ARHGEF10

Chr 8AD

Rho guanine nucleotide exchange factor 10

Also known as: GEF10, SNCV

This protein functions as a Rho guanine nucleotide exchange factor that regulates small Rho GTPases and may be involved in developmental myelination of peripheral nerves. Mutations cause slowed nerve conduction velocity with autosomal dominant inheritance. The gene shows minimal constraint against loss-of-function variants (pLI near zero), suggesting the phenotype may not result from simple protein loss.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

?Slowed nerve conduction velocity, ADMIM #608236
AD
0
Active trials
6
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.98
LOEUF
GOF
Mechanism· predicted
Clinical SummaryARHGEF10
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Gene-Disease Validity (ClinGen)
autosomal dominant slowed nerve conduction velocity · ADLimited

Limited evidence — not for standalone diagnostic reporting

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
0.98LOEUF
pLI 0.000
Z-score 1.72
OE 0.78 (0.620.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-2.72Z-score
OE missense 1.27 (1.211.34)
1013 obs / 796.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.78 (0.620.98)
00.351.4
Missense OE1.27 (1.211.34)
00.61.4
Synonymous OE1.38
01.21.6
LoF obs/exp: 54 / 69.4Missense obs/exp: 1013 / 796.8Syn Z: -5.54
DN
0.4685th %ile
GOF
0.5562th %ile
LOF
0.56top 25%

The Badonyi & Marsh model scores loss-of-function highest, but genomic evidence most strongly supports gain-of-function as the primary mechanism.

GOF1 literature citation

Literature Evidence

GOFIn HeLa, HEK293T, and murine Schwann cells, Chaya et al. (2011) found that the T332I mutation caused constitutive activation of ARHGEF10 and a gain of function resulting in significantly increased cellular contraction time compared to wildtype.PMID:21719701

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ARHGEF10 · 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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