Genes in panel
STRs in panel
Prev Next

Primary immunodeficiency

Gene: NLRP1

Amber List (moderate evidence)

NLRP1 (NLR family pyrin domain containing 1)
EnsemblGeneIds (GRCh38): ENSG00000091592
EnsemblGeneIds (GRCh37): ENSG00000091592
OMIM: 606636, Gene2Phenotype
NLRP1 is in 4 panels

7 reviews

Eleanor Williams (Genomics England Curator)

Comment on list classification: Changed rating of gene from Red to Amber. This gene was rated as Amber in v2.208 and incorrectly automatically demoted to Red in v2.209. This was due to a defect in the automatic PanelApp uploading tool when a set of publications was added to the panel with the source ‘Other’, and under certain conditions associated to previous sources listed, resulted in the rating of the gene being automatically changed when it should not have been.
Created: 14 Oct 2020, 12:14 p.m. | Last Modified: 14 Oct 2020, 12:14 p.m.
Panel Version: 2.213
The following PubMed IDs were added to entity NLRP1: 27965258. These publications have been associated with OMIM phenotype MIM#617388, which is listed for this entity, by the autoinflammation subgroup of the Human Phenotype Ontology Immune Mediated Disorders Consortium (https://hpo-immune-mediated-disorders.groups.io/g/update) in August 2020.
Created: 13 Oct 2020, 9:36 a.m. | Last Modified: 13 Oct 2020, 9:36 a.m.
Panel Version: 2.208

Publications

Rebecca Foulger (Genomics England curator)

PMID:27662089: Zhong et al., 2016 report germline GOF variants in NLRP1 which cause two overlapping skin disorders (MSPC and FKLC), linking NLRP1 to skin inflammatory syndromes.
Created: 29 Apr 2020, 8:33 p.m. | Last Modified: 29 Apr 2020, 8:33 p.m.
Panel Version: 2.138
PMID:31484767: Drutman et al., 2019 report 2 siblings with syndromic JRRP and a homozygous GOF variant in NLRP1.
Created: 29 Apr 2020, 8:33 p.m. | Last Modified: 29 Apr 2020, 8:33 p.m.
Panel Version: 2.138

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Multiple phenotypes resulting from abnormal inflammatory response associated with this gene, both mono-allelic and bi-allelic, some gain-of-function (including bi-allelic).
Bi-allelic disease: single family with dyskeratosis, autoimmunity and arthritis and another family with bi-allelic GoF and recurrent respiratory papillomatosis phenotype
Mono-allelic disease: mostly pertains to the association with multiple self-healing palmoplantar carcinomas (MSPC). One consanguineous family in which a sister and brother with clinical features of MSPC as well as multiple discrete and semiconfluent lichenoid papules on the arms, legs, and lower trunk were homozygous for an in-frame deletion in the NLRP1 gene, and parents had milder skin defects. The clinical diagnosis in this family was familial keratosis lichenoides chronica (Nekam disease).
Created: 11 Apr 2020, 4:44 a.m. | Last Modified: 11 Apr 2020, 4:44 a.m.
Panel Version: 2.51

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Autoinflammation with arthritis and dyskeratosis, MIM# 617388; Palmoplantar carcinoma, multiple self-healing 615225; Recurrent respiratory papillomatosis

Publications

Mode of pathogenicity
Other

Variants in this GENE are reported as part of current diagnostic practice

Kimberly Gilmour (Great Ormond Street Hopsital)

Green List (high evidence)

agree with green gene
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94

Tracy Briggs (Manchester Genomic Medicine Centre)

Green List (high evidence)

YES- this is covered on our targeted exome
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94

Louise Daugherty (Genomics England Curator)

I don't know

Added publication referenced by IUIS december 2019 update
Created: 28 Feb 2020, 8:49 p.m. | Last Modified: 28 Feb 2020, 8:49 p.m.
Panel Version: 2.36
Original Metadata from IUIS classification table (December, 2019). IUIS Genetic defect (original gene symbol in IUIS download): NLRP1 .PanelApp HGNC gene symbol check: NLRP1 . IUIS Disease: NLRP1 deficiency . IUIS Inheritance: AR / AD GOF .T cells: Normal / Normal, .B cells: Normal / Normal, Immunoglobulin levels: Normal / Normal, Neutrophil count: Normal / Normal IUIS Other affected cells: leukocytes / Keratinocytes. IUIS Associated features: Dyskeratosis, autoimmunity and arthritis / Palmoplantar carcinoma, corneal scarring, IUIS Major category: Autoinflammatory Disorders. IUIS Subcategory: Defects Affecting the Inflammasome
Created: 28 Feb 2020, 4:41 p.m. | Last Modified: 28 Feb 2020, 4:41 p.m.
Panel Version: 2.27
Gene was flagged as requiring further clinical input from the Immunology Test Group, but no additional information was submitted to support the Green rating. In view of a lack of clear evidence the current recommendation is Amber.
Created: 12 Nov 2019, 5:02 p.m. | Last Modified: 12 Nov 2019, 5:02 p.m.
Panel Version: 1.137
Autoinflammation - two cases, ?AD / AR – unclear
Created: 26 Sep 2019, 3:57 p.m. | Last Modified: 26 Sep 2019, 3:57 p.m.
Panel Version: 1.130
Comment on list classification: Upgraded from Red to Amber. This is a relevant phenotype but there is not enough evidence in the literature to date (only two reported cases) and there has been no further evidence in terms of unpublished cases other than a Green rating recommendation from the Immunology Specialist Test Group. To remain Amber unless further supporting evidence from the Test Group.
Created: 17 Sep 2019, 5:14 p.m. | Last Modified: 17 Sep 2019, 5:22 p.m.
Panel Version: 1.101
Gene rating submitted by Kimberly Gilmour and Austen Worth on behalf of London North GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email 6th September the Specialist Test Group all agreed there is enough evidence to rate this gene Green.
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email on 20th June the Specialist Test Group all agreed there is enough evidence to rate this gene Green.
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Comment on publications: PMID: 29850521- Psoriasis Vulgaris Risk
Created: 6 Jul 2018, 3:36 p.m.
Comment on publications: added publications suggested from external expert review
Created: 6 Jul 2018, 3:13 p.m.
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): NLRP1 .PanelApp HGNC gene symbol check: NLRP1 . IUIS Disease: NLRP1 deficiency . IUIS Inheritance: AR .T cells: Normal, .B cells: N/A, .IUIS Other affected cells: leukocytes. IUIS Associated features: Dyskeratosis, autoimmunity and arthritis. IUIS Major category: Autoinflammatory Disorders. IUIS Subcategory: Defects Affecting the Inflammasome
Created: 6 Jul 2018, 12:30 p.m.

Publications

Sophie Hambleton (Newcastle University)

I don't know

Single report, 2 sibs with homozygous variant and one singleton with a heterozygous missense mutation
Created: 29 Jun 2018, 9:57 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Autoinflammation with arthritis and dyskeratosis

Publications

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Other
  • NHS GMS
  • North West GLH
  • London North GLH
  • IUIS Classification February 2018
Phenotypes
  • Dyskeratosis, autoimmunity and arthritis
  • Palmoplantar carcinoma, corneal scarring
  • Autoinflammatory Disorders
  • Autoinflammation with arthritis and dyskeratosis, 617388
OMIM
606636
Clinvar variants
Variants in NLRP1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

14 Oct 2020, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: nlrp1 has been classified as Amber List (Moderate Evidence).

13 Oct 2020, Gel status: 1

Added New Source, Set publications, Status Update

Eleanor Williams (Genomics England Curator)

Source Other was added to NLRP1. Publications for gene NLRP1 were updated from 29850521; 27662089; 31484767; 27965258 to 27965258; 31484767; 27662089; 29850521 Rating Changed from Amber List (moderate evidence) to Red List (low evidence)

22 Sep 2020, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: NLRP1 were changed from Dyskeratosis, autoimmunity and arthritis; Palmoplantar carcinoma, corneal scarring; Autoinflammatory Disorders; Autoinflammation with arthritis and dyskeratosis to Dyskeratosis, autoimmunity and arthritis; Palmoplantar carcinoma, corneal scarring; Autoinflammatory Disorders; Autoinflammation with arthritis and dyskeratosis, 617388

28 Feb 2020, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene NLRP1 were updated from 27965258; 29850521 to 29850521; 27662089; 31484767; 27965258

28 Feb 2020, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: NLRP1 were changed from Dyskeratosis, autoimmunity and arthritis; Autoinflammatory Disorders; Autoinflammation with arthritis and dyskeratosis to Dyskeratosis, autoimmunity and arthritis; Palmoplantar carcinoma, corneal scarring; Autoinflammatory Disorders; Autoinflammation with arthritis and dyskeratosis

17 Sep 2019, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: nlrp1 has been classified as Amber List (Moderate Evidence).

17 Sep 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to NLRP1.

17 Sep 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source North West GLH was added to NLRP1.

17 Sep 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to NLRP1.

12 Jul 2018, Gel status: 1

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

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.

6 Jul 2018, Gel status: 1

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: nlrp1 has been classified as Red List (Low Evidence).

6 Jul 2018, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: NLRP1 were set to 27965258; 29850521

6 Jul 2018, Gel status: 1

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: NLRP1 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

6 Jul 2018, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: NLRP1 were set to Dyskeratosis, autoimmunity and arthritis; Autoinflammatory Disorders; Autoinflammation with arthritis and dyskeratosis

6 Jul 2018, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: NLRP1 were set to 27965258

1 Jul 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene NLRP1 were set to Dyskeratosis, autoimmunity and arthritis, Autoinflammatory Disorders

26 Jun 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

NLRP1 was added to Primary immunodeficiency disorders panel. Sources: IUIS Classification February 2018

26 Jun 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

NLRP1 was created by Louise Daugherty