ARHGEF17

Chr 11

Rho guanine nucleotide exchange factor 17

Also known as: P164RHOGEF, RHOGEF17, TEM4, p164-RhoGEF

NCBI Gene: 9828 ENSG00000110237 UniProt: Q96PE2 OMIM: 617043

The protein acts as a guanine nucleotide exchange factor for RhoA GTPases and regulates actin cytoskeleton organization. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and developmental delay. The gene is highly constrained against loss-of-function variation (pLI 0.98, LOEUF 0.29), indicating that heterozygous mutations are likely pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

Enables guanyl-nucleotide exchange factor activity. Acts upstream of or within actin cytoskeleton organization. Predicted to be located in cytosol. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.29

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.29LOEUF

pLI 0.984

Z-score 6.66

OE 0.19 (0.13–0.29)

Highly constrained

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

Missense Constraint?

0.75Z-score

OE missense 0.94 (0.90–0.99)

1176 obs / 1250.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.19 (0.13–0.29)

0≤0.351.4

Missense OE?0.94 (0.90–0.99)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 15 / 78.8Missense obs/exp: 1176 / 1250.6Syn Z: -1.53

Background carrier burden — how many people carry a rare variant somewhere in ARHGEF17?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 19

3,238 rare PASS variants

Rare truncating (LoF)

1 in 1,400

188 rare PASS variants

Rare synonymous (reference)

1 in 33

1,441 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ARHGEF17. 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 25	1 in 1,400
South Asian	~43k	1 in 15	1 in 1,000
Remaining (unassigned)	~30k	1 in 18	1 in 2,500
European (Finnish)	~27k	1 in 54	1 in 1,000
Admixed American	~22k	1 in 16	1 in 1,900
African / African American	~21k	1 in 18	1 in 690
East Asian	~20k	1 in 18	1 in 2,300
Ashkenazi Jewish	~13k	1 in 68	1 in 710
Middle Eastern	~2,884	1 in 20	≈ 1 in 1,400

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): 20 of 21 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 21.? see exons ↓