reviews 4 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Expert Review Green IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Phenotypes Hyperpigmentation, characteristic facies, lung and GI involvement Autoinflammatory Disorders Pigmentary disorder, reticulate, with systemic manifestations, X-linked 301220 X-linked reticulate pigmentary disorder x-linked cutaneous amyloidosis with systemic features Tags
Green Green List (high evidence)	POLE	6 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 Victorian Clinical Genetics Services Phenotypes FILS syndrome 615139 Facial dysmorphism, immunodeficiency, livedo, and short stature (FILS syndrome) Recurrent respiratory infections, meningitis, facial dysmorphism, livido, short stature Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	POMP	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green London North GLH NHS GMS North West GLH Phenotypes CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome) Proteasome-associated autoinflammatory syndrome 2, 618048 combined immunodeficiency with autoinflammation Tags
Green Green List (high evidence)	PRF1	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Hemophagocytic lymphohistiocytosis, familial, 2, OMIM:603553 Tags early-onset
Green Green List (high evidence)	PRIM1	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature NHS GMS Phenotypes Microcephalic primordial dwarfism, MONDO:0017950 Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, OMIM:620005 Tags
Green Green List (high evidence)	PRKCD	6 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Autoimmune lymphoproliferative syndrome, type III 615559 Immunodeficiency, common variable, 9 Autoimmune lymphoproliferative syndrome (ALPS) Unclassified antibody deficiency Recurrent infections, EBV chronic infection, lymphoproliferation, SLE-like autoimmunity (nephrotic and antiphospholipid syndromes), low IgG Diseases of Immune Dysregulation Tags
Green Green List (high evidence)	PRKDC	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH SCID v1.6 Victorian Clinical Genetics Services Phenotypes Immunodeficiency 26, with or without neurologic abnormalities Immunodeficiency, with or without neurologic abnormalities DNA Pkcs deficiency Combined immunodeficiency Severe combined immunodeficiency (SCID) Nl NK, radiation sensitive, microcephaly Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	PSMB8	6 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Proteasome-associated autoinflammatory syndrome 1 and digenic forms, OMIM:256040 Autoinflammation, lipodystrophy, and dermatosis syndrome Contractures, panniculitis, ICC, fevers Autoinflammatory Disorders CANDLE syndrome Tags
Green Green List (high evidence)	PSTPIP1	6 reviews 4 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, OMIM:604416 Destructive arthritis, inflammatory skin rash, myositis Hyperzincaemia hypercalprotectinaemia Autoinflammatory Disorders Tags
Green Green List (high evidence)	PTPRC	8 reviews 6 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other SCID v1.6 Victorian Clinical Genetics Services Phenotypes Severe combined immunodeficiency, T cell-negative, B-cell/natural killer-cell positive {Hepatitic C virus, susceptibility to}, 609532 T-B+ SCID CD45 deficiency Omenn syndrome Severe combined immunodeficiency (SCID) Nl g/d T cells Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	RAB27A	6 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Griscelli syndrome, type 2 607624 Partial albinism, fever, HSM, HLH, cytopenias Diseases of Immune Dysregulation Tags
Green Green List (high evidence)	RAC2	9 reviews 1 green 4 red	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Combined B and T cell defect v1.12 Congenital neutropaenia v1.22 ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 SCID v1.6 Victorian Clinical Genetics Services Phenotypes T-B- SCID T-B+ SCID Neutrophil immunodeficiency syndrome 608203 Neutrophil immunodeficiency syndrome RAS-related C3 Bolutinum toxin substrate 2 deficiency (RAC2) Poor wound healing, leukocytosis Congenital defects of phagocyte number or function Reticular dysgenesis Recurrent sinopulmonary infections, selective IgA defiency poststreptococcal glomerulonephritis urticaria Tags
Green Green List (high evidence)	RAG1	8 reviews 6 green	BIALLELIC, autosomal or pseudoautosomal	Sources Combined B and T cell defect v1.12 ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other SCID v1.6 Victorian Clinical Genetics Services Phenotypes Severe combined immunodeficiency, B cell-negative Severe Combined Immune Deficiency Severe combined immunodeficiency, B cell-negative, 601457 T-B- SCID T-B+ SCID RAG1 deficiency Atypical Severe Combined Immunodeficiency (Atypical SCID) Omenn syndrome Severe combined immunodeficiency (SCID) Nl NK Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	RAG2	8 reviews 6 green	BIALLELIC, autosomal or pseudoautosomal	Sources Combined B and T cell defect v1.12 ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other SCID v1.6 Victorian Clinical Genetics Services Phenotypes Severe combined immunodeficiency, B cell-negative Severe Combined Immune Deficiency Severe combined immunodeficiency, B cell-negative, 601457 T-B- SCID T-B+ SCID Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Negative, Nk Cell-Positive RAG2 deficiency Atypical Severe Combined Immunodeficiency (Atypical SCID) Omenn syndrome Severe combined immunodeficiency (SCID) Nl NK Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	RASGRP1	6 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Phenotypes Recurrent pneumonia, herpesvirus infections, EBV associated lymphoma Diseases of Immune Dysregulation EBV-induced lymphoma Immunodeficiency Immunodeficiency 64, 618534 Immunodeficiency immunde dysregulation EBV-induced lymphoma Tags
Green Green List (high evidence)	RBCK1	6 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Polyglucosan body myopathy 1 with or without immunodeficiency, OMIM:615895 Bacterial infections, autoinflammation, amylopectinosis Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	RECQL4	4 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green Phenotypes Combined immunodeficiency Rothmund-Thomson syndrome, 268400 Tags
Green Green List (high evidence)	RFX5	6 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Combined B and T cell defect v1.12 ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Bare lymphocyte syndrome, type II, complementation group C Bare lymphocyte syndrome, type II, complementation group E HLA class II deficiency Combined immunodeficiency Bare lymphocyte syndrome (MHC class II deficiency) Respiratory and gastrointestinal infections, liver/biliary tract disease Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	RFXANK	6 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Combined B and T cell defect v1.12 ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes MHC class II deficiency, complementation group B, OMIM:209920 HLA class II deficiency Respiratory and gastrointestinal infections, liver/biliary tract disease Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	RFXAP	6 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Combined B and T cell defect v1.12 ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Bare lymphocyte syndrome, type II, complementation group D Combined immunodeficiency (MHC class II deficiency, bare lymphocyte syndrome) HLA class II deficiency Respiratory and gastrointestinal infections, liver/biliary tract disease Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	RIPK1	7 reviews 5 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green Literature London North GLH NHS GMS North West GLH Phenotypes Immunodeficiency 57, 618108 Severe immunodeficiency, arthritis, and intestinal inflammation Tags
Green Green List (high evidence)	RMRP	7 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources Combined B and T cell defect v1.12 ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Anauxetic dysplasia 1, 232220 Cartilage-hair hypoplasia, with or without immunodeficiency Cartilage-hair hypoplasia Omenn syndrome Cartilage hair hypoplasia Short-limbed dwarfism with metaphyseal dysostosis, sparse hair, bone marrow failure, autoimmunity, susceptibility to lymphoma and other cancers, impaired spermatogenesis, neuronal dysplasia of the intestine Combined immunodeficiencies with associated or syndromic features Tags locus-type-rna-ribosomal
Green Green List (high evidence)	RNASEH2A	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Aicardi-Goutieres syndrome 4 610333, Lupus Type 1 interferonopathies Classical AGS Autoinflammatory Disorders Tags
Green Green List (high evidence)	RNASEH2B	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Aicardi-Goutieres syndrome 2, OMIM:610181 Tags
Green Green List (high evidence)	RNASEH2C	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Aicardi-Goutieres syndrome 3 610329 Type 1 interferonopathies Classical AGS Autoinflammatory Disorders Tags
Green Green List (high evidence)	RNF168	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes RIDDLE syndrome 611943 RNF168 deficiency Short stature, mild defect of motor control to ataxia, normal intelligence to learning difficulties, mild facial dysmorphism to microcephaly, increased radiosensitivity Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	RNU7-1	3 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Aicardi-Goutières syndrome-like Type 1 interferonopathy Tags gene-checked
Green Green List (high evidence)	RORC	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Immunodeficiency 42 616622 Susceptibility to candidasis & Mycobacterial infection Susceptibility to mycobacteria and candida Defects in Intrinsic and Innate Immunity Tags
Green Green List (high evidence)	RPSA	5 reviews 4 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Isolated congential asplenia 271400 Bacteremia (encapsulated bacteria) Defects in Intrinsic and Innate Immunity Tags
Green Green List (high evidence)	RTEL1	5 reviews 4 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Hoyeraal-Hreidarsson syndrome/ Dyskeratosis congenita, 4 615190 Dyskeratosis congenita, 5 615190 Intrauterine growth retardation, microcephaly, nail dystrophy, sparse scalp hair and eyelashes, hyperpigmentation of skin, palmar hyperkeratosis, premalignant oral leukoplakia, pancytopenia, myelodysplasia, +/- recurrent infections. A severe phenotype with developmental delay and cerebellar hypoplasia known as Hoyeraal-Hreidarsson Syndrome (HHS) may occur in some DKC patients Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	SAMHD1	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Aicardi-Goutieres syndrome 5 612952 Type 1 interferonopathies Classical AGS, FCL Autoinflammatory Disorders Tags
Green Green List (high evidence)	SASH3	4 reviews 2 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Expert Review Green Literature Phenotypes Immunodeficiency 102, OMIM:301082 Tags
Green Green List (high evidence)	SBDS	6 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources Congenital neutropaenia v1.22 ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Shwachman-Diamond syndrome, 260400 Shwachman-Bodian-Diamond syndrome Shwachman-Diamond-syndrome Pancytopenia, exocrine pancreatic insufficiency, chondrodysplasia Congenital defects of phagocyte number or function Tags
Green Green List (high evidence)	SERPING1	5 reviews 5 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Angioedema, hereditary, types I and II 106100 Hereditary Angioedema (C1inh) Complement component 4, partial deficiency of 120790 Hereditary angioedema Complement Deficiencies Tags
Green Green List (high evidence)	SGPL1	5 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources Combined B and T cell defect v1.12 Expert Review Green London North GLH NHS GMS North West GLH Phenotypes Nephrotic syndrome 14, 617575 drenal insufficiency steroid-resistant nephrotic syndrome focal segmental glomerulosclerosis lymphopenia Tags
Green Green List (high evidence)	SH2D1A	5 reviews 4 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Lymphoproliferative syndrome, X-linked, 1 308240 Lymphoproliferative syndrome, X-linked, 1 (XLP1) X-linked lymphoproliferative syndrome (XLP) EBV, HLH, Lymphoproliferation, Aplastic anaemia, Lymphoma. Hypogammaglobulinemia, Absent iNKT cells Diseases of Immune Dysregulation Tags
Green Green List (high evidence)	SKIV2L	6 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 London North GLH NHS GMS North West GLH Phenotypes Trichohepatoenteric syndrome 2,614602 Trichohepatoenteric syndrome Immune dysfunction Tags early-onset new-gene-name
Green Green List (high evidence)	SLC29A3	5 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Histiocytosis-lymphadenopathy plus syndrome, OMIM:602782 Hyperpigmentation hypertrichosis, histiocytosis-lymphadenopathy plus syndrome Autoinflammatory Disorders Tags
Green Green List (high evidence)	SLC35C1	5 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Congenital disorder of glycosylation, type IIc 266265 Leukocyte adhesion deficiency (LAD) Mild LAD type 1 features with hh-blood group, growth retardation, developmental delay Congenital defects of phagocyte number or function Tags
Green Green List (high evidence)	SLC37A4	6 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources Congenital neutropaenia v1.22 ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Glycogen storage disease Ib, OMIM:232220 Glycogen storage disease Ic, OMIM:232240 Fasting hypoglycemia, lactic acidosis, hyperlipidemia, hepatomegaly Congenital defects of phagocyte number or function Tags
Green Green List (high evidence)	SLC39A7	5 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification December 2019 Literature Phenotypes Early onset infections, blistering dermatosis, failure to thrive, thrombocytopenia Predominantly Antibody Deficiencies B cell deficiency Agammaglobulinemia Tags
Green Green List (high evidence)	SLC46A1	5 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Folate malabsorption, hereditary 229050 Defects of Vitamin B12 and Folate metabolism Congenital defect of folate absorption Megaloblastic anemia, failure to thrive, if untreated for prolonged periods results in intellectual disability Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	SLC7A7	4 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification December 2019 Phenotypes Lysinuric protein intolerance SLC7A7 deficiency Severe bacterial infections Predominantly Antibody Deficiencies Lysinuric protein intolerance, 222700 Tags
Green Green List (high evidence)	SLCO2A1	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Phenotypes Prostaglandin transporter deficiency Tags
Green Green List (high evidence)	SMARCAL1	5 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Schimke immunoosseous dysplasia 242900 Schimke disease Short stature, spondiloepiphyseal dysplasia, intrauterine growth retardation, nephropathy, bacterial, viral, fungal infections, may present as SCID, bone marrow failure Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	SMARCD2	4 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification December 2019 IUIS Classification February 2018 Phenotypes Neutropenia, developmental aberrations, skeletal abnormalities, hematopoietic stem cells, myelodysplasia Congenital defects of phagocyte number or function Specific granule deficiency 2, 617475 Tags
Green Green List (high evidence)	SNORA31	4 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green Literature Phenotypes Herpes simplex encephalitis Tags gene-checked
Green Green List (high evidence)	SOCS1	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Phenotypes Common variable immunodeficiency Early-onset autoimmunity Tags
Green Green List (high evidence)	SP110	5 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Hepatic venoocclusive disease with immunodeficiency 235550 Hepatic venoocclusive disease with immunodeficiency (VODI) Hepatic veno-occlusive disease, Susceptibility to Pneumocystis jirovecii pneumonia, CMV, candida, thrombocytopenia, hepatosplenomegaly, cerebrospinal leukodystrophy Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	SPINK5	6 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Netherton syndrome 256500 Congenital ichthyosis, bamboo hair, atopic diathesis, increased bacterial infections, failure to thrive Combined immunodeficiencies with associated or syndromic features Tags early-onset gene-therapy-trial
Green Green List (high evidence)	SPPL2A	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Green Literature London North GLH NHS GMS North West GLH Phenotypes Defects with susceptibility to mycobacterial infection (MSMD) Susceptibility to mycobacteria Defects in Intrinsic and Innate Immunity Tags
Green Green List (high evidence)	SRP54	4 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green IUIS Classification December 2019 IUIS Classification February 2018 Phenotypes Congenital defects of phagocyte number or function Schwachman Diamond features Neutropenia, severe congenital, 8, autosomal dominant, 618752 Tags
Green Green List (high evidence)	STAT1	5 reviews 4 green	BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Immunodeficiency 31A, mycobacteriosis, autosomal dominant 614892 Immunodeficiency 31B, mycobacterial and viral infections, autosomal recessive 613796 Immunodeficiency 31C, autosomal dominant 614162 Immunodeficiency 31A, mycobacteriosis Candidiasis, familial, 7 Combined immunodeficiency Chronic mucocutaneous candidiasis (CMC) Defects with susceptibility to mycobacterial infection (MSMD) Severe viral infections, mycobacterial infection CMC, various fungal, bacterial and viral (HSV) infections, auto-immunity (thyroiditis, diabetes, cytopenias), enteropathy Susceptibility to mycobacteria, Salmonella Defects in Intrinsic and Innate Immunity Tags
Green Green List (high evidence)	STAT2	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes STAT2 deficiency Predisposition to several viral infection Immunodeficiency 44, 616636 Severe viral infections (disseminated vaccine-strain measles) Defects in Intrinsic and Innate Immunity Tags
Green Green List (high evidence)	STAT3	5 reviews 4 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Autoimmune disease, multisystem, infantile-onset, 1 615952 Hyper-IgE recurrent infection syndrome 147060 Autoimmune disease, multisystem, infantile-onset Early-onset multi-organ autoimmune disease Hyper IgE syndrome (HIES) Combined immunodeficiencies with associated or syndromic features Diseases of Immune Dysregulation Tags early-onset
Green Green List (high evidence)	STAT5B	9 reviews 5 green 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other SCID v1.6 Victorian Clinical Genetics Services Phenotypes Growth hormone insensitivity with immune dysregulation 1, autosomal recessive, OMIM:245590 Growth hormone insensitivity with immune dysregulation 2, autosomal dominant, OMIM:618985 T-B+ SCID Combined immunodeficiency Growth-hormone insensitive dwarfism, dysmorphic features, eczema, lymphocytic interstitial pneumonitis, autoimmunity Combined immunodeficiencies with associated or syndromic features Tags for-review to_be_confirmed_NHSE
Green Green List (high evidence)	STIM1	6 reviews 4 green 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other SCID v1.6 Victorian Clinical Genetics Services Phenotypes T-B+ SCID Immunodeficiency 10, 612783 Combined immunodeficiency Combined immunodeficiency due to STIM1 deficiency Autoimmunity, EDA, non-progressive myopathy Combined immunodeficiencies with associated or syndromic features Combined immunodeficiency due to STIM1 deficiency ORPHA:317430 Tags
Green Green List (high evidence)	STK4	6 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Combined B and T cell defect v1.12 ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Hypergammaglobulinaemia, lymphopenia, combined immunodeficiency, congenital heart disease, autoimmunity T-cell immunodeficiency, recurrent infections, autoimmunity, and cardiac malformations, 614868 AR hyperimmunoglobulin E syndrome Combined immunodeficiency Intermittent neutropenia, bacterial, viral (HPV), candidal infections, EBV lymphoproliferation, autoimmune cytopenias, lymphoma, congenital heart disease Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	STX11	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Hemophagocytic lymphohistiocytosis, familial 4, 603552 FHL4 Familial hemophagocytic lymphohistiocytosis syndromes (FHLH) HPLH4 HLH4 Fever, HSM, cHLH, cytopenias, Diseases of Immune Dysregulation Tags early-onset
Green Green List (high evidence)	STXBP2	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Hemophagocytic lymphohistiocytosis, familial 5, 613101 FHL5 Familial hemophagocytic lymphohistiocytosis syndromes (FHLH) Fever, HSM, cHLH, cytopenias, enteropathy Diseases of Immune Dysregulation Tags
Green Green List (high evidence)	STXBP3	4 reviews 2 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Expert Review Green Phenotypes Very Early Onset Inflammatory Bowel Disease Sensorineural hearing loss Syntaxin binding protein 3 defect Tags gene-checked
Green Green List (high evidence)	SYK	3 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Phenotypes immunodeficiency hypogammaglobulinemia multi-organ inflammatory disease Tags
Green Green List (high evidence)	TAP1	5 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Bare lymphocyte syndrome, type I 604571 HLA class I deficiency Vasculitis, pyoderma gangrenosum Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	TAP2	5 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Bare lymphocyte syndrome, type I, due to TAP2 deficiency 604571 HLA class I deficiency Wegener-like granulomatosis Vasculitis, pyoderma gangrenosum Immunodeficiencies affecting cellular and humoral immunity Tags
Green Green List (high evidence)	TAZ	6 reviews 4 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Congenital neutropaenia v1.22 ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Barth syndrome Cardioskeletal myopathy with neutropenia and abnormal mitochondria 3-methylglutaconic aciduria, type II, 302060 Cardiomyopathy, myopathy, growth retardation, neutropenia Congenital defects of phagocyte number or function Tags new-gene-name
Green Green List (high evidence)	TBK1	5 reviews 5 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Herpes simplex encephalitis, susceptibility to Herpetic encephalitis (HSE) {Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 8} 617900 Herpes simplex virus 1 encephalitis Defects in Intrinsic and Innate Immunity Tags
Green Green List (high evidence)	TBX1	9 reviews 2 green 3 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 NHS GMS Other SCID v1.6 Victorian Clinical Genetics Services Phenotypes DiGeorge syndrome, OMIM:188400 Conotruncal anomaly face syndrome, OMIM:217095 Velocardiofacial syndrome, OMIM:192430 Tags
Green Green List (high evidence)	TCF3	10 reviews 6 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources A- or hypo-gammaglobulinaemia v1.25 ESID Registry 20171117 Expert Review Green IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Agammaglobulinemia 8A, autosomal dominant, OMIM:616941 Agammaglobulinemia 8B, autosomal recessive, OMIM:619824 Recurrent bacterial infections Predominantly Antibody Deficiencies Tags
Green Green List (high evidence)	TCN2	10 reviews 7 green	BIALLELIC, autosomal or pseudoautosomal	Sources Agranulocytosis v1.3 A- or hypo-gammaglobulinaemia v1.25 Combined B and T cell defect v1.12 Congenital neutropaenia v1.22 ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other SCID v1.6 Victorian Clinical Genetics Services Phenotypes Transcobalamin II deficiency, 275350 Transcobalamin II deficiency can have a presentation similar to severe combined immunodeficiency pancytopenia neutropenic colitis Agammaglobulinemia megaloblastic bone Transcobalamin-2 precursor Defects of Vitamin B12 and Folate metabolism Megaloblastic anemia, pancytopenia, if untreated for prolonged periods results in intellectual disability Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	TGFB1	4 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification December 2019 Phenotypes Inflammatory bowel disease, immunodeficiency, and encephalopathy, OMIM:618213 Tags
Green Green List (high evidence)	TGFBR1	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green IUIS Classification December 2019 Phenotypes Loeys-Dietz syndrome 1, 609192 Loeys Dietz syndrome due to TGFBR1 deficiency Recurrent respiratory infectons, eczema, food allergies, hyperextensible joints, scoliosis, retention of primary teeths, aortic anuerysms Combined immunodeficiencies with associated or syndromic features Loeys-Dietz syndrome 1, OMIM:609192 Tags
Green Green List (high evidence)	TGFBR2	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green IUIS Classification December 2019 Phenotypes ALPS-FAS Loeys-Dietz syndrome 2, OMIM:610168 Combined immunodeficiencies with associated or syndromic features Recurrent respiratory infections, eczema, food allergies, hyperextensible joints, scoliosis, retention of primary teeths, aortic anuerysms Tags
Green Green List (high evidence)	TICAM1	5 reviews 4 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Encephalopathy, acute, infection-induced, susceptibility to, 6 614850 Herpetic encephalitis (HSE) Herpes simplex virus 1 encephalitis Defects in Intrinsic and Innate Immunity Tags
Green Green List (high evidence)	TLR3	5 reviews 4 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Herpes simplex encephalitis, susceptibility to, 2 Herpetic encephalitis (HSE) Herpes simplex virus 1 encephalitis (incomplete clinical penetrance for all etiologies listed here) Defects in Intrinsic and Innate Immunity Tags missense
Green Green List (high evidence)	TLR7	4 reviews 4 green	X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)	Sources Expert Review Green Literature NHS GMS Phenotypes Systemic lupus erythematosus 17, OMIM:301080 Immunodeficiency 74, COVID19-related, X-linked, OMIM:301051 Tags
Green Green List (high evidence)	TLR8	4 reviews 2 green	X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)	Sources Expert Review Green Literature NHS GMS Phenotypes Immunodeficiency 98 with autoinflammation, X-linked, OMIM:301078 Tags mosaicism somatic
Green Green List (high evidence)	TMC6	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Epidermodysplasia verruciformis, 226400 Human papillomavirus (HPV) (group B1) infections and cancer of the skin (typical EV) Defects in Intrinsic and Innate Immunity Tags
Green Green List (high evidence)	TMC8	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Epidermodysplasia verruciformis, 226400 HPV (group B1) infections and cancer of the skin (typical EV) Defects in Intrinsic and Innate Immunity Tags
Green Green List (high evidence)	TMEM173	6 reviews 4 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes STING-associated vasculopathy, infantile-onset, OMIM:615934 Type 1 interferonopathies Skin vasculopathy, inflammatory lung disease, systemic autoinflammation and ICC Autoinflammatory Disorders Tags new-gene-name
Green Green List (high evidence)	TNFAIP3	5 reviews 4 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ESID Registry 20171117 Expert Review Green IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Autoinflammatory syndrome, familial, Behcet-like, OMIM:616744 Autoimmune lymphoproliferative syndrome Arthralgia, mucosal ulcers, ocular inflammation Tags
Green Green List (high evidence)	TNFRSF1A	6 reviews 4 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Periodic fever, familial, OMIM:142680 TNF-receptor associated periodic fever syndrome (TRAPS) Recurrent fever, serositis, rash, and ocular or joint inflammation Autoinflammatory Disorders Tags
Green Green List (high evidence)	TNFRSF9	4 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification December 2019 Phenotypes Immunodeficiency 109 with lymphoproliferation, OMIM:620282 Tags
Green Green List (high evidence)	TOP2B	4 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green IUIS Classification December 2019 Phenotypes Recurrent infections, facial dysmorphism, limb anomalies Predominantly Antibody Deficiencies Hoffman syndrome/TOP2B deficiency Tags
Green Green List (high evidence)	TPP2	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Tripeptidyl-Peptidase II Deficiency TPP2 deficiency Autoimmune hemolytic anemia-autoimmune thrombocytopenia-primary immunodeficiency syndrome immune thrombocytopenia and autoimmune hemolytic anemia Evans syndrome Variable lymphoproliferation, severe autoimmune cytopenias, hypergammaglobulinemia, recurrent infections Diseases of Immune Dysregulation Immunodeficiency 78 with autoimmunity and developmental delay, OMIM:619220 Tags
Green Green List (high evidence)	TRAC	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Phenotypes Immunodeficiency 7, TCR-alpha/beta deficient, 615387 Combined immunodeficiency Recurrent viral, bacterial, fungal infections, immune dysregulation and autoimmunity, diarrhea Immunodeficiencies affecting cellular and humoral immunity Tags founder-effect
Green Green List (high evidence)	TREX1	5 reviews 4 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Aicardi-Goutieres syndrome 1, dominant and recessive, 225750 Type 1 interferonopathies Classical AGS, SLE, FCL Autoinflammatory Disorders Tags
Green Green List (high evidence)	TRIM22	4 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification December 2019 Phenotypes Autoinflammatory Disorders Granulomatous colitis Diseases of Immune Dysregulation TRIM22 Inflammatory bowel disease Tags gene-checked
Green Green List (high evidence)	TRNT1	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Congenital sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD) Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay, 616084 congenital sideroblastic anemia, deafness, developmental delay Predominantly Antibody Deficiencies Tags
Green Green List (high evidence)	TTC37	6 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources A- or hypo-gammaglobulinaemia v1.25 ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Trichohepatoenteric syndrome 1, 222470 Intrauterine growth retardation, woolly hair facial dysmorphism intractable diarrhoea in infancy requiring total parenteral nutrition Hypogammaglobulinaemia Trichohepatoenteric syndrome immune dysfunction Recurrent bacterial and viral infections, Abnormal hair findings: trichorrhexis nodosa Predominantly Antibody Deficiencies Tags early-onset new-gene-name
Green Green List (high evidence)	TTC7A	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Gastrointestinal defects and immunodeficiency syndrome, 243150 Multiple intestinal atresia and severe combined immunodeficiency Combined immunodeficiency Immunodeficiencies with multiple intestinal atresias Combined immunodeficiency-enteropathy spectrum Bacterial (sepsis), fungal, viral infections, multiple intestinal atresias, often with intrauterine polyhydramnios and early demise, some with SCID phenotype Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	TYK2	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Immunodeficiency 35 611521 Hyper IgE syndrome (HIES) Susceptibility to intracellular bacteria (mycobacteria, Salmonella), viruses, +/- elevated IgE Defects in Intrinsic and Innate Immunity Tags
Green Green List (high evidence)	UNC13D	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Hemophagocytic lymphohistiocytosis, familial 3, 608898 FHL3 Familial hemophagocytic lymphohistiocytosis syndromes (FHLH) HPLH3 HLH3 Fever, HSM, HLH, cytopenias, Diseases of Immune Dysregulation Tags age-specific-variation
Green Green List (high evidence)	UNC93B1	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Herpes simplex encephalitis, susceptibility to, 1 Herpetic encephalitis (HSE) {Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 1} 610551 Herpes simplex virus 1 encephalitis Defects in Intrinsic and Innate Immunity Tags
Green Green List (high evidence)	UNG	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources A- or hypo-gammaglobulinaemia v1.25 ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Immunodeficiency with hyper IgM, type 5 Hyper IgM syndrome with lymphoid hyperplasia CSR defects and Hyper IgM (HIGM) syndromes Immunodeficiency with hyper IgM, type 5, 608106 Enlarged lymph nodes and germinal centers Predominantly Antibody Deficiencies Tags
Green Green List (high evidence)	USB1	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Poikiloderma with neutropenia, 604173 Clericuzio-type poikiloderma with neutropenia syndrome Retinopathy, developmental delay, facial dysmorphisms, poikiloderma Congenital defects of phagocyte number or function Tags
Green Green List (high evidence)	USP18	7 reviews 3 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification December 2019 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Phenotypes Pseudo-TORCH syndrome 2, 617397 Autoinflammatory Disorders Tags
Green Green List (high evidence)	VPS13B	5 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources Congenital neutropaenia v1.22 ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Cohen syndrome, 216550 Cohen syndrome Dysmorphism, mental retardation, obesity, deafness, neutropenia Congenital defects of phagocyte number or function Tags
Green Green List (high evidence)	VPS45	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Congenital neutropaenia v1.22 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Neutropenia, severe congenital, 5, autosomal recessive, 615285 Neutropenia, severe congenital 5 VPS45 deficiency (SCN5) Extramedullary hematopoiesis, bone marrow fibrosis, nephromegaly Congenital defects of phagocyte number or function Tags
Green Green List (high evidence)	WAS	8 reviews 6 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Combined B and T cell defect v1.12 Congenital neutropaenia v1.22 ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Wiskott-Aldrich syndrome Neutropenia, severe congenital, X-linked, 300299 X-linked thrombocytopenia Wiskott-Aldrich syndrome (WAS) X-linked thrombocytopenia with mutations in WASP Congenital neutropenia Thrombocytopenia with small platelets, recurrent bacterial and viral infections, bloody diarrhea, eczema, lymphoma, autoimmune disease, IgA nephropathy, vasculitis XL thrombocytopenia is a mild form of WAS, and XL neutropenia is caused by missense mutations in the GTPase binding domain of WASp Combined immunodeficiencies with associated or syndromic features Neutropenia, myeloid maturation arrest, monocytopenia, variable lymphoid anomalies Congenital defects of phagocyte number or function Tags gene-therapy-trial
Green Green List (high evidence)	WDR1	7 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification December 2019 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Phenotypes Mild neutropenia, poor wound healing, severe stomatitis, neutrophil nuclei herniate Congenital defects of phagocyte number or function Tags
Green Green List (high evidence)	WIPF1	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Wiskott-Aldrich syndrome like, WIP deficiency WIP deficiency ?Wiskott-Aldrich syndrome 2 614493 Thrombocytopenia with or without small platelets, recurrent bacterial and viral infections, eczema, bloody diarrhea, WAS protein absent Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	XIAP	6 reviews 4 green	X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Lymphoproliferative syndrome, X-linked, 2 300635 Lymphoproliferative syndrome, X-linked, 2 (XLP2) X-linked lymphoproliferative syndrome (XLP) haemophagocytic lymphohistiocytosis inflammatory bowel disease splenomegaly EBV infection, Splenomegaly, lymphoproliferation, HLH, Colitis, IBD, hepatitis, Low iNKT cells, hypogammaglobulinemia Diseases of Immune Dysregulation Tags
Green Green List (high evidence)	ZAP70	7 reviews 5 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GOSH PID v.8.0 GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other SCID v1.6 Victorian Clinical Genetics Services Phenotypes Autoimmune disease, multisystem, infantile-onset, 2 Immunodeficiency 48 Severe Combined Immune Deficiency Selective T-cell defect Zap-70 deficiency Combined immunodeficiency Severe combined immunodeficiency (SCID) May have immune dysregulation, autoimmunity Immunodeficiencies affecting cellular and humoral immunity Severe autoimmunity Diseases of Immune Dysregulation Tags
Green Green List (high evidence)	ZBTB24	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Green GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Immunodeficiency-centromeric instability-facial anomalies syndrome-2 614069 Immunodeficiency centromeric instability facial anomalies syndrome (ICF) Facial dysmorphic features, macroglossia, bacterial/opportunistic infections, malabsorption, cytopenias, malignancies, multiradial configurations of chromosomes 1, 9, 16 Combined immunodeficiencies with associated or syndromic features Tags
Green Green List (high evidence)	ZNF341	5 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green IUIS Classification December 2019 Literature Phenotypes Hyper-IgE syndrome Bacterial infections, mild facial dysmorphism, pneumatoceles, hyperextensible joints, bone fractures, retention of primary teeth Combined immunodeficiencies with associated or syndromic features Tags gene-checked
Green Green List (high evidence)	ZNFX1	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes mendelian susceptibility to mycobacterial disease MSMD monocytosis. Tags gene-checked
Amber Amber List (moderate evidence)	ANGPT1	2 reviews	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Amber Literature Phenotypes Angioedema, hereditary, 5, OMIM:619361 Tags watchlist
Amber Amber List (moderate evidence)	AP1S3	5 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber IUIS Classification December 2019 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Pustular psoriasis, 616106 Pustular psoriasis Autoinflammatory Disorders Tags
Amber Amber List (moderate evidence)	AP3D1	3 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber IUIS Classification December 2019 IUIS Classification February 2018 Literature Other Phenotypes Oculocutaneous albinism, recurrent infections, seizures, hearing loss and neurodevelopmental delay Diseases of Immune Dysregulation Hermansky-Pudlak syndrome with neutropenia Oculocutaneous albinism, severe neutropenia, recurrent infections, seizures, hearing loss and neurodevelopmental delay albinism HSP10 seizures neutropenia Immunodeficient HPS neuordevelopmental delay Hermansky-Pudlak syndrome ?Hermansky-Pudlak syndrome 10, 617050 Tags
Amber Amber List (moderate evidence)	ARPC5	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber Literature Phenotypes combined immunodeficiency, MONDO:0015131 Tags Q3_23_promote_green
Amber Amber List (moderate evidence)	ATAD3A	2 reviews 1 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Amber Literature Phenotypes Developmental delay Hypotonia Dystonia Systemic sclerosis Autoimmunity Contractures Basal ganglia calcifications Interferonopathy Tags
Amber Amber List (moderate evidence)	BCL11B	4 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Amber IUIS Classification December 2019 IUIS Classification February 2018 Other Phenotypes ?Immunodeficiency 49, 617237 leaky SCID Congenital abnormalities, neonatal teeth, dysmorphic facies, absent corpus callosum, neurocognitive deficits Immunodeficiencies affecting cellular and humoral immunity Combined immunodeficiencies with associated or syndromic features Tags
Amber Amber List (moderate evidence)	CD4	6 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Amber Phenotypes Immunodeficiency 79, OMIM:619238 OKT4 epitope deficiency, OMIM:613949 Tags Q4_23_NHS_review Q4_23_promote_green
Amber Amber List (moderate evidence)	CD81	4 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Amber GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Victorian Clinical Genetics Services Phenotypes Immunodeficiency, common variable, 6, OMIM:613496 Tags Q4_23_NHS_review Q4_23_promote_green
Amber Amber List (moderate evidence)	CD8A	4 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Amber GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Other Victorian Clinical Genetics Services Phenotypes CD8 deficiency familial, 608957 Susceptibility to respiratory infections associated with CD8alpha chain mutation Recurrent infections, may be asymptomatic Immunodeficiencies affecting cellular and humoral immunity Tags founder-effect
Amber Amber List (moderate evidence)	CFB	4 reviews 3 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Amber GRID V2.0 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Complement factor B deficiency, 615561 Atypical Hemolytic-uremic syndrome Infections with encapsulated organisms Complement Deficiencies Susceptibility to atypical haemolytic uraemic syndrome 4 (AD) complement factor B deficiency (AR) Tags
Amber Amber List (moderate evidence)	CFTR	3 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber IUIS Classification December 2019 IUIS Classification February 2018 Phenotypes Respiratory infections, pancreatic insufficiency, elevated sweat chloride Cystic fibrosis, 219700 Congenital defects of phagocyte number or function Tags
Amber Amber List (moderate evidence)	CR2	6 reviews 3 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources A- or hypo-gammaglobulinaemia v1.25 ESID Registry 20171117 Expert Review Amber GRID V2.0 IUIS Classification February 2018 Victorian Clinical Genetics Services Phenotypes ?Immunodeficiency, common variable, 7, OMIM:614699 Tags Q4_23_NHS_review Q4_23_promote_green
Amber Amber List (moderate evidence)	CTC1	4 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber IUIS Classification December 2019 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Phenotypes Combined immunodeficiencies with associated or syndromic features Intrauterine growth retardation, sparse graying hair, dystrophic nails, trilinear bone marrow failure, osteopenia, gastrointestinal hemorrhage due to vascular ectasia, retinal telangiectasia, intracranial calcification, abnormal telomeres Bone marrow failure Cerebroretinal microangiopathy with calcifications and cysts, 612199 Tags
Amber Amber List (moderate evidence)	CXCR2	5 reviews 2 green 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber Literature Phenotypes WHIM syndrome 2, OMIM:619407 Tags Q4_23_NHS_review Q4_23_promote_green
Amber Amber List (moderate evidence)	DIAPH1	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Amber Literature Phenotypes Seizures, cortical blindness, microcephaly syndrome, OMIM:616632 Tags Q3_23_promote_green
Amber Amber List (moderate evidence)	DOCK11	2 reviews 2 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Expert Review Amber Literature Phenotypes Autoinflammatory disease, multisystem, with immune dysregulation, X-linked, OMIM:301109 Tags Q3_23_promote_green
Amber Amber List (moderate evidence)	ERBIN	3 reviews	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Amber IUIS Classification December 2019 Phenotypes ERBIN deficiency Combined immunodeficiencies with associated or syndromic features Recurrent respiratory infections, susceptibility to S. aureus, eczema, hyperextensible joints, scoliosis, arterial dilatation in some Tags new-gene-name
Amber Amber List (moderate evidence)	FCGR3A	3 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Amber GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Victorian Clinical Genetics Services Phenotypes Immunodeficiency 20, 615707 CD16 deficiency Defects in Intrinsic and Innate Immunity Fc receptor deficiencies predisposition to severe viral infection severe herpes viral infections, particularly VZV, Epstein Barr virus (EBV), and (HPV) Autosomal recessive primary immunodeficiency with defective spontaneous NK cell cytotoxicity Tags watchlist
Amber Amber List (moderate evidence)	FMNL2	2 reviews	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Amber Literature Phenotypes inflammatory bowel disease, MONDO:0005265 Tags
Amber Amber List (moderate evidence)	FPR1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Amber GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Victorian Clinical Genetics Services Phenotypes Periodontitis Periodontitis only Congenital defects of phagocyte number or function Localized juvenile peridontitis Tags
Amber Amber List (moderate evidence)	GIMAP5	5 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber Literature Phenotypes Portal hypertension, noncirrhotic, 2, OMIM:619463 lymphopenia autoimmunity immunodeficiency liver disease Tags treatable watchlist
Amber Amber List (moderate evidence)	HMOX1	4 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber IUIS Classification February 2018 Phenotypes Heme oxygenase-1 deficiency, OMIM:614034 Hemolysis, nephritis, inflammation Defects in Intrinsic and Innate Immunity amyloidosis Tags Q4_23_NHS_review Q4_23_promote_green
Amber Amber List (moderate evidence)	HYOU1	5 reviews 1 green 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber IUIS Classification December 2019 IUIS Classification February 2018 Phenotypes ?Immunodeficiency 59 and hypoglycemia, OMIM:233600 Hypoglycemia, inflammatory complications Congenital defects of phagocyte number or function Tags Q4_23_NHS_review Q4_23_promote_green
Amber Amber List (moderate evidence)	IFNAR1	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Amber Literature Phenotypes IFNAR1 associated adverse reactions to certain live attenuated viral vaccines Tags
Amber Amber List (moderate evidence)	IGKC	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Amber GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Phenotypes Immunoglobulin chain deficiencies Asymptomatic Kappa light chain deficiency, 614102 Predominantly Antibody Deficiencies Tags
Amber Amber List (moderate evidence)	IL17F	3 reviews 2 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ESID Registry 20171117 Expert Review Amber GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Victorian Clinical Genetics Services Phenotypes Candidiasis, familial, 6, 613956 Chronic mucocutaneous candidiasis (CMC) Defects in Intrinsic and Innate Immunity CMC, folliculitis Tags
Amber Amber List (moderate evidence)	IL21	4 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Other Victorian Clinical Genetics Services Phenotypes Immunodeficiency, common variable, 11 , OMIM:615767 Severe early onset colitis, recurrent sinopulmonary infections Immunodeficiencies affecting cellular and humoral immunity Tags
Amber Amber List (moderate evidence)	IPO8	3 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber Literature Phenotypes cardiovascular anomalies joint hyperlaxity dysmorphic features developmental delay immune dysregulation allergy Tags watchlist
Amber Amber List (moderate evidence)	IRF2BP2	4 reviews 2 green 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Amber IUIS Classification December 2019 IUIS Classification February 2018 Phenotypes Recurrent infections, possible autoimmunity and inflammatory disease CVID Predominantly Antibody Deficiencies Tags Q4_23_NHS_review Q4_23_promote_green
Amber Amber List (moderate evidence)	IRF3	2 reviews	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Amber IUIS Classification December 2019 IUIS Classification February 2018 Phenotypes Defects in Intrinsic and Innate Immunity {Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 7}, 616532 Herpes simplex virus 1 encephalitis Tags
Amber Amber List (moderate evidence)	IRF4	4 reviews 2 green 1 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Amber Phenotypes combined immunodeficiency, MONDO:0015131 Tags Q4_23_NHS_review Q4_23_promote_green
Amber Amber List (moderate evidence)	IRF9	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Amber Phenotypes Immunodeficiency 65, susceptibility to viral infections, 618648 Tags
Amber Amber List (moderate evidence)	ITPKB	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber Literature Phenotypes Severe combined immunodeficiency, absent T cells, present B cells and NK cells Tags
Amber Amber List (moderate evidence)	IVNS1ABP	3 reviews 1 green 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Amber Literature Phenotypes Immunodeficiency 70, MIM#618969 Tags watchlist
Amber Amber List (moderate evidence)	JAK1	5 reviews 2 green 1 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Amber IUIS Classification December 2019 IUIS Classification February 2018 Other Phenotypes Autoinflammation, immune dysregulation, and eosinophilia, OMIM:618999 Tags mosaicism Q4_23_NHS_review Q4_23_promote_green somatic
Amber Amber List (moderate evidence)	KRAS	2 reviews	Unknown	Sources ESID Registry 20171117 Expert Review Amber GRID V2.0 Phenotypes RAS associated lymphoproliferative disease, 614470 RALD Tags
Amber Amber List (moderate evidence)	MBL2	2 reviews	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Amber GRID V2.0 Inherited complement deficiency v0.11 London North GLH NHS GMS North West GLH Phenotypes Mannose-Binding Protein Deficiency, 614372 Chronic infections, due to MBL deficiency Mannose-binding lectin deficiency (MBL) Tags curated-variant-list
Amber Amber List (moderate evidence)	MKL1	4 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber IUIS Classification December 2019 IUIS Classification February 2018 Phenotypes Susceptibility to severe bacterial infection Mild thrombocytopenia Congenital defects of phagocyte number or function Tags new-gene-name
Amber Amber List (moderate evidence)	MPO	3 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Amber GRID V2.0 Phenotypes Myeloperoxidase deficiency 254600 Tags
Amber Amber List (moderate evidence)	NCSTN	2 reviews	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Amber IUIS Classification December 2019 IUIS Classification February 2018 Phenotypes Defects in Intrinsic and Innate Immunity familial hydradenitis suppurativa Hidradenitis suppurativa with acne, 142690 Defects in intrinsic and innate immunity Hidradenitis suppurativa with acne Tags
Amber Amber List (moderate evidence)	NFAT5	6 reviews 2 green 3 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Amber GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Other Victorian Clinical Genetics Services Phenotypes Diseases of Immune Dysregulation IBD, recurrent sinopulmonary infections NFAT5 haploinsufficieny Tags Q4_23_NHS_review Q4_23_promote_green
Amber Amber List (moderate evidence)	NLRP1	9 reviews 4 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Amber IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Phenotypes Autoinflammation with arthritis and dyskeratosis, OMIM:617388 ?Respiratory papillomatosis, juvenile recurrent, congenital, OMIM:618803 Palmoplantar carcinoma, multiple self-healing, OMIM:615225 {Vitiligo-associated multiple autoimmune disease susceptibility 1}, OMIM:606579 Tags Q4_23_NHS_review Q4_23_promote_green
Amber Amber List (moderate evidence)	NOP10	4 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Amber GRID V2.0 IUIS Classification February 2018 Victorian Clinical Genetics Services Phenotypes Dyskeratosis congenita, autosomal recessive 1 224230 Dyskeratosis congenita 1 Dyskeratosis congenita Hoyeraal-Hreidarsson syndrome Intrauterine growth retardation, microcephaly, nail dystrophy, sparse scalp hair and eyelashes, hyperpigmentation of skin, palmar hyperkeratosis, premalignant oral leukoplakia, pancytopenia, myelodysplasia, +/- recurrent infections. A severe phenotype with developmental delay and cerebellar hypoplasia known as Hoyeraal-Hreidarsson Syndrome (HHS) may occur in some DKC patients Combined immunodeficiencies with associated or syndromic features Tags
Amber Amber List (moderate evidence)	NRAS	5 reviews 2 green	Other - please specifiy in evaluation comments	Sources ESID Registry 20171117 Expert Review Amber GOSH PID v.8.0 GRID V2.0 London North GLH NHS GMS North West GLH Phenotypes ?RAS-associated autoimmune lymphoproliferative syndrome type IV, somatic 614470 Autoimmune lymphoproliferative syndrome type IV Ras associated lymphoproliferative disease (RALD) Tags mosaicism somatic
Amber Amber List (moderate evidence)	POLD1	5 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber IUIS Classification December 2019 Phenotypes Recurrent respiratory tract infections, skin infections, warts and molluscum, short stature, intellectual disability Polymerase d 1 deficiency Immunodeficiencies affecting cellular and humoral immunity Tags Q4_23_NHS_review Q4_23_promote_green
Amber Amber List (moderate evidence)	POLD3	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber Literature Phenotypes severe combined immunodeficiency, MONDO:0015974 Tags
Amber Amber List (moderate evidence)	POLR3A	2 reviews	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Amber Phenotypes Severe VZV infection Tags
Amber Amber List (moderate evidence)	POLR3C	2 reviews	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Amber Phenotypes Severe VZV infection Tags
Amber Amber List (moderate evidence)	PSENEN	3 reviews	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Amber IUIS Classification December 2019 IUIS Classification February 2018 Phenotypes Defects in intrinsic and innate immunity Acne inversa, familial, 2, with or without Dowling-Degos disease 613736 Defects in Intrinsic and Innate Immunity Hidradenitis suppurativa Tags
Amber Amber List (moderate evidence)	PSMA3	5 reviews 1 green 1 red	Not set	Sources Expert Review Amber London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome) Tags
Amber Amber List (moderate evidence)	PSMB10	5 reviews 3 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber Literature Phenotypes Proteasome-associated autoinflammatory syndrome 5, OMIM:619175 Tags Q4_23_NHS_review Q4_23_promote_green
Amber Amber List (moderate evidence)	PSMB4	5 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Proteasome-associated autoinflammatory syndrome 3 and digenic forms, OMIM:617591 CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome) Tags digenic
Amber Amber List (moderate evidence)	PSMB9	5 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Amber London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Proteasome-associated autoinflammatory syndrome 3, digenic, OMIM:617591 CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome) Tags digenic
Amber Amber List (moderate evidence)	PTEN	5 reviews	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Amber IUIS Classification December 2019 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Phenotypes Recurrent infections, Lymphoproliferation, Autoimmunity developmental delay Predominantly Antibody Deficiencies Lymphoproliferation, Autoimmunity Tags
Amber Amber List (moderate evidence)	PTPN2	4 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Amber Literature Phenotypes Lupus arthritis common variable immunodeficiency Very early onset inflammatory bowel disease Tags Q4_23_NHS_review Q4_23_promote_green
Amber Amber List (moderate evidence)	RC3H1	3 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber Literature Phenotypes Hemophagocytic lymphohistiocytosis Tags
Amber Amber List (moderate evidence)	REL	4 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber IUIS Classification December 2019 Phenotypes Immunodeficiency 92, OMIM:619652 Tags Q4_23_NHS_review Q4_23_promote_green
Amber Amber List (moderate evidence)	RELA	5 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Amber IUIS Classification December 2019 Phenotypes Autoinflammatory disease, familial, Behcet-like-3, OMIM:618287 Tags Q4_23_NHS_review Q4_23_promote_green
Amber Amber List (moderate evidence)	RHBDF2	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber Literature Phenotypes Pneumonia Colitis Immunodeficiency Tags
Amber Amber List (moderate evidence)	RHOH	4 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Amber GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Other Victorian Clinical Genetics Services Phenotypes RhoH deficiency T cell deficiency and various infectious diseases Epidermodysplasia verruciformis HPV infection, lung granulomas, molluscum contagiosum, lymphoma Immunodeficiencies affecting cellular and humoral immunity Combined immunodeficiency Tags
Amber Amber List (moderate evidence)	RNF31	6 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Other Victorian Clinical Genetics Services Phenotypes Bacterial infections, autoinflammation, amylopectinosis, lymphangiectasia Autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis Polyglucosan body myopathy, early-onset, with or without immunodeficiency autoinflammation and combined immunodeficiency Combined immunodeficiencies with associated or syndromic features Tags
Amber Amber List (moderate evidence)	SAMD9	2 reviews	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Amber IUIS Classification December 2019 IUIS Classification February 2018 Phenotypes ataxia-thrombocytopenia syndrome IUGR with gonadal abnormalities, adrenal failure, MDS with chromosome 7 aberrations, predisposition to infections, enteropathy, absent spleen MIRAGE syndrome (Myelodysplasia, Infection, Restriction of growth, Adrenal insufficiency, Genital phenotypes, and Enteropathy) Bone marrow failure Combined immunodeficiencies with associated or syndromic features Tags
Amber Amber List (moderate evidence)	SAMD9L	6 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Amber IUIS Classification December 2019 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Phenotypes Cytopenia, predisposition to MDS with chromosome 7 aberrations, immunodeficiency, and progressive cerebellar dysfunction MDS, neurological features Bone marrow failure Combined immunodeficiencies with associated or syndromic features Tags Q4_23_NHS_review Q4_23_promote_green
Amber Amber List (moderate evidence)	SEC61A1	6 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Amber IUIS Classification December 2019 Phenotypes SEC61A1 deficiency Severe recurrent respiratory tract infections Hyperuricemic nephropathy, familial juvenile, 4, 617056 Predominantly Antibody Deficiencies Hypogammaglobulinaemia Severe congenital neutropenia Tags Q4_23_NHS_review Q4_23_promote_green
Amber Amber List (moderate evidence)	SLC9A3	3 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Amber Phenotypes Very Early Onset Inflammatory Bowel Disease Diarrhea 8, secretory sodium, congenital, OMIM:616868 Tags
Amber Amber List (moderate evidence)	SPI1	4 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Amber Literature Phenotypes Agammaglobulinemia 10, autosomal dominant, OMIM:619707 Tags Q4_23_NHS_review Q4_23_promote_green
Amber Amber List (moderate evidence)	TAPBP	3 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Amber GOSH PID v.8.0 GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Other Victorian Clinical Genetics Services Phenotypes Vasculitis, pyoderma gangrenosum Bare lymphocyte syndrome, type I 604571 HLA class I deficiency Immunodeficiencies affecting cellular and humoral immunity Vasculitis,pyoderma gangrenosum Tags deletions
Amber Amber List (moderate evidence)	TERC	3 reviews	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ESID Registry 20171117 Expert Review Amber GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Victorian Clinical Genetics Services Phenotypes Intrauterine growth retardation, microcephaly, nail dystrophy, sparse scalp hair and eyelashes, hyperpigmentation of skin, palmar hyperkeratosis, premalignant oral leukoplakia, pancytopenia, myelodysplasia, +/- recurrent infections. A severe phenotype with developmental delay and cerebellar hypoplasia known as Hoyeraal-Hreidarsson Syndrome (HHS) may occur in some DKC patients Dyskeratosis congenita Hoyeraal-Hreidarsson syndrome microcephaly, neurodevelopmental delay Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation Bone marrow failure Dyskeratosis congenita 1 Combined immunodeficiencies with associated or syndromic features Tags locus-type-rna-misc
Amber Amber List (moderate evidence)	TERT	3 reviews	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Amber GRID V2.0 IUIS Classification February 2018 Victorian Clinical Genetics Services Phenotypes Dyskeratosis congenita, autosomal dominant 2, OMIM:613989 Dyskeratosis congenita, autosomal recessive 4, OMIM:613989 Tags missense
Amber Amber List (moderate evidence)	TET2	3 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber Literature Phenotypes Primary Immunodeficiency Lymphoma Hepatosplenomegaly Autoimmunity Developmental delay Tags
Amber Amber List (moderate evidence)	TFRC	6 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber IUIS Classification December 2019 IUIS Classification February 2018 Other Phenotypes Immunodeficiency 46, OMIM:616740 Tags founder-effect Q4_23_NHS_review Q4_23_promote_green
Amber Amber List (moderate evidence)	TINF2	3 reviews	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ESID Registry 20171117 Expert Review Amber GRID V2.0 IUIS Classification February 2018 Victorian Clinical Genetics Services Phenotypes Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation microcephaly, neurodevelopmental delay Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation microcephaly, neurodevelopmental delay exudative retinopathy Tags
Amber Amber List (moderate evidence)	TNFRSF11A	4 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber IUIS Classification December 2019 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Phenotypes Osteopetrosis Defects in Intrinsic and Innate Immunity Defects in intrinsic and innate immunity Tags
Amber Amber List (moderate evidence)	TNFRSF13C	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Amber GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Victorian Clinical Genetics Services Phenotypes Variable clinical expression Common variable immunodeficiency disorders (CVID) Immunodeficiency, common variable, 4 Isolated IgG subclass deficiency Predominantly Antibody Deficiencies Tags
Amber Amber List (moderate evidence)	TRAF3IP2	7 reviews 1 green 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Amber GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Victorian Clinical Genetics Services Phenotypes ?Candidiasis, familial, 8, OMIM:615527 Defects in Intrinsic and Innate Immunity CMC, blepharitis, folliculitis and macroglossia Chronic mucocutaneous candidiasis (CMC) Defects in intrinsic and innate immunity Tags Q4_23_NHS_review Q4_23_promote_green
Red Red List (low evidence)	ABI3	1 review 1 red	Unknown	Sources Literature Phenotypes primary immunodeficiency Tags
Red Red List (low evidence)	ACTB	2 reviews 2 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ESID Registry 20171117 Expert Review Red GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Victorian Clinical Genetics Services Phenotypes Actin beta deficiency (ACTB) Poor neutrophil chemotaxis, oxidative burst and actin remodeling. Thrombocytopenia neutrophil dysfunction Phagocytic disorder Mental retardation, short stature Baraitser-Winter syndrome 1, 243310 Congenital defects of phagocyte number or function Tags
Red Red List (low evidence)	APOL1	2 reviews 2 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ESID Registry 20171117 Expert Review Red GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Victorian Clinical Genetics Services Phenotypes Trypanosomias Trypanosomiasis Defects in Intrinsic and Innate Immunity Trypanosomiasis, susceptibility to Tags
Red Red List (low evidence)	ARHGAP42	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes Interstitial lung disease systemic hypertension immunological abnormalities Tags
Red Red List (low evidence)	ARHGEF1	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources IUIS Classification December 2019 Phenotypes Predominantly Antibody Deficiencies Recurrent infections, bronchiectasis Immunodeficiency 62, 618459 ARHGEF1 deficiency Tags
Red Red List (low evidence)	ATG4A	2 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Red Literature Phenotypes Mollaret’s meningitis recurrent HSV2 meningitis Tags
Red Red List (low evidence)	BRCA1	0 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources IUIS Classification December 2019 Phenotypes Fanconi anemia, complementation group S, OMIM:617883 Normal to low NK, CNS, skeletal, skin, cardiac, GI, urogenital anomalies, increased chromosomal breakage Bone marrow failure Tags
Red Red List (low evidence)	BRCA2	0 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources IUIS Classification December 2019 Phenotypes Fanconi anemia, complementation group D1, OMIM:605724 Normal to low NK, CNS, skeletal, skin, cardiac, GI, urogenital anomalies, increased chromosomal breakage Bone marrow failure Tags
Red Red List (low evidence)	C8G	2 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Red GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Victorian Clinical Genetics Services Phenotypes Complement Deficiencies Disseminated neisserial infections Complement component 8 deficiency Complement factor 8 defect Tags
Red Red List (low evidence)	CARD10	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes Immunodeficiency 89 and autoimmunity, OMIM:619632 Tags
Red Red List (low evidence)	CD28	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes cutaneous horn immunodeficiency papillomavirus infection tree man syndrome warts Tags
Red Red List (low evidence)	CFHR1	4 reviews 1 red	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Red GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Victorian Clinical Genetics Services Phenotypes Older onset atypical hemolytic-uremic syndrome, disseminated neisserial infections Age related macular degeneration Complement Deficiencies Atypical hemolytic uremic syndrome susceptibility Tags
Red Red List (low evidence)	CFHR2	2 reviews 1 red	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Red GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Victorian Clinical Genetics Services Phenotypes Older onset atypical hemolytic-uremic syndrome, disseminated neisserial infections Age related macular degeneration Complement Deficiencies Atypical hemolytic uremic syndrome susceptibility Tags
Red Red List (low evidence)	CFHR3	4 reviews 1 red	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Red GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Victorian Clinical Genetics Services Phenotypes Older onset atypical hemolytic-uremic syndrome, disseminated neisserial infections Age related macular degeneration Complement Deficiencies Atypical hemolytic uremic syndrome susceptibility Tags
Red Red List (low evidence)	CFHR4	4 reviews 1 red	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Red GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Victorian Clinical Genetics Services Phenotypes Older onset atypical hemolytic-uremic syndrome, disseminated neisserial infections Age related macular degeneration Complement Deficiencies Atypical hemolytic uremic syndrome susceptibility Tags
Red Red List (low evidence)	CFHR5	6 reviews 1 red	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Red GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes Complement Deficiencies Older onset atypical hemolytic-uremic syndrome, disseminated neisserial infections Nephropathy due to CFHR5 deficiency, 614809 Atypical hemolytic-uremic syndrome with anti-factor H antibodies Atypical hemolytic uremic syndrome susceptibility Tags
Red Red List (low evidence)	CHUK	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Red Literature Phenotypes recurrent infections skeletal abnormalities absent secondary lymphoid structures reduced B cell numbers hypogammaglobulinemia lymphocytic infiltration of intestine and liver Tags
Red Red List (low evidence)	CLCN7	2 reviews 1 red	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Red IUIS Classification December 2019 IUIS Classification February 2018 Phenotypes Osteopetrosis, autosomal recessive 4, OMIM:611490 Osteopetrosis, autosomal dominant 2, OMIM:166600 Tags
Red Red List (low evidence)	CNBP	4 reviews 1 green 1 red	Other	Sources ESID Registry 20171117 Expert Review Red Phenotypes Myotonic dystrophy 2, OMIM:602668 Myotonic dystrophy type 2, MONDO:0011266 Tags currently-ngs-unreportable nucleotide-repeat-expansion
Red Red List (low evidence)	COLEC11	2 reviews 1 red	Not set	Sources ESID Registry 20171117 Expert Review Red Phenotypes Mannan-binding lectin serine protease (MASP) deficiency Tags
Red Red List (low evidence)	COPG1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Red Literature Phenotypes persistent bacterial infection persistent viral infections defective humoral and cellular immunity Tags
Red Red List (low evidence)	CRACR2A	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes late onset combined immunodeficiency Tags
Red Red List (low evidence)	CSF2	2 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Red Literature Phenotypes Behcet-like disease Pathergy Tags
Red Red List (low evidence)	CTNNBL1	3 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes Primary Immunodeficiency Autoimmune Cytopenias Common variable immunodeficiency Tags
Red Red List (low evidence)	CXorf36	1 review 1 red	Unknown	Sources Literature Phenotypes primary immunodeficiency Tags
Red Red List (low evidence)	EPCAM	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red GOSH PID v.8.0 Phenotypes Diarrhea 5, with tufting enteropathy, congenital, OMIM:613217 Tags
Red Red List (low evidence)	ERCC2	2 reviews 1 red	Unknown	Sources Expert Review Red London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Combined immunodeficiency (CID) in a child affected by trichothiodystrophy (TTD) CD4 + lymphopenia Tags
Red Red List (low evidence)	ERCC3	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes none Tags
Red Red List (low evidence)	ERCC4	0 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources IUIS Classification December 2019 Phenotypes Fanconi anemia, complementation group Q, 615272 Bone marrow failure Fanconi Anemia Type Q Normal to low NK, CNS, skeletal, skin, cardiac, GI, urogenital anomalies, increased chromosomal breakage Tags
Red Red List (low evidence)	FAAP24	3 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red IUIS Classification December 2019 IUIS Classification February 2018 Other Phenotypes Diseases of Immune Dysregulation EBV infection-driven lymphoproliferative disease Tags
Red Red List (low evidence)	FANCF	0 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources IUIS Classification December 2019 Phenotypes Normal to low NK, CNS, skeletal, skin, cardiac, GI, urogenital anomalies, increased chromosomal breakage Fanconi Anemia Type F Fanconi anemia, complementation group F, 603467 Bone marrow failure Tags
Red Red List (low evidence)	FANCI	0 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources IUIS Classification December 2019 Phenotypes Fanconi anemia, complementation group I, 609053 Normal to low NK, CNS, skeletal, skin, cardiac, GI, urogenital anomalies, increased chromosomal breakage Fanconi Anemia Type I Bone marrow failure Tags
Red Red List (low evidence)	FANCM	0 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources IUIS Classification December 2019 Phenotypes Bone marrow failure Normal to low NK, CNS, skeletal, skin, cardiac, GI, urogenital anomalies, increased chromosomal breakage Fanconi Anemia Type M Tags
Red Red List (low evidence)	FBF1	2 reviews 1 red	Not set	Sources Expert Review Red Victorian Clinical Genetics Services Tags
Red Red List (low evidence)	FBRS	1 review 1 red	Unknown	Sources Literature Phenotypes primary immunodeficiency Tags
Red Red List (low evidence)	FCGR1A	2 reviews 1 red	Not set	Sources ESID Registry 20171117 Expert Review Red Phenotypes Fc receptor deficiencies Tags
Red Red List (low evidence)	FCGR2A	2 reviews 1 red	Not set	Sources ESID Registry 20171117 Expert Review Red Phenotypes Fc receptor deficiencies Tags
Red Red List (low evidence)	FCGR2B	2 reviews 1 red	Not set	Sources ESID Registry 20171117 Expert Review Red Phenotypes Fc receptor deficiencies Tags
Red Red List (low evidence)	FCGR3B	4 reviews 2 red	Unknown	Sources Congenital neutropaenia v1.22 ESID Registry 20171117 Expert Review Red GRID V2.0 Phenotypes Neutropenia,alloimmuneneonatal Neutropenia, alloimmune neonatal Fc receptor deficiencies Neutropenia, autoimmune neonatal Neutropenia, autoimmune neonatal Tags
Red Red List (low evidence)	FCGRT	2 reviews 1 red	Not set	Sources ESID Registry 20171117 Expert Review Red Phenotypes Fc receptor deficiencies Tags
Red Red List (low evidence)	FCN3	4 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Red GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Victorian Clinical Genetics Services Phenotypes Immunodeficiency due to ficolin 3 deficiency, OMIM:613860 Tags
Red Red List (low evidence)	FOXM1	1 review 1 red	Unknown	Sources Literature Phenotypes primary immunodeficiency Tags
Red Red List (low evidence)	FPR2	2 reviews 1 red	Not set	Sources ESID Registry 20171117 Expert Review Red Phenotypes Localized juvenile peridontitis Tags
Red Red List (low evidence)	FPR3	2 reviews 1 red	Not set	Sources ESID Registry 20171117 Expert Review Red Phenotypes Localized juvenile peridontitis Tags
Red Red List (low evidence)	GAD1	5 reviews 3 red	BIALLELIC, autosomal or pseudoautosomal	Sources A- or hypo-gammaglobulinaemia v1.25 Expert Review Red Phenotypes ?Cerebral palsy, spastic quadriplegic, 1, 603513 Tags
Red Red List (low evidence)	GIMAP6	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes Lymphopenia Sinopulmonary Infections Tags
Red Red List (low evidence)	GTF2H5	1 review 1 red	Not set	Sources London North GLH NHS GMS North West GLH Tags
Red Red List (low evidence)	HCK	2 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Red Literature Phenotypes Autoinflammatory disease Cutaneous vasculitis Lung inflammation Lung fibrosis Interstitial lung disease Tags
Red Red List (low evidence)	HS3ST6	2 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Red Literature Phenotypes ?Angioedema, hereditary, 8, OMIM:619367 Tags
Red Red List (low evidence)	ICOSLG	4 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red IUIS Classification December 2019 Victorian Clinical Genetics Services Phenotypes Recurrent bacterial and viral infections Immunodeficiencies affecting cellular and humoral immunity Tags
Red Red List (low evidence)	IFNG	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes Mendelian susceptibility to mycobacterial disease Tags
Red Red List (low evidence)	IGHG2	2 reviews 1 red	Not set	Sources ESID Registry 20171117 Expert Review Red Phenotypes Immunoglobulin chain deficiencies Tags
Red Red List (low evidence)	IL12RB2	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Red Phenotypes Susceptibility to mycobacteria and Salmonella Tags
Red Red List (low evidence)	IL17A	2 reviews 1 red	Not set	Sources Expert Review Red GRID V2.0 Phenotypes Immunodeficiency 5 Arthritis Tags
Red Red List (low evidence)	IL18	2 reviews 1 red	Not set	Sources ESID Registry 20171117 Expert Review Red Phenotypes Defects with susceptibility to mycobacterial infection (MSMD) Tags
Red Red List (low evidence)	IL18BP	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Red Phenotypes {?Hepatitis, fulminant viral, susceptibility to} 618549 Tags
Red Red List (low evidence)	IL22	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red GRID V2.0 Phenotypes AutoAb Chronic Mucocutaneous Candidiasis Tags
Red Red List (low evidence)	IL23A	2 reviews 1 red	Not set	Sources ESID Registry 20171117 Expert Review Red Phenotypes Defects with susceptibility to mycobacterial infection (MSMD) Tags
Red Red List (low evidence)	IL23R	3 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Red Phenotypes Susceptibility to mycobacteria and Salmonella Tags
Red Red List (low evidence)	IL31RA	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Red London North GLH NHS GMS Phenotypes ?Amyloidosis, primary localized cutaneous 2, 613955 Tags
Red Red List (low evidence)	IL37	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes Infantile inflammatory bowel disease Tags
Red Red List (low evidence)	IL6	1 review 1 red	Unknown	Sources Literature Phenotypes Potential marker for respiratory failure when infected with COVID-19 Tags
Red Red List (low evidence)	IRAK1	2 reviews 1 red	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Expert Review Red IUIS Classification December 2019 IUIS Classification February 2018 Phenotypes Defects in Intrinsic and Innate Immunity Bacterial infections, X-linked MECP2 deficiency-related syndrome due to a large de novo Xq28 chromosomal deletion encompassing both MECP2 and IRAK1 Tags
Red Red List (low evidence)	ITGAM	2 reviews 1 red	Unknown	Sources Expert Review Red GRID V2.0 Victorian Clinical Genetics Services Phenotypes Systemic lupus erythematous Tags
Red Red List (low evidence)	LCP2	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes SCID combined T and B cell immunodeficiency severe neutrophil defects impaired platelet aggregation Tags watchlist
Red Red List (low evidence)	LRRC32	2 reviews 1 red	Unknown	Sources Expert Review Red Literature Phenotypes Common variable immunodeficiency Enteropathy Lymphopenia Reduced Tregs Tags
Red Red List (low evidence)	LRRC8A	5 reviews 3 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources A- or hypo-gammaglobulinaemia v1.25 ESID Registry 20171117 Expert Review Red Phenotypes Agammaglobulinemia 5, 613506 Agammaglobulinemia Tags
Red Red List (low evidence)	LSM11	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes Type I interferonopathy Aicardi-Goutières syndrome Tags
Red Red List (low evidence)	LYZ	2 reviews 2 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Red London North GLH NHS GMS Phenotypes Amyloidosis, renal, 105200 Tags
Red Red List (low evidence)	MAN2B2	3 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Other Phenotypes congenital disorder of glycosylation, MONDO:0015286 Tags
Red Red List (low evidence)	MAP1LC3B2	2 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Red Literature Phenotypes Mollaret’s meningitis recurrent HSV2 meningitis Tags
Red Red List (low evidence)	MAPK8	2 reviews	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Red Literature Phenotypes chronic mucocutaneous candidiasis connective tissue disorders Tags
Red Red List (low evidence)	MASP1	2 reviews 1 red	Not set	Sources ESID Registry 20171117 Expert Review Red Phenotypes Mannan-binding lectin serine protease (MASP) deficiency Tags
Red Red List (low evidence)	MASP2	4 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Red GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Victorian Clinical Genetics Services Phenotypes MASP2 deficiency, OMIM:613791 Mannan-binding lectin serine protease (MASP) deficiency Pyogenic infections, inflammatory lung disease, autoimmunity Tags
Red Red List (low evidence)	MCM10	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Tags
Red Red List (low evidence)	MED13L	1 review 1 red	Unknown	Sources Literature Phenotypes primary immunodeficiency Tags
Red Red List (low evidence)	MICA	1 review 1 red	Unknown	Sources Literature Phenotypes primary immunodeficiency Tags
Red Red List (low evidence)	MPI	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Victorian Clinical Genetics Services Phenotypes Congenital disorder of glycosylation, type Ib, OMIM:602579 MPI-CDG, MONDO:0011257 Tags
Red Red List (low evidence)	MR1	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes Warts, bacterial infections, MAIT cells deficiency Tags
Red Red List (low evidence)	MRE11	3 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Red GRID V2.0 Phenotypes Ataxia-telangiectasia-like disorder 1 604391 AT-like disorder Tags
Red Red List (low evidence)	MS4A1	3 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Red GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Victorian Clinical Genetics Services Phenotypes Common variable immunodeficiency disorders (CVID) Recurrent infections Immunodeficiency, common variable, 5 613495 Predominantly Antibody Deficiencies Tags
Red Red List (low evidence)	MSH6	3 reviews 3 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Phenotypes Family or personal history of cancer Mismatch repair cancer syndrome 276300 Endometrial cancer, familial 608089 Predominantly Antibody Deficiencies Colorectal cancer, hereditary nonpolyposis, type 5 614350 Tags
Red Red List (low evidence)	MTPAP	1 review 1 red	Unknown	Sources Literature Phenotypes primary immunodeficiency Tags
Red Red List (low evidence)	MYOF	2 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Red Literature Phenotypes ?Angioedema, hereditary, 7, OMIM:619366 Tags
Red Red List (low evidence)	NBAS	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red IUIS Classification December 2019 IUIS Classification February 2018 Phenotypes Defects in Intrinsic and Innate Immunity Infantile liver failure syndrome 2, 616483 Fever induces liver failure Fever induced liver failure Defects in intrinsic and innate immunity Tags
Red Red List (low evidence)	NFKBID	3 reviews 1 red	Not set	Sources Expert Review Red Victorian Clinical Genetics Services Tags
Red Red List (low evidence)	NOS2	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes {Malaria, resistance to} 611162 Disseminated CMV disease Tags
Red Red List (low evidence)	ODC1	1 review 1 red	Unknown	Sources Literature Phenotypes primary immunodeficiency Tags
Red Red List (low evidence)	OSTM1	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red IUIS Classification December 2019 IUIS Classification February 2018 Phenotypes Defects in Intrinsic and Innate Immunity Osteopetrosis with hypocalcemia, neurologic features Defects in intrinsic and innate immunity Tags
Red Red List (low evidence)	PARP1	1 review 1 red	Unknown	Sources Literature Tags
Red Red List (low evidence)	PDCD1	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes Autoimmunity splenomegaly pneumonitis tubercolosis Tags
Red Red List (low evidence)	PLEKHM1	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red IUIS Classification December 2019 IUIS Classification February 2018 Phenotypes Osteopetrosis Defects in Intrinsic and Innate Immunity Defects in intrinsic and innate immunity Tags
Red Red List (low evidence)	PMS2	5 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Red GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Phenotypes Recurrent infections, caf-au-lait spots, lymphoma, colorectal carcinoma, brain tumors Mismatch repair cancer syndrome 276300 Post-Meiotic Segregation 2 (PMS2) deficiency CSR defects and Hyper IgM (HIGM) syndromes Recurrent infections, cafe-au-lait spots, lymphoma, colorectal carcinoma, brain tumors Combined immunodeficiencies with associated or syndromic features Tags
Red Red List (low evidence)	POLD2	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources IUIS Classification December 2019 Phenotypes Polymerase d 2 deficiency Recurrent respiratory tract infections, skin infections, warts and molluscum, short stature, intellectual disability Immunodeficiencies affecting cellular and humoral immunity Low CD4 T cells Low B cells, normal maturation Tags
Red Red List (low evidence)	POLE2	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red IUIS Classification December 2019 IUIS Classification February 2018 Phenotypes Recurrent infections, disseminated BCG infections, autoimmunity (type 1 diabetes, hypothyroidism, facial dysmorphism) Recurrent infections, disseminated BCG infections, autoimmunity (type 1 diabetes, hypothyroidism, facial dysmorphism Combined immunodeficiencies with associated or syndromic features Tags
Red Red List (low evidence)	POLR3F	2 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Red Phenotypes Severe VZV infection Tags
Red Red List (low evidence)	POU2AF1	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes Agammaglobulinemia Immunodeficiency Bob1 deficiency Tags
Red Red List (low evidence)	PSEN1	3 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Red IUIS Classification February 2018 Phenotypes Hidradenitis suppurative with cutaneous hyperpigmentation Defects in Intrinsic and Innate Immunity Acne inversa, familial, 3 613737 Tags
Red Red List (low evidence)	PSMG2	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources IUIS Classification December 2019 Phenotypes CANDLE (chronic atypical neutrophilic dermatitis with lipodystrophy) Panniculitis, lipodystrophy, autoimmune hemolytic anemia Autoinflammatory Disorders Tags
Red Red List (low evidence)	PTPN22	1 review 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Red London North GLH NHS GMS North West GLH Phenotypes {Systemic lupus erythematosus susceptibility to} Lupus susceptibility Tags
Red Red List (low evidence)	RAD50	2 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes Nijmegen breakage syndrome-like disorder, OMIM:613078 Bone marrow failure Immunodeficiency Tags
Red Red List (low evidence)	RANBP2	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources IUIS Classification December 2019 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Phenotypes Defects in intrinsic and innate immunity Defects in Intrinsic and Innate Immunity Fever induces acute encephalopathy Tags
Red Red List (low evidence)	RELB	4 reviews 3 red	BIALLELIC, autosomal or pseudoautosomal	Sources Combined B and T cell defect v1.12 Expert Review Red IUIS Classification December 2019 IUIS Classification February 2018 Other Phenotypes Recurrent infections Recurrent infectionsImmunodeficiencies affecting cellular and humoral immunity Immunodeficiencies affecting cellular and humoral immunity ?Immunodeficiency 53, 617585 Tags
Red Red List (low evidence)	RELN	1 review 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Literature Phenotypes Ankylosing spondylitis Tags
Red Red List (low evidence)	RET	3 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Red GOSH PID v.8.0 London North GLH NHS GMS North West GLH Phenotypes Central hypoventilation syndrome, congenital 209880 Tags
Red Red List (low evidence)	RGS10	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes short stature GH deficiency immunodeficiency hypergammaglobulinemia reduced lymphocyte chemotaxis Tags
Red Red List (low evidence)	RHOG	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes HLH hemophagocytic lymphohistiocytosis Tags
Red Red List (low evidence)	RNU4ATAC	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources IUIS Classification December 2019 IUIS Classification February 2018 Other Phenotypes Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly, short stature Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly Combined immunodeficiencies with associated or syndromic features Tags
Red Red List (low evidence)	SAMD3	1 review 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Red London North GLH NHS GMS Phenotypes HLH, abnormal GRA Tags
Red Red List (low evidence)	SART3	3 reviews 2 red	Unknown	Sources Expert Review Red GRID V2.0 Phenotypes Porokeratosis Tags
Red Red List (low evidence)	SEMA3E	3 reviews 2 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ESID Registry 20171117 Expert Review Red GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Other Victorian Clinical Genetics Services Phenotypes CHARGE syndrome immune-mediated cerebellar ataxia Coloboma, heart anomaly, choanal atresia, intellectual retardation, genital and ear anomalies, CNS malformation, some are SCID-like and have low TRECs Charge syndrome 214800 Combined immunodeficiencies with associated or syndromic features Tags
Red Red List (low evidence)	SH3BP2	3 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ESID Registry 20171117 Expert Review Red GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 London North GLH NHS GMS North West GLH Other Victorian Clinical Genetics Services Phenotypes Cherubism, OMIM:118400 Autoinflammatory Disorders Tags
Red Red List (low evidence)	SH3KBP1	2 reviews 1 red	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources IUIS Classification December 2019 Phenotypes SH3KBP1 (CIN85) deficiency Severe bacterial infections Predominantly Antibody Deficiencies Immunodeficiency 61, 300310 Tags
Red Red List (low evidence)	SLC13A4	1 review 1 red	Unknown	Sources Literature Phenotypes primary immunodeficiency Tags
Red Red List (low evidence)	SNX10	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources IUIS Classification December 2019 IUIS Classification February 2018 Phenotypes Defects in Intrinsic and Innate Immunity Osteopetrosis with visual impairment Defects in intrinsic and innate immunity Tags
Red Red List (low evidence)	STAT4	3 reviews 2 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Red London North GLH NHS GMS Phenotypes Paracoccidioidomycosis Impaired IFN-γ Immunity {Systemic lupus erythematosus, susceptibility to, 11}, 612253 Tags
Red Red List (low evidence)	STAT5A	3 reviews 3 red	Unknown	Sources ESID Registry 20171117 Expert Review Red GOSH PID v.8.0 Phenotypes Combined immunodeficiency Defects with susceptibility to mycobacterial infection (MSMD) Tags
Red Red List (low evidence)	STAT6	3 reviews 1 green 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Red Literature Phenotypes Primary Atopic Disorder Atopy Vascular anomalies Atopic dermamatitis Allergy Atopy Hyper-IgE elevated IgE Eosinophilic esophagitis Food allergies Tags watchlist
Red Red List (low evidence)	STN1	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources IUIS Classification December 2019 IUIS Classification February 2018 Phenotypes Intrauterine growth retardation, premature aging, pancytopenia, hypocellular bone marrow, gastrointestinal hemorrhage due to vascular ectasia, intracranial calcification, abnormal telomeres Bone marrow failure Combined immunodeficiencies with associated or syndromic features Tags
Red Red List (low evidence)	TBX21	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes Defects with susceptibility to mycobacterial infection (MSMD) Defects in Intrinsic and Innate Immunity Tags
Red Red List (low evidence)	TCIRG1	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources IUIS Classification December 2019 IUIS Classification February 2018 Phenotypes Defects in Intrinsic and Innate Immunity Defects in intrinsic and innate immunity Osteopetrosis with hypocalcemia Tags
Red Red List (low evidence)	THBD	3 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ESID Registry 20171117 Expert Review Red GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Victorian Clinical Genetics Services Phenotypes Hemolytic uremic syndrome, atypical, susceptibility to, 6 Atypical hemolytic-uremic syndrome Complement Deficiencies Thrombomodulin deficiency Tags
Red Red List (low evidence)	TIRAP	2 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Red IUIS Classification December 2019 IUIS Classification February 2018 Phenotypes Defects in Intrinsic and Innate Immunity Staphylococcal disease during childhood Defects of TLR/NFkappa-B signalling TIRAP deficiency Defects in intrinsic and innate immunity Tags
Red Red List (low evidence)	TLN1	1 review 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Literature Phenotypes lymphopenia, MONDO:0003783 Tags
Red Red List (low evidence)	TNFRSF13B	8 reviews 5 red	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources A- or hypo-gammaglobulinaemia v1.25 ESID Registry 20171117 Expert Review Red GOSH PID v.8.0 GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Victorian Clinical Genetics Services Phenotypes Immunodeficiency, common variable, 2, 240500 Variable clinical expression Common variable immunodeficiency disorders (CVID) Immunodeficiency, common variable, 2 IgA with IgG subclass deficiency IGAD Isolated IgG subclass deficiency Selective IgA deficiency Immunoglobulin A deficiency 2, 609529 Predominantly Antibody Deficiencies CVID Tags
Red Red List (low evidence)	TNFRSF4	3 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources ESID Registry 20171117 Expert Review Red GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Other Victorian Clinical Genetics Services Phenotypes Kaposi's Sarcoma, impaired immunity to HHV8, OX40 deficiency Immunodeficiencies affecting cellular and humoral immunity Impaired immunity to HHV8, Kaposis sarcoma Combined immunodeficiency Tags
Red Red List (low evidence)	TNFSF11	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources IUIS Classification December 2019 IUIS Classification February 2018 Phenotypes Defects in Intrinsic and Innate Immunity Osteopetrosis with severe growth retardation Defects in intrinsic and innate immunity Tags
Red Red List (low evidence)	TNFSF12	2 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ESID Registry 20171117 Expert Review Red GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Victorian Clinical Genetics Services Phenotypes Common variable immunodeficiency disorders (CVID) Immunodeficiency, common variable with lack of anti-pneumococcal antibody Pneumonia, bacterial infections, warts, thrombocytopenia. neutropenia Predominantly Antibody Deficiencies Pneumonia, bacterial infections, warts, thrombocytopenia Tags
Red Red List (low evidence)	TNFSF13	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes APRIL deficiency Common variable immunodeficiency Tags
Red Red List (low evidence)	TNIP1	1 review 1 red	Unknown	Sources Literature Phenotypes primary immunodeficiency Tags
Red Red List (low evidence)	TOM1	2 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Red Literature Phenotypes early-onset autoimmunity antibody deficiency combined immunodeficiency primary immunodeficiency Tags
Red Red List (low evidence)	TRAF3	3 reviews 2 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ESID Registry 20171117 Expert Review Red GRID V2.0 IUIS Classification December 2019 IUIS Classification February 2018 Victorian Clinical Genetics Services Phenotypes Herpes simplex encephalitis, susceptibility to, 3 Defects in Intrinsic and Innate Immunity {?Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 5},614849 Herpes simplex virus 1 encephalitis Herpetic encephalitis (HSE) Defects in intrinsic and innate immunity Tags
Red Red List (low evidence)	TSPAN14	1 review 1 red	Unknown	Sources Literature Phenotypes primary immunodeficiency Tags
Red Red List (low evidence)	TUBGCP3	1 review 1 red	Unknown	Sources Literature Phenotypes primary immunodeficiency Tags
Red Red List (low evidence)	UBA1	5 reviews 2 green 1 red	Other	Sources Expert Review Red Literature Phenotypes VEXAS syndrome, somatic, OMIM:301054 Tags somatic
Red Red List (low evidence)	UNC119	3 reviews 2 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ESID Registry 20171117 Expert Review Red GRID V2.0 Phenotypes Immunodeficiency 13/ UNC119 deficiency Combined immunodeficiency Immunodeficiency 13 615518 Tags
Red Red List (low evidence)	WRAP53	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources IUIS Classification December 2019 IUIS Classification February 2018 Phenotypes Intrauterine growth retardation, microcephaly, nail dystrophy, sparse scalp hair and eyelashes, hyperpigmentation of skin, palmar hyperkeratosis, premalignant oral leukoplakia, pancytopenia, myelodysplasia, +/- recurrent infections. A severe phenotype with developmental delay and cerebellar hypoplasia known as Hoyeraal-Hreidarsson Syndrome (HHS) may occur in some DKC patients microcephaly, neurodevelopmental delay Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation Bone marrow failure Combined immunodeficiencies with associated or syndromic features Tags
Red Red List (low evidence)	ZC3HC1	1 review 1 red	Unknown	Sources Literature Phenotypes primary immunodeficiency Tags
Red Red List (low evidence)	ZFP36	1 review 1 red	Unknown	Sources Literature Phenotypes primary immunodeficiency Tags
Red Red List (low evidence)	ZNF34	1 review 1 red	Unknown	Sources Literature Phenotypes primary immunodeficiency Tags
No list No list	CBLB	1 review 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Literature Phenotypes immunedysregulation autoimmunity hypothyroidism diabetes mellitus type I vitiligo urticaria HLH ITP autoimmune hemolytic anemia Tags
No list No list	CREBBP	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Literature Phenotypes Rubinstein-Taybi Syndrome Hypogammaglobulinemia short stature Intellectual disability broad thumbs and first toes highly arched eyebrows long eyelashes downslanting palpebral fissures convex nasal ridge low hanging columella highly arched palate micrognathia Tags
No list No list	DUT	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Literature Phenotypes Bone marrow failure and diabetes mellitus syndrome Tags
No list No list	EP300	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Literature Phenotypes Rubinstein-Taybi Syndrome Hypogammaglobulinemia short stature Intellectual disability broad thumbs and first toes highly arched eyebrows long eyelashes downslanting palpebral fissures convex nasal ridge low hanging columella highly arched palate micrognathia Tags
No list No list	EZR	1 review 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Literature Phenotypes hypogammaglobulinemia immunodeficiency Tags
No list No list	FGL2	1 review 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Literature Phenotypes immunedysregulation autoimmunity arthritis Treg dysfunction leukocytoclastic vasculitis Tags
No list No list	FOXI3	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Literature Phenotypes T-cell lymphopenia low TREC thymic hypoplasia Tags
No list No list	KCNA5	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Literature Phenotypes autoimmunity autoinflammation Tags
No list No list	LYN	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Literature Phenotypes Autoinflammatory Neutrophilic vasculitis Liver fibrosis Chronic urticaria Atopic dermatitis Fever Tags
No list No list	MCTS1	1 review 1 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Literature Phenotypes MSMD non tubercular mycobacteria infection BCGtis BCG infection Tags
No list No list	MECOM	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Literature Phenotypes Radioulnar synostosis with amegakaryocytic thrombocytopenia 2, OMIM:616738 Hypocellular bone marrow congenital thrombocytopenia B-cell lymphopenia hypogammaglobulinemia radioulnar synostosis digit abnormalities clubfoot cardiac defects facial dysmorphism Tags
No list No list	SRP72	0 reviews	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Literature Research Phenotypes Familial MDS/AML inherited bone marrow failure syndromes (IBMFS) congenital neutropenia Shwachman-Diamond syndrome Tags

Major version comments

2023-03-22 16:47 Catherine Snow (Genomics England) promoted panel to 4.0
The content of this panel has been updated in accordance with changes agreed with the NHS Genomic Medicine Service. The panel was promoted to the next major version (4.0) following this.

2022-11-30 13:07 Eleanor Williams (Genomics England Curator) promoted panel to 3.0
The content of this panel has been updated in accordance with changes agreed with the NHS Genomic Medicine Service. The panel was promoted to the next major version (3.0) following this.

2019-11-12 17:19 Louise Daugherty (Genomics England Curator) promoted panel to 2.0
The content of this panel (version 1.137) was signed off under NHS Genomic Medicine Service governance on (12/11/2019). The panel was promoted to the next major version (version 2.0) as a result of this.

2018-07-12 09:00 Louise Daugherty (Genomics England Curator) promoted panel to 1.0
2018-07-12 Louise Daugherty (Genomics England Curator) promoted panel to v1.0. Reviews were assessed, and panel was revised according to expert reviews and further in-house curation based on PanelApp guidelines. Previous panels (A- or hypo-gammaglobulinaemia, Congenital neutropaenia, Agranulocytosis, Combined B and T cell defect, Inherited complement deficiency and SCID panels)
that were merged with this panel, were checked again for any changes/new reviews prior to versioning of this panel, these merged panels are now retired/made internal.

Primary immunodeficiency or monogenic inflammatory bowel disease (Version 4.125)

32 reviewers

554 Entities

547 reviewed, 327 green

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