Patterned macular dystrophy 2

Summary

Patterned macular dystrophy 2 (MONDO:0012162) is a disease caused by CTNNA1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: CTNNA1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 141

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	patterned macular dystrophy 2
Mondo ID	MONDO:0012162
OMIM	608970
DOID	DOID:0060864
UMLS	C1837029
MedGen	332348
GARD	0018238
Is cancer (heuristic)	no

Also known as: CTNNA1 patterned macular dystrophy · macular dystrophy, patterned, type 2 · MDPT2 · patterned macular dystrophy caused by mutation in CTNNA1 · patterned macular dystrophy type 2

Data availability: 141 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › macular degeneration › patterned macular dystrophy › patterned macular dystrophy 2

Related subtypes (2): patterned macular dystrophy 1, 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

ClinVar germline variants

141 retrieved; paginated sample, class counts are floors:

64 uncertain significance, 45 conflicting classifications of pathogenicity, 14 benign/likely benign, 6 pathogenic/likely pathogenic, 4 likely benign, 4 pathogenic, 3 likely pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1958939	NM_001903.5(CTNNA1):c.1205del (p.Leu402fs)	CTNNA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2018557	NM_001903.5(CTNNA1):c.1571del (p.Asn524fs)	CTNNA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2028938	NM_001903.5(CTNNA1):c.302-2_302-1del	CTNNA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
225126	NM_001903.5(CTNNA1):c.953T>C (p.Leu318Ser)	CTNNA1	Pathogenic	no assertion criteria provided
225128	NM_001903.5(CTNNA1):c.919G>A (p.Glu307Lys)	CTNNA1	Pathogenic	no assertion criteria provided
2673292	NM_001903.5(CTNNA1):c.1480C>T (p.Gln494Ter)	CTNNA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3236050	NM_001290310.3(CTNNA1):c.-5-62_-5-49del	CTNNA1	Pathogenic	criteria provided, single submitter
639104	NM_001903.5(CTNNA1):c.406dup (p.Thr136fs)	CTNNA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
659725	NM_001903.5(CTNNA1):c.2191C>T (p.Arg731Ter)	CTNNA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
659776	NM_001903.5(CTNNA1):c.1351C>T (p.Arg451Ter)	CTNNA1	Pathogenic	criteria provided, multiple submitters, no conflicts
2681004	NM_001903.5(CTNNA1):c.728_731dup (p.Tyr245fs)	CTNNA1	Likely pathogenic	criteria provided, single submitter
3241221	NM_001903.5(CTNNA1):c.733_736del (p.Tyr245fs)	CTNNA1	Likely pathogenic	criteria provided, single submitter
3241222	NM_001903.5(CTNNA1):c.930_949del (p.Glu310fs)	CTNNA1	Likely pathogenic	criteria provided, single submitter
1039044	NM_001903.5(CTNNA1):c.1401T>A (p.Ala467=)	CTNNA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
224567	NM_001903.5(CTNNA1):c.1185G>A (p.Leu395=)	CTNNA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
239066	NM_001903.5(CTNNA1):c.589-5T>C	CTNNA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
408999	NM_001903.5(CTNNA1):c.2558A>G (p.Asn853Ser)	CTNNA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
409008	NM_001903.5(CTNNA1):c.409C>T (p.Arg137Trp)	CTNNA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
415351	NM_001903.5(CTNNA1):c.2714G>A (p.Ser905Asn)	CTNNA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
437999	NM_001903.5(CTNNA1):c.965C>T (p.Ser322Leu)	CTNNA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
639160	NM_001903.5(CTNNA1):c.293G>A (p.Arg98Gln)	CTNNA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
640294	NM_001903.5(CTNNA1):c.370A>G (p.Met124Val)	CTNNA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
640852	NM_001903.5(CTNNA1):c.2023C>T (p.Gln675Ter)	CTNNA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
643191	NM_001903.5(CTNNA1):c.2493G>C (p.Gln831His)	CTNNA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
644044	NM_001903.5(CTNNA1):c.469-5TA[3]	CTNNA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
644657	NM_001903.5(CTNNA1):c.479G>A (p.Gly160Asp)	CTNNA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
645011	NM_001903.5(CTNNA1):c.339T>A (p.Asp113Glu)	CTNNA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
645100	NM_001903.5(CTNNA1):c.1663G>A (p.Val555Ile)	CTNNA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
646977	NM_001903.5(CTNNA1):c.1192A>G (p.Asn398Asp)	CTNNA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
647541	NM_001903.5(CTNNA1):c.1352G>A (p.Arg451Gln)	CTNNA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · 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

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

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
CTNNA1	HGNC:2509	ENSG00000044115	P35221	Catenin alpha-1	gencc,clinvar

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.

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)
CTNNA1	Other/Unknown	no		Vinculin_CS, Alpha_catenin, Vinculin/catenin

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
amniotic fluid	1
calcaneal tendon	1
colonic epithelium	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CTNNA1	3,128

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CTNNA1	P35221	10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. 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
CDH11 homotypic and heterotypic interactions	1	1631.4×	0.003	CTNNA1
Regulation of CDH19 Expression and Function	1	1427.5×	0.003	CTNNA1
Regulation of CDH11 function	1	1038.2×	0.003	CTNNA1
Regulation of CDH1 Function	1	951.7×	0.003	CTNNA1
SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)	1	496.5×	0.004	CTNNA1
VEGFR2 mediated vascular permeability	1	407.9×	0.004	CTNNA1
Myogenesis	1	380.7×	0.004	CTNNA1
RHO GTPases activate IQGAPs	1	346.1×	0.004	CTNNA1
Adherens junctions interactions	1	248.3×	0.005	CTNNA1
Degradation of CDH1	1	196.9×	0.006	CTNNA1
Activation of STAT3 by cadherin engagement	1	163.1×	0.006	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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of integrin-mediated signaling pathway	1	4213.0×	0.002	CTNNA1
cellular response to indole-3-methanol	1	3370.4×	0.002	CTNNA1
gap junction assembly	1	2106.5×	0.002	CTNNA1
apical junction assembly	1	2106.5×	0.002	CTNNA1
positive regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	1532.0×	0.002	CTNNA1
negative regulation of cell motility	1	1296.3×	0.002	CTNNA1
negative regulation of neuroblast proliferation	1	1203.7×	0.002	CTNNA1
epithelial cell-cell adhesion	1	1203.7×	0.002	CTNNA1
axon regeneration	1	1123.5×	0.002	CTNNA1
negative regulation of protein localization to nucleus	1	842.6×	0.003	CTNNA1
extrinsic apoptotic signaling pathway in absence of ligand	1	468.1×	0.004	CTNNA1
positive regulation of smoothened signaling pathway	1	421.3×	0.004	CTNNA1
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	411.0×	0.004	CTNNA1
establishment or maintenance of cell polarity	1	401.2×	0.004	CTNNA1
ovarian follicle development	1	391.9×	0.004	CTNNA1
neuroblast proliferation	1	366.4×	0.004	CTNNA1
response to estrogen	1	343.9×	0.004	CTNNA1
odontogenesis of dentin-containing tooth	1	300.9×	0.005	CTNNA1
smoothened signaling pathway	1	181.2×	0.007	CTNNA1
integrin-mediated signaling pathway	1	160.5×	0.008	CTNNA1
male gonad development	1	156.0×	0.008	CTNNA1
intracellular protein localization	1	104.7×	0.011	CTNNA1
cell-cell adhesion	1	101.5×	0.011	CTNNA1
cell migration	1	61.5×	0.017	CTNNA1
cell adhesion	1	37.5×	0.027	CTNNA1

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
CTNNA1	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: 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	CTNNA1

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)
CTNNA1	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.