ARHGAP44

Chr 17

Rho GTPase activating protein 44

Also known as: NPC-A-10, RICH2

NCBI Gene: 9912 ENSG00000006740 UniProt: Q17R89 OMIM: 617716

ARHGAP44 encodes a GTPase-activating protein that regulates CDC42 and RAC1 signaling to control actin cytoskeleton organization, dendritic spine formation, and synaptic plasticity in neurons. This gene is highly constrained against loss-of-function variants (pLI=1.0, LOEUF=0.22), suggesting that mutations would likely cause severe neurodevelopmental disorders. The inheritance pattern and specific disease associations have not yet been established in the literature.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.22

Clinical Summary— ARHGAP44

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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.

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ClinVar Variants

86 VUS of 113 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

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?

LoF OE?0.10 (0.05–0.22)

0≤0.351.4

Missense OE?0.68 (0.62–0.75)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 5 / 47.7Missense obs/exp: 310 / 453.2Syn Z: -1.51

This gene — mechanism propensity

0.4487th %ile

GOF

0.5465th %ile

LOF

0.68top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.22

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

113 submitted variants in ClinVar

ClinVar

Classification Summary

VUS86

Likely Benign5

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	86	0	86
Likely Benign	1	4	5
Benign	0	1	1
Total	87	5	92

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap ARHGAP44 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →