Patterned dystrophy of the retinal pigment epithelium

Summary

Patterned dystrophy of the retinal pigment epithelium (MONDO:0018973) is a disease (an umbrella term covering 5 Mondo subtypes) with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 1
• ClinVar variants: 30

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	patterned dystrophy of the retinal pigment epithelium
Mondo ID	MONDO:0018973
MeSH	C536309
Orphanet	63454
UMLS	C1868569
MedGen	357005
GARD	0009821
Is cancer (heuristic)	no

Data availability: 30 ClinVar variants.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › inherited retinal dystrophy › hereditary macular dystrophy › patterned dystrophy of the retinal pigment epithelium

Related subtypes (16): vitelliform macular dystrophy, cone dystrophy, coloboma of macula, coloboma of macula-brachydactyly type B syndrome, benign concentric annular macular dystrophy, macular dystrophy, fenestrated sheen type, macular coloboma-cleft palate-hallux valgus syndrome, macular corneal dystrophy, EEM syndrome, renal hypomagnesemia 5 with ocular involvement, macular dystrophy, X-linked, AICA-ribosiduria, occult macular dystrophy, familial flecked retinopathy, macular dystrophy, retinal, macular dystrophy with or without cone dysfunction

Subtypes (5): reticular dystrophy of the retinal pigment epithelium, patterned macular dystrophy, multifocal pattern dystrophy simulating fundus flavimaculatus, fundus pulverulentus, butterfly-shaped pigment dystrophy

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

30 retrieved; paginated sample, class counts are floors:

17 pathogenic/likely pathogenic, 6 pathogenic, 3 conflicting classifications of pathogenicity, 2 uncertain significance, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
13164	NM_000322.5(PRPH2):c.647C>T (p.Pro216Leu)	PRPH2	Pathogenic	criteria provided, multiple submitters, no conflicts
13165	NM_000322.5(PRPH2):c.554T>C (p.Leu185Pro)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13167	NM_000322.5(PRPH2):c.515G>A (p.Arg172Gln)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13170	NM_000322.5(PRPH2):c.514C>T (p.Arg172Trp)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13173	NM_000322.5(PRPH2):c.629C>G (p.Pro210Arg)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13179	NM_000322.5(PRPH2):c.136C>T (p.Arg46Ter)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13183	NM_000322.5(PRPH2):c.424C>T (p.Arg142Trp)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
623212	NM_000322.5(PRPH2):c.584G>A (p.Arg195Gln)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
813079	NM_000322.5(PRPH2):c.653C>A (p.Ser218Ter)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
860907	NM_000322.5(PRPH2):c.659G>C (p.Arg220Pro)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
866239	NM_000322.5(PRPH2):c.903_906del (p.Ser301fs)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
866925	NM_000322.5(PRPH2):c.708C>G (p.Tyr236Ter)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
866955	NM_000322.5(PRPH2):c.537G>T (p.Trp179Cys)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
941494	NM_000322.5(PRPH2):c.639C>G (p.Cys213Trp)	PRPH2	Pathogenic	criteria provided, multiple submitters, no conflicts
956620	NM_000322.5(PRPH2):c.318del (p.Leu107fs)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
958838	NM_000322.5(PRPH2):c.310_313del (p.Ile104fs)	PRPH2	Pathogenic	criteria provided, multiple submitters, no conflicts
973706	NM_000322.5(PRPH2):c.597del (p.Asn199fs)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
973708	NM_000322.5(PRPH2):c.612C>A (p.Tyr204Ter)	PRPH2	Pathogenic	criteria provided, multiple submitters, no conflicts
973718	NM_000322.5(PRPH2):c.761T>A (p.Leu254Gln)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
973722	NM_000322.5(PRPH2):c.583C>T (p.Arg195Ter)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
98666	NM_000322.5(PRPH2):c.422A>G (p.Tyr141Cys)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
98703	NM_000322.5(PRPH2):c.715C>T (p.Gln239Ter)	PRPH2	Pathogenic	criteria provided, multiple submitters, no conflicts
98713	NM_000322.5(PRPH2):c.828+3A>T	PRPH2	Pathogenic	criteria provided, multiple submitters, no conflicts
2628027	NM_000322.5(PRPH2):c.917G>A (p.Trp306Ter)	PRPH2	Likely pathogenic	criteria provided, single submitter
847943	NM_000322.5(PRPH2):c.683C>T (p.Thr228Ile)	PRPH2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
356777	NM_000322.5(PRPH2):c.649A>G (p.Ser217Gly)	PRPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
98698	NM_000322.5(PRPH2):c.658C>T (p.Arg220Trp)	PRPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
98721	NM_000322.5(PRPH2):c.938C>T (p.Pro313Leu)	PRPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
193083	NM_000322.5(PRPH2):c.271T>A (p.Tyr91Asn)	PRPH2	Uncertain significance	criteria provided, multiple submitters, no conflicts
866564	NM_000322.5(PRPH2):c.610T>C (p.Tyr204His)	PRPH2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 9 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PRPH2	Orphanet:1872	Cone rod dystrophy
PRPH2	Orphanet:227796	Fundus albipunctatus
PRPH2	Orphanet:52427	Retinitis punctata albescens
PRPH2	Orphanet:75377	Central areolar choroidal dystrophy
PRPH2	Orphanet:791	Retinitis pigmentosa
PRPH2	Orphanet:827	Stargardt disease
PRPH2	Orphanet:99000	Adult-onset foveomacular vitelliform dystrophy
PRPH2	Orphanet:99001	Butterfly-shaped pigment dystrophy
PRPH2	Orphanet:99003	Multifocal pattern dystrophy simulating fundus flavimaculatus

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
PRPH2	HGNC:9942	ENSG00000112619	P23942	Peripherin-2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PRPH2	Peripherin-2	Essential for retina photoreceptor outer segment disk morphogenesis, may also play a role with ROM1 in the maintenance of outer segment disk structure.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PRPH2	Other/Unknown	no		Peripherin/rom-1, Tetraspanin_EC2_sf, Peripherin/rom-1_CS

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
hindlimb stylopod muscle	1
quadriceps femoris	1
vastus lateralis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PRPH2	176	tissue_specific	marker	quadriceps femoris, vastus lateralis, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRPH2	1,234

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PRPH2	P23942	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
response to low light intensity stimulus	1	16852.0×	6e-04	PRPH2
photoreceptor cell outer segment organization	1	1053.2×	0.003	PRPH2
protein heterooligomerization	1	1053.2×	0.003	PRPH2
detection of light stimulus involved in visual perception	1	648.1×	0.004	PRPH2
retina development in camera-type eye	1	255.3×	0.008	PRPH2
protein maturation	1	163.6×	0.010	PRPH2
protein homooligomerization	1	122.1×	0.011	PRPH2
protein localization to plasma membrane	1	108.7×	0.011	PRPH2
visual perception	1	79.5×	0.014	PRPH2
cell adhesion	1	37.5×	0.027	PRPH2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
PRPH2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	PRPH2

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)
PRPH2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.