Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: RELB

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 24 Feb 2025, 12:01 p.m. | Last Modified: 24 Feb 2025, 12:01 p.m.

Panel Version: 7.26

Comment on list classification: As reviewed by Dmitrijs Rots, there is sufficient evidence available (four unrelated cases and functional work) for the promotion of this gene to green rating in the next GMS update.

Created: 7 Nov 2024, 6:40 p.m. | Last Modified: 7 Nov 2024, 6:40 p.m.

Panel Version: 7.9

PMID:26385063 reported three male patients from a related kindred with primary immunodeficiency and with a homozygous truncating variant in RELB (p.Tyr397Ter). All had recurrent upper and lower respiratory infections, one had ecthyma gangrenosum and developed a polyarticular arthritis with joint swelling, and another had a urinary tract infection.

PMID:36402602 reported three siblings presenting with predominately severe autoimmune manifestations involving the liver, gut, lung, and skin, as well as repeated infections. They were identified with homozygous p.Pro364Leu variant.

PMID:39231201 reported two unrelated adult patients with either homozygous (p.Q72Tfs*152) or compound heterozygous (p.Glu145Lys & p.Pro364Leu) loss-of-function variants. Both of them presented with combined immunodeficiency with early-onset severe bacterial, viral, and fungal diseases.

Functional evidence is also available from all three publications mentioned above.

This gene has been associated with immunodeficiency phenotype in OMIM (MIM #617585).

Created: 7 Nov 2024, 6:36 p.m. | Last Modified: 7 Nov 2024, 6:36 p.m.

Panel Version: 7.6

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Immunodeficiency 53, OMIM:617585

Publications

• 26385063
• 36402602
• 39231201

Green List (high evidence)

New cases reported in PMID: 39231201. Now at least 3 cases are reported with functional work - enough for the green rating.

Created: 17 Oct 2024, 4:22 p.m. | Last Modified: 17 Oct 2024, 4:22 p.m.

Panel Version: 6.16

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• PMID: 39231201

The following PubMed IDs were added to gene RELB (OMIM gene MIM#604758): 26385063. These publications have been associated with the gene by the immunodeficiencies 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

• 26385063

Red List (low evidence)

Single kindred with 3 individuals, however strong biological case that loss of function of RELB is causative

Created: 11 Jun 2018, 12:56 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Red List (low evidence)

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): RELB .PanelApp HGNC gene symbol check: RELB . IUIS Disease: RelB deficiency . IUIS Inheritance: AR .T cells: Decreased or normal, response to PHA may be decreased, .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: Recurrent infections. IUIS Major category: Immunodeficiencies affecting cellular and humoral immunity. IUIS Subcategory: Combined Immunodeficiencies Generally Less Profound than Severe Combined Immunodeficiency

Created: 2 Jul 2018, 10:35 a.m.

External expert review notes Red status, although there is strong biological evidence there is not enough unrelated cases (only one family reported Sharfe N et al, in 2015) so I have kept this gene Red on this panel

Created: 13 Jun 2018, 10 a.m.

Comment on phenotypes: added OMIM MIMid

Created: 13 Jun 2018, 9:54 a.m.

Comment on publications: changed doi into PMID

Created: 26 Apr 2018, 9:20 a.m.

Red List (low evidence)

Associated with phenotype in OMIM, not in G2P. At least one variant reported in 3 male patients from a consanguineous family of Irish descent with immunodeficiency-53.

Created: 5 Sep 2017, 10:01 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Immunodeficiency 53

Publications

• https://doi.org/10.14785/lpsn-2015-0005