Immunodeficiency, common variable, 5

Summary

Immunodeficiency, common variable, 5 (MONDO:0013285) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	immunodeficiency, common variable, 5
Mondo ID	MONDO:0013285
OMIM	613495
DOID	DOID:0081148
UMLS	C3150740
MedGen	462090
GARD	0015670
Is cancer (heuristic)	no

Also known as: common variable immunodeficiency caused by mutation in MS4A1 · CVID5 · immunodeficiency, common variable, 5 · immunodeficiency, common variable, type 5 · MS4A1 common variable immunodeficiency

Data availability: 9 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › syndromic agammaglobulinemia › common variable immunodeficiency › immunodeficiency, common variable, 5

Related subtypes (15): immune deficiency, familial variable, immunodeficiency, common variable, 2, immunodeficiency, common variable, 1, immunodeficiency, common variable, 3, immunodeficiency, common variable, 4, immunodeficiency, common variable, 6, immunodeficiency, common variable, 7, combined immunodeficiency due to LRBA deficiency, immunodeficiency, common variable, 10, IL21-related infantile inflammatory bowel disease, immunodeficiency, common variable, 12, pancytopenia due to IKZF1 mutations, immunodeficiency, common variable, 14, immunodeficiency, common variable, due to APRIL deficiency, immunodeficiency, common variable, 15

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

9 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 2 benign, 1 no classifications from unflagged records

ClinVar	Variant (HGVS)	Gene	Classification	Review
1037439	NM_152866.3(MS4A1):c.352A>C (p.Ile118Leu)	MS4A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1370098	NM_152866.3(MS4A1):c.279+1G>A	MS4A1	Uncertain significance	criteria provided, single submitter
1520800	NM_152866.3(MS4A1):c.718A>G (p.Ile240Val)	MS4A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
17705	NM_152866.3(MS4A1):c.336+6_336+7delinsGACATATGGTT	MS4A1	no classifications from unflagged records	no classifications from unflagged records
2431671	NM_152866.3(MS4A1):c.-279-10del	MS4A1	Uncertain significance	criteria provided, single submitter
626143	NM_152866.3(MS4A1):c.315G>C (p.Glu105Asp)	MS4A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
811262	NM_152866.3(MS4A1):c.194C>T (p.Ala65Val)	MS4A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
618716	NM_152866.3(MS4A1):c.216C>T (p.Ile72=)	MS4A1	Benign	criteria provided, multiple submitters, no conflicts
742969	NM_152866.3(MS4A1):c.123G>A (p.Thr41=)	MS4A1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · 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
MS4A1	Moderate	Autosomal recessive	immunodeficiency, common variable, 5	3

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
MS4A1	HGNC:7315	ENSG00000156738	P11836	B-lymphocyte antigen CD20	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MS4A1	B-lymphocyte antigen CD20	B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MS4A1	Other/Unknown	no		CD20-like_TM, MS4A

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
epithelium of nasopharynx	1
lymph node	1
spleen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MS4A1	197	broad	marker	epithelium of nasopharynx, spleen, lymph node

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MS4A1	166

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MS4A1	P11836	10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
calcium ion import into cytosol	1	8426.0×	0.001	MS4A1
store-operated calcium entry	1	1685.2×	0.002	MS4A1
positive regulation of calcium ion import across plasma membrane	1	1685.2×	0.002	MS4A1
protein tetramerization	1	624.1×	0.004	MS4A1
B cell proliferation	1	481.5×	0.004	MS4A1
B cell activation	1	455.5×	0.004	MS4A1
B cell receptor signaling pathway	1	401.2×	0.004	MS4A1
humoral immune response	1	280.9×	0.005	MS4A1
B cell differentiation	1	218.9×	0.006	MS4A1
response to bacterium	1	193.7×	0.006	MS4A1
cell surface receptor signaling pathway	1	64.1×	0.016	MS4A1

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
MS4A1	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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MS4A1

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)
MS4A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.