Hypertrophic cardiomyopathy 16

Summary

Hypertrophic cardiomyopathy 16 (MONDO:0013455) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 38

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypertrophic cardiomyopathy 16
Mondo ID	MONDO:0013455
OMIM	613838
DOID	DOID:0110322
UMLS	C3151204
MedGen	462554
GARD	0024927
Is cancer (heuristic)	no

Also known as: cardiomyopathy, familial hypertrophic, 16 · cardiomyopathy, familial hypertrophic, type 16 · cardiomyopathy, hypertrophic, 16 · CMH16 · hypertrophic cardiomyopathy caused by mutation in MYOZ2 · hypertrophic cardiomyopathy type 16 · MYOZ2 hypertrophic cardiomyopathy

Data availability: 38 ClinVar variants · 3 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 16

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 17, hypertrophic cardiomyopathy 18, 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

38 retrieved; paginated sample, class counts are floors:

22 uncertain significance, 6 benign, 5 benign/likely benign, 3 conflicting classifications of pathogenicity, 1 likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
30508	NM_016599.5(MYOZ2):c.142T>C (p.Ser48Pro)	MYOZ2	Likely pathogenic	criteria provided, single submitter
1329303	NM_016599.5(MYOZ2):c.106G>C (p.Val36Leu)	MYOZ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191744	NM_016599.5(MYOZ2):c.666T>A (p.Phe222Leu)	MYOZ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
45784	NM_016599.5(MYOZ2):c.488T>C (p.Leu163Ser)	MYOZ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1041934	NM_016599.5(MYOZ2):c.19A>G (p.Met7Val)	MYOZ2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1421517	NM_016599.5(MYOZ2):c.11A>T (p.His4Leu)	MYOZ2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1450707	NM_016599.5(MYOZ2):c.751G>A (p.Glu251Lys)	MYOZ2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1465143	NM_016599.5(MYOZ2):c.1A>T (p.Met1Leu)	MYOZ2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1677519	NM_016599.5(MYOZ2):c.327del (p.Asn110fs)	MYOZ2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1787895	NM_016599.5(MYOZ2):c.221A>G (p.Gln74Arg)	MYOZ2	Uncertain significance	criteria provided, multiple submitters, no conflicts
191742	NM_016599.5(MYOZ2):c.302C>A (p.Ser101Ter)	MYOZ2	Uncertain significance	criteria provided, multiple submitters, no conflicts
191745	NM_016599.5(MYOZ2):c.674C>T (p.Pro225Leu)	MYOZ2	Uncertain significance	criteria provided, multiple submitters, no conflicts
213655	NM_016599.5(MYOZ2):c.479C>T (p.Pro160Leu)	MYOZ2	Uncertain significance	criteria provided, multiple submitters, no conflicts
213656	NM_016599.5(MYOZ2):c.181C>T (p.Arg61Cys)	MYOZ2	Uncertain significance	criteria provided, multiple submitters, no conflicts
225418	NM_016599.5(MYOZ2):c.560+1G>T	MYOZ2	Uncertain significance	criteria provided, single submitter
3298116	NM_016599.5(MYOZ2):c.772G>C (p.Val258Leu)	MYOZ2	Uncertain significance	criteria provided, multiple submitters, no conflicts
347407	NM_016599.5(MYOZ2):c.712G>A (p.Gly238Arg)	MYOZ2	Uncertain significance	criteria provided, single submitter
347423	NM_016599.5(MYOZ2):c.*1262dup	MYOZ2	Uncertain significance	criteria provided, single submitter
347424	NM_016599.5(MYOZ2):c.*1262del	MYOZ2	Uncertain significance	criteria provided, single submitter
412240	NM_016599.5(MYOZ2):c.343C>T (p.Arg115Ter)	MYOZ2	Uncertain significance	criteria provided, multiple submitters, no conflicts
454464	NM_016599.5(MYOZ2):c.745A>G (p.Thr249Ala)	MYOZ2	Uncertain significance	criteria provided, multiple submitters, no conflicts
45781	NM_016599.5(MYOZ2):c.29A>G (p.Gln10Arg)	MYOZ2	Uncertain significance	criteria provided, multiple submitters, no conflicts
45783	NM_016599.5(MYOZ2):c.447A>T (p.Gln149His)	MYOZ2	Uncertain significance	criteria provided, multiple submitters, no conflicts
504932	NM_016599.5(MYOZ2):c.-3A>G	MYOZ2	Uncertain significance	criteria provided, multiple submitters, no conflicts
560148	Single allele	MYOZ2	Uncertain significance	criteria provided, single submitter
809673	NM_016599.5(MYOZ2):c.415T>A (p.Phe139Ile)	MYOZ2	Uncertain significance	criteria provided, multiple submitters, no conflicts
138409	NM_016599.5(MYOZ2):c.76+19C>T	MYOZ2	Benign	criteria provided, multiple submitters, no conflicts
138410	NM_016599.5(MYOZ2):c.76+20G>A	MYOZ2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
227711	NM_016599.5(MYOZ2):c.39G>A (p.Gln13=)	MYOZ2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
30509	NM_016599.5(MYOZ2):c.738A>G (p.Ile246Met)	MYOZ2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
MYOZ2	Limited	Autosomal dominant	hypertrophic cardiomyopathy 16	3

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MYOZ2	HGNC:1330	ENSG00000172399	Q9NPC6	Myozenin-2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYOZ2	Myozenin-2	Myozenins may serve as intracellular binding proteins involved in linking Z line proteins such as alpha-actinin, gamma-filamin, TCAP/telethonin, LDB3/ZASP and localizing calcineurin signaling to the sarcomere.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MYOZ2	Other/Unknown	no		MYOZ

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
heart right ventricle	1
left ventricle myocardium	1
myocardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYOZ2	179	broad	marker	heart right ventricle, left ventricle myocardium, myocardium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYOZ2	1,388

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MYOZ2	Q9NPC6	65.51

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 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
skeletal muscle fiber adaptation	1	5617.3×	9e-04	MYOZ2
negative regulation of calcineurin-NFAT signaling cascade	1	936.2×	0.003	MYOZ2
sarcomere organization	1	383.0×	0.004	MYOZ2
skeletal muscle tissue development	1	290.6×	0.004	MYOZ2
negative regulation of transcription by RNA polymerase II	1	17.7×	0.056	MYOZ2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
MYOZ2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	1	MYOZ2

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)
MYOZ2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.