ARHGAP28

Chr 18

Rho GTPase activating protein 28

NCBI Gene: 79822ENSG00000088756UniProt: Q9P2N2

Predicted to enable GTPase activator activity. Predicted to be involved in negative regulation of stress fiber assembly; regulation of actin filament polymerization; and regulation of small GTPase mediated signal transduction. Located in cell junction and nucleoplasm. Implicated in allergic disease. Biomarker of meningioma. [provided by Alliance of Genome Resources, Jul 2025]

230
ClinVar variants
108
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ARHGAP28
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
108 Pathogenic / Likely Pathogenic· 100 VUS of 230 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 2.20
OE 0.58 (0.41–0.86)
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.
0.78Z-score
OE missense 0.87 (0.79–0.97)
266 obs / 304.5 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.0.58 (0.41–0.86)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.79–0.97)
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.0.97
0≤1.21.6
LoF obs/exp: 19 / 32.6Missense obs/exp: 266 / 304.5Syn Z: 0.22

ClinVar Variant Classifications

230 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic107
Likely Pathogenic1
VUS100
Likely Benign9
Benign2
107
Pathogenic
1
Likely Pathogenic
100
VUS
9
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
107
0
107
Likely Pathogenic
0
0
1
0
1
VUS
0
77
23
0
100
Likely Benign
0
4
3
2
9
Benign
0
1
1
0
2
Total0821352219

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

View in ClinVar →

Protein Context — Lollipop Plot

ARHGAP28 · 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
Array expression meta-analysis of cancer stem cell genes identifies upregulation of PODXL especially in DCC low expression meningiomas.
Schulten HJ et al.·PLoS One
2019Meta-analysis
Genome-Wide Association Analysis of Single-Breath Dl(CO).
Sakornsakolpat P et al.·Am J Respir Cell Mol Biol
2019
Construction of a prognostic risk score model based on the ARHGAP family to predict the survival of osteosarcoma.
Liu W et al.·BMC Cancer
2023Functional
Arhgap28 is a RhoGAP that inactivates RhoA and downregulates stress fibers.
Yeung CY et al.·PLoS One
2014
Class II Human Leukocyte Antigen Variants Associate With Risk of Pegaspargase Hypersensitivity.
Liu Y et al.·Clin Pharmacol Ther
2021
Association of substance dependence phenotypes in the COGA sample.
Wetherill L et al.·Addict Biol
2015
Genome-wide association study of inhaled corticosteroid response in admixed children with asthma.
Hernandez-Pacheco N et al.·Clin Exp Allergy
2019Clinical trial
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