ARHGEF10

Chr 8

Rho guanine nucleotide exchange factor 10

Also known as: GEF10, SNCV

NCBI Gene: 9639 ENSG00000104728 UniProt: O15013

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.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a Rho guanine nucleotide exchange factor (GEF). Rho GEFs regulate the activity of small Rho GTPases by stimulating the exchange of guanine diphosphate (GDP) for guanine triphosphate (GTP) and may play a role in neural morphogenesis. Mutations in this gene are associated with slowed nerve conduction velocity (SNCV). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSlowed nerve conduction velocity

Clinical highlights

Gene–disease validity (ClinGen)

Limited · autosomal dominant slowed nerve conduction velocity · AD · ClinGen 2026

not for standalone diagnostic reporting

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.98

LOEUF

GOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.98LOEUF

pLI 0.000

Z-score 1.72

OE 0.78 (0.62–0.98)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-2.72Z-score

OE missense 1.27 (1.21–1.34)

1013 obs / 796.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.78 (0.62–0.98)

0≤0.351.4

Missense OE?1.27 (1.21–1.34)

0≤0.61.4

Synonymous OE?1.38

0≤1.21.6

LoF obs/exp: 54 / 69.4Missense obs/exp: 1013 / 796.8Syn Z: -5.54

Background carrier burden — how many people carry a rare variant somewhere in ARHGEF10?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 21

2,444 rare PASS variants

Rare truncating (LoF)

1 in 300

285 rare PASS variants

Rare synonymous (reference)

1 in 41

958 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ARHGEF10. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 33	1 in 690
South Asian	~43k	1 in 20	1 in 570
Remaining (unassigned)	~30k	1 in 21	1 in 280
European (Finnish)	~27k	1 in 70	1 in 490
Admixed American	~22k	1 in 26	1 in 200
African / African American	~21k	1 in 21	1 in 1,100
East Asian	~20k	1 in 21	1 in 610
Ashkenazi Jewish	~13k	1 in 160	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 19	1 in 570

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 28 coding exons well covered in gnomAD exomes and genomes.? see exons ↓