ARFGAP3

Chr 22

ARF GTPase activating protein 3

Also known as: ARFGAP1

NCBI Gene: 26286ENSG00000242247UniProt: Q9NP61

The protein encoded by this gene is a GTPase-activating protein (GAP) that associates with the Golgi apparatus and regulates the early secretory pathway of proteins. The encoded protein promotes hydrolysis of ADP-ribosylation factor 1 (ARF1)-bound GTP, which is required for the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is a prerequisite for the fusion of these vesicles with target compartments. The activity of this protein is sensitive to phospholipids. Multiple transcript variants encoding different isoforms have been found for this gene. This gene was originally known as ARFGAP1, but that is now the name of a related but different gene. [provided by RefSeq, Nov 2008]

155
ClinVar variants
39
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ARFGAP3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
39 Pathogenic / Likely Pathogenic· 88 VUS of 155 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.94LOEUF
pLI 0.000
Z-score 1.81
OE 0.66 (0.46–0.94)
Tolerant

Typical tolerance to LoF variation

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.
0.47Z-score
OE missense 0.92 (0.83–1.02)
255 obs / 276.9 exp
Tolerant

Mild missense constraint

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.0.66 (0.46–0.94)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.83–1.02)
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.1.01
0≤1.21.6
LoF obs/exp: 21 / 32.0Missense obs/exp: 255 / 276.9Syn Z: -0.05

ClinVar Variant Classifications

155 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic39
VUS88
Likely Benign4
Benign1
39
Pathogenic
88
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
39
0
39
Likely Pathogenic
0
0
0
0
0
VUS
0
80
8
0
88
Likely Benign
0
3
0
1
4
Benign
0
1
0
0
1
Total084471132

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

View in ClinVar →

Protein Context — Lollipop Plot

ARFGAP3 · 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
Expression of ArfGAP3 in Vaginal Anterior Wall of Patients With Pelvic Floor Organ Prolapse in Pelvic Organ Prolapse and Non-Pelvic Organ Prolapse Patients.
Sun Y et al.·Female Pelvic Med Reconstr Surg
2021Cohort
ArfGAP3 regulates the transport of cation-independent mannose 6-phosphate receptor in the post-Golgi compartment.
Shiba Y et al.·Curr Biol
2013
Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals.
Eicher JD et al.·Am J Hum Genet
2016Meta-analysis
Copy number variation analysis detects novel candidate genes involved in follicular growth and oocyte maturation in a cohort of premature ovarian failure cases.
Tšuiko O et al.·Hum Reprod
2016Cohort
Lentiviral vector-mediated insertional mutagenesis screen identifies genes that influence androgen independent prostate cancer progression and predict clinical outcome.
Nalla AK et al.·Mol Carcinog
2016
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