RGS8

Chr 1

regulator of G protein signaling 8

NCBI Gene: 85397 ENSG00000135824 UniProt: P57771 OMIM: 607189

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]

OMIM Research

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

0.62

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.62LOEUF

pLI 0.302

Z-score 2.50

OE 0.24 (0.11–0.62)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.28Z-score

OE missense 0.66 (0.54–0.80)

72 obs / 109.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.24 (0.11–0.62)

0≤0.351.4

Missense OE?0.66 (0.54–0.80)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 3 / 12.6Missense obs/exp: 72 / 109.7Syn Z: 0.08

Background carrier burden — how many people carry a rare variant somewhere in RGS8?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 280

204 rare PASS variants

Rare truncating (LoF)

1 in 6,500

21 rare PASS variants

Rare synonymous (reference)

1 in 410

97 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RGS8. 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 360	1 in 19,000
South Asian	~43k	1 in 480	1 in 1,500
Remaining (unassigned)	~30k	1 in 540	≈ 1 in 6,000
European (Finnish)	~27k	1 in 1,700	none seen
Admixed American	~22k	1 in 200	1 in 2,800
African / African American	~21k	1 in 630	1 in 3,800
East Asian	~20k	1 in 770	1 in 2,200
Ashkenazi Jewish	~13k	1 in 1,100	none seen
Middle Eastern	~2,884	≈ 1 in 2,900	none seen

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 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓