SPACA7

Chr 13

sperm acrosome associated 7

Also known as: C13orf28

NCBI Gene: 122258ENSG00000153498UniProt: Q96KW9

SPACA7 encodes a protein involved in fertilization that localizes to the acrosomal vesicle and regulates cell adhesion during the fertilization process. Loss-of-function mutations in SPACA7 cause autosomal recessive male infertility due to defects in sperm function. This gene is not highly constrained against loss-of-function variation in the general population.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
118
P/LP submissions
0%
P/LP missense
1.41
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— SPACA7
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
118 unique Pathogenic / Likely Pathogenic· 32 VUS of 156 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
1.41LOEUF
pLI 0.000
Z-score 0.53
OE 0.83 (0.51–1.41)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.12Z-score
OE missense 0.97 (0.82–1.14)
100 obs / 103.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.83 (0.51–1.41)
0≤0.351.4
Missense OE0.97 (0.82–1.14)
0≤0.61.4
Synonymous OE1.17
0≤1.21.6
LoF obs/exp: 10 / 12.0Missense obs/exp: 100 / 103.5Syn Z: -0.82
DN
0.7229th %ile
GOF
0.7030th %ile
LOF
0.2485th %ile

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

DNprediction above median
GOFprediction 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

156 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic115
Likely Pathogenic3
VUS32
Likely Benign4
115
Pathogenic
3
Likely Pathogenic
32
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
115
0
115
Likely Pathogenic
0
0
3
0
3
VUS
0
24
8
0
32
Likely Benign
0
3
0
1
4
Benign
0
0
0
0
0
Total0271261154

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

View in ClinVar →

Protein Context — Lollipop Plot

SPACA7 · protein map & ClinVar variants

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

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 1 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