RGS8

Chr 1

regulator of G protein signaling 8

This gene is a member of the regulator of G protein signaling (RGS) family and encodes a protein with a single RGS domain. Regulator of G protein signaling (RGS) proteins are regulatory and structural components of G protein-coupled receptor complexes. They accelerate transit through the cycle of GTP binding and hydrolysis to GDP, thereby terminating signal transduction, but paradoxically, also accelerate receptor-stimulated activation. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
MultiplemechanismLOEUF 0.62
Clinical SummaryRGS8
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.62LOEUF
pLI 0.302
Z-score 2.50
OE 0.24 (0.110.62)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.28Z-score
OE missense 0.66 (0.540.80)
72 obs / 109.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.24 (0.110.62)
00.351.4
Missense OE?0.66 (0.540.80)
00.61.4
Synonymous OE?0.98
01.21.6
LoF obs/exp: 3 / 12.6Missense obs/exp: 72 / 109.7Syn Z: 0.08

This gene — mechanism propensity

DN
0.7036th %ile
GOF
0.7028th %ile
LOF
0.2678th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

RGS8 · 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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