ARHGAP26

Chr 5

Rho GTPase activating protein 26

ENSG00000145819UniProt: Q9UNA1

GTPase-activating protein for RHOA and CDC42. Facilitates mitochondrial quality control by promoting Parkin-mediated recruitment of autophagosomes to damaged mitochondria (PubMed:38081847). Negatively regulates the growth of human parainfluenza virus type 2 by inhibiting hPIV-2-mediated RHOA activation via interaction with two of its viral proteins P and V (PubMed:27512058)

Primary Disease Associations & Inheritance

Leukemia, juvenile myelomonocytic, somaticMIM #607785
67
ClinVar variants
1
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— ARHGAP26
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
1 Pathogenic / Likely Pathogenic· 54 VUS of 67 total submissions
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.28LOEUF
pLI 0.997
Z-score 5.45
OE 0.15 (0.08–0.28)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
2.11Z-score
OE missense 0.72 (0.66–0.79)
329 obs / 456.0 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.0.15 (0.08–0.28)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.72 (0.66–0.79)
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.0.84
0≤1.21.6
LoF obs/exp: 7 / 47.6Missense obs/exp: 329 / 456.0Syn Z: 1.67

ClinVar Variant Classifications

67 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1
VUS54
Likely Benign8
Benign4
1
Pathogenic
54
VUS
8
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
1
0
1
Likely Pathogenic
0
0
0
0
0
VUS
0
53
1
0
54
Likely Benign
0
1
3
4
8
Benign
1
0
0
3
4
Total1545767

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

View in ClinVar →

Protein Context — Lollipop Plot

ARHGAP26 · 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

Leukemia, juvenile myelomonocytic, somatic

MIM #607785

Molecular basis of disorder known

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening.
Yan HHN et al.·Cell Stem Cell
2018
Diffuse Gastric Cancer: A Comprehensive Review of Molecular Features and Emerging Therapeutics.
Wu LW et al.·Target Oncol
2024Review
The role of GTPase-activating protein ARHGAP26 in human cancers.
Zhang L et al.·Mol Cell Biochem
2022Review
Associations of ARHGAP26 Polymorphisms with Alzheimer's Disease and Cardiovascular Disease.
Wang K et al.·J Mol Neurosci
2022
RhoA/ROCK/ARHGAP26 signaling in the eutopic and ectopic endometrium is involved in clinical characteristics of adenomyosis.
Jiang C et al.·J Int Med Res
2018
Review: Gastric cancer-Clinical aspects.
Venerito M et al.·Helicobacter
2019Review
Prognostic significance of frequent CLDN18-ARHGAP26/6 fusion in gastric signet-ring cell cancer.
Shu Y et al.·Nat Commun
2018
Recurrent Fusion Genes in Gastric Cancer: CLDN18-ARHGAP26 Induces Loss of Epithelial Integrity.
Yao F et al.·Cell Rep
2015
Anti-Ca/anti-ARHGAP26 antibodies associated with cerebellar atrophy and cognitive decline.
Doss S et al.·J Neuroimmunol
2014Case report
Rho GTPase-activating protein 10 (ARHGAP10/GRAF2) is a novel autoantibody target in patients with autoimmune encephalitis.
Jarius S et al.·J Neurol
2022Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Evaluation of ARHGAP26 expression, prognostic significance, and immune infiltration in clear cell renal cell carcinoma.
Long A et al.·J Genet Eng Biotechnol
2025🔓 Open Access
Liposome-loaded miR-34c-5p attenuates apoptosis and oxidative stress following hypoxia-ischemia brain damage in neonatal mice by targeting Arhgap26.
Song Y et al.·Eur J Pharmacol
2025
ARHGAP26 deficiency drives the oocyte aneuploidy and early embryonic development failure.
Li S et al.·Cell Death Differ
2025
Recurrent RhoGAP gene fusion CLDN18-ARHGAP26 promotes RHOA activation and focal adhesion kinase and YAP-TEAD signalling in diffuse gastric cancer.
Zhang F et al.·Gut
2024🔓 Open Access
ARHGAP26/GRAF1 orchestrates actin remodeling and membrane dynamics to drive mitochondrial clearance and promote fuel flexibility.
Zhu Q et al.·Autophagy
2024Functional
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