Agammaglobulinemia 6, autosomal recessive

Summary

Agammaglobulinemia 6, autosomal recessive (MONDO:0012987) is a disease caused by CD79B (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CD79B (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 170

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	agammaglobulinemia 6, autosomal recessive
Mondo ID	MONDO:0012987
OMIM	612692
DOID	DOID:0081138
UMLS	C3150207
MedGen	461557
GARD	0015579
Is cancer (heuristic)	no

Also known as: agammaglobulinemia 6, autosomal recessive · AGM6 · autosomal agammaglobulinemia caused by mutation in CD79B · CD79B autosomal agammaglobulinemia

Data availability: 170 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › inborn error of immunity › B cell deficiency › agammaglobulinemia › isolated agammaglobulinemia › autosomal agammaglobulinemia › agammaglobulinemia 6, autosomal recessive

Related subtypes (7): agammaglobulinemia 2, autosomal recessive, agammaglobulinemia 3, autosomal recessive, agammaglobulinemia 4, autosomal recessive, agammaglobulinemia 5, autosomal dominant, agammaglobulinemia 7, autosomal recessive, agammaglobulinemia 8, autosomal dominant, autosomal recessive agammaglobulinemia 1

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

170 retrieved; paginated sample, class counts are floors:

104 likely benign, 51 uncertain significance, 7 benign, 4 conflicting classifications of pathogenicity, 2 pathogenic, 1 benign/likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
14802	NM_000626.4(CD79B):c.409G>A (p.Gly137Ser)	CD79B	Pathogenic	no assertion criteria provided
14803	NM_000626.4(CD79B):c.238C>T (p.Gln80Ter)	CD79B	Pathogenic	no assertion criteria provided
4716696	NM_000626.4(CD79B):c.431-1G>A	GH-LCR	Likely pathogenic	criteria provided, single submitter
1504174	NM_000626.4(CD79B):c.389C>T (p.Ser130Leu)	CD79B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
567186	NM_000626.4(CD79B):c.250G>A (p.Glu84Lys)	CD79B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
626079	NM_000626.4(CD79B):c.414A>G (p.Thr138=)	CD79B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
644087	NM_000626.4(CD79B):c.338G>A (p.Arg113Gln)	GH-LCR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1005019	NM_000626.4(CD79B):c.341T>G (p.Phe114Cys)	CD79B	Uncertain significance	criteria provided, single submitter
1019051	NM_000626.4(CD79B):c.542T>A (p.Leu181Gln)	CD79B	Uncertain significance	criteria provided, single submitter
1038551	NM_000626.4(CD79B):c.93GGA[1] (p.Glu32del)	CD79B	Uncertain significance	criteria provided, single submitter
1046774	NM_000626.4(CD79B):c.131C>T (p.Ser44Leu)	CD79B	Uncertain significance	criteria provided, single submitter
1051842	NM_000626.4(CD79B):c.106C>T (p.Arg36Trp)	CD79B	Uncertain significance	criteria provided, multiple submitters, no conflicts
133838	NM_000626.4(CD79B):c.218A>C (p.Asn73Thr)	CD79B	Uncertain significance	criteria provided, single submitter
133840	NM_000626.4(CD79B):c.497C>T (p.Thr166Met)	CD79B	Uncertain significance	criteria provided, single submitter
1359969	NM_000626.4(CD79B):c.563_564delinsGG (p.Ala188Gly)	CD79B	Uncertain significance	criteria provided, single submitter
1407172	NM_000626.4(CD79B):c.679G>A (p.Gly227Ser)	CD79B	Uncertain significance	criteria provided, single submitter
1414841	NM_000626.4(CD79B):c.304G>A (p.Glu102Lys)	CD79B	Uncertain significance	criteria provided, single submitter
1418607	NM_000626.4(CD79B):c.591G>A (p.Glu197=)	CD79B	Uncertain significance	criteria provided, single submitter
1430567	NM_000626.4(CD79B):c.379A>G (p.Asn127Asp)	CD79B	Uncertain significance	criteria provided, single submitter
1437604	NM_000626.4(CD79B):c.591+4A>T	CD79B	Uncertain significance	criteria provided, single submitter
1441648	NM_000626.4(CD79B):c.67+3A>G	CD79B	Uncertain significance	criteria provided, single submitter
1462264	NM_000626.4(CD79B):c.664G>A (p.Val222Ile)	CD79B	Uncertain significance	criteria provided, single submitter
1471750	NM_000626.4(CD79B):c.205A>G (p.Ser69Gly)	CD79B	Uncertain significance	criteria provided, single submitter
1488824	NM_000626.4(CD79B):c.152G>A (p.Arg51His)	CD79B	Uncertain significance	criteria provided, single submitter
1489625	NM_000626.4(CD79B):c.552T>A (p.Asp184Glu)	CD79B	Uncertain significance	criteria provided, single submitter
1513156	NM_000626.4(CD79B):c.329A>G (p.Gln110Arg)	CD79B	Uncertain significance	criteria provided, single submitter
1513391	NM_000626.4(CD79B):c.467C>T (p.Thr156Met)	CD79B	Uncertain significance	criteria provided, single submitter
1917206	NM_000626.4(CD79B):c.217A>G (p.Asn73Asp)	CD79B	Uncertain significance	criteria provided, single submitter
1929246	NM_000626.4(CD79B):c.160G>A (p.Ala54Thr)	CD79B	Uncertain significance	criteria provided, single submitter
1950880	NM_000626.4(CD79B):c.94G>C (p.Glu32Gln)	CD79B	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CD79B	Strong	Autosomal recessive	agammaglobulinemia 6, autosomal recessive	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CD79B	Orphanet:33110	Autosomal non-syndromic agammaglobulinemia

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CD79B	HGNC:1699	ENSG00000007312	P40259	B-cell antigen receptor complex-associated protein beta chain	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CD79B	B-cell antigen receptor complex-associated protein beta chain	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 presentati…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CD79B	Antibody/Immunoglobulin	yes		Phos_immunorcpt_sig_ITAM, Ig_sub, Ig-like_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	1
lymph node	1
spleen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CD79B	210	broad	marker	granulocyte, spleen, lymph node

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CD79B	2,382

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CD79B	P40259	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
CD22 mediated BCR regulation	1	2284.0×	0.004	CD79B
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	1	356.9×	0.010	CD79B
Signaling by the B Cell Receptor (BCR)	1	346.1×	0.010	CD79B
Potential therapeutics for SARS	1	114.2×	0.022	CD79B
SARS-CoV Infections	1	55.4×	0.036	CD79B
Viral Infection Pathways	1	30.8×	0.048	CD79B
Adaptive Immune System	1	29.8×	0.048	CD79B
Infectious disease	1	24.8×	0.050	CD79B
Disease	1	13.1×	0.077	CD79B
Immune System	1	13.0×	0.077	CD79B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
B cell receptor signaling pathway	1	401.2×	0.010	CD79B
B cell differentiation	1	218.9×	0.010	CD79B
response to bacterium	1	193.7×	0.010	CD79B
adaptive immune response	1	84.3×	0.018	CD79B
immune response	1	47.1×	0.025	CD79B
signal transduction	1	16.1×	0.062	CD79B

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CD79B	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CD79B	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	CD79B
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CD79B	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.