ARHGAP21

Chr 10

Rho GTPase activating protein 21

Also known as: ARHGAP10

ARHGAP21 functions as a GTPase-activating protein (GAP) for CDC42 and RHOA, regulating actin dynamics at the Golgi apparatus and adherens junctions. Mutations cause autosomal recessive intellectual disability with macrocephaly, seizures, and spasticity. This gene is highly constrained against loss-of-function variants, indicating intolerance to protein-disrupting mutations.

Summary from RefSeq, UniProt
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0
Active trials
1
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.20
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryARHGAP21
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
0.20LOEUF
pLI 1.000
Z-score 7.45
OE 0.12 (0.070.20)
Highly constrained

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

Missense Constraint
0.96Z-score
OE missense 0.92 (0.870.97)
969 obs / 1056.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.12 (0.070.20)
00.351.4
Missense OE0.92 (0.870.97)
00.61.4
Synonymous OE1.13
01.21.6
LoF obs/exp: 10 / 83.5Missense obs/exp: 969 / 1056.4Syn Z: -2.03
DN
0.3793th %ile
GOF
0.4381th %ile
LOF
0.79top 5%

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

LOFprediction above median · LOEUF 0.20

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

ARHGAP21 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

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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