ARAP1

Chr 11

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1

Also known as: CENTD2, cnt-d2

NCBI Gene: 116985ENSG00000186635UniProt: Q96P48

The protein encoded by this gene contains SAM, ARF-GAP, RHO-GAP, ankyrin repeat, RAS-associating, and pleckstrin homology (PH) domains. In vitro, this protein displays RHO-GAP and phosphatidylinositol (3,4,5) trisphosphate (PIP3)-dependent ARF-GAP activity. The encoded protein associates with the Golgi, and the ARF-GAP activity mediates changes in the Golgi and the formation of filopodia. It is thought to regulate the cell-specific trafficking of a receptor protein involved in apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

262
ClinVar variants
8
Pathogenic / LP
0.12
pLI score
0
Active trials
Clinical Summary— ARAP1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 238 VUS of 262 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.35LOEUF
pLI 0.123
Z-score 6.14
OE 0.24 (0.16–0.35)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.14Z-score
OE missense 0.80 (0.75–0.85)
729 obs / 910.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.24 (0.16–0.35)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.80 (0.75–0.85)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.94
0≤1.21.6
LoF obs/exp: 18 / 75.7Missense obs/exp: 729 / 910.4Syn Z: 0.98

ClinVar Variant Classifications

262 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
VUS238
Likely Benign10
Benign6
8
Pathogenic
238
VUS
10
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
0
0
0
VUS
0
234
4
0
238
Likely Benign
0
8
1
1
10
Benign
0
3
1
2
6
Total0245143262

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

View in ClinVar →

Protein Context — Lollipop Plot

ARAP1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Association of MIF rs1007888 and ARAP1 rs1552224 genetic variants with the risk of gestational diabetes mellitus in a chinese population; case study and meta-analysis.
Zhang Y et al.·Front Endocrinol (Lausanne)
2025Meta-analysis
Arap1 loss causes retinal pigment epithelium phagocytic dysfunction and subsequent photoreceptor death.
Shao A et al.·Dis Model Mech
2022
Angiotensin II and the vascular phenotype in hypertension.
Savoia C et al.·Expert Rev Mol Med
2011Review
Increased long non-coding RNA ARAP1-AS1 expression and its prognostic significance in human gastric cancer: a preliminary study.
Jiang YH et al.·Eur Rev Med Pharmacol Sci
2020
ARAP1 is an independent prognostic biomarker in older women with ovarian high-grade serous adenocarcinoma receiving first-line platinum-based antineoplastic therapy.
Nadaraja S et al.·Acta Oncol
2020
A common functional regulatory variant at a type 2 diabetes locus upregulates ARAP1 expression in the pancreatic beta cell.
Kulzer JR et al.·Am J Hum Genet
2014Functional
Exome sequencing and genetic testing for MODY.
Johansson S et al.·PLoS One
2012
Chromatin 3D interaction analysis of the STARD10 locus unveils FCHSD2 as a regulator of insulin secretion.
Hu M et al.·Cell Rep
2021
Decreased STARD10 Expression Is Associated with Defective Insulin Secretion in Humans and Mice.
Carrat GR et al.·Am J Hum Genet
2017
Characterizing Common and Rare Variations in Nontraditional Glycemic Biomarkers Using Multivariate Approaches on Multiancestry ARIC Study.
Ray D et al.·Diabetes
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools