Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: CD81

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 3 May 2024, 8:36 p.m. | Last Modified: 3 May 2024, 8:36 p.m.

Panel Version: 5.3

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on list classification: There are two unrelated cases and functional evidence available in support of the association of this gene to common variable immunodeficiency (MIM #613496). Hence, this gene can be promoted to green rating in the next GMS review.

Created: 1 Nov 2023, 10:51 p.m. | Last Modified: 1 Nov 2023, 10:51 p.m.

Panel Version: 4.100

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Immunodeficiency, common variable, 6, OMIM:613496

Publications

• 20237408
• 25739915
• 35849269

I don't know

PMID: 35849269 - second patient reported. Compound heterozygous variants(c.67–1 G > T and p.D137Mfs*10)

Created: 13 Oct 2023, 2:43 p.m. | Last Modified: 13 Oct 2023, 2:43 p.m.

Panel Version: 4.41

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Immunodeficiency, common variable, 6

Publications

• 35849269

I don't know

Single patient described, but strong evidence for pathogenicity

Created: 24 Jun 2018, 9:17 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
hypogammaglobulinaemia

Publications

• 20237408
• 25739915

I don't know

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): CD81 .PanelApp HGNC gene symbol check: CD81 . IUIS Disease: CD81 deficiency . IUIS Inheritance: AR .T cells: N/A, .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: Recurrent infections, may have glomerulonephritis. IUIS Major category: Predominantly Antibody Deficiencies. IUIS Subcategory: Severe Reduction in at Least 2 Serum Immunoglobulin Isotypes with Normal or Low Number of B Cells, CVID Phenotype

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

Keep amber after external expert review until more info on gene and disease association

Created: 27 Jun 2018, 7:15 p.m.

Reviewed and decided to keep amber until more info on gene and disease association.

Created: 11 Jun 2018, 2:18 p.m.

Comment on publications: added publication from OMIM : a single report van Zelm et al. (2010) PMID:20237408 (2010) In a Moroccan girl, born of consanguineous parents, with common variable immunodeficiency-6, van Zelm et al. (2010) identified a homozygous G-to-A transition in intron 6 of the CD81 gene, resulting in use of a cryptic splice site, generation of a frameshift, and premature termination. The CD81-deficient case showed autoimmune and inflammatory complications. Initially, this CD81 mutation was assumed to completely abolish CD81 protein expression, and thought in the absence of expression, CD19 expression was halved as it was thought that it provides docking sites for various signal transduction pathway molecules PMID: 14530327, 20237408. However, it was recently demonstrated by Vences-Catalán et al. (2015) PMID:25739915 that in fact a truncated CD81 protein was produced, both the mutant CD81 and the normal CD19 protein were retained intracellularly, resulting in absent CD81 and CD19 surface expression. However, it was recently demonstrated that in fact a truncated CD81 protein was produced.47 Both the mutant CD81 and the normal CD19 protein were retained intracellularly, resulting in absent CD81 and CD19 surface expression.47

Created: 11 Jun 2018, 2:04 p.m.

Comment on phenotypes: added MIMid from OMIM. Common variable immunodeficiency (CVID) is the largest group of symptomatic primary immune deficiencies; it is characterized by hypogammaglobulinemia, poor response to vaccines and increased susceptibility to infections.

Created: 11 Jun 2018, 1:40 p.m.

This gene was absent from the original PanelApp PID panel dataset (review April 2018). However it was listed in external expert immunodeficiency diagnostic gene list(s) GOSH or GRID. In this combined PID panel, this gene has been rated as AMBER and needs further curational review to assess pertinence prior to v1.

Created: 20 Apr 2018, 12:25 p.m.

Original metadata downloaded from ESID Registry. ESID_Gene_original: CD81, PanelApp HGNC gene symbol check: CD81, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Predominantly antibody disorders / Hypogammaglobulinemias / Common variable immunodeficiency disorders (CVID); Predominantly antibody disorders / Hypogammaglobulinemias / Isolated IgG subclass deficiency

Created: 17 Apr 2018, 12:29 p.m.

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: CD81, GRID_Gene_Symbol: CD81, GRID_Transcript_ENS_Community submitted: ENST00000263645, GRID_Transcript_RefSeq: NM_004356.3, GRID_Transcript_ENS_used_on_Production: ENST00000263645

Created: 17 Apr 2018, 12:12 p.m.