Retinitis pigmentosa 4

Summary

Retinitis pigmentosa 4 (MONDO:0013395) is a disease caused by RHO (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: RHO (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 128

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 4
Mondo ID	MONDO:0013395
MeSH	C566706
OMIM	613731
DOID	DOID:0110372
UMLS	C3151001
MedGen	462351
GARD	0010405
Is cancer (heuristic)	no

Also known as: retinitis pigmentosa 4 · retinitis pigmentosa 4, autosomal dominant or recessive · retinitis pigmentosa caused by mutation in RHO · retinitis pigmentosa type 4 · RHO retinitis pigmentosa · RP 4 · RP4

Data availability: 128 ClinVar variants · 7 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › inherited retinal dystrophy › retinitis pigmentosa › retinitis pigmentosa 4

Related subtypes (101): retinitis pigmentosa 6, cone-rod dystrophy 2, retinitis pigmentosa 1, retinitis pigmentosa 9, retinitis pigmentosa 10, dominant pericentral pigmentary retinopathy, late-adult onset retinitis pigmentosa, autosomal recessive pericentral pigmentary retinopathy, retinitis pigmentosa 3, retinitis pigmentosa 24, retinitis pigmentosa 23, retinitis pigmentosa 34, retinitis pigmentosa 2, retinitis pigmentosa Y-linked, retinitis pigmentosa 13, retinitis pigmentosa 12, retinitis pigmentosa 14, retinitis pigmentosa 11, retinitis pigmentosa 17, retinitis pigmentosa 18, retinitis pigmentosa 19, retinitis pigmentosa 22, retinitis pigmentosa 25, retinitis pigmentosa 28, retinitis pigmentosa 30, retinitis pigmentosa 7, retinitis pigmentosa 26, retinitis pigmentosa 32, retinitis pigmentosa 31, retinitis pigmentosa 35, retinitis pigmentosa 33, retinitis pigmentosa 36, retinitis pigmentosa 37, retinitis pigmentosa 41, retinitis pigmentosa 29, retinitis pigmentosa 46, retinitis pigmentosa 42, retinitis pigmentosa 50, retinitis pigmentosa 54, retinitis pigmentosa 51, retinitis pigmentosa 55, retinitis pigmentosa 56, retinitis pigmentosa 57, retinitis pigmentosa 58, cone-rod dystrophy 15, retinitis pigmentosa 27, retinitis pigmentosa 49, retinitis pigmentosa 47, retinitis pigmentosa 45, retinitis pigmentosa 44, retinitis pigmentosa 20, retinitis pigmentosa 40, retinitis pigmentosa 39, retinitis pigmentosa 43, retinitis pigmentosa 48, retinitis pigmentosa 59, retinitis pigmentosa 38, retinitis pigmentosa 60, retinitis pigmentosa 61, retinitis pigmentosa 62, retinitis pigmentosa 63, cone-rod dystrophy 16, retinitis pigmentosa 66, retinitis pigmentosa with or without situs inversus, retinitis pigmentosa 67, retinitis pigmentosa 68, retinitis pigmentosa 69, retinitis pigmentosa 70, retinal dystrophy and obesity, retinitis pigmentosa 71, retinitis pigmentosa 72, retinitis pigmentosa 73, retinitis pigmentosa 74, retinitis pigmentosa 75, retinitis pigmentosa 76, retinitis pigmentosa 77, retinitis pigmentosa 92, retinitis pigmentosa 93, retinitis pigmentosa 83, retinitis pigmentosa 84, retinitis pigmentosa 85, retinitis pigmentosa 86, retinitis pigmentosa 87 with choroidal involvement, retinitis pigmentosa 88, retinitis pigmentosa 90, retinitis pigmentosa 81, retinitis pigmentosa 78, retinitis pigmentosa 79, retinitis pigmentosa 80, retinitis pigmentosa 94, variable age at onset, retinitis pigmentosa 53, retinitis pigmentosa 65, retinitis pigmentosa 64, retinitis pigmentosa 95, retinitis pigmentosa 96, retinitis pigmentosa 97, retinitis pigmentosa 98, retinitis pigmentosa 99, retinitis pigmentosa 100, retinitis pigmentosa 101, retinitis pigmentosa 7, digenic

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

128 retrieved; paginated sample, class counts are floors:

39 pathogenic/likely pathogenic, 32 pathogenic, 24 likely pathogenic, 19 uncertain significance, 11 conflicting classifications of pathogenicity, 3 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1213895	NM_000539.3(RHO):c.937-2A>G	RHO	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13013	NM_000539.3(RHO):c.68C>A (p.Pro23His)	RHO	Pathogenic	criteria provided, multiple submitters, no conflicts
13014	NM_000539.3(RHO):c.1040C>T (p.Pro347Leu)	RHO	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13015	NM_000539.3(RHO):c.1039C>T (p.Pro347Ser)	RHO	Pathogenic	criteria provided, single submitter
13016	NM_000539.3(RHO):c.173C>G (p.Thr58Arg)	RHO	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13018	NM_000539.3(RHO):c.50C>T (p.Thr17Met)	RHO	Pathogenic	criteria provided, multiple submitters, no conflicts
13021	NM_000539.3(RHO):c.266G>A (p.Gly89Asp)	RHO	Pathogenic	criteria provided, multiple submitters, no conflicts
13022	NM_000539.3(RHO):c.316G>T (p.Gly106Trp)	RHO	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13023	NM_000539.3(RHO):c.568G>A (p.Asp190Asn)	RHO	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13024	NM_000539.3(RHO):c.404G>T (p.Arg135Leu)	RHO	Pathogenic	criteria provided, multiple submitters, no conflicts
13025	NM_000539.3(RHO):c.533A>G (p.Tyr178Cys)	RHO	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13026	NM_000539.3(RHO):c.569A>G (p.Asp190Gly)	RHO	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13028	NM_000539.3(RHO):c.403C>T (p.Arg135Trp)	RHO	Pathogenic	criteria provided, multiple submitters, no conflicts
13029	NM_000539.3(RHO):c.1030C>T (p.Gln344Ter)	RHO	Pathogenic	criteria provided, multiple submitters, no conflicts
13030	NM_000539.3(RHO):c.886A>G (p.Lys296Glu)	RHO	Pathogenic	criteria provided, multiple submitters, no conflicts
13032	NM_000539.3(RHO):c.1040C>G (p.Pro347Arg)	RHO	Pathogenic	criteria provided, single submitter
13033	NM_000539.3(RHO):c.544G>A (p.Gly182Ser)	RHO	Pathogenic	criteria provided, multiple submitters, no conflicts
13034	NM_000539.3(RHO):c.800C>T (p.Pro267Leu)	RHO	Pathogenic	criteria provided, multiple submitters, no conflicts
13035	NM_000539.3(RHO):c.329G>A (p.Cys110Tyr)	RHO	Pathogenic	criteria provided, multiple submitters, no conflicts
13037	NM_000539.3(RHO):c.158C>G (p.Pro53Arg)	RHO	Pathogenic	criteria provided, multiple submitters, no conflicts
13038	NM_000539.3(RHO):c.316G>A (p.Gly106Arg)	RHO	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13040	NM_000539.3(RHO):c.568G>T (p.Asp190Tyr)	RHO	Pathogenic	criteria provided, multiple submitters, no conflicts
13042	NM_000539.3(RHO):c.44A>G (p.Asn15Ser)	RHO	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13043	NM_000539.3(RHO):c.620T>G (p.Met207Arg)	RHO	Pathogenic	criteria provided, multiple submitters, no conflicts
13046	NM_000539.3(RHO):c.448G>A (p.Glu150Lys)	RHO	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13047	NM_000539.3(RHO):c.151G>C (p.Gly51Arg)	RHO	Pathogenic	criteria provided, multiple submitters, no conflicts
13048	NM_000539.3(RHO):c.341G>A (p.Gly114Asp)	RHO	Pathogenic	criteria provided, multiple submitters, no conflicts
13049	NM_000539.3(RHO):c.491C>A (p.Ala164Glu)	RHO	Pathogenic	criteria provided, multiple submitters, no conflicts
13050	NM_000539.3(RHO):c.511C>T (p.Pro171Ser)	RHO	Pathogenic	criteria provided, multiple submitters, no conflicts
13051	NM_000539.3(RHO):c.789CTG[1] (p.Cys264del)	RHO	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · 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
RHO	Definitive	Semidominant	retinitis pigmentosa 4	13

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RHO	Orphanet:215	Congenital stationary night blindness
RHO	Orphanet:52427	Retinitis punctata albescens
RHO	Orphanet:791	Retinitis pigmentosa

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
RHO	HGNC:10012	ENSG00000163914	P08100	Rhodopsin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RHO	Rhodopsin	Photoreceptor required for image-forming vision at low light intensity.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
GPCR	1	23.9×	0.042

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RHO	GPCR	yes		GPCR_Rhodpsn, Rhodopsin, Opsin

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
diaphragm	1
neuron projection bundle connecting eye with brain	1
optic choroid	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RHO	38	tissue_specific	marker	optic choroid, neuron projection bundle connecting eye with brain, diaphragm

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RHO	3,578

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RHO	P08100	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Opsins	1	1268.9×	0.003	RHO
Activation of the phototransduction cascade	1	951.7×	0.003	RHO
The canonical retinoid cycle in rods (twilight vision)	1	519.1×	0.003	RHO
VxPx cargo-targeting to cilium	1	519.1×	0.003	RHO
Inactivation, recovery and regulation of the phototransduction cascade	1	317.2×	0.004	RHO
G alpha (i) signalling events	1	39.0×	0.026	RHO

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
thermotaxis	1	8426.0×	9e-04	RHO
rod bipolar cell differentiation	1	8426.0×	9e-04	RHO
detection of temperature stimulus involved in thermoception	1	5617.3×	9e-04	RHO
G protein-coupled opsin signaling pathway	1	3370.4×	0.001	RHO
absorption of visible light	1	2808.7×	0.001	RHO
response to light intensity	1	2106.5×	0.001	RHO
podosome assembly	1	2106.5×	0.001	RHO
phototransduction, visible light	1	1296.3×	0.001	RHO
cellular response to light stimulus	1	1053.2×	0.002	RHO
phototransduction	1	495.6×	0.003	RHO
photoreceptor cell maintenance	1	358.6×	0.004	RHO
microtubule cytoskeleton organization	1	121.2×	0.010	RHO
gene expression	1	79.9×	0.013	RHO
visual perception	1	79.5×	0.013	RHO
G protein-coupled receptor signaling pathway	1	36.2×	0.028	RHO

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RHO	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
RHO	1	Binding:1

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	1	RHO
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
RHO	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.