RGS17

Chr 6

regulator of G protein signaling 17

NCBI Gene: 26575ENSG00000091844UniProt: Q9UGC6

Regulates G protein-coupled receptor signaling cascades, including signaling via muscarinic acetylcholine receptor CHRM2 and dopamine receptor DRD2. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form (PubMed:15096504). Binds selectively to GNAZ and GNAI2 subunits, accelerates their GTPase activity and regulates their signaling activities. Negatively regulates mu-opioid receptor-mediated activation of the G-proteins (By similarity)

43
ClinVar variants
23
Pathogenic / LP
0.27
pLI score
0
Active trials
Clinical Summary— RGS17
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 20 VUS of 43 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.64LOEUF
pLI 0.267
Z-score 2.42
OE 0.25 (0.11–0.64)
Tolerant

Typical tolerance to LoF variation

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.
0.94Z-score
OE missense 0.74 (0.62–0.90)
79 obs / 106.2 exp
Tolerant

Mild missense constraint

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.0.25 (0.11–0.64)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.62–0.90)
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.0.86
0≤1.21.6
LoF obs/exp: 3 / 12.1Missense obs/exp: 79 / 106.2Syn Z: 0.63

ClinVar Variant Classifications

43 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic1
VUS20
22
Pathogenic
1
Likely Pathogenic
20
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
0
0
1
0
1
VUS
0
17
3
0
20
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total01726043

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

View in ClinVar →

Protein Context — Lollipop Plot

RGS17 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
RGS17/RGSZ2 and the RZ/A family of regulators of G-protein signaling.
Nunn C et al.·Semin Cell Dev Biol
2006Review
Regulator of G Protein Signaling 17 as a Negative Modulator of GPCR Signaling in Multiple Human Cancers.
Hayes MP et al.·AAPS J
2016Review
NRF2 activation by cysteine as a survival mechanism for triple-negative breast cancer cells.
Bottoni L et al.·Oncogene
2024Functional
G-Protein Signaling Protein-17 (RGS17) Is Upregulated and Promotes Tumor Growth and Migration in Human Colorectal Carcinoma.
Li L et al.·Oncol Res
2018
Genetic Background of Mesalamine-induced Fever and Diarrhea in Japanese Patients with Inflammatory Bowel Disease.
Suzuki K et al.·Inflamm Bowel Dis
2022Meta-analysis
RGS17, an overexpressed gene in human lung and prostate cancer, induces tumor cell proliferation through the cyclic AMP-PKA-CREB pathway.
James MA et al.·Cancer Res
2009
Long non-coding RNA Linc00483 accelerated tumorigenesis of cervical cancer by regulating miR-508-3p/RGS17 axis.
Hu P et al.·Life Sci
2019
Concurrent novel RGS17::BCL9 fusion and basophilia in T/B mixed phenotype acute lymphoblastic leukemia/lymphoma.
Huang X et al.·Int J Lab Hematol
2024Case report
Clinical and Genome-Wide Analysis of Multiple Severe Cisplatin-Induced Neurotoxicities in Adult-Onset Cancer Survivors.
Trendowski MR et al.·Clin Cancer Res
2020
MiR-203 inhibits the malignant behavior of prostate cancer cells by targeting RGS17.
Zhang LS et al.·Eur Rev Med Pharmacol Sci
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Retraction Note: MiRNA-199 inhibits malignant progression of lung cancer through mediating RGS17.
Su WZ et al.·Eur Rev Med Pharmacol Sci
2025
Tumor-secreted RGS17 impairs CD8 + T cell function in lung adenocarcinoma through affecting glucose metabolism mediated by PI3K/AKT pathway.
Lou M et al.·Discov Oncol
2025🔓 Open Access
Role of RGS17 in cisplatin-induced cochlear inflammation and ototoxicity via caspase-3 activation.
Al Aameri RFH et al.·Front Immunol
2025🔓 Open Access
Hsa_circ_0000285-Mediated miR-599/RGS17 Axis Participates in the Pathogenesis of Abdominal Aortic Aneurysm by Regulating the Functions of Vascular Smooth Muscle Cells.
Ren J et al.·Ann Clin Lab Sci
2023
Circ_0006220 promotes non-small cell lung cancer progression via sponging miR-203-3p and regulating RGS17 expression.
Wang S et al.·Hum Exp Toxicol
2022
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