ARHGAP17

Chr 16

Rho GTPase activating protein 17

Also known as: MST066, MST110, MSTP038, MSTP066, MSTP110, NADRIN, PP367, PP4534

NCBI Gene: 55114 ENSG00000140750 UniProt: Q68EM7 OMIM: 608293

RICH1 is a GTPase-activating protein that regulates CDC42 and other Rho family GTPases to maintain tight junctions and apical polarity in epithelial cells, and participates in calcium-dependent exocytosis. The gene is highly constrained against loss-of-function variants (LOEUF 0.442), suggesting intolerance to protein-disrupting mutations. No established Mendelian disease associations have been reported for ARHGAP17 mutations.

OMIM ResearchSummary from RefSeq, UniProt

RICH1 is a GTPase-activating protein (GAP). GAPs stimulate the intrinsic GTP hydrolysis of small G proteins, such as RHOA (MIM 165390), RAC1 (MIM 602048), and CDC42 (MIM 116952).[supplied by OMIM, Apr 2004]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.44

Clinical Summary— ARHGAP17

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.

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ClinVar Variants

103 VUS of 133 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.44LOEUF

pLI 0.020

Z-score 4.47

OE 0.27 (0.17–0.44)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.57Z-score

OE missense 0.80 (0.74–0.87)

402 obs / 501.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.27 (0.17–0.44)

0≤0.351.4

Missense OE?0.80 (0.74–0.87)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 12 / 44.0Missense obs/exp: 402 / 501.0Syn Z: -0.13

This gene — mechanism propensity

0.6355th %ile

GOF

0.6053th %ile

LOF

0.4430th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

133 submitted variants in ClinVar

ClinVar

Classification Summary

VUS103

Likely Benign5

103

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	103	0	103
Likely Benign	3	2	5
Benign	0	0	0
Total	106	2	108

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

30 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap ARHGAP17 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →