VCX3B

Chr X

variable charge X-linked 3B

Also known as: VCX-C, VCXC

NCBI Gene: 425054ENSG00000205642UniProt: Q9H321OMIM: 300981

The VCX3B protein is expressed exclusively in male germ cells and may regulate mRNA stability by inhibiting mRNA decapping, with a possible role in ribosome assembly during spermatogenesis. Currently, no definitive human diseases have been associated with VCX3B mutations in the clinical literature. This X-linked gene shows copy number variation between individuals and has relatively low constraint scores, suggesting tolerance to loss-of-function variants.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.83
Clinical Summary— VCX3B
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.
📋
ClinVar Variants
57 unique Pathogenic / Likely Pathogenic· 108 VUS of 200 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.83LOEUF
pLI 0.337
Z-score 0.66
OE 0.00 (0.00–1.83)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.64Z-score
OE missense 1.57 (1.34–1.84)
102 obs / 64.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.00 (0.00–1.83)
0≤0.351.4
Missense OE1.57 (1.34–1.84)
0≤0.61.4
Synonymous OE1.38
0≤1.21.6
LoF obs/exp: 0 / 0.5Missense obs/exp: 102 / 64.9Syn Z: -1.61
DN
0.77top 25%
GOF
0.88top 5%
LOF
0.2190th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

200 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic56
Likely Pathogenic1
VUS108
Likely Benign28
Conflicting6
56
Pathogenic
1
Likely Pathogenic
108
VUS
28
Likely Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
56
0
56
Likely Pathogenic
0
0
1
0
1
VUS
0
88
20
0
108
Likely Benign
0
8
5
15
28
Benign
0
0
0
0
0
Conflicting
—6
Total0968215199

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

VCX3B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients