dilated cardiomyopathy 1J

Summary

dilated cardiomyopathy 1J (MONDO:0011541) is a disease with 3 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 3
• ClinVar variants: 911
• Phenotypes (HPO): 5

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		2	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

5 HPO clinical features (Orphanet curated; top 5 by frequency):

HPO ID	Term	Frequency
HP:0000365	Hearing impairment	Very frequent (80-99%)
HP:0000403	Recurrent otitis media	Very frequent (80-99%)
HP:0001635	Congestive heart failure	Very frequent (80-99%)
HP:0001644	Dilated cardiomyopathy	Very frequent (80-99%)
HP:0030872	Abnormal cardiac ventricular function	Very frequent (80-99%)

Identifiers

Disease identifiers

Field	Value
Canonical name	dilated cardiomyopathy 1J
Mondo ID	MONDO:0011541
MeSH	C565337
OMIM	605362
Orphanet	217622
DOID	DOID:0110440
UMLS	C1854368
MedGen	343105
GARD	0017128
Is cancer (heuristic)	no

Also known as: cardiomyopathy, dilated, 1J · cardiomyopathy, dilated, type 1J · CMD1J · dilated cardiomyopathy 1J · dilated cardiomyopathy type 1J · EYA4 familial dilated cardiomyopathy · familial dilated cardiomyopathy caused by mutation in EYA4 · neurosensory deafness with dilated cardiomyopathy · neurosensory hearing loss with dilated cardiomyopathy · sensorineural deafness with dilated cardiomyopathy · sensorineural hearing loss with dilated cardiomyopathy

Data availability: 911 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › cardiomyopathy › intrinsic cardiomyopathy › dilated cardiomyopathy › familial dilated cardiomyopathy › dilated cardiomyopathy 1J

Related subtypes (28): autosomal recessive limb-girdle muscular dystrophy type 2C, Barth syndrome, histiocytoid cardiomyopathy, Kearns-Sayre syndrome, Leber hereditary optic neuropathy, autosomal recessive limb-girdle muscular dystrophy type 2F, myofibrillar myopathy 1, autosomal recessive limb-girdle muscular dystrophy type 2E, hypertrophic cardiomyopathy 25, autosomal recessive limb-girdle muscular dystrophy type 2D, DK1-congenital disorder of glycosylation, autosomal recessive limb-girdle muscular dystrophy type 2M, early-onset myopathy with fatal cardiomyopathy, PGM1-congenital disorder of glycosylation, autosomal recessive limb-girdle muscular dystrophy type 2W, symptomatic form of muscular dystrophy of Duchenne and Becker in female carriers, Emery-Dreifuss muscular dystrophy, familial isolated dilated cardiomyopathy, cardiomyopathy, dilated, 1LL, cardiomyopathy, dilated, 1MM, cardiomyopathy, dilated, 100, cardiomyopathy, dilated, 2I, cardiomyopathy, dilated, 2j, cardiomyopathy, dilated, 2K, cardiomyopathy, dilated, 2l, cardiomyopathy, dilated, 1QQ, cardiomyopathy, dilated, 2M, cardiomyopathy, dilated, 3C

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:

311 uncertain significance, 206 likely benign, 30 conflicting classifications of pathogenicity, 15 pathogenic, 14 benign, 11 benign/likely benign, 10 likely pathogenic, 3 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1317222	NM_004100.5(EYA4):c.580G>A (p.Asp194Asn)	EYA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1380128	NM_004100.5(EYA4):c.832C>T (p.Gln278Ter)	EYA4	Pathogenic	criteria provided, single submitter
1419206	NM_004100.5(EYA4):c.67C>T (p.Gln23Ter)	EYA4	Pathogenic	criteria provided, single submitter
1896684	NM_004100.5(EYA4):c.61del (p.Val21fs)	EYA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1916328	NM_004100.5(EYA4):c.223_224del (p.Val75fs)	EYA4	Pathogenic	criteria provided, single submitter
1965243	NM_004100.5(EYA4):c.242G>A (p.Trp81Ter)	EYA4	Pathogenic	criteria provided, single submitter
2112319	NM_004100.5(EYA4):c.1574G>A (p.Trp525Ter)	EYA4	Pathogenic	criteria provided, single submitter
2126137	NM_004100.5(EYA4):c.1472del (p.Leu491fs)	EYA4	Pathogenic	criteria provided, single submitter
2425022	NC_000006.11:g.(?133782232)(133783922_?)del	EYA4	Pathogenic	criteria provided, single submitter
2743050	NM_004100.5(EYA4):c.211G>T (p.Glu71Ter)	EYA4	Pathogenic	criteria provided, single submitter
2783559	NM_004100.5(EYA4):c.579C>G (p.Tyr193Ter)	EYA4	Pathogenic	criteria provided, single submitter
2833829	NM_004100.5(EYA4):c.1776dup (p.Gly593fs)	EYA4	Pathogenic	criteria provided, single submitter
3246004	NC_000006.11:g.(?133595919)(133595971_?)del	EYA4	Pathogenic	criteria provided, single submitter
3630137	NM_004100.5(EYA4):c.222del (p.Val75fs)	EYA4	Pathogenic	criteria provided, single submitter
3632752	NM_004100.5(EYA4):c.243del (p.Trp81fs)	EYA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2630897	NM_004100.5(EYA4):c.1241_1248del (p.Phe414fs)	LOC126859796	Pathogenic	criteria provided, multiple submitters, no conflicts
2102688	NM_004100.5(EYA4):c.1291C>T (p.Gln431Ter)	TARID	Pathogenic	criteria provided, single submitter
2825147	NM_004100.5(EYA4):c.1416_1417del (p.Gly473fs)	TARID	Pathogenic	criteria provided, single submitter
1065975	NM_004100.5(EYA4):c.970+1G>T	EYA4	Likely pathogenic	criteria provided, single submitter
1066352	NM_004100.5(EYA4):c.33+2T>G	EYA4	Likely pathogenic	criteria provided, single submitter
1066753	NM_004100.5(EYA4):c.209-1G>A	EYA4	Likely pathogenic	criteria provided, single submitter
1465552	NM_004100.5(EYA4):c.971-2A>G	EYA4	Likely pathogenic	criteria provided, single submitter
1510215	NM_004100.5(EYA4):c.970+1G>A	EYA4	Likely pathogenic	criteria provided, single submitter
2014972	NM_004100.5(EYA4):c.370+1G>T	EYA4	Likely pathogenic	criteria provided, single submitter
2101519	NM_004100.5(EYA4):c.371-2A>G	EYA4	Likely pathogenic	criteria provided, single submitter
2876182	NM_004100.5(EYA4):c.277+1G>A	EYA4	Likely pathogenic	criteria provided, single submitter
3246005	NC_000006.11:g.(?133783902)(133788747_?)del	EYA4	Likely pathogenic	criteria provided, single submitter
208577	NM_004100.5(EYA4):c.1739-1G>A	TARID	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1372072	NM_004100.5(EYA4):c.213A>C (p.Glu71Asp)	EYA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1502779	NM_004100.5(EYA4):c.949C>T (p.Pro317Ser)	EYA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
EYA4	Moderate	Autosomal dominant	dilated cardiomyopathy 1J	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EYA4	Orphanet:217622	Sensorineural deafness with dilated cardiomyopathy
EYA4	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA

Cohort genes → proteins

3 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EYA4	HGNC:3522	ENSG00000112319	O95677	Protein phosphatase EYA4	gencc,clinvar
TARID	HGNC:50506	ENSG00000227954		TCF21 antisense RNA inducing promoter demethylation	clinvar
EYA4-AS2	HGNC:58230	ENSG00000234567		EYA4 antisense RNA 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EYA4	Protein phosphatase EYA4	Tyrosine phosphatase that specifically dephosphorylates ‘Tyr-142’ of histone H2AX (H2AXY142ph). ‘Tyr-142’ phosphorylation of histone H2AX plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair…

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · 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	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EYA4	Other/Unknown	no		EYA_dom, EYA, EYA_dom_sf
TARID	Other/Unknown	no
EYA4-AS2	Other/Unknown	no

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
biceps brachii	1
seminal vesicle	1
skeletal muscle tissue of biceps brachii	1
left ovary	1
ovary	1
sural nerve	1
calcaneal tendon	1
corpus callosum	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EYA4	208	broad	marker	biceps brachii, skeletal muscle tissue of biceps brachii, seminal vesicle
TARID	123	tissue_specific	marker	sural nerve, left ovary, ovary
EYA4-AS2	108		yes	calcaneal tendon, primordial germ cell in gonad, corpus callosum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EYA4	1,679
TARID	0
EYA4-AS2	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
EYA4	O95677	63.79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 3 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
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	1	146.4×	0.007	EYA4

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 extrinsic apoptotic signaling pathway in absence of ligand	1	411.0×	0.007	EYA4
inner ear development	1	374.5×	0.007	EYA4
positive regulation of DNA repair	1	358.6×	0.007	EYA4
anatomical structure morphogenesis	1	139.3×	0.014	EYA4
chromatin organization	1	99.1×	0.016	EYA4
visual perception	1	79.5×	0.017	EYA4
DNA repair	1	63.8×	0.018	EYA4
cell differentiation	1	29.1×	0.034	EYA4

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
EYA4	0	0
TARID	0	0
EYA4-AS2	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	3	EYA4, TARID, EYA4-AS2

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)
EYA4	0	—
TARID	0	—
EYA4-AS2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.