Immunodeficiency, common variable, 6

Summary

Immunodeficiency, common variable, 6 (MONDO:0013286) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	immunodeficiency, common variable, 6
Mondo ID	MONDO:0013286
OMIM	613496
DOID	DOID:0081149
UMLS	C3150741
MedGen	462091
GARD	0015671
Is cancer (heuristic)	no

Also known as: CD81 common variable immunodeficiency · common variable immunodeficiency caused by mutation in CD81 · CVID6 · immunodeficiency, common variable, 6 · immunodeficiency, common variable, type 6

Data availability: 11 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › syndromic agammaglobulinemia › common variable immunodeficiency › immunodeficiency, common variable, 6

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, 5, 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

11 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 3 benign/likely benign, 1 no classifications from unflagged records, 1 likely benign, 1 conflicting classifications of pathogenicity, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
626080	NM_004356.4(CD81):c.182-5G>A	CD81	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
12743	NM_004356.4(CD81):c.561+1G>A	CD81	no classifications from unflagged records	no classifications from unflagged records
1347538	NM_004356.4(CD81):c.409G>A (p.Asp137Asn)	CD81	Uncertain significance	criteria provided, multiple submitters, no conflicts
2439820	NM_004356.4(CD81):c.352C>T (p.Gln118Ter)	CD81	Uncertain significance	criteria provided, single submitter
3599525	NM_004356.4(CD81):c.423C>G (p.Asn141Lys)	CD81	Uncertain significance	criteria provided, multiple submitters, no conflicts
992559	NM_004356.4(CD81):c.583G>A (p.Asp195Asn)	CD81	Uncertain significance	criteria provided, multiple submitters, no conflicts
1645740	NM_004356.4(CD81):c.159C>T (p.Pro53=)	CD81	Likely benign	criteria provided, multiple submitters, no conflicts
439472	NM_004356.4(CD81):c.414T>C (p.Asp138=)	CD81	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
707872	NM_004356.4(CD81):c.648+10C>T	CD81	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
784183	NM_004356.4(CD81):c.459+4C>T	CD81	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
810931	NM_004356.4(CD81):c.597C>T (p.Ser199=)	CD81	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
CD81	Supportive	Autosomal dominant	common variable immunodeficiency	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CD81	Orphanet:696881	Common variable immunodeficiency phenotype due to CD19/CD81 deficiency

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
CD81	HGNC:1701	ENSG00000110651	P60033	CD81 antigen	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CD81	CD81 antigen	Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling.

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)
CD81	Other/Unknown	no		Tetraspanin_animals, Tetraspanin_EC2_sf, Tetraspanin/Peripherin

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
body of uterus	1
seminal vesicle	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CD81	302	ubiquitous	marker	stromal cell of endometrium, seminal vesicle, body of uterus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CD81	516

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CD81	P60033	16

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Complement cascade	1	634.4×	0.009	CD81
Regulation of Complement cascade	1	233.1×	0.013	CD81
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1	87.2×	0.023	CD81
Adaptive Immune System	1	29.8×	0.047	CD81
Innate Immune System	1	25.5×	0.047	CD81
Immune System	1	13.0×	0.077	CD81

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
macrophage fusion	1	16852.0×	5e-04	CD81
CD4-positive, alpha-beta T cell costimulation	1	16852.0×	5e-04	CD81
positive regulation of adaptive immune memory response	1	16852.0×	5e-04	CD81
positive regulation of receptor clustering	1	8426.0×	6e-04	CD81
positive regulation of protein catabolic process in the vacuole	1	8426.0×	6e-04	CD81
positive regulation of inflammatory response to antigenic stimulus	1	5617.3×	6e-04	CD81
positive regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell	1	5617.3×	6e-04	CD81
regulation of macrophage migration	1	4213.0×	7e-04	CD81
humoral immune response mediated by circulating immunoglobulin	1	3370.4×	7e-04	CD81
myoblast fusion involved in skeletal muscle regeneration	1	3370.4×	7e-04	CD81
osteoclast fusion	1	2808.7×	8e-04	CD81
positive regulation of B cell receptor signaling pathway	1	2407.4×	9e-04	CD81
positive regulation of protein exit from endoplasmic reticulum	1	2106.5×	9e-04	CD81
positive regulation of CD4-positive, alpha-beta T cell proliferation	1	1685.2×	0.001	CD81
positive regulation of T-helper 2 cell cytokine production	1	1532.0×	0.001	CD81
immunological synapse formation	1	1296.3×	0.001	CD81
protein localization to lysosome	1	1053.2×	0.001	CD81
cellular response to low-density lipoprotein particle stimulus	1	887.0×	0.002	CD81
positive regulation of T cell receptor signaling pathway	1	766.0×	0.002	CD81
positive regulation of B cell proliferation	1	343.9×	0.004	CD81
receptor internalization	1	324.1×	0.004	CD81
regulation of protein stability	1	125.8×	0.009	CD81
protein localization to plasma membrane	1	108.7×	0.010	CD81
positive regulation of MAPK cascade	1	80.6×	0.013	CD81
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	CD81

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
CD81	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
CD81	7	Binding:7

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	CD81

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)
CD81	7	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.