Bradyopsia

Summary

Bradyopsia (MONDO:0012033) is a disease caused by variants in RGS9 and RGS9BP, with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal genes: RGS9 (GenCC Strong), RGS9BP (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 8
• Phenotypes (HPO): 2

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		5	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

2 HPO clinical features (Orphanet curated; top 2 by frequency):

HPO ID	Term	Frequency
HP:0000505	Visual impairment	Very frequent (80-99%)
HP:0000613	Photophobia	Very frequent (80-99%)

Identifiers

Disease identifiers

Field	Value
Canonical name	bradyopsia
Mondo ID	MONDO:0012033
MeSH	C564243
OMIM	608415
Orphanet	75374
DOID	DOID:0050335
ICD-11	1497247503
SNOMED CT	711163009
UMLS	C1842073
MedGen	331206
GARD	0012299
Is cancer (heuristic)	no

Also known as: bradyopsia · PERRS · prolonged electroretinal response suppression

Data availability: 8 ClinVar variants · 5 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › bradyopsia

Related subtypes (31): retinal ischemia, rubeosis iridis, retinal vascular disorder, retinitis, retinal nerve fiber layer disorder, retinal edema, retinal degeneration, night blindness, hypertensive retinopathy, macular holes, retinal detachment, iris hypoplasia with glaucoma, angioid streaks, myopic macular degeneration, osteogenesis imperfecta-retinopathy-seizures-intellectual disability syndrome, congenital retinal arteriovenous communication, Eales disease, central serous chorioretinopathy, achromatopsia, cancer-associated retinopathy, persistent placoid maculopathy, inherited vitreoretinopathy, retina neoplasm, retinal ciliopathy, melanoma associated retinopathy, isolated foveal hypoplasia, acute macular neuroretinopathy, autoimmune retinopathy, proliferative vitreoretinopathy, isolated chorioretinal dystrophy, torpedo maculopathy

Subtypes (2): prolonged electroretinal response suppression 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

8 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 4 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2073786	NM_003835.4(RGS9):c.382C>T (p.Arg128Ter)	RGS9	Pathogenic	criteria provided, single submitter
5862	NM_003835.4(RGS9):c.895T>C (p.Trp299Arg)	RGS9	Pathogenic	criteria provided, single submitter
2831	NM_207391.3(RGS9BP):c.193dup (p.Arg65fs)	RGS9BP	Pathogenic	no assertion criteria provided
993023	NM_207391.3(RGS9BP):c.323_342delinsACCGGCG (p.Pro108fs)	RGS9BP	Pathogenic	no assertion criteria provided
1284843	NM_003835.4(RGS9):c.1867C>T (p.Arg623Ter)	RGS9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1383368	NM_003835.4(RGS9):c.136G>A (p.Val46Ile)	RGS9	Uncertain significance	criteria provided, multiple submitters, no conflicts
635083	NM_003835.4(RGS9):c.458A>G (p.Tyr153Cys)	RGS9	Uncertain significance	criteria provided, multiple submitters, no conflicts
522947	NM_207391.3(RGS9BP):c.365C>G (p.Ser122Cys)	RGS9BP	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 2 · 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	Strong	Autosomal recessive	bradyopsia	5
RGS9BP	Strong	Autosomal recessive	bradyopsia	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RGS9	Orphanet:75374	Bradyopsia
RGS9BP	Orphanet:75374	Bradyopsia

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RGS9	HGNC:10004	ENSG00000108370	O75916	Regulator of G-protein signaling 9	gencc,clinvar
RGS9BP	HGNC:30304	ENSG00000186326	Q6ZS82	Regulator of G-protein signaling 9-binding protein	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.
RGS9BP	Regulator of G-protein signaling 9-binding protein	Regulator of G protein-coupled receptor (GPCR) signaling in phototransduction.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RGS9	Other/Unknown	no		DEP_dom, G-protein_gamma-like_dom, RGS
RGS9BP	Other/Unknown	no		RGS7BP/RGS9BP

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
caudate nucleus	1
islet of Langerhans	1
putamen	1
gastrocnemius	1
hindlimb stylopod muscle	1
male germ line stem cell (sensu Vertebrata) in testis	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
RGS9BP	90	broad	yes	male germ line stem cell (sensu Vertebrata) in testis, hindlimb stylopod muscle, gastrocnemius

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RGS9	795
RGS9BP	543

Intra-cohort edges

A	B	Sources
RGS9	RGS9BP	biogrid_interaction, string_interaction

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RGS9BP	Q6ZS82	82.45
RGS9	O75916	74.35

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 evidence-associated genes (2 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 2 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	2	317.2×	3e-05	RGS9, RGS9BP
Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding	1	150.3×	0.010	RGS9
G alpha (i) signalling events	1	19.5×	0.051	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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of signal transduction	2	374.5×	9e-05	RGS9, RGS9BP
regulation of calcium ion export across plasma membrane	1	8426.0×	8e-04	RGS9
dark adaptation	1	4213.0×	0.001	RGS9
light adaption	1	2808.7×	0.001	RGS9
G protein-coupled receptor signaling pathway	2	36.2×	0.002	RGS9, RGS9BP
G protein-coupled dopamine receptor signaling pathway	1	936.2×	0.002	RGS9
detection of light stimulus involved in visual perception	1	324.1×	0.006	RGS9BP
response to amphetamine	1	247.8×	0.007	RGS9
regulation of G protein-coupled receptor signaling pathway	1	187.2×	0.008	RGS9
response to estradiol	1	99.1×	0.013	RGS9
visual perception	1	39.8×	0.030	RGS9
nervous system development	1	23.0×	0.047	RGS9
intracellular signal transduction	1	19.1×	0.052	RGS9

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
RGS9BP	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	RGS9, RGS9BP

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RGS9	0	—
RGS9BP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.