Patterned macular dystrophy

Summary

Patterned macular dystrophy (MONDO:0020381) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	patterned macular dystrophy
Mondo ID	MONDO:0020381
OMIM	169150
DOID	DOID:0060863
GARD	0025158
Is cancer (heuristic)	no

Also known as: macular dystrophy, patterned

Data availability: 3 GenCC gene-disease records.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › macular degeneration › patterned macular dystrophy

Related subtypes (8): vitelliform macular dystrophy, degeneration of macula and posterior pole, macular retinal edema, autosomal recessive bestrophinopathy, occult macular dystrophy, macular degeneration, early-onset, Stargardt disease, isolated macular dystrophy

Subtypes (3): patterned macular dystrophy 1, patterned macular dystrophy 2, patterned macular dystrophy 3

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 38 · Orphanet: 18 · 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
CTNNA1	Definitive	Autosomal dominant	patterned macular dystrophy 2	6
PRPH2	Definitive	Autosomal dominant	hereditary macular dystrophy	21
OTX2	Supportive	Autosomal dominant	patterned macular dystrophy	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CTNNA1	Orphanet:26106	Hereditary diffuse gastric cancer
CTNNA1	Orphanet:99001	Butterfly-shaped pigment dystrophy
OTX2	Orphanet:178364	Syndromic microphthalmia type 5
OTX2	Orphanet:3157	Septo-optic dysplasia spectrum
OTX2	Orphanet:35612	Nanophthalmos
OTX2	Orphanet:95494	Combined pituitary hormone deficiencies, genetic forms
OTX2	Orphanet:98938	Colobomatous microphthalmia
OTX2	Orphanet:990	Agnathia-holoprosencephaly-situs inversus syndrome
OTX2	Orphanet:99001	Butterfly-shaped pigment dystrophy
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

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CTNNA1	HGNC:2509	ENSG00000044115	P35221	Catenin alpha-1	gencc
OTX2	HGNC:8522	ENSG00000165588	P32243	Homeobox protein OTX2	gencc
PRPH2	HGNC:9942	ENSG00000112619	P23942	Peripherin-2	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CTNNA1	Catenin alpha-1	Associates with the cytoplasmic domain of a variety of cadherins.
OTX2	Homeobox protein OTX2	Transcription factor probably involved in the development of the brain and the sense organs.
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: 1 · Unknown: 2 · 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	1	2.8×	0.587
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CTNNA1	Other/Unknown	no		Vinculin_CS, Alpha_catenin, Vinculin/catenin
OTX2	Transcription factor	no		HD, Otx2_TF, Otx_TF
PRPH2	Other/Unknown	no		Peripherin/rom-1, Tetraspanin_EC2_sf, Peripherin/rom-1_CS

Expression context

Cohort genes with no expression data: 0.

3 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
amniotic fluid	1
calcaneal tendon	1
colonic epithelium	1
oocyte	1
pigmented layer of retina	1
secondary oocyte	1
hindlimb stylopod muscle	1
quadriceps femoris	1
vastus lateralis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CTNNA1	305	ubiquitous	marker	colonic epithelium, calcaneal tendon, amniotic fluid
OTX2	62	broad	marker	secondary oocyte, oocyte, pigmented layer of retina
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
CTNNA1	3,128
OTX2	2,368
PRPH2	1,234

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CTNNA1	P35221	10
PRPH2	P23942	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
OTX2	P32243	60.99

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
CDH11 homotypic and heterotypic interactions	1	815.7×	0.005	CTNNA1
Regulation of CDH19 Expression and Function	1	713.8×	0.005	CTNNA1
Formation of the posterior neural plate	1	571.0×	0.005	OTX2
Regulation of CDH11 function	1	519.1×	0.005	CTNNA1
Formation of the anterior neural plate	1	519.1×	0.005	OTX2
Regulation of CDH1 Function	1	475.8×	0.005	CTNNA1
SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)	1	248.3×	0.007	CTNNA1
VEGFR2 mediated vascular permeability	1	203.9×	0.008	CTNNA1
Myogenesis	1	190.3×	0.008	CTNNA1
RHO GTPases activate IQGAPs	1	173.0×	0.008	CTNNA1
Adherens junctions interactions	1	124.1×	0.010	CTNNA1
Degradation of CDH1	1	98.5×	0.011	CTNNA1
Activation of STAT3 by cadherin engagement	1	81.6×	0.012	CTNNA1

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
response to low light intensity stimulus	1	5617.3×	0.008	PRPH2
negative regulation of integrin-mediated signaling pathway	1	1404.3×	0.008	CTNNA1
cellular response to indole-3-methanol	1	1123.5×	0.008	CTNNA1
regulation of fibroblast growth factor receptor signaling pathway	1	802.5×	0.008	OTX2
positive regulation of gastrulation	1	802.5×	0.008	OTX2
gap junction assembly	1	702.2×	0.008	CTNNA1
apical junction assembly	1	702.2×	0.008	CTNNA1
positive regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	510.7×	0.008	CTNNA1
primitive streak formation	1	468.1×	0.008	OTX2
negative regulation of cell motility	1	432.1×	0.008	CTNNA1
negative regulation of neuroblast proliferation	1	401.2×	0.008	CTNNA1
epithelial cell-cell adhesion	1	401.2×	0.008	CTNNA1
axon regeneration	1	374.5×	0.008	CTNNA1
positive regulation of embryonic development	1	374.5×	0.008	OTX2
photoreceptor cell outer segment organization	1	351.1×	0.008	PRPH2
protein heterooligomerization	1	351.1×	0.008	PRPH2
cell adhesion	2	25.0×	0.008	CTNNA1, PRPH2
negative regulation of protein localization to nucleus	1	280.9×	0.009	CTNNA1
detection of light stimulus involved in visual perception	1	216.1×	0.011	PRPH2
regulation of smoothened signaling pathway	1	208.1×	0.011	OTX2
dopaminergic neuron differentiation	1	208.1×	0.011	OTX2
midbrain development	1	200.6×	0.011	OTX2
extrinsic apoptotic signaling pathway in absence of ligand	1	156.0×	0.013	CTNNA1
positive regulation of smoothened signaling pathway	1	140.4×	0.013	CTNNA1
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	137.0×	0.013	CTNNA1
establishment or maintenance of cell polarity	1	133.8×	0.013	CTNNA1
ovarian follicle development	1	130.6×	0.013	CTNNA1
neuroblast proliferation	1	122.1×	0.014	CTNNA1
forebrain development	1	117.0×	0.014	OTX2
response to estrogen	1	114.6×	0.014	CTNNA1

Therapeutics

Drug target analysis

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

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CTNNA1	0	0
OTX2	0	0
PRPH2	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
CTNNA1	2	Binding:2

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	CTNNA1, OTX2, PRPH2

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)
CTNNA1	2	—
OTX2	0	—
PRPH2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.