Hypertrophic cardiomyopathy 18

Summary

Hypertrophic cardiomyopathy 18 (MONDO:0013475) is a disease caused by PLN (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: PLN (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 22

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypertrophic cardiomyopathy 18
Mondo ID	MONDO:0013475
OMIM	613874
DOID	DOID:0110324
UMLS	C3151265
MedGen	462615
GARD	0024930
Is cancer (heuristic)	no

Also known as: cardiomyopathy, familial hypertrophic, 18 · cardiomyopathy, familial hypertrophic, type 18 · cardiomyopathy, hypertrophic, 18 · CMH18 · hypertrophic cardiomyopathy caused by mutation in PLN · hypertrophic cardiomyopathy type 18 · PLN hypertrophic cardiomyopathy

Data availability: 22 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 › hypertrophic cardiomyopathy › familial hypertrophic cardiomyopathy › hypertrophic cardiomyopathy 18

Related subtypes (39): hypertrophic cardiomyopathy 2, hypertrophic cardiomyopathy 3, hypertrophic cardiomyopathy 4, Beckwith-Wiedemann syndrome, myotonic dystrophy type 1, hypertrophic cardiomyopathy 1, very long chain acyl-CoA dehydrogenase deficiency, multiple acyl-CoA dehydrogenase deficiency, 46,XY complete gonadal dysgenesis, hypertrophic cardiomyopathy 6, dilated cardiomyopathy 1C, hypertrophic cardiomyopathy 25, hypertrophic cardiomyopathy 8, hypertrophic cardiomyopathy 10, long chain 3-hydroxyacyl-CoA dehydrogenase deficiency, cardiomyopathy-hypotonia-lactic acidosis syndrome, hypertrophic cardiomyopathy 11, hypertrophic cardiomyopathy 12, hypertrophic cardiomyopathy 13, hypertrophic cardiomyopathy 14, hypertrophic cardiomyopathy 15, hypertrophic cardiomyopathy 7, hypertrophic cardiomyopathy 9, hypertrophic cardiomyopathy 16, hypertrophic cardiomyopathy 17, hypertrophic cardiomyopathy 19, hypertrophic cardiomyopathy 20, hypertrophic cardiomyopathy 21, dilated cardiomyopathy 1KK, hypertrophic cardiomyopathy 26, Noonan syndrome and Noonan-related syndrome, long chain acyl-CoA dehydrogenase deficiency, cardiomyopathy, familial hypertrophic, 28, cardiomyopathy, familial hypertrophic 27, cardiomyopathy, familial hypertrophic, 23, with or without ventricular noncompaction, cardiomyopathy, familial restrictive, 5, cardiomyopathy, familial hypertrophic, 29, with polyglucosan bodies, cardiomyopathy, familial hypertrophic, 30, atrial, cardiomyopathy, familial hypertrophic, 31

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

22 retrieved; paginated sample, class counts are floors:

18 uncertain significance, 1 pathogenic/likely pathogenic, 1 likely pathogenic, 1 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
13637	NM_002667.5(PLN):c.116T>G (p.Leu39Ter)	PLN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
44580	NM_002667.5(PLN):c.37AGA[1] (p.Arg14del)	PLN	Pathogenic	criteria provided, multiple submitters, no conflicts
1709041	NM_002667.5(PLN):c.63_64del (p.Gln22fs)	CEP85L	Likely pathogenic	criteria provided, single submitter
202040	NM_002667.5(PLN):c.73C>T (p.Arg25Cys)	CEP85L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1504806	NC_000006.12:g.118548182T>C	CEP85L	Uncertain significance	criteria provided, multiple submitters, no conflicts
202184	NM_002667.5(PLN):c.131T>C (p.Leu44Pro)	CEP85L	Uncertain significance	criteria provided, multiple submitters, no conflicts
220851	NC_000006.12:g.118548254C>G	CEP85L	Uncertain significance	criteria provided, multiple submitters, no conflicts
355134	NM_002667.5(PLN):c.-142T>A	CEP85L	Uncertain significance	criteria provided, single submitter
355142	NM_002667.5(PLN):c.*415T>C	CEP85L	Uncertain significance	criteria provided, multiple submitters, no conflicts
355147	NM_002667.5(PLN):c.*891C>T	CEP85L	Uncertain significance	criteria provided, multiple submitters, no conflicts
355149	NM_002667.5(PLN):c.*1135C>T	CEP85L	Uncertain significance	criteria provided, multiple submitters, no conflicts
44582	NM_002667.5(PLN):c.61C>A (p.Pro21Thr)	CEP85L	Uncertain significance	criteria provided, multiple submitters, no conflicts
904851	NM_002667.5(PLN):c.*1279G>A	CEP85L	Uncertain significance	criteria provided, multiple submitters, no conflicts
907408	NM_002667.5(PLN):c.*1007T>A	CEP85L	Uncertain significance	criteria provided, multiple submitters, no conflicts
1029623	NM_002667.5(PLN):c.61C>T (p.Pro21Ser)	PLN	Uncertain significance	criteria provided, multiple submitters, no conflicts
202036	NM_002667.5(PLN):c.145G>A (p.Val49Met)	PLN	Uncertain significance	criteria provided, multiple submitters, no conflicts
29836	NC_000006.12:g.118548219A>G	PLN	Uncertain significance	criteria provided, single submitter
355135	NM_002667.5(PLN):c.-120C>T	PLN	Uncertain significance	criteria provided, multiple submitters, no conflicts
355152	NM_002667.5(PLN):c.*1225C>T	PLN	Uncertain significance	criteria provided, multiple submitters, no conflicts
355153	NM_002667.5(PLN):c.*1243C>T	PLN	Uncertain significance	criteria provided, multiple submitters, no conflicts
573774	NM_002667.5(PLN):c.53T>C (p.Ile18Thr)	PLN	Uncertain significance	criteria provided, multiple submitters, no conflicts
907406	NM_002667.5(PLN):c.*277A>G	PLN	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.