CD79B
protein-codingCD79b molecule, the group of V-set domain containing|CD molecules
Gene summary
The B lymphocyte antigen receptor is a multimeric complex that includes the antigen-specific component, surface immunoglobulin (Ig). Surface Ig non-covalently associates with two other proteins, Ig-alpha and Ig-beta, which are necessary for expression and function of the B-cell antigen receptor. This gene encodes the Ig-beta protein of the B-cell antigen component. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
- IGB
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0012987
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0012987
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0012987
Submitter: ClinGen
The relationship between CD79B and Agammaglobulinemia 6, an autosomal recessive disorder, was evaluated using the ClinGen Clinical Validity Framework as of December, 2020. CD79B encodes the Ig-beta protein of the B-cell antigen receptor. Agammaglobulinemia is characterized by absence of circulating B cells and low or absent serum immunoglobulin levels (PMID: 18978465). CD79B was first reported in relation to autosomal recessive Agammaglobulinemia 6 in 2007 (Dobbs et al, PMID: 17675462; Ferrari et al, PMID: 17709424). Variants reported in this gene thus far include missense and nonsense variants. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Summary of Case Level Data (6.25 points): There have been 3 patients from 3 publications and 1 unpublished proband, till date, reported with homozygous variants in CD79B (PMID: 17675462; 17709424, 24722855). The mechanism of disease is expected to be biallelic loss of function. Summary of experimental data (6 points): This gene-disease association is supported by in-vitro functional assays and animal models. Igβ is expressed on B cells (PMID: 10383452), and together with Igα, it forms a hetetrodimer on the surface of B cells. The Igα/Igβ complex is involved in signal transduction that induces B-cell differentiation (PMID: 9354476). B cells lacking Igβ are arrested in the proB cell stage of development (PMID: 12165571). A targeted knock-out mouse model (PMID: 8602530) and a naturally occurring mouse model with a spontaneous nonsense mutation (PMID: 19727123) have been reported, which recapitulate the arrest of B-cell development at the early pre-B cell stage, as noted in patient cells. In summary, the evidence to support the gene-disease relationship of CD79B and Agammaglobulinemia 6 is moderate. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged.
Inheritance Pattern: AD
Disease ID:MONDO:0011096
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious
Intervention: Allergy/Immunology/Infectious
Rationale: Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CD79B variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000626.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 60 | 1 | 62 | ||
| missense | 1 | 1 | 64 | 5 | 71 | |
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 2 | 2 | 66 | 65 | 1 | 136 |
Highest pathogenic variant AF is 0.0000020524412
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000617.1 | 6 | MANE Select | |
| Ensembl | ENSP00000006750.4 | 6 | MANE Select | |
| RefSeq | NP_001035022.1 | 6 | Standard | |
| RefSeq | NP_001315979.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- B cell receptor signaling pathway - Homo sapiens (human)
- B Cell Receptor Signaling Pathway
- Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
- bcr signaling pathway
- ctcf: first multivalent nuclear factor
Biological Process
- adaptive immune response
- immune response
- signal transduction
- response to bacterium
- B cell differentiation
Molecular Function
- transmembrane signaling receptor activity
- protein binding
- protein homodimerization activity
Cellular Component
- nucleoplasm
- Golgi apparatus
- cytosol
- plasma membrane
- integral component of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000392795
- Coding exons
- 6
- Length
- 3615
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.31 | 93 | 136 | 0.683 | 0.00000880 | 1508 |
| Missense (PolyPhen) | 28 | 56.117 | 0.49896 | 668 | ||
| Synonymous | -0.111 | 58 | 56.9 | 1.02 | 0.00000400 | 438 |
| Loss of Function | 2.99 | 1 | 12.4 | 0.0809 | 6.28e-7 | 131 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Required in cooperation with CD79A for initiation of the signal transduction cascade activated by the B-cell antigen receptor complex (BCR) which leads to internalization of the complex, trafficking to late endosomes and antigen presentation. Enhances phosphorylation of CD79A, possibly by recruiting kinases which phosphorylate CD79A or by recruiting proteins which bind to CD79A and protect it from dephosphorylation. {ECO:0000269|PubMed:12097390, ECO:0000269|PubMed:8617796, ECO:0000269|PubMed:9057631}.;
- Disease
- DISEASE: Agammaglobulinemia 6, autosomal recessive (AGM6) [MIM:612692]: A primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B-cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life. {ECO:0000269|PubMed:17675462}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.322
Intolerance Scores
- RVIS EVS
- -0.45
- RVIS percentile EVS
- 24
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.769
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |