RGS9

Chr 17AR

regulator of G protein signaling 9

Also known as: PERRS, PERRS1, RGS9L

NCBI Gene: 8787ENSG00000108370UniProt: O75916

This gene encodes a member of the RGS family of GTPase activating proteins that function in various signaling pathways by accelerating the deactivation of G proteins. This protein is anchored to photoreceptor membranes in retinal cells and deactivates G proteins in the rod and cone phototransduction cascades. Mutations in this gene result in bradyopsia. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

Primary Disease Associations & Inheritance

Prolonged electroretinal response suppression 1MIM #608415
AR
0
Active trials
29
Pathogenic / LP
488
ClinVar variants
2
Pubs (1 yr)
0.0
Missense Z
0.85
LOEUF
Clinical Summary— RGS9
🧬
Gene-Disease Validity (ClinGen)
bradyopsia · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
29 Pathogenic / Likely Pathogenic· 213 VUS of 488 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

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.
0.85LOEUF
pLI 0.000
Z-score 2.41
OE 0.62 (0.47–0.85)
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.
0.04Z-score
OE missense 0.99 (0.91–1.08)
377 obs / 379.1 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.0.62 (0.47–0.85)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.91–1.08)
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.1.15
0≤1.21.6
LoF obs/exp: 30 / 48.0Missense obs/exp: 377 / 379.1Syn Z: -1.40

ClinVar Variant Classifications

488 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic17
VUS213
Likely Benign234
Benign9
Conflicting3
12
Pathogenic
17
Likely Pathogenic
213
VUS
234
Likely Benign
9
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
7
0
12
Likely Pathogenic
13
0
4
0
17
VUS
0
193
18
2
213
Likely Benign
0
7
97
130
234
Benign
0
1
7
1
9
Conflicting
—3
Total18201133133488

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

View in ClinVar →

Protein Context — Lollipop Plot

RGS9 · protein map & ClinVar variants

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

Gene2Phenotype Curations

RGS9-related bradyopsia

definitive
ARLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Prolonged electroretinal response suppression 1

MIM #608415

Molecular basis of disorder known

Autosomal recessive

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Phenotyping and genotyping inherited retinal diseases: Molecular genetics, clinical and imaging features, and therapeutics of macular dystrophies, cone and cone-rod dystrophies, rod-cone dystrophies, Leber congenital amaurosis, and cone dysfunction syndromes.
Georgiou M et al.·Prog Retin Eye Res
2024Review
Monogenic Retinal Diseases Associated With Genes Encoding Phototransduction Proteins: A Review.
Wong WM et al.·Clin Exp Ophthalmol
2025Review
Novel mutations and electrophysiologic findings in RGS9- and R9AP-associated retinal dysfunction (Bradyopsia).
Michaelides M et al.·Ophthalmology
2010
Regulator of G-protein signaling expression in human intestinal enteroendocrine cells and potential role in satiety hormone secretion in health and obesity.
McRae AN et al.·EBioMedicine
2024
Clinical vision and molecular loss: Integrating visual psychophysics with molecular genetics reveals key details of normal and abnormal visual processing.
Stockman A et al.·Prog Retin Eye Res
2021Review
Pathognomonic (diagnostic) ERGs. A review and update.
Vincent A et al.·Retina
2013Review
Defects in RGS9 or its anchor protein R9AP in patients with slow photoreceptor deactivation.
Nishiguchi KM et al.·Nature
2004Cohort
Retinal Architecture in ​RGS9- and ​R9AP-Associated Retinal Dysfunction (Bradyopsia).
Strauss RW et al.·Am J Ophthalmol
2015Case report
Structure, alternative splicing, and expression of the human RGS9 gene.
Zhang K et al.·Gene
1999
The clinical presentation of bradyopsia in children.
Khan AO·J AAPOS
2017Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Multimodal imaging and electrophysiological features in bradyopsia associated with homozygous variants (c.895T>C) in Regulator of G-protein Signaling 9 (RGS9).
Borchert GA et al.·Ophthalmic Genet
2026
Human cone elongation responses can be explained by photoactivated cone opsin and membrane swelling and osmotic response to phosphate produced by RGS9-catalyzed GTPase.
Pandiyan VP et al.·Proc Natl Acad Sci U S A
2022Open Access
Structural information and membrane binding of truncated RGS9-1 Anchor Protein and its C-terminal hydrophobic segment.
Bernier SC et al.·Biochim Biophys Acta Biomembr
2021
RGS9-2 rescues dopamine D2 receptor levels and signaling in DYT1 dystonia mouse models.
Bonsi P et al.·EMBO Mol Med
2019Open AccessFunctional
Selective Role of RGS9-2 in Regulating Retrograde Synaptic Signaling of Indirect Pathway Medium Spiny Neurons in Dorsal Striatum.
Song C et al.·J Neurosci
2018
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Pepperberg plot: Modeling flash response saturation in retinal rods of mouse
Caruso G et al.·Front Mol Neurosci
2023Functional
Co-Expression of Adaptor Protein FAM159B with Different Markers for Neuroendocrine Cells: An Immunocytochemical and Immunohistochemical Study
Beyer AL et al.·Int J Mol Sci
2022
Transcriptomic analysis of rat brain response to alternating current electrical stimulation: unveiling insights via single-nucleus RNA sequencing
Wang Y et al.·MedComm (2020)
2024
Regulator of G-Protein Signalling 9: A New Candidate Gene for Sweet Food Liking?
Graham CA et al.·Foods
2023
Allosteric Pathways Originating at Cysteine Residues in Regulators of G-Protein Signaling Proteins
Liu Y et al.·Biophys J
2021
Age-Induced Changes in mu-Opioid Receptor Signaling in the Midbrain Periaqueductal Gray of Male and Female Rats.
Fullerton EF et al.·J Neurosci
2022
Single nucleus transcriptomic analysis of rat nucleus accumbens reveals cell type-specific patterns of gene expression associated with volitional morphine intake
Reiner BC et al.·Transl Psychiatry
2022
Top 7 full-text resultsSearch PubTator3 ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients