Hypertrophic cardiomyopathy 20

Summary

Hypertrophic cardiomyopathy 20 (MONDO:0013477) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 449

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypertrophic cardiomyopathy 20
Mondo ID	MONDO:0013477
OMIM	613876
DOID	DOID:0110326
UMLS	C3151267
MedGen	462617
GARD	0024932
Is cancer (heuristic)	no

Also known as: cardiomyopathy, familial hypertrophic, 20 · cardiomyopathy, familial hypertrophic, type 20 · cardiomyopathy, hypertrophic, 20 · CMH20 · hypertrophic cardiomyopathy caused by mutation in NEXN · hypertrophic cardiomyopathy type 20 · NEXN hypertrophic cardiomyopathy

Data availability: 449 ClinVar variants · 1 GenCC gene-disease record.

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 20

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 18, hypertrophic cardiomyopathy 19, 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

449 retrieved; paginated sample, class counts are floors:

215 uncertain significance, 138 likely benign, 50 conflicting classifications of pathogenicity, 20 benign/likely benign, 17 pathogenic, 5 likely pathogenic, 3 benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2023692	NM_144573.4(NEXN):c.354_357del (p.Lys119fs)	LOC126805765	Pathogenic	criteria provided, single submitter
30993	NM_144573.4(NEXN):c.391C>G (p.Gln131Glu)	LOC126805765	Pathogenic	no assertion criteria provided
4786625	NM_144573.4(NEXN):c.265A>T (p.Lys89Ter)	LOC126805765	Pathogenic	criteria provided, single submitter
1018253	NM_144573.4(NEXN):c.1302del (p.Ile435fs)	NEXN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1382020	NM_144573.4(NEXN):c.1233_1234insGCCGGGCCCGGTGGCTCACGCCTGTAATCCCAGCACATTGGGAGGCCGAGACTGGAGGATCACGAGTTCAGGAGATCGATACCATACANNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAGAATTTGAACAACTG (p.Arg412delinsAlaGlyProGlyGlySerArgLeuTer)	NEXN	Pathogenic	criteria provided, single submitter
1993576	NM_144573.4(NEXN):c.1170del (p.Lys390fs)	NEXN	Pathogenic	criteria provided, single submitter
2103973	NM_144573.4(NEXN):c.717dup (p.Glu240fs)	NEXN	Pathogenic	criteria provided, single submitter
2118680	NM_144573.4(NEXN):c.676del (p.Ser226fs)	NEXN	Pathogenic	criteria provided, single submitter
2123226	NM_144573.4(NEXN):c.1501A>T (p.Arg501Ter)	NEXN	Pathogenic	criteria provided, single submitter
2132590	NM_144573.4(NEXN):c.1084A>T (p.Lys362Ter)	NEXN	Pathogenic	criteria provided, single submitter
2936967	NM_144573.4(NEXN):c.298G>T (p.Gly100Ter)	NEXN	Pathogenic	criteria provided, multiple submitters, no conflicts
2947595	NM_144573.4(NEXN):c.1536dup (p.Met513fs)	NEXN	Pathogenic	criteria provided, single submitter
2949465	NM_144573.4(NEXN):c.813_814insGG (p.Lys272fs)	NEXN	Pathogenic	criteria provided, single submitter
2953278	NM_144573.4(NEXN):c.798del (p.Glu267fs)	NEXN	Pathogenic	criteria provided, single submitter
3751520	NM_144573.4(NEXN):c.518_519del (p.Val173fs)	NEXN	Pathogenic	criteria provided, single submitter
4787364	NM_144573.4(NEXN):c.1015del (p.Glu339fs)	NEXN	Pathogenic	criteria provided, single submitter
4787433	NM_144573.4(NEXN):c.718del (p.Glu240fs)	NEXN	Pathogenic	criteria provided, single submitter
538107	NM_144573.4(NEXN):c.1348dup (p.Ser450fs)	NEXN	Pathogenic	criteria provided, single submitter
2940524	NM_144573.4(NEXN):c.298+2T>C	LOC126805765	Likely pathogenic	criteria provided, single submitter
1461682	NM_144573.4(NEXN):c.1251+1del	NEXN	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2156496	NM_144573.4(NEXN):c.688-1G>A	NEXN	Likely pathogenic	criteria provided, single submitter
2929334	NM_144573.4(NEXN):c.865-9_892del	NEXN	Likely pathogenic	criteria provided, single submitter
3748873	NM_144573.4(NEXN):c.687+2T>C	NEXN	Likely pathogenic	criteria provided, single submitter
806155	NM_144573.4(NEXN):c.380G>A (p.Arg127His)	LOC126805765	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1017027	NM_144573.4(NEXN):c.962del (p.Arg321fs)	NEXN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1020992	NM_144573.4(NEXN):c.1502del (p.Arg501fs)	NEXN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1032442	NM_144573.4(NEXN):c.991G>T (p.Glu331Ter)	NEXN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1158112	NM_144573.4(NEXN):c.1662A>G (p.Lys554=)	NEXN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1403122	NM_144573.4(NEXN):c.688-1G>C	NEXN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1409607	NM_144573.4(NEXN):c.201G>A (p.Trp67Ter)	NEXN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
NEXN	Strong	Semidominant	dilated cardiomyopathy 1CC	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NEXN	Orphanet:154	Familial isolated dilated cardiomyopathy

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
NEXN	HGNC:29557	ENSG00000162614	Q0ZGT2	Nexilin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NEXN	Nexilin	Involved in regulating cell migration through association with the actin cytoskeleton.

Protein-family classification

Druggable: 1 · 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	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NEXN	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_I-set

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
left ventricle myocardium	1
myocardium	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NEXN	229	ubiquitous	marker	left ventricle myocardium, skeletal muscle tissue of rectus abdominis, myocardium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NEXN	1,200

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NEXN	Q0ZGT2	70.78

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
dendrite self-avoidance	1	1053.2×	0.004	NEXN
regulation of cytoskeleton organization	1	648.1×	0.004	NEXN
regulation of cell migration	1	157.5×	0.009	NEXN
homophilic cell-cell adhesion	1	140.4×	0.009	NEXN
axon guidance	1	90.6×	0.011	NEXN

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
NEXN	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	1	NEXN
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)
NEXN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.