Retinitis pigmentosa 25

Summary

Retinitis pigmentosa 25 (MONDO:0011272) is a disease caused by EYS (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: EYS (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 1,334

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 25
Mondo ID	MONDO:0011272
MeSH	C566425
OMIM	602772
DOID	DOID:0110384
UMLS	C1864446
MedGen	350427
GARD	0010384
Is cancer (heuristic)	no

Also known as: EYS retinitis pigmentosa · retinitis pigmentosa 25 · retinitis pigmentosa caused by mutation in EYS · retinitis pigmentosa type 25 · RP 25 · RP25

Data availability: 1,334 ClinVar variants · 4 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 25

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 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 4, 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

600 retrieved; paginated sample, class counts are floors:

142 pathogenic/likely pathogenic, 142 likely pathogenic, 135 uncertain significance, 66 pathogenic, 42 conflicting classifications of pathogenicity, 29 likely benign, 26 benign, 18 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1032663	NM_001142800.2(EYS):c.78_79dup (p.Gln27fs)	EYS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065702	NM_001142800.2(EYS):c.2461G>T (p.Gly821Ter)	EYS	Pathogenic	criteria provided, single submitter
1065732	NM_001142800.2(EYS):c.3567del (p.Gly1190fs)	EYS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065997	NM_001142800.2(EYS):c.2641+2T>C	EYS	Pathogenic	criteria provided, single submitter
1066963	NM_001142800.2(EYS):c.5836-1G>C	EYS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1068376	NM_001142800.2(EYS):c.6725+1G>A	EYS	Pathogenic	criteria provided, multiple submitters, no conflicts
1068377	NM_001142800.2(EYS):c.1184+1G>A	EYS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069602	NM_001142800.2(EYS):c.7842C>A (p.Cys2614Ter)	EYS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069772	NM_001142800.2(EYS):c.3443+1G>A	EYS	Pathogenic	criteria provided, multiple submitters, no conflicts
1070197	NM_001142800.2(EYS):c.3573G>A (p.Trp1191Ter)	EYS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070198	NM_001142800.2(EYS):c.3562C>T (p.Gln1188Ter)	EYS	Pathogenic	criteria provided, multiple submitters, no conflicts
1070536	NM_001142800.2(EYS):c.3951_3952del (p.Pro1318fs)	EYS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070910	NM_001142800.2(EYS):c.1641_1644del (p.Ser547fs)	EYS	Pathogenic	criteria provided, multiple submitters, no conflicts
1071606	NM_001142800.2(EYS):c.5511G>A (p.Trp1837Ter)	EYS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072357	NM_001142800.2(EYS):c.3862dup (p.Tyr1288fs)	EYS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072642	NM_001142800.2(EYS):c.4152dup (p.Pro1385fs)	EYS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073395	NM_001142800.2(EYS):c.1637_1640del (p.Asp546fs)	EYS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074003	NM_001142800.2(EYS):c.5834del (p.Lys1945fs)	EYS	Pathogenic	criteria provided, multiple submitters, no conflicts
1074399	NM_001142800.2(EYS):c.1603del (p.Cys535fs)	EYS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074492	NM_001142800.2(EYS):c.637_643del (p.Glu213fs)	EYS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074625	NM_001142800.2(EYS):c.7540_7541del (p.Val2514fs)	EYS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075666	NM_001142800.2(EYS):c.8868del (p.Ala2957fs)	EYS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075860	NM_001142800.2(EYS):c.3768_3769dup (p.Ser1257fs)	EYS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075992	NM_001142800.2(EYS):c.6812_6813del (p.Thr2271fs)	EYS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076062	NM_001142800.2(EYS):c.8150del (p.Lys2717fs)	EYS	Pathogenic	criteria provided, multiple submitters, no conflicts
1076098	NM_001142800.2(EYS):c.3266del (p.Met1089fs)	EYS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076293	NM_001142800.2(EYS):c.607C>T (p.Gln203Ter)	EYS	Pathogenic	criteria provided, multiple submitters, no conflicts
1076301	NM_001142800.2(EYS):c.7970del (p.Asp2657fs)	EYS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076446	NM_001142800.2(EYS):c.8543del (p.Ile2848fs)	EYS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076583	NM_001142800.2(EYS):c.511C>T (p.Gln171Ter)	EYS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
EYS	Definitive	Autosomal recessive	retinitis pigmentosa 25	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EYS	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
EYS	HGNC:21555	ENSG00000188107	Q5T1H1	Protein eyes shut homolog	gencc,clinvar
ZC3H11C	HGNC:56304	ENSG00000214558	P0DQW0	Zinc finger CCCH domain-containing protein 11C	clinvar
PHF3	HGNC:8921	ENSG00000118482	Q92576	PHD finger protein 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EYS	Protein eyes shut homolog	Required to maintain the integrity of photoreceptor cells.

Protein-family classification

Druggable: 0 · Difficult: 2 · 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
Transcription factor	2	5.5×	0.081
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EYS	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Laminin_G
ZC3H11C	Transcription factor	no		Znf_CCCH, Znf-CCCH_3
PHF3	Transcription factor	no		Znf_PHD, TFIIS_cen_dom, Znf_FYVE_PHD

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)	1
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
islet of Langerhans	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
left testis	1
right testis	1
testis	1
calcaneal tendon	1
tendon	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EYS	153	tissue_specific	marker	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, islet of Langerhans
ZC3H11C	4		yes	testis, left testis, right testis
PHF3	303	ubiquitous	marker	tendon of biceps brachii, calcaneal tendon, tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PHF3	1,976
EYS	1,877
ZC3H11C	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PHF3	Q92576	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ZC3H11C	P0DQW0	56.43
EYS	Q5T1H1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 3 evidence-associated genes (0 with Reactome annotation).

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
skeletal muscle tissue regeneration	1	295.6×	0.008	EYS
poly(A)+ mRNA export from nucleus	1	224.7×	0.008	ZC3H11C
detection of light stimulus involved in visual perception	1	216.1×	0.008	EYS
DNA-templated transcription	1	74.9×	0.017	PHF3
regulation of transcription by RNA polymerase II	1	3.9×	0.236	PHF3

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 3 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
EYS	0	0
ZC3H11C	0	0
PHF3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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	3	EYS, ZC3H11C, PHF3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
EYS	0	—
ZC3H11C	0	—
PHF3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.