Retinitis pigmentosa 20

disease

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Also known as retinitis pigmentosa caused by mutation in RPE65retinitis pigmentosa type 20RP 20RP20RPE65 retinitis pigmentosa

Summary

Retinitis pigmentosa 20 (MONDO:0013425) is a disease caused by RPE65 (GenCC Strong), with 2 cohort genes and 1 clinical trial.

At a glance

Causal gene: RPE65 (GenCC Strong)
Cohort genes: 2
ClinVar variants: 865
Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 20
Mondo ID	MONDO:0013425
MeSH	C566718
OMIM	613794
DOID	DOID:0110353
UMLS	C3151086
MedGen	462436
GARD	0010404
Is cancer (heuristic)	no

Also known as: retinitis pigmentosa 20 · retinitis pigmentosa caused by mutation in RPE65 · retinitis pigmentosa type 20 · RP 20 · RP20 · RPE65 retinitis pigmentosa

Data availability: 865 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 › retinal degeneration › inherited retinal dystrophy › retinitis pigmentosa › retinitis pigmentosa 20

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

600 retrieved; paginated sample, class counts are floors:

316 likely benign, 148 uncertain significance, 77 pathogenic, 31 likely pathogenic, 16 pathogenic/likely pathogenic, 6 conflicting classifications of pathogenicity, 5 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1067769	NM_000329.3(RPE65):c.3G>A (p.Met1Ile)	RPE65	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1067786	NM_000329.3(RPE65):c.496-1G>A	RPE65	Pathogenic	reviewed by expert panel
1068757	NM_000329.3(RPE65):c.200T>G (p.Leu67Arg)	RPE65	Pathogenic	reviewed by expert panel
1068758	NM_000329.3(RPE65):c.94G>T (p.Gly32Cys)	RPE65	Pathogenic	criteria provided, multiple submitters, no conflicts
1069087	NM_000329.3(RPE65):c.943_950del (p.Ile315fs)	RPE65	Pathogenic	criteria provided, single submitter
1069898	NM_000329.3(RPE65):c.1399C>G (p.Pro467Ala)	RPE65	Pathogenic	reviewed by expert panel
1070055	NM_000329.3(RPE65):c.61del (p.Glu21fs)	RPE65	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070297	NM_000329.3(RPE65):c.912C>G (p.Tyr304Ter)	RPE65	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070754	NM_000329.3(RPE65):c.1409C>T (p.Pro470Leu)	RPE65	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070755	NM_000329.3(RPE65):c.886dup (p.Arg296fs)	RPE65	Pathogenic	reviewed by expert panel
1072065	NM_000329.3(RPE65):c.777dup (p.Asn260Ter)	RPE65	Pathogenic	criteria provided, single submitter
1072114	NM_000329.3(RPE65):c.1028T>G (p.Leu343Ter)	RPE65	Pathogenic	criteria provided, single submitter
1072483	NM_000329.3(RPE65):c.886del (p.Arg296fs)	RPE65	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074826	NM_000329.3(RPE65):c.545A>G (p.His182Arg)	RPE65	Pathogenic	reviewed by expert panel
1076002	NM_000329.3(RPE65):c.637C>T (p.Gln213Ter)	RPE65	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076977	NC_000001.10:g.(?68912383)(68912553_?)del	RPE65	Pathogenic	criteria provided, single submitter
1213911	NM_000329.3(RPE65):c.1443del (p.Asp482fs)	RPE65	Pathogenic	criteria provided, single submitter
1213916	NM_000329.3(RPE65):c.1229C>A (p.Ser410Ter)	RPE65	Pathogenic	criteria provided, single submitter
13114	NM_000329.3(RPE65):c.700C>T (p.Arg234Ter)	RPE65	Pathogenic	reviewed by expert panel
13115	NM_000329.3(RPE65):c.271C>T (p.Arg91Trp)	RPE65	Pathogenic	reviewed by expert panel
13117	NM_000329.3(RPE65):c.1087C>A (p.Pro363Thr)	RPE65	Pathogenic	reviewed by expert panel
13118	NM_000329.3(RPE65):c.1022T>C (p.Leu341Ser)	RPE65	Pathogenic	reviewed by expert panel
13120	NM_000329.3(RPE65):c.1543C>T (p.Arg515Trp)	RPE65	Pathogenic	reviewed by expert panel
1321180	NM_000329.3(RPE65):c.1451-1G>A	RPE65	Pathogenic	reviewed by expert panel
1355343	NM_000329.3(RPE65):c.46_49del (p.Phe16fs)	RPE65	Pathogenic	criteria provided, multiple submitters, no conflicts
1380598	NM_000329.3(RPE65):c.775dup (p.Ile259fs)	RPE65	Pathogenic	criteria provided, single submitter
1381188	NM_000329.3(RPE65):c.504_580del (p.Cys169fs)	RPE65	Pathogenic	criteria provided, single submitter
1384701	NM_000329.3(RPE65):c.1501_1505del (p.Tyr501fs)	RPE65	Pathogenic	reviewed by expert panel
1416497	NM_000329.3(RPE65):c.644-2A>C	RPE65	Pathogenic	criteria provided, multiple submitters, no conflicts
1429329	NM_000329.3(RPE65):c.1115dup (p.Leu372fs)	RPE65	Pathogenic	criteria provided, single submitter

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
RPE65	Definitive	Autosomal recessive	retinitis pigmentosa	13

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RPE65	Orphanet:364055	Severe early-childhood-onset retinal dystrophy
RPE65	Orphanet:65	Leber congenital amaurosis
RPE65	Orphanet:791	Retinitis pigmentosa

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
RPE65	HGNC:10294	ENSG00000116745	Q16518	Retinoid isomerohydrolase	gencc,clinvar
DEPDC1	HGNC:22949	ENSG00000024526	Q5TB30	DEP domain-containing protein 1A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPE65	Retinoid isomerohydrolase	Critical isomerohydrolase in the retinoid cycle involved in regeneration of 11-cis-retinal, the chromophore of rod and cone opsins.
DEPDC1	DEP domain-containing protein 1A	May be involved in transcriptional regulation as a transcriptional corepressor.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPE65	Enzyme (other)	yes	3.1.1.64	Carotenoid_Oase
DEPDC1	Other/Unknown	no		DEP_dom, Rho_GTPase_activation_prot, WH-like_DNA-bd_sf

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	2
pigmented layer of retina	1
retina	1
primordial germ cell in gonad	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPE65	92	tissue_specific	marker	pigmented layer of retina, retina, male germ line stem cell (sensu Vertebrata) in testis
DEPDC1	173	ubiquitous	marker	ventricular zone, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RPE65	1,414
DEPDC1	1,354

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DEPDC1	Q5TB30	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RPE65	Q16518	95.34

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 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
The canonical retinoid cycle in rods (twilight vision)	1	519.1×	0.006	RPE65
Visual phototransduction	1	259.6×	0.006	RPE65
Sensory Perception	1	95.2×	0.011	RPE65

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
zeaxanthin biosynthetic process	1	8426.0×	0.001	RPE65
vitamin A metabolic process	1	1203.7×	0.005	RPE65
retina homeostasis	1	561.7×	0.005	RPE65
neural retina development	1	468.1×	0.005	RPE65
retinal metabolic process	1	468.1×	0.005	RPE65
detection of light stimulus involved in visual perception	1	324.1×	0.006	RPE65
retinoid metabolic process	1	247.8×	0.006	RPE65
circadian rhythm	1	122.1×	0.011	RPE65
visual perception	1	39.8×	0.031	RPE65
intracellular signal transduction	1	19.1×	0.057	DEPDC1
negative regulation of DNA-templated transcription	1	15.8×	0.062	DEPDC1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RPE65	0	0
DEPDC1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RPE65	3.1.1.64, 5.3.3.22	retinoid isomerohydrolase, lutein isomerase

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	1	RPE65
E	Difficult family or no structure, no drug	1	DEPDC1

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)
RPE65	0	—
DEPDC1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04525261	Not specified	COMPLETED	Natural History of Patients With Inherited Retinal Diseases Due to Mutations in RPE65 Gene

Cohort genes: RPE65, DEPDC1