dilated cardiomyopathy 1P

Summary

dilated cardiomyopathy 1P (MONDO:0012362) is a disease caused by PLN (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: PLN (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 116

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dilated cardiomyopathy 1P
Mondo ID	MONDO:0012362
MeSH	C563690
OMIM	609909
DOID	DOID:0110439
UMLS	C1835928
MedGen	322782
GARD	0015469
Is cancer (heuristic)	no

Also known as: cardiomyopathy, dilated, 1P · cardiomyopathy, dilated, type 1P · CMD1P · dilated cardiomyopathy type 1P · familial isolated dilated cardiomyopathy caused by mutation in PLN · PLN familial isolated dilated cardiomyopathy

Data availability: 116 ClinVar variants · 3 GenCC gene-disease records · 16 cell lines.

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 › familial isolated dilated cardiomyopathy › dilated cardiomyopathy 1P

Related subtypes (44): dilated cardiomyopathy 1A, dilated cardiomyopathy 3B, dilated cardiomyopathy 1B, dilated cardiomyopathy 1E, dilated cardiomyopathy 1C, dilated cardiomyopathy 1D, dilated cardiomyopathy 1G, dilated cardiomyopathy 1H, dilated cardiomyopathy 1I, dilated cardiomyopathy 1K, dilated cardiomyopathy 1L, dilated cardiomyopathy 1M, dilated cardiomyopathy 1O, dilated cardiomyopathy 1Q, dilated cardiomyopathy 1W, dilated cardiomyopathy 1X, dilated cardiomyopathy 1Y, dilated cardiomyopathy 1Z, dilated cardiomyopathy 2A, dilated cardiomyopathy 1AA, dilated cardiomyopathy 1BB, dilated cardiomyopathy 1CC, dilated cardiomyopathy 1DD, dilated cardiomyopathy 1EE, dilated cardiomyopathy 1FF, dilated cardiomyopathy 1R, dilated cardiomyopathy 1S, dilated cardiomyopathy 1GG, dilated cardiomyopathy 1U, dilated cardiomyopathy 1V, dilated cardiomyopathy 1HH, dilated cardiomyopathy 2B, dilated cardiomyopathy 1II, dilated cardiomyopathy 1JJ, dilated cardiomyopathy 1KK, left ventricular noncompaction 8, left ventricular noncompaction 10, dilated cardiomyopathy 1NN, cardiomyopathy, dilated, 2D, cardiomyopathy, dilated, 2E, cardiomyopathy, dilated, 2F, cardiomyopathy, dilated, 2G, cardiomyopathy, dilated, 2c, cardiomyopathy, dilated, 2H

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

116 retrieved; paginated sample, class counts are floors:

77 uncertain significance, 14 likely benign, 11 pathogenic, 9 conflicting classifications of pathogenicity, 2 benign, 1 pathogenic/likely pathogenic, 1 benign/likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1459545	NC_000006.11:g.(?118880085)(118880243_?)del	CEP85L	Pathogenic	criteria provided, single submitter
3655536	NM_002667.5(PLN):c.2T>G (p.Met1Arg)	CEP85L	Pathogenic	criteria provided, single submitter
1072579	NM_002667.5(PLN):c.9dup (p.Val4fs)	PLN	Pathogenic	criteria provided, single submitter
13636	NM_002667.5(PLN):c.25C>T (p.Arg9Cys)	PLN	Pathogenic	criteria provided, multiple submitters, no conflicts
13637	NM_002667.5(PLN):c.116T>G (p.Leu39Ter)	PLN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1453340	NM_002667.5(PLN):c.95_98del (p.Phe32fs)	PLN	Pathogenic	criteria provided, single submitter
1977709	NM_002667.5(PLN):c.105_106del (p.Phe35fs)	PLN	Pathogenic	criteria provided, single submitter
239214	NM_002667.4(PLN):c.-97-?_*1344+?del	PLN	Pathogenic	criteria provided, single submitter
3706363	NM_002667.5(PLN):c.4G>T (p.Glu2Ter)	PLN	Pathogenic	criteria provided, single submitter
44580	NM_002667.5(PLN):c.37AGA[1] (p.Arg14del)	PLN	Pathogenic	criteria provided, multiple submitters, no conflicts
657898	NC_000006.12:g.(?118548061)(118559090_?)del	PLN	Pathogenic	criteria provided, single submitter
940239	NM_002667.5(PLN):c.26_29dup (p.Ala11fs)	PLN	Pathogenic	criteria provided, single submitter
3720713	NM_002667.5(PLN):c.26G>T (p.Arg9Leu)	PLN	Likely pathogenic	criteria provided, single submitter
164971	NM_002667.5(PLN):c.2T>C (p.Met1Thr)	CEP85L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
202039	NM_002667.5(PLN):c.63_64dup (p.Gln22fs)	CEP85L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
202040	NM_002667.5(PLN):c.73C>T (p.Arg25Cys)	CEP85L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
44578	NM_002667.5(PLN):c.27C>T (p.Arg9=)	CEP85L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
44581	NM_002667.5(PLN):c.43G>A (p.Ala15Thr)	CEP85L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
906401	NM_002667.5(PLN):c.-56C>T	CEP85L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
906402	NM_002667.5(PLN):c.90T>C (p.Asn30=)	CEP85L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
202037	NM_002667.5(PLN):c.26G>A (p.Arg9His)	PLN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
949832	NM_002667.5(PLN):c.85C>T (p.Gln29Ter)	PLN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1017276	NM_002667.5(PLN):c.149T>C (p.Met50Thr)	CEP85L	Uncertain significance	criteria provided, multiple submitters, no conflicts
1046834	NC_000006.11:g.(?118879986)(118880253_?)dup	CEP85L	Uncertain significance	criteria provided, single submitter
1059005	NM_002667.5(PLN):c.154C>A (p.Leu52Ile)	CEP85L	Uncertain significance	criteria provided, multiple submitters, no conflicts
1315107	NM_002667.5(PLN):c.151C>T (p.Leu51Phe)	CEP85L	Uncertain significance	criteria provided, multiple submitters, no conflicts
1346972	NM_002667.5(PLN):c.79A>G (p.Lys27Glu)	CEP85L	Uncertain significance	criteria provided, single submitter
1385567	NM_002667.5(PLN):c.31G>A (p.Ala11Thr)	CEP85L	Uncertain significance	criteria provided, single submitter
1399599	NM_002667.5(PLN):c.141C>G (p.Ile47Met)	CEP85L	Uncertain significance	criteria provided, single submitter
1415631	NM_002667.5(PLN):c.56A>G (p.Glu19Gly)	CEP85L	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 3 · 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
PLN	Definitive	Autosomal dominant	dilated cardiomyopathy 1P	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PLN	Orphanet:154	Familial isolated dilated cardiomyopathy
PLN	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
CEP85L	Orphanet:572013	Posterior-predominant lissencephaly-broad flat pons and medulla-midline crossing defects 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
PLN	HGNC:9080	ENSG00000198523	P26678	Phospholamban	gencc,clinvar
CEP85L	HGNC:21638	ENSG00000111860	Q5SZL2	Centrosomal protein of 85 kDa-like	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PLN	Phospholamban	Reversibly inhibits the activity of ATP2A2/SERCA2 in cardiac sarcoplasmic reticulum by decreasing the apparent affinity of the ATPase for Ca(2+).
CEP85L	Centrosomal protein of 85 kDa-like	Plays an essential role in neuronal cell migration.

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)
PLN	Other/Unknown	no		PLB
CEP85L	Other/Unknown	no		Cep85/Cep85L, CC4_CEP85

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
heart right ventricle	1
left ventricle myocardium	1
myocardium	1
pylorus	1
thymus	1
tibialis anterior	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PLN	243	broad	marker	heart right ventricle, myocardium, left ventricle myocardium
CEP85L	248	ubiquitous	marker	thymus, tibialis anterior, pylorus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PLN	1,080
CEP85L	581

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PLN	P26678	7

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CEP85L	Q5SZL2	64.98

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 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
Ion transport by P-type ATPases	1	207.6×	0.005	PLN
Ion homeostasis	1	203.9×	0.005	PLN

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
circadian sleep/wake cycle, sleep	1	8426.0×	0.002	PLN
adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process	1	8426.0×	0.002	PLN
regulation of the force of heart contraction by cardiac conduction	1	4213.0×	0.002	PLN
regulation of relaxation of cardiac muscle	1	4213.0×	0.002	PLN
regulation of ATPase-coupled calcium transmembrane transporter activity	1	2808.7×	0.002	PLN
negative regulation of ATPase-coupled calcium transmembrane transporter activity	1	2808.7×	0.002	PLN
negative regulation of calcium ion import into sarcoplasmic reticulum	1	2106.5×	0.002	PLN
regulation of cardiac muscle cell membrane potential	1	1203.7×	0.003	PLN
negative regulation of calcium ion import	1	1203.7×	0.003	PLN
negative regulation of calcium ion transport	1	842.6×	0.004	PLN
negative regulation of heart rate	1	648.1×	0.004	PLN
relaxation of cardiac muscle	1	648.1×	0.004	PLN
regulation of cardiac muscle cell contraction	1	561.7×	0.004	PLN
locomotor rhythm	1	526.6×	0.004	PLN
regulation of the force of heart contraction	1	495.6×	0.004	PLN
cardiac muscle tissue development	1	443.5×	0.004	PLN
regulation of calcium ion transport	1	401.2×	0.005	PLN
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	1	337.0×	0.005	PLN
muscle cell cellular homeostasis	1	324.1×	0.005	PLN
response to zinc ion	1	312.1×	0.005	PLN
blood circulation	1	255.3×	0.006	PLN
regulation of heart contraction	1	247.8×	0.006	PLN
response to testosterone	1	234.1×	0.006	PLN
acrosome assembly	1	227.7×	0.006	PLN
regulation of cytosolic calcium ion concentration	1	191.5×	0.006	PLN
visual learning	1	153.2×	0.008	PLN
response to insulin	1	115.4×	0.010	PLN
calcium ion transport	1	90.6×	0.012	PLN
intracellular calcium ion homeostasis	1	72.6×	0.015	PLN
Notch signaling pathway	1	70.8×	0.015	PLN

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
PLN	0	0
CEP85L	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	PLN, CEP85L

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)
PLN	0	—
CEP85L	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.