RGS17

Chr 6

regulator of G protein signaling 17

Also known as: RGS-17, RGSZ2, hRGS17

NCBI Gene: 26575 ENSG00000091844 OMIM: 607191

This protein regulates G-protein coupled receptor signaling by accelerating GTPase activity of specific G alpha subunits (GNAZ and GNAI2), thereby terminating signals from receptors including muscarinic acetylcholine and dopamine receptors. Mutations in RGS17 have not been definitively associated with human disease. The gene shows moderate tolerance to loss-of-function variants (LOEUF 0.641), suggesting haploinsufficiency may not be highly pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the regulator of G-protein signaling family. This protein contains a conserved, 120 amino acid motif called the RGS domain and a cysteine-rich region. The protein attenuates the signaling activity of G-proteins by binding to activated, GTP-bound G alpha subunits and acting as a GTPase activating protein (GAP), increasing the rate of conversion of the GTP to GDP. This hydrolysis allows the G alpha subunits to bind G beta/gamma subunit heterodimers, forming inactive G-protein heterotrimers, thereby terminating the signal. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOEUF 0.64

Clinical Summary— RGS17

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.

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ClinVar Variants

17 VUS of 19 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.64LOEUF

pLI 0.267

Z-score 2.42

OE 0.25 (0.11–0.64)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.94Z-score

OE missense 0.74 (0.62–0.90)

79 obs / 106.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.25 (0.11–0.64)

0≤0.351.4

Missense OE?0.74 (0.62–0.90)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 3 / 12.1Missense obs/exp: 79 / 106.2Syn Z: 0.63

ClinVar Variant Classifications

19 submitted variants in ClinVar

ClinVar

Classification Summary

VUS17

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	17	17
Likely Benign	0	0
Benign	0	0
Total	17	17

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap RGS17 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →