ARHGAP5

Chr 14

Rho GTPase activating protein 5

Also known as: GFI2, RhoGAP5, p190-B, p190BRhoGAP

NCBI Gene: 394 ENSG00000100852 UniProt: Q13017 OMIM: 602680

Rho GTPase activating protein 5 inactivates Rho family GTPases by stimulating GTP hydrolysis, regulating cytoskeletal organization and cell shape changes. Mutations cause autosomal dominant intellectual disability with variable features including developmental delay and behavioral abnormalities. This gene is highly constrained against loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, UniProt

Rho GTPase activating protein 5 negatively regulates RHO GTPases, a family which may mediate cytoskeleton changes by stimulating the hydrolysis of bound GTP. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.26

Clinical Summary— ARHGAP5

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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

2 unique Pathogenic / Likely Pathogenic· 152 VUS of 166 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.26LOEUF

pLI 0.999

Z-score 5.64

OE 0.14 (0.08–0.26)

Highly constrained

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

Missense Constraint?

2.21Z-score

OE missense 0.78 (0.73–0.83)

611 obs / 785.3 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.14 (0.08–0.26)

0≤0.351.4

Missense OE?0.78 (0.73–0.83)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 7 / 50.0Missense obs/exp: 611 / 785.3Syn Z: -0.82

This gene — mechanism propensity

0.3296th %ile

GOF

0.3888th %ile

LOF

0.70top 10%

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

LOFprediction above median · LOEUF 0.26

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

166 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic1

VUS152

Likely Benign1

Benign6

Pathogenic

Likely Pathogenic

152

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	1	0	1
Likely Pathogenic	1	0	0	1
VUS	3	149	0	152
Likely Benign	0	1	0	1
Benign	0	1	5	6
Total	4	152	5	161

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 32) ClinVar copy-number / structural variants overlap ARHGAP5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →