VCX3A

Chr X

variable charge X-linked 3A

Also known as: VCX-8r, VCX-A, VCX3, VCX8R, VCXA

NCBI Gene: 51481ENSG00000169059UniProt: Q9NNX9OMIM: 300533

VCX3A encodes a small, highly charged nuclear protein that may mediate processes in spermatogenesis, with exclusive expression in male germ cells. This gene belongs to a polymorphic gene family clustered on chromosome Xp22, where copy number varies between individuals. No established human diseases have been definitively associated with VCX3A mutations.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.87
Clinical Summary— VCX3A
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.
📋
ClinVar Variants
145 unique Pathogenic / Likely Pathogenic· 117 VUS of 300 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
1.87LOEUF
pLI 0.310
Z-score 0.48
OE 0.00 (0.00–1.87)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-2.14Z-score
OE missense 1.89 (1.56–1.98)
86 obs / 45.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.00 (0.00–1.87)
0≤0.351.4
Missense OE1.89 (1.56–1.98)
0≤0.61.4
Synonymous OE1.79
0≤1.21.6
LoF obs/exp: 0 / 0.3Missense obs/exp: 86 / 45.4Syn Z: -3.02
DN
0.7131th %ile
GOF
0.83top 10%
LOF
0.2091th %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

300 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic138
Likely Pathogenic7
VUS117
Likely Benign26
Benign7
Conflicting2
138
Pathogenic
7
Likely Pathogenic
117
VUS
26
Likely Benign
7
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
138
0
138
Likely Pathogenic
0
0
7
0
7
VUS
0
95
22
0
117
Likely Benign
0
7
10
9
26
Benign
0
3
4
0
7
Conflicting
—2
Total01051819297

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

View in ClinVar →

Protein Context — Lollipop Plot

VCX3A · 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