ACAP3

Chr 1

ArfGAP with coiled-coil, ankyrin repeat and PH domains 3

Also known as: CENTB5

NCBI Gene: 116983ENSG00000131584UniProt: Q96P50

ACAP3 encodes a GTPase-activating protein for the ADP ribosylation factor family that regulates neuron migration and projection development. The gene is highly constrained against loss-of-function variants (LOEUF 0.586), suggesting that mutations would likely cause severe developmental phenotypes. However, no definitive human disease associations have been established for this gene.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
137
P/LP submissions
0%
P/LP missense
0.59
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— ACAP3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
130 unique Pathogenic / Likely Pathogenic· 153 VUS of 329 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.59LOEUF
pLI 0.000
Z-score 3.73
OE 0.39 (0.27–0.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.67Z-score
OE missense 0.79 (0.73–0.86)
410 obs / 516.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.39 (0.27–0.59)
0≤0.351.4
Missense OE0.79 (0.73–0.86)
0≤0.61.4
Synonymous OE1.12
0≤1.21.6
LoF obs/exp: 17 / 43.5Missense obs/exp: 410 / 516.9Syn Z: -1.40
DN
0.6744th %ile
GOF
0.76top 25%
LOF
0.3163th %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

329 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic123
Likely Pathogenic7
VUS153
Likely Benign5
Benign2
123
Pathogenic
7
Likely Pathogenic
153
VUS
5
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
123
0
123
Likely Pathogenic
0
0
7
0
7
VUS
0
134
19
0
153
Likely Benign
0
2
1
2
5
Benign
0
0
2
0
2
Total01361522290

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

View in ClinVar →

Protein Context — Lollipop Plot

ACAP3 · 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 4 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