ARHGAP18

Chr 6

Rho GTPase activating protein 18

Also known as: MacGAP, SENEX, bA307O14.2

NCBI Gene: 93663ENSG00000146376UniProt: Q8N392

Enables GTPase activator activity. Involved in several processes, including regulation of actin filament polymerization; regulation of small GTPase mediated signal transduction; and small GTPase-mediated signal transduction. Located in cytosol; nuclear speck; and plasma membrane. Part of cytoplasmic microtubule and ruffle. Implicated in schizophrenia. [provided by Alliance of Genome Resources, Jul 2025]

122
ClinVar variants
15
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ARHGAP18
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
15 Pathogenic / Likely Pathogenic· 98 VUS of 122 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.
0.86LOEUF
pLI 0.000
Z-score 2.26
OE 0.61 (0.44–0.86)
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.
0.72Z-score
OE missense 0.89 (0.81–0.98)
309 obs / 346.6 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.0.61 (0.44–0.86)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.81–0.98)
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.1.03
0≤1.21.6
LoF obs/exp: 24 / 39.3Missense obs/exp: 309 / 346.6Syn Z: -0.24

ClinVar Variant Classifications

122 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic5
VUS98
Likely Benign7
Benign2
10
Pathogenic
5
Likely Pathogenic
98
VUS
7
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
5
0
5
VUS
0
91
7
0
98
Likely Benign
0
4
1
2
7
Benign
0
1
1
0
2
Total096242122

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

View in ClinVar →

Protein Context — Lollipop Plot

ARHGAP18 · 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
YAP and the RhoC regulator ARHGAP18, are required to mediate flow-dependent endothelial cell alignment.
Coleman PR et al.·Cell Commun Signal
2020
ARHGAP18 Protects Against Thoracic Aortic Aneurysm Formation by Mitigating the Synthetic and Proinflammatory Smooth Muscle Cell Phenotype.
Liu R et al.·Circ Res
2017
Caveolae control the anti-inflammatory phenotype of senescent endothelial cells.
Powter EE et al.·Aging Cell
2015
Identifying gene regulatory networks in schizophrenia.
Potkin SG et al.·Neuroimage
2010Review
Association of ARHGAP18 polymorphisms with schizophrenia in the Chinese-Han population.
Guo W et al.·PLoS One
2017
ARHGAP18: A Flow-Responsive Gene That Regulates Endothelial Cell Alignment and Protects Against Atherosclerosis.
Lay AJ et al.·J Am Heart Assoc
2019
Transcript profile of cellular senescence-related genes in Fuchs endothelial corneal dystrophy.
Matthaei M et al.·Exp Eye Res
2014Review
The Imatinib-miR-335-5p-ARHGAP18 Axis Attenuates PDGF-Driven Pathological Responses in Pulmonary Artery Smooth Muscle Cells.
Lee Y et al.·Int J Mol Sci
2025
Development and clinical validation of a novel 9-gene prognostic model based on multi-omics in pancreatic adenocarcinoma.
Xu D et al.·Pharmacol Res
2021Functional
Gene discovery through imaging genetics: identification of two novel genes associated with schizophrenia.
Potkin SG et al.·Mol Psychiatry
2009
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