ARHGAP44

Chr 17

Rho GTPase activating protein 44

Also known as: NPC-A-10, RICH2

NCBI Gene: 9912ENSG00000006740UniProt: Q17R89

Enables phospholipid binding activity. Predicted to be involved in negative regulation of Rac protein signal transduction; regulation of actin cytoskeleton organization; and regulation of plasma membrane bounded cell projection organization. Located in leading edge membrane. Implicated in acquired immunodeficiency syndrome and skin melanoma. Biomarker of hepatocellular carcinoma and lung carcinoma. [provided by Alliance of Genome Resources, Jul 2025]

105
ClinVar variants
9
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— ARHGAP44
⚡
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
9 Pathogenic / Likely Pathogenic· 90 VUS of 105 total submissions

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.
0.22LOEUF
pLI 1.000
Z-score 5.73
OE 0.10 (0.05–0.22)
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.
2.39Z-score
OE missense 0.68 (0.62–0.75)
310 obs / 453.2 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.0.10 (0.05–0.22)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.68 (0.62–0.75)
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.1.14
0≤1.21.6
LoF obs/exp: 5 / 47.7Missense obs/exp: 310 / 453.2Syn Z: -1.51

ClinVar Variant Classifications

105 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic1
VUS90
Likely Benign5
Benign1
8
Pathogenic
1
Likely Pathogenic
90
VUS
5
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
1
0
1
VUS
0
86
4
0
90
Likely Benign
0
1
0
4
5
Benign
0
0
0
1
1
Total087135105

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

View in ClinVar →

Protein Context — Lollipop Plot

ARHGAP44 · 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
ARHGAP44 expression is associated with the metastasis of osteosarcoma and is a promising prognostic biomarker.
Hu S et al.·J Orthop Res
2023
Genome-wide association study of post COVID-19 syndrome in a population-based cohort in Germany.
Ruß AK et al.·Sci Rep
2025Cohort
Mutant p53 promotes cell spreading and migration via ARHGAP44.
Xu J et al.·Sci China Life Sci
2017
ARHGAP44-mediated regulation of the p53/C-myc/Cyclin D1 pathway in modulating the malignant biological behavior of osteosarcoma cells.
Li S et al.·J Orthop Surg Res
2023
Synergistic DBNDD1-GDF15 Signaling Activates the NF-κB Pathway to Promote Colorectal Cancer Progression.
Qi X et al.·Mol Cancer Res
2026
Evidence of a novel gene locus ARHGAP44 for longitudinal change in hemoglobin A1c levels among subjects without diabetes from the Long Life Family Study.
Wang S et al.·Physiol Genomics
2025Natural history
A comprehensive landscape of transcription profiles and data resources for human leukemia.
Luo M et al.·Blood Adv
2023
Identification of Key MicroRNAs and Genes between Colorectal Adenoma and Colorectal Cancer via Deep Learning on GEO Databases and Bioinformatics.
Zhang X et al.·Contrast Media Mol Imaging
2023
Dynamic recruitment of the curvature-sensitive protein ArhGAP44 to nanoscale membrane deformations limits exploratory filopodia initiation in neurons.
Galic M et al.·Elife
2014
Retroviral retention activates a Syk-dependent HemITAM in human tetherin.
Galão RP et al.·Cell Host Microbe
2014
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