ARHGAP44

Chr 17

Rho GTPase activating protein 44

Also known as: NPC-A-10, RICH2

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.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.22
Clinical SummaryARHGAP44
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 unique Pathogenic / Likely Pathogenic· 90 VUS of 127 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.22LOEUF
pLI 1.000
Z-score 5.73
OE 0.10 (0.050.22)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.39Z-score
OE missense 0.68 (0.620.75)
310 obs / 453.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.10 (0.050.22)
00.351.4
Missense OE0.68 (0.620.75)
00.61.4
Synonymous OE1.14
01.21.6
LoF obs/exp: 5 / 47.7Missense obs/exp: 310 / 453.2Syn Z: -1.51
DN
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

127 submitted variants in 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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