ARHGAP42

Chr 11

Rho GTPase activating protein 42

Also known as: AD031, GRAF3, TMEM133

This gene encodes a Rho GTPase-activating protein that inhibits RhoA activity in vascular smooth muscle cells to regulate vascular tone and blood pressure. The gene is highly constrained against loss-of-function variation (pLI=1.0, LOEUF=0.16), suggesting that mutations would likely cause severe developmental disorders, though specific pediatric phenotypes have not yet been established. Currently, only intronic variants affecting gene expression have been associated with blood pressure regulation in adults.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.15
Clinical SummaryARHGAP42
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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.15LOEUF
pLI 1.000
Z-score 6.16
OE 0.06 (0.030.15)
Highly constrained

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

Missense Constraint
2.96Z-score
OE missense 0.58 (0.520.65)
228 obs / 393.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.06 (0.030.15)
00.351.4
Missense OE0.58 (0.520.65)
00.61.4
Synonymous OE0.79
01.21.6
LoF obs/exp: 3 / 50.0Missense obs/exp: 228 / 393.5Syn Z: 1.94
DN
0.4488th %ile
GOF
0.4973th %ile
LOF
0.69top 10%

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

LOFprediction above median · LOEUF 0.15

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ARHGAP42 · 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.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC