dilated cardiomyopathy 1KK

Summary

dilated cardiomyopathy 1KK (MONDO:0014100) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 1,228

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dilated cardiomyopathy 1KK
Mondo ID	MONDO:0014100
OMIM	615248
DOID	DOID:0110445
UMLS	C3714995
MedGen	811544
GARD	0015926
Is cancer (heuristic)	no

Also known as: cardiomyopathy, dilated, 1KK · cardiomyopathy, dilated, type 1Kk · cardiomyopathy, hypertrophic, 22 · CMD1KK · dilated cardiomyopathy caused by mutation in MYPN · dilated cardiomyopathy type 1KK · MYPN dilated cardiomyopathy

Data availability: 1,228 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 › restrictive cardiomyopathy › familial restrictive cardiomyopathy › dilated cardiomyopathy 1KK

Related subtypes (9): cardiomyopathy, familial restrictive, 1, Gaucher disease type I, glycogen storage disease II, idiopathic hypereosinophilic syndrome, cardiomyopathy, familial restrictive, 2, cardiomyopathy, familial restrictive, 3, atrial standstill, ATTRV122I amyloidosis, cardiomyopathy, familial restrictive, 6

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:

305 uncertain significance, 204 likely benign, 41 conflicting classifications of pathogenicity, 16 benign/likely benign, 13 benign, 12 pathogenic, 8 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1437195	NM_032578.4(MYPN):c.3057del (p.Met1020fs)	LOC132089829	Pathogenic	criteria provided, single submitter
1070620	NC_000010.10:g.(?69918233)(69926433_?)del	MYPN	Pathogenic	criteria provided, single submitter
1354074	NM_032578.4(MYPN):c.1722del (p.Lys575fs)	MYPN	Pathogenic	criteria provided, single submitter
1362406	NM_032578.4(MYPN):c.3403_3404del (p.Pro1135fs)	MYPN	Pathogenic	criteria provided, single submitter
1374949	NM_032578.4(MYPN):c.1910dup (p.Thr639fs)	MYPN	Pathogenic	criteria provided, single submitter
1448371	NM_032578.4(MYPN):c.1990C>T (p.Gln664Ter)	MYPN	Pathogenic	criteria provided, single submitter
1455552	NM_032578.4(MYPN):c.2689A>T (p.Arg897Ter)	MYPN	Pathogenic	criteria provided, single submitter
1526172	NM_032578.4(MYPN):c.608C>A (p.Ser203Ter)	MYPN	Pathogenic	criteria provided, single submitter
1798443	NM_032578.4(MYPN):c.2986C>T (p.Arg996Ter)	MYPN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1941324	NM_032578.4(MYPN):c.211G>T (p.Glu71Ter)	MYPN	Pathogenic	criteria provided, single submitter
2025137	NM_032578.4(MYPN):c.781_784del (p.Tyr261fs)	MYPN	Pathogenic	criteria provided, single submitter
2112550	NM_032578.4(MYPN):c.3409dup (p.Thr1137fs)	MYPN	Pathogenic	criteria provided, single submitter
2177807	NM_032578.4(MYPN):c.1465C>T (p.Arg489Ter)	MYPN	Pathogenic	criteria provided, multiple submitters, no conflicts
1515967	NM_032578.4(MYPN):c.1317+1G>A	MYPN	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1525540	NM_032578.4(MYPN):c.2565-2A>G	MYPN	Likely pathogenic	criteria provided, single submitter
1709003	NM_032578.4(MYPN):c.688C>T (p.Gln230Ter)	MYPN	Likely pathogenic	criteria provided, single submitter
2024191	NM_032578.4(MYPN):c.2598_2703+9delinsCAACAATC	MYPN	Likely pathogenic	criteria provided, single submitter
2028672	NM_032578.4(MYPN):c.1974-1G>A	MYPN	Likely pathogenic	criteria provided, single submitter
2035275	NM_032578.4(MYPN):c.1079-2A>G	MYPN	Likely pathogenic	criteria provided, single submitter
2108623	NM_032578.4(MYPN):c.3660-2A>C	MYPN	Likely pathogenic	criteria provided, single submitter
2122465	NM_032578.4(MYPN):c.1973+1G>A	MYPN	Likely pathogenic	criteria provided, single submitter
1005533	NM_032578.4(MYPN):c.207A>G (p.Gln69=)	MYPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1010575	NM_032578.4(MYPN):c.3306G>A (p.Pro1102=)	MYPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1026611	NM_032578.4(MYPN):c.2384C>G (p.Pro795Arg)	MYPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1041935	NM_032578.4(MYPN):c.404C>G (p.Ala135Gly)	MYPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1057240	NM_032578.4(MYPN):c.2246G>A (p.Ser749Asn)	MYPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1057875	NM_032578.4(MYPN):c.2389T>C (p.Phe797Leu)	MYPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1060811	NM_032578.4(MYPN):c.987G>A (p.Ala329=)	MYPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1063051	NM_032578.4(MYPN):c.650C>T (p.Ala217Val)	MYPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1085072	NM_032578.4(MYPN):c.1152G>T (p.Val384=)	MYPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 4 · 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
MYPN	Strong	Autosomal dominant	dilated cardiomyopathy	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYPN	Orphanet:154	Familial isolated dilated cardiomyopathy
MYPN	Orphanet:171439	Childhood-onset nemaline myopathy
MYPN	Orphanet:171881	Cap myopathy
MYPN	Orphanet:75249	Familial isolated restrictive cardiomyopathy

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
MYPN	HGNC:23246	ENSG00000138347	Q86TC9	Myopalladin	gencc,clinvar
MYLK2	HGNC:16243	ENSG00000101306	Q9H1R3	Myosin light chain kinase 2, skeletal/cardiac muscle	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYPN	Myopalladin	Component of the sarcomere that tethers together nebulin (skeletal muscle) and nebulette (cardiac muscle) to alpha-actinin, at the Z lines.
MYLK2	Myosin light chain kinase 2, skeletal/cardiac muscle	Implicated in the level of global muscle contraction and cardiac function.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Antibody/Immunoglobulin	1	14.6×	0.071
Kinase	1	13.9×	0.071

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MYPN	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
MYLK2	Kinase	yes	2.7.11.18	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gastrocnemius	2
hindlimb stylopod muscle	2
vastus lateralis	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYPN	116	broad	marker	hindlimb stylopod muscle, gastrocnemius, vastus lateralis
MYLK2	148	tissue_specific	yes	hindlimb stylopod muscle, skeletal muscle tissue of rectus abdominis, gastrocnemius

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYLK2	2,040
MYPN	1,764

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MYLK2	Q9H1R3	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MYPN	Q86TC9	52.71

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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of muscle filament sliding	1	4213.0×	0.004	MYLK2
skeletal muscle satellite cell differentiation	1	1053.2×	0.006	MYLK2
cardiac muscle tissue morphogenesis	1	702.2×	0.006	MYLK2
dendrite self-avoidance	1	526.6×	0.006	MYPN
peptidyl-threonine phosphorylation	1	443.5×	0.006	MYLK2
striated muscle contraction	1	421.3×	0.006	MYLK2
neuromuscular synaptic transmission	1	300.9×	0.007	MYLK2
cardiac muscle contraction	1	200.6×	0.009	MYLK2
sarcomere organization	1	191.5×	0.009	MYPN
skeletal muscle cell differentiation	1	172.0×	0.009	MYLK2
protein autophosphorylation	1	72.6×	0.018	MYLK2
homophilic cell-cell adhesion	1	70.2×	0.018	MYPN
axon guidance	1	45.3×	0.025	MYPN
positive regulation of gene expression	1	19.4×	0.055	MYLK2
signal transduction	1	8.0×	0.121	MYLK2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
MYLK2	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MYLK2	19	4
MYPN	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	MYLK2
AXITINIB	4	MYLK2
SORAFENIB	4	MYLK2
PAZOPANIB	4	MYLK2
NINTEDANIB	4	MYLK2
SUNITINIB	4	MYLK2
DASATINIB	4	MYLK2
ERLOTINIB	4	MYLK2
GEFITINIB	4	MYLK2
LINIFANIB	3	MYLK2
DOVITINIB	3	MYLK2
LESTAURTINIB	3	MYLK2
FORETINIB	2	MYLK2
SU-014813	2	MYLK2
TOZASERTIB	2	MYLK2
PELITINIB	2	MYLK2
KW-2449	1	MYLK2
BMS-387032	1	MYLK2
AST-487	1	MYLK2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
MYLK2	196	Binding:196

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MYLK2	2.7.11.18	myosin-light-chain kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
MYLK2	196

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

19 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.

Compound	Max phase	Cohort target (bioactivity)
FEDRATINIB	4	MYLK2
AXITINIB	4	MYLK2
SORAFENIB	4	MYLK2
PAZOPANIB	4	MYLK2
NINTEDANIB	4	MYLK2
SUNITINIB	4	MYLK2
DASATINIB	4	MYLK2
ERLOTINIB	4	MYLK2
GEFITINIB	4	MYLK2
LINIFANIB	3	MYLK2
DOVITINIB	3	MYLK2
LESTAURTINIB	3	MYLK2
FORETINIB	2	MYLK2
SU-014813	2	MYLK2
TOZASERTIB	2	MYLK2
PELITINIB	2	MYLK2
KW-2449	1	MYLK2
BMS-387032	1	MYLK2
AST-487	1	MYLK2

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	MYLK2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	MYPN
E	Difficult family or no structure, no drug	0

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)
MYPN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.