ACAP1

Chr 17

ArfGAP with coiled-coil, ankyrin repeat and PH domains 1

Also known as: CENTB1

NCBI Gene: 9744ENSG00000072818UniProt: Q15027

Predicted to enable GTPase activator activity and zinc ion binding activity. Predicted to be involved in protein transport. Located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

0
Active trials
29
Pathogenic / LP
136
ClinVar variants
3
Pubs (1 yr)
2.3
Missense Z
0.42
LOEUF
Clinical Summary— ACAP1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
29 Pathogenic / Likely Pathogenic· 106 VUS of 136 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.42LOEUF
pLI 0.068
Z-score 4.53
OE 0.26 (0.16–0.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.30Z-score
OE missense 0.69 (0.63–0.76)
311 obs / 447.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.26 (0.16–0.42)
0≤0.351.4
Missense OE0.69 (0.63–0.76)
0≤0.61.4
Synonymous OE0.85
0≤1.21.6
LoF obs/exp: 11 / 43.0Missense obs/exp: 311 / 447.7Syn Z: 1.53
GOFDN
DN
0.6937th %ile
GOF
0.76top 25%
LOF
0.3066th %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

136 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic3
VUS106
Likely Benign1
26
Pathogenic
3
Likely Pathogenic
106
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
26
0
26
Likely Pathogenic
0
0
3
0
3
VUS
0
99
7
0
106
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total0100360136

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

View in ClinVar →

ACAP1 · 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
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 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