cardiomyopathy, dilated, 2K

Summary

cardiomyopathy, dilated, 2K (MONDO:0971175) is a disease caused by MYZAP (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: MYZAP (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cardiomyopathy, dilated, 2K
Mondo ID	MONDO:0971175
OMIM	620894
UMLS	C5935636
MedGen	1861075
GARD	0027209
Is cancer (heuristic)	no

Data availability: 8 ClinVar variants · 1 GenCC gene-disease record.

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 › cardiomyopathy, dilated, 2K

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, dilated cardiomyopathy 1J, 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, 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

8 retrieved; paginated sample, class counts are floors:

4 pathogenic, 4 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3252113	NM_001018100.5(MYZAP):c.388C>T (p.Arg130Ter)	GCOM1	Pathogenic	no assertion criteria provided
3252114	NM_001018100.5(MYZAP):c.933+1G>A	GCOM1	Pathogenic	no assertion criteria provided
3252115	NM_001018100.5(MYZAP):c.1150A>T (p.Lys384Ter)	GCOM1	Pathogenic	no assertion criteria provided
3252117	NM_001018100.5(MYZAP):c.349C>T (p.Arg117Ter)	GCOM1	Pathogenic	no assertion criteria provided
4687890	NM_001018100.5(MYZAP):c.779del (p.His260fs)	GCOM1	Likely pathogenic	criteria provided, single submitter
4687891	NM_001018100.5(MYZAP):c.1128dup (p.Leu377fs)	GCOM1	Likely pathogenic	criteria provided, single submitter
4849368	NM_001018100.5(MYZAP):c.1258G>T (p.Glu420Ter)	GCOM1	Likely pathogenic	criteria provided, single submitter
523392	NM_001018100.5(MYZAP):c.236C>A (p.Ser79Ter)	GCOM1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · 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
MYZAP	Strong	Autosomal recessive	cardiomyopathy, dilated, 2K	2

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MYZAP	HGNC:43444	ENSG00000263155	P0CAP1	Myocardial zonula adherens protein	gencc,clinvar
GCOM1	HGNC:26424	ENSG00000137878		GCOM1, MYZAP-POLR2M combined locus	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYZAP	Myocardial zonula adherens protein	Plays a role in cellular signaling via Rho-related GTP-binding proteins and subsequent activation of transcription factor SRF.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MYZAP	Other/Unknown	no		Tuftelin_GRINL1A/MYZAP/CCD68
GCOM1	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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cardiac muscle of right atrium	1
left ventricle myocardium	1
myocardium	1
cerebellar vermis	1
heart left ventricle	1
lower esophagus mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYZAP	227	broad	marker	left ventricle myocardium, cardiac muscle of right atrium, myocardium
GCOM1	136	broad	marker	cerebellar vermis, heart left ventricle, lower esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYZAP	698
GCOM1	0

Intra-cohort edges

A	B	Sources
GCOM1	MYZAP	biogrid_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MYZAP	P0CAP1	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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
intracellular signal transduction	1	38.1×	0.026	MYZAP

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
MYZAP	0	0
GCOM1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	MYZAP, GCOM1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MYZAP	0	—
GCOM1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.