ARHGAP11B

Chr 15

Rho GTPase activating protein 11B

Also known as: B'-T, FAM7B1, GAP (1-8)

This hominin-specific protein promotes neocortex development by inhibiting mitochondrial permeability transition pores and enhancing basal progenitor proliferation during fetal brain development. Mutations cause autosomal recessive polymicrogyria with seizures and developmental delay. The gene shows low constraint to loss-of-function variation and has an associated GeneReviews entry for detailed clinical information.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.56
Clinical SummaryARHGAP11B
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.56LOEUF
pLI 0.000
Z-score 0.28
OE 0.91 (0.541.56)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.35Z-score
OE missense 1.08 (0.951.24)
154 obs / 142.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.91 (0.541.56)
00.351.4
Missense OE1.08 (0.951.24)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 9 / 9.9Missense obs/exp: 154 / 142.4Syn Z: -0.10
DN
0.6745th %ile
GOF
0.6735th %ile
LOF
0.3260th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ARHGAP11B · 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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