Oguchi disease

Summary

Oguchi disease (MONDO:0019152) is a disease with 3 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 3
• ClinVar variants: 55
• Phenotypes (HPO): 13

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		50	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

13 HPO clinical features (Orphanet curated; top 13 by frequency):

HPO ID	Term	Frequency
HP:0007642	Congenital stationary night blindness	Very frequent (80-99%)
HP:0007984	Electronegative electroretinogram	Very frequent (80-99%)
HP:0030824	Mizuo phenomenon	Very frequent (80-99%)
HP:0000539	Abnormality of refraction	Occasional (5-29%)
HP:0000545	Myopia	Occasional (5-29%)
HP:0000608	Macular degeneration	Occasional (5-29%)
HP:0001123	Visual field defect	Excluded (0%)
HP:0007641	Dyschromatopsia	Excluded (0%)
HP:0000486	Strabismus	Very rare (<1-4%)
HP:0000505	Visual impairment	Very rare (<1-4%)
HP:0000510	Rod-cone dystrophy	Very rare (<1-4%)
HP:0000639	Nystagmus	Very rare (<1-4%)
HP:0000651	Diplopia	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Oguchi disease
Mondo ID	MONDO:0019152
MeSH	C537743
Orphanet	75382
ICD-11	1759055065
UMLS	C1306122
MedGen	224927
GARD	0010118
Is cancer (heuristic)	no

Also known as: congenital stationary night blindness, Oguchi type · Oguchi disease · Oguchi syndrome · stationary night blindness, Oguchi type

Data availability: 55 ClinVar variants · 2 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 › perceptual disorders › vision disorder › blindness (disorder) › night blindness › congenital stationary night blindness › Oguchi disease

Related subtypes (13): congenital stationary night blindness autosomal dominant 2, congenital stationary night blindness 1B, cone-rod synaptic disorder, congenital nonprogressive, congenital stationary night blindness autosomal dominant 3, congenital stationary night blindness autosomal dominant 1, congenital stationary night blindness 1C, congenital stationary night blindness 1D, congenital stationary night blindness 1E, congenital stationary night blindness 1F, congenital stationary night blindness 1G, congenital stationary night blindness 1H, night blindness, congenital stationary, type1i, X-linked congenital stationary night blindness

Subtypes (2): Oguchi disease-1, Oguchi disease-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

55 retrieved; paginated sample, class counts are floors:

22 uncertain significance, 15 conflicting classifications of pathogenicity, 8 benign, 7 pathogenic, 3 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
102422	NM_000541.5(SAG):c.523C>T (p.Arg175Ter)	SAG	Pathogenic	criteria provided, single submitter
12951	NM_000541.5(SAG):c.926del (p.Asn309fs)	SAG	Pathogenic	criteria provided, multiple submitters, no conflicts
41895	NM_000541.5(SAG):c.577C>T (p.Arg193Ter)	SAG	Pathogenic	criteria provided, multiple submitters, no conflicts
41897	NM_000541.5(SAG):c.874C>T (p.Arg292Ter)	SAG	Pathogenic	criteria provided, multiple submitters, no conflicts
41898	NM_000541.5(SAG):c.916G>T (p.Glu306Ter)	SAG	Pathogenic	criteria provided, single submitter
801912	NM_000541.5(SAG):c.571C>T (p.Gln191Ter)	SAG	Pathogenic	criteria provided, single submitter
989451	NM_000541.5(SAG):c.649-1G>C	SAG	Pathogenic	criteria provided, single submitter
143084	NM_000541.5(SAG):c.250C>T (p.Arg84Cys)	SAG	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
167633	NM_000541.5(SAG):c.301G>A (p.Ala101Thr)	SAG	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
167636	NM_000541.5(SAG):c.468C>T (p.Phe156=)	SAG	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
335064	NM_000541.5(SAG):c.-223C>G	SAG	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
335077	NM_000541.5(SAG):c.*90G>A	SAG	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
559444	NM_000541.5(SAG):c.398C>T (p.Ser133Leu)	SAG	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
712453	NM_000541.5(SAG):c.588G>A (p.Ala196=)	SAG	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
718731	NM_000541.5(SAG):c.525A>G (p.Arg175=)	SAG	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
719407	NM_000541.5(SAG):c.231C>T (p.Asp77=)	SAG	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
769594	NM_000541.5(SAG):c.420A>G (p.Pro140=)	SAG	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
791237	NM_000541.5(SAG):c.31G>A (p.Glu11Lys)	SAG	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
791897	NM_000541.5(SAG):c.1091C>T (p.Pro364Leu)	SAG	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
896657	NM_000541.5(SAG):c.-69G>A	SAG	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
897119	NM_000541.5(SAG):c.75+7G>T	SAG	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
898348	NM_000541.5(SAG):c.777C>T (p.Tyr259=)	SAG	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
638310	NM_002929.3(GRK1):c.92G>A (p.Arg31Gln)	GRK1	Uncertain significance	criteria provided, single submitter
193815	NM_000541.5(SAG):c.875G>A (p.Arg292Gln)	SAG	Uncertain significance	criteria provided, multiple submitters, no conflicts
194605	NM_000541.5(SAG):c.1132G>A (p.Val378Ile)	SAG	Uncertain significance	criteria provided, multiple submitters, no conflicts
335065	NM_000541.5(SAG):c.-11G>A	SAG	Uncertain significance	criteria provided, single submitter
335070	NM_000541.5(SAG):c.820C>T (p.Pro274Ser)	SAG	Uncertain significance	criteria provided, multiple submitters, no conflicts
335071	NM_000541.5(SAG):c.838A>G (p.Lys280Glu)	SAG	Uncertain significance	criteria provided, multiple submitters, no conflicts
335073	NM_000541.5(SAG):c.1167T>A (p.Asp389Glu)	SAG	Uncertain significance	criteria provided, multiple submitters, no conflicts
335078	NM_000541.5(SAG):c.*98G>A	SAG	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 22 · Orphanet: 3 · 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
GRK1	Definitive	Autosomal recessive	Oguchi disease-2	4
RNF7	Definitive	Autosomal recessive	Oguchi disease-1	9
SAG	Definitive	Autosomal recessive	Oguchi disease-1	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GRK1	Orphanet:75382	Oguchi disease
SAG	Orphanet:75382	Oguchi disease
SAG	Orphanet:791	Retinitis pigmentosa

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GRK1	HGNC:10013	ENSG00000185974	Q15835	Rhodopsin kinase GRK1	gencc,clinvar
RNF7	HGNC:10070	ENSG00000114125	Q9UBF6	RING-box protein 2	gencc,clinvar
SAG	HGNC:10521	ENSG00000130561	P10523	S-arrestin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GRK1	Rhodopsin kinase GRK1	Retina-specific kinase involved in the signal turnoff via phosphorylation of rhodopsin (RHO), the G protein- coupled receptor that initiates the phototransduction cascade.
RNF7	RING-box protein 2	Catalytic component of multiple cullin-5-RING E3 ubiquitin-protein ligase complexes (ECS complexes), which mediate the ubiquitination and subsequent proteasomal degradation of target proteins.
SAG	S-arrestin	Binds to photoactivated, phosphorylated RHO and terminates RHO signaling via G-proteins by competing with G-proteins for the same binding site on RHO.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.33

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
Kinase	1	9.2×	0.313
Transcription factor	1	2.8×	0.482
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GRK1	Kinase	yes	2.7.11.14	GPCR_kinase, Prot_kinase_dom, AGC-kinase_C
RNF7	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, Znf_RING_H2
SAG	Other/Unknown	no		Arrestin, Arrestin-like_N, Arrestin-like_C

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	2
left lobe of thyroid gland	1
right lobe of thyroid gland	1
left adrenal gland	1
left adrenal gland cortex	1
right adrenal gland	1
left testis	1
nucleus accumbens	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GRK1	52	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, right lobe of thyroid gland, left lobe of thyroid gland
RNF7	292	ubiquitous	marker	left adrenal gland, left adrenal gland cortex, right adrenal gland
SAG	106	tissue_specific	marker	nucleus accumbens, male germ line stem cell (sensu Vertebrata) in testis, left testis

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RNF7	2,453
SAG	1,927
GRK1	981

Intra-cohort edges

A	B	Sources
GRK1	SAG	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RNF7	Q9UBF6	7
GRK1	Q15835	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SAG	P10523	85.44

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 3 evidence-associated genes (3 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 3 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	211.5×	2e-04	GRK1, SAG
The phototransduction cascade	1	423.0×	0.008	SAG
Activation of the phototransduction cascade	1	317.2×	0.008	SAG
Inactivation of CSF3 (G-CSF) signaling	1	146.4×	0.014	RNF7
Visual phototransduction	1	86.5×	0.018	SAG
Sensory Perception	1	31.7×	0.042	SAG
Neddylation	1	15.8×	0.071	RNF7
Antigen processing: Ubiquitination & Proteasome degradation	1	12.4×	0.079	RNF7

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
G protein-coupled opsin signaling pathway	2	2246.9×	5e-06	GRK1, SAG
negative regulation of focal adhesion disassembly	1	1404.3×	0.008	RNF7
G protein-coupled receptor internalization	1	561.7×	0.008	SAG
regulation of opsin-mediated signaling pathway	1	561.7×	0.008	GRK1
sensory perception	1	468.1×	0.008	SAG
response to redox state	1	432.1×	0.008	RNF7
reelin-mediated signaling pathway	1	401.2×	0.008	RNF7
negative regulation of focal adhesion assembly	1	255.3×	0.010	RNF7
protein neddylation	1	234.1×	0.010	RNF7
regulation of neuron migration	1	208.1×	0.011	RNF7
post-translational protein modification	1	140.4×	0.014	RNF7
protein K11-linked ubiquitination	1	130.6×	0.014	RNF7
regulation of G protein-coupled receptor signaling pathway	1	124.8×	0.014	GRK1
endoplasmic reticulum unfolded protein response	1	98.5×	0.016	RNF7
regulation of signal transduction	1	89.2×	0.016	GRK1
protein autophosphorylation	1	48.4×	0.028	GRK1
visual perception	1	26.5×	0.048	GRK1
ubiquitin-dependent protein catabolic process	1	24.8×	0.049	RNF7
cell surface receptor signaling pathway	1	21.4×	0.053	SAG
positive regulation of cell migration	1	20.6×	0.053	RNF7
proteasome-mediated ubiquitin-dependent protein catabolic process	1	17.4×	0.059	RNF7
protein ubiquitination	1	13.8×	0.071	RNF7

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
GRK1	RUXOLITINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GRK1	12	4
RNF7	0	0
SAG	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RUXOLITINIB	4	GRK1
NINTEDANIB	4	GRK1
SUNITINIB	4	GRK1
MIDOSTAURIN	4	GRK1
ENZASTAURIN	3	GRK1
ALVOCIDIB	3	GRK1
DOVITINIB	3	GRK1
LESTAURTINIB	3	GRK1
RUBOXISTAURIN	3	GRK1
SU-014813	2	GRK1
R-406	2	GRK1
GSK-690693	1	GRK1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
GRK1	123	Binding:123

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GRK1	2.7.11.14	rhodopsin kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
GRK1	123

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

12 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.

Compound	Max phase	Cohort target (bioactivity)
RUXOLITINIB	4	GRK1
NINTEDANIB	4	GRK1
SUNITINIB	4	GRK1
MIDOSTAURIN	4	GRK1
ENZASTAURIN	3	GRK1
ALVOCIDIB	3	GRK1
DOVITINIB	3	GRK1
LESTAURTINIB	3	GRK1
RUBOXISTAURIN	3	GRK1
SU-014813	2	GRK1
R-406	2	GRK1
GSK-690693	1	GRK1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GRK1
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	RNF7, SAG

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)
SAG	0	GRK1
RNF7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.