Prolonged electroretinal response suppression 1

Summary

Prolonged electroretinal response suppression 1 (MONDO:0958180) is a disease caused by RGS9 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: RGS9 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	prolonged electroretinal response suppression 1
Mondo ID	MONDO:0958180
OMIM	608415
DOID	DOID:0070363
UMLS	C5829874
MedGen	1840510
GARD	0026957
Is cancer (heuristic)	no

Data availability: 3 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › bradyopsia › prolonged electroretinal response suppression 1

Related subtypes (1): prolonged electroretinal response suppression 2

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

3 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity, 1 likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
962370	NM_003835.4(RGS9):c.82C>T (p.Gln28Ter)	RGS9	Pathogenic	criteria provided, multiple submitters, no conflicts
4531278	NM_003835.4(RGS9):c.922C>T (p.Arg308Ter)	RGS9	Likely pathogenic	criteria provided, single submitter
1008906	NM_003835.4(RGS9):c.1637T>C (p.Met546Thr)	RGS9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
RGS9	Definitive	Autosomal recessive	prolonged electroretinal response suppression 1	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RGS9	Orphanet:75374	Bradyopsia

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RGS9	HGNC:10004	ENSG00000108370	O75916	Regulator of G-protein signaling 9	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RGS9	Regulator of G-protein signaling 9	Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RGS9	Other/Unknown	no		DEP_dom, G-protein_gamma-like_dom, RGS

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
caudate nucleus	1
islet of Langerhans	1
putamen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RGS9	178	ubiquitous	marker	putamen, caudate nucleus, islet of Langerhans

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RGS9	795

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RGS9	O75916	74.35

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Inactivation, recovery and regulation of the phototransduction cascade	1	317.2×	0.005	RGS9
Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding	1	300.5×	0.005	RGS9
G alpha (i) signalling events	1	39.0×	0.026	RGS9

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of calcium ion export across plasma membrane	1	16852.0×	7e-04	RGS9
dark adaptation	1	8426.0×	7e-04	RGS9
light adaption	1	5617.3×	7e-04	RGS9
G protein-coupled dopamine receptor signaling pathway	1	1872.4×	0.002	RGS9
response to amphetamine	1	495.6×	0.005	RGS9
regulation of G protein-coupled receptor signaling pathway	1	374.5×	0.005	RGS9
negative regulation of signal transduction	1	374.5×	0.005	RGS9
response to estradiol	1	198.3×	0.008	RGS9
visual perception	1	79.5×	0.017	RGS9
nervous system development	1	45.9×	0.026	RGS9
intracellular signal transduction	1	38.1×	0.028	RGS9
G protein-coupled receptor signaling pathway	1	36.2×	0.028	RGS9

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RGS9	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	RGS9

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
RGS9	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.