Agammaglobulinemia 3, autosomal recessive

Summary

Agammaglobulinemia 3, autosomal recessive (MONDO:0013288) is a disease caused by CD79A (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: CD79A (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 163

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	agammaglobulinemia 3, autosomal recessive
Mondo ID	MONDO:0013288
OMIM	613501
DOID	DOID:0081137
UMLS	C3150751
MedGen	462101
GARD	0015673
Is cancer (heuristic)	no

Also known as: agammaglobulinemia 3, autosomal recessive · AGM3 · autosomal agammaglobulinemia caused by mutation in CD79A · CD79A autosomal agammaglobulinemia

Data availability: 163 ClinVar variants · 3 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 3, autosomal recessive

Related subtypes (7): agammaglobulinemia 6, autosomal recessive, agammaglobulinemia 2, 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

163 retrieved; paginated sample, class counts are floors:

80 likely benign, 68 uncertain significance, 5 conflicting classifications of pathogenicity, 5 pathogenic, 3 benign, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
17706	NM_001783.4(CD79A):c.380-2A>G	CD79A	Pathogenic	no assertion criteria provided
2128215	NC_000019.10:g.41878996_41879009del	CD79A	Pathogenic	criteria provided, single submitter
4702574	NM_001783.4(CD79A):c.465C>A (p.Cys155Ter)	CD79A	Pathogenic	criteria provided, single submitter
4781785	NM_001783.4(CD79A):c.67_73del (p.Ala23fs)	CD79A	Pathogenic	criteria provided, single submitter
570771	NM_001783.4(CD79A):c.198G>A (p.Trp66Ter)	CD79A	Pathogenic	criteria provided, single submitter
17707	NM_001783.4(CD79A):c.379+1G>A	CD79A	Likely pathogenic	criteria provided, single submitter
2105348	NM_001783.4(CD79A):c.499-1G>A	CD79A	Likely pathogenic	criteria provided, single submitter
133831	NM_001783.4(CD79A):c.28G>A (p.Ala10Thr)	CD79A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
133835	NM_001783.4(CD79A):c.419C>A (p.Thr140Asn)	CD79A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1387579	NM_001783.4(CD79A):c.164C>T (p.Pro55Leu)	CD79A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
834558	NM_001783.4(CD79A):c.203G>A (p.Arg68His)	CD79A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
842297	NM_001783.4(CD79A):c.309A>G (p.Ile103Met)	CD79A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1000084	NM_001783.4(CD79A):c.80-3C>T	CD79A	Uncertain significance	criteria provided, single submitter
1003780	NM_001783.4(CD79A):c.179A>G (p.Asn60Ser)	CD79A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1014689	NM_001783.4(CD79A):c.182A>T (p.Asn61Ile)	CD79A	Uncertain significance	criteria provided, single submitter
1020949	NM_001783.4(CD79A):c.377G>A (p.Arg126His)	CD79A	Uncertain significance	criteria provided, single submitter
1025028	NM_001783.4(CD79A):c.137T>C (p.Leu46Pro)	CD79A	Uncertain significance	criteria provided, single submitter
1035578	NM_001783.4(CD79A):c.373G>A (p.Val125Met)	CD79A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1036112	NM_001783.4(CD79A):c.128T>A (p.Met43Lys)	CD79A	Uncertain significance	criteria provided, single submitter
1037005	NM_001783.4(CD79A):c.202C>T (p.Arg68Cys)	CD79A	Uncertain significance	criteria provided, single submitter
1048795	NM_001783.4(CD79A):c.374T>G (p.Val125Gly)	CD79A	Uncertain significance	criteria provided, single submitter
1054078	NM_001783.4(CD79A):c.653T>A (p.Ile218Lys)	CD79A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1055887	NM_001783.4(CD79A):c.259C>T (p.Pro87Ser)	CD79A	Uncertain significance	criteria provided, single submitter
1057644	NM_001783.4(CD79A):c.677C>T (p.Pro226Leu)	CD79A	Uncertain significance	criteria provided, single submitter
1059609	NM_001783.4(CD79A):c.523G>A (p.Gly175Arg)	CD79A	Uncertain significance	criteria provided, single submitter
133832	NM_001783.4(CD79A):c.258C>A (p.Asp86Glu)	CD79A	Uncertain significance	criteria provided, single submitter
133833	NM_001783.4(CD79A):c.320G>A (p.Arg107Gln)	CD79A	Uncertain significance	criteria provided, single submitter
133834	NM_001783.4(CD79A):c.371G>A (p.Arg124His)	CD79A	Uncertain significance	criteria provided, multiple submitters, no conflicts
133836	NM_001783.4(CD79A):c.643A>G (p.Ser215Gly)	CD79A	Uncertain significance	criteria provided, multiple submitters, no conflicts
133837	NM_001783.4(CD79A):c.593T>C (p.Met198Thr)	CD79A	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
CD79A	Definitive	Autosomal recessive	agammaglobulinemia 3, autosomal recessive	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CD79A	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
CD79A	HGNC:1698	ENSG00000105369	P11912	B-cell antigen receptor complex-associated protein alpha chain	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CD79A	B-cell antigen receptor complex-associated protein alpha chain	Required in cooperation with CD79B for initiation of the signal transduction cascade activated by binding of antigen to the B-cell antigen receptor complex (BCR) which leads to internalization of the complex, trafficking to late endosomes…

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)
CD79A	Antibody/Immunoglobulin	yes		Phos_immunorcpt_sig_ITAM, Ig_sub2, Ig_sub

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
CD79A	182	broad	marker	spleen, granulocyte, lymph node

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CD79A	3,177

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CD79A	P11912	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	CD79A
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	1	356.9×	0.010	CD79A
Signaling by the B Cell Receptor (BCR)	1	346.1×	0.010	CD79A
Potential therapeutics for SARS	1	114.2×	0.022	CD79A
SARS-CoV Infections	1	55.4×	0.036	CD79A
Viral Infection Pathways	1	30.8×	0.048	CD79A
Adaptive Immune System	1	29.8×	0.048	CD79A
Infectious disease	1	24.8×	0.050	CD79A
Disease	1	13.1×	0.077	CD79A
Immune System	1	13.0×	0.077	CD79A

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 proliferation	1	481.5×	0.004	CD79A
B cell activation	1	455.5×	0.004	CD79A
B cell receptor signaling pathway	1	401.2×	0.004	CD79A
B cell differentiation	1	218.9×	0.006	CD79A
adaptive immune response	1	84.3×	0.012	CD79A

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CD79A	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	CD79A
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)
CD79A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.