Non-compaction cardiomyopathy

Summary

Non-compaction cardiomyopathy (MONDO:0005418) is a disease with 2 cohort genes and 2 clinical trials.

At a glance

• Cohort genes: 2
• ClinVar variants: 2
• Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	non-compaction cardiomyopathy
Mondo ID	MONDO:0005418
EFO	EFO:0004686
UMLS	C4324548
MedGen	1843481
GARD	0024182
Is cancer (heuristic)	no

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › cardiomyopathy › non-compaction cardiomyopathy

Related subtypes (11): Keshan disease, intrinsic cardiomyopathy, extrinsic cardiomyopathy, idiopathic cardiomyopathy, familial cardiomyopathy, Chagas cardiomyopathy, Uhl anomaly, Tako-tsubo cardiomyopathy, cardiomyopathy due to anthracyclines, doxorubicin induced cardiomyopathy, autoimmune cardiomyopathy

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

2 retrieved; paginated sample, class counts are floors:

2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4077156	NM_004415.4(DSP):c.3954del (p.Thr1319fs)	DSP	Likely pathogenic	criteria provided, single submitter
3223215	NM_001267550.2(TTN):c.47486_47498del (p.Glu15828_Tyr15829insTer)	TTN	Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 24 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TTN	Orphanet:140922	Titin-related limb-girdle muscular dystrophy R10
TTN	Orphanet:154	Familial isolated dilated cardiomyopathy
TTN	Orphanet:169186	Autosomal recessive centronuclear myopathy
TTN	Orphanet:178464	Hereditary myopathy with early respiratory failure
TTN	Orphanet:289377	Early-onset myopathy with fatal cardiomyopathy
TTN	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
TTN	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
TTN	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
TTN	Orphanet:324604	Classic multiminicore myopathy
TTN	Orphanet:334	Hereditary atrial fibrillation
TTN	Orphanet:466921	Childhood-onset progressive contractures-limb-girdle weakness-muscle dystrophy syndrome
TTN	Orphanet:609	Tibial muscular dystrophy
TTN	Orphanet:707983	Early-onset autosomal recessive TTN-related distal myopathy
DSP	Orphanet:154	Familial isolated dilated cardiomyopathy
DSP	Orphanet:158687	Lethal acantholytic erosive disorder
DSP	Orphanet:2032	Idiopathic pulmonary fibrosis
DSP	Orphanet:293165	Skin fragility-woolly hair-palmoplantar keratoderma syndrome
DSP	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
DSP	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
DSP	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
DSP	Orphanet:369992	Severe dermatitis-multiple allergies-metabolic wasting syndrome
DSP	Orphanet:476096	Erythrokeratodermia-cardiomyopathy syndrome
DSP	Orphanet:50942	Striate palmoplantar keratoderma
DSP	Orphanet:65282	Carvajal syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TTN	HGNC:12403	ENSG00000155657	Q8WZ42	Titin	clinvar
DSP	HGNC:3052	ENSG00000096696	P15924	Desmoplakin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TTN	Titin	Key component in the assembly and functioning of vertebrate striated muscles.
DSP	Desmoplakin	A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.5

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
Kinase	1	13.9×	0.112
Scaffold/PPI	1	8.6×	0.112

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TTN	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ig_sub2, Ig_sub
DSP	Scaffold/PPI	no		Plectin_repeat, SH3_domain, Spectrin/alpha-actinin

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
biceps brachii	1
gluteal muscle	1
skeletal muscle tissue of biceps brachii	1
hair follicle	1
skin of hip	1
upper leg skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TTN	223	broad	marker	biceps brachii, gluteal muscle, skeletal muscle tissue of biceps brachii
DSP	253	ubiquitous	marker	skin of hip, upper leg skin, hair follicle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TTN	4,237
DSP	2,897

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TTN	Q8WZ42	64
DSP	P15924	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 2 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
Apoptotic cleavage of cell adhesion proteins	1	519.1×	0.015	DSP
Striated Muscle Contraction	1	154.3×	0.015	TTN
RND1 GTPase cycle	1	132.8×	0.015	DSP
RND3 GTPase cycle	1	129.8×	0.015	DSP
Platelet degranulation	1	43.9×	0.030	TTN
Formation of the cornified envelope	1	43.9×	0.030	DSP
Keratinization	1	27.9×	0.041	DSP
Neutrophil degranulation	1	11.5×	0.085	DSP

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
skeletal muscle myosin thick filament assembly	1	2808.7×	0.004	TTN
sarcomerogenesis	1	2808.7×	0.004	TTN
skeletal muscle thin filament assembly	1	1404.3×	0.004	TTN
ventricular compact myocardium morphogenesis	1	1203.7×	0.004	DSP
detection of muscle stretch	1	1203.7×	0.004	TTN
bundle of His cell-Purkinje myocyte adhesion involved in cell communication	1	1203.7×	0.004	DSP
desmosome organization	1	1053.2×	0.004	DSP
protein localization to cell-cell junction	1	936.2×	0.004	DSP
cardiac muscle hypertrophy	1	842.6×	0.004	TTN
obsolete protein kinase A signaling	1	702.2×	0.004	TTN
peptide cross-linking	1	702.2×	0.004	DSP
cardiac muscle tissue morphogenesis	1	702.2×	0.004	TTN
regulation of ventricular cardiac muscle cell action potential	1	702.2×	0.004	DSP
cardiac myofibril assembly	1	648.1×	0.004	TTN
epithelial cell-cell adhesion	1	601.9×	0.004	DSP
muscle filament sliding	1	526.6×	0.004	TTN
mitotic chromosome condensation	1	495.6×	0.004	TTN
intermediate filament cytoskeleton organization	1	468.1×	0.004	DSP
striated muscle contraction	1	421.3×	0.004	TTN
cardiac muscle cell development	1	312.1×	0.006	TTN
skeletal muscle contraction	1	255.3×	0.006	TTN
adherens junction organization	1	255.3×	0.006	DSP
skin development	1	221.7×	0.007	DSP
cardiac muscle contraction	1	200.6×	0.007	TTN
sarcomere organization	1	191.5×	0.007	TTN
regulation of heart rate by cardiac conduction	1	187.2×	0.007	DSP
positive regulation of protein secretion	1	172.0×	0.008	TTN
response to calcium ion	1	159.0×	0.008	TTN
keratinocyte differentiation	1	123.9×	0.010	DSP
intermediate filament organization	1	120.4×	0.010	DSP

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 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
TTN	0	0
DSP	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
DSP	2	Binding:2
TTN	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TTN	2.7.11.1	non-specific serine/threonine protein kinase

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

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)
TTN	1	—
DSP	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04424030	Not specified	ACTIVE_NOT_RECRUITING	International Consortium for Multimodality Phenotyping in Adults With Non-compaction
NCT06546137	Not specified	RECRUITING	National Network for Cardiovascular Genomics: Advancing Cardiovascular Healthcare for Hereditary Diseases in Brazil’s Unified Health System Through a Multicenter Registry