RGS7

Chr 1

regulator of G protein signaling 7

NCBI Gene: 6000ENSG00000182901UniProt: P49802

Enables G-protein alpha-subunit binding activity; G-protein beta-subunit binding activity; and GTPase activator activity. Involved in G protein-coupled receptor signaling pathway; negative regulation of G protein-coupled receptor signaling pathway; and positive regulation of GTPase activity. Located in cytosol. Is active in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

132
ClinVar variants
65
Pathogenic / LP
0.78
pLI score
0
Active trials
Clinical Summary— RGS7
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.78) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
65 Pathogenic / Likely Pathogenic· 57 VUS of 132 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.37LOEUF
pLI 0.777
Z-score 4.46
OE 0.20 (0.11–0.37)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.47Z-score
OE missense 0.58 (0.50–0.66)
155 obs / 269.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.20 (0.11–0.37)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.58 (0.50–0.66)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 7 / 35.8Missense obs/exp: 155 / 269.2Syn Z: 0.00

ClinVar Variant Classifications

132 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic62
Likely Pathogenic3
VUS57
Likely Benign7
Benign3
62
Pathogenic
3
Likely Pathogenic
57
VUS
7
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
62
0
62
Likely Pathogenic
0
0
3
0
3
VUS
0
37
20
0
57
Likely Benign
0
2
2
3
7
Benign
0
0
0
3
3
Total039876132

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

View in ClinVar →

Protein Context — Lollipop Plot

RGS7 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

RGS7-related intellectual developmental disorder

limited
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A RGS7-CaMKII complex drives myocyte-intrinsic and myocyte-extrinsic mechanisms of chemotherapy-induced cardiotoxicity.
Basak M et al.·Proc Natl Acad Sci U S A
2023Functional
RGS7 balances acetylation/de-acetylation of p65 to control chemotherapy-dependent cardiac inflammation.
Basak M et al.·Cell Mol Life Sci
2023
RGS7 is recurrently mutated in melanoma and promotes migration and invasion of human cancer cells.
Qutob N et al.·Sci Rep
2018
Non-Ceruloplasmin Copper Identifies a Subtype of Alzheimer's Disease (CuAD): Characterization of the Cognitive Profile and Case of a CuAD Patient Carrying an RGS7 Stop-Loss Variant.
Squitti R et al.·Int J Mol Sci
2023Case report
Genetic markers of thrombophilia as predictors of outcome in colorectal cancer.
Tavares V et al.·J Thromb Thrombolysis
2025
GPR179 is required for high sensitivity of the mGluR6 signaling cascade in depolarizing bipolar cells.
Ray TA et al.·J Neurosci
2014
Fine Mapping of the Body Fat QTL on Human Chromosome 1q43.
Aissani B et al.·PLoS One
2016
Thrombogenesis-associated genetic determinants as predictors of thromboembolism and prognosis in cervical cancer.
Neto BV et al.·Sci Rep
2023
Clinical report of a pure subtelomeric 1qter deletion in a boy with mental retardation and multiple anomalies adds further evidence for a specific phenotype.
van Bever Y et al.·Am J Med Genet A
2005Review
A longitudinal genome-wide association study of bone mineral density mean and variability in the UK Biobank.
He D et al.·Osteoporos Int
2023Natural history
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools