Cardiomyopathy, familial hypertrophic, 28

Summary

Cardiomyopathy, familial hypertrophic, 28 (MONDO:0030317) is a disease caused by FHOD3 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: FHOD3 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 43

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cardiomyopathy, familial hypertrophic, 28
Mondo ID	MONDO:0030317
OMIM	619402
UMLS	C5543616
MedGen	1779612
GARD	0025536
Is cancer (heuristic)	no

Also known as: cardiomyopathy, familial hypertrophic, 28 · CMH28

Data availability: 43 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 › cardiomyopathy, familial hypertrophic, 28

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 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 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

43 retrieved; paginated sample, class counts are floors:

36 uncertain significance, 2 pathogenic/likely pathogenic, 2 conflicting classifications of pathogenicity, 1 pathogenic, 1 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1174141	NM_001281740.3(FHOD3):c.1583A>G (p.Tyr528Cys)	FHOD3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1174142	NM_001281740.3(FHOD3):c.1580_1582del (p.Ser527del)	FHOD3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1174143	NM_001281740.3:c.1836-1527_2022-2042del	FHOD3	Pathogenic	no assertion criteria provided
3065960	NM_001281740.3(FHOD3):c.4787-1G>A	FHOD3	Likely pathogenic	criteria provided, single submitter
1805290	NM_001281740.3(FHOD3):c.1646+2T>C	FHOD3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2500031	NM_001281740.3(FHOD3):c.3662G>A (p.Ser1221Asn)	FHOD3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1698945	NM_001281740.3(FHOD3):c.1913G>A (p.Arg638Gln)	FHOD3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1698997	NM_001281740.3(FHOD3):c.3128G>A (p.Ser1043Asn)	FHOD3	Uncertain significance	criteria provided, single submitter
1699163	NM_001281740.3(FHOD3):c.2263T>A (p.Ser755Thr)	FHOD3	Uncertain significance	criteria provided, single submitter
1699167	NM_001281740.3(FHOD3):c.1016G>A (p.Arg339Gln)	FHOD3	Uncertain significance	criteria provided, single submitter
1699268	NM_001281740.3(FHOD3):c.1909C>T (p.Arg637Trp)	FHOD3	Uncertain significance	criteria provided, single submitter
1708103	NM_001281740.3(FHOD3):c.172G>C (p.Asp58His)	FHOD3	Uncertain significance	criteria provided, single submitter
1709576	NM_001281740.3(FHOD3):c.1721+1G>A	FHOD3	Uncertain significance	criteria provided, single submitter
1805091	NM_001281740.3(FHOD3):c.4430A>G (p.Asp1477Gly)	FHOD3	Uncertain significance	criteria provided, single submitter
1805274	NM_001281740.3(FHOD3):c.3218C>G (p.Pro1073Arg)	FHOD3	Uncertain significance	criteria provided, single submitter
2441437	NM_001281740.3(FHOD3):c.1910G>C (p.Arg637Pro)	FHOD3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2459969	NM_001281740.3(FHOD3):c.2888A>G (p.Lys963Arg)	FHOD3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2582611	NM_001281740.3(FHOD3):c.2481C>A (p.Ser827Arg)	FHOD3	Uncertain significance	criteria provided, single submitter
2584574	NM_001281740.3(FHOD3):c.1097C>T (p.Ser366Leu)	FHOD3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2585290	NM_001281740.3(FHOD3):c.4324G>T (p.Ala1442Ser)	FHOD3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2665092	NM_001281740.3(FHOD3):c.1912C>T (p.Arg638Trp)	FHOD3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2665093	NM_001281740.3(FHOD3):c.928G>A (p.Asp310Asn)	FHOD3	Uncertain significance	criteria provided, multiple submitters, no conflicts
3024547	NM_001281740.3(FHOD3):c.2890G>T (p.Val964Phe)	FHOD3	Uncertain significance	criteria provided, multiple submitters, no conflicts
3062011	NM_001281740.3(FHOD3):c.1066G>A (p.Gly356Ser)	FHOD3	Uncertain significance	criteria provided, multiple submitters, no conflicts
3238795	NM_001281740.3(FHOD3):c.1355C>G (p.Pro452Arg)	FHOD3	Uncertain significance	criteria provided, single submitter
3254770	NM_001281740.3(FHOD3):c.1702C>T (p.Arg568Ter)	FHOD3	Uncertain significance	criteria provided, single submitter
3254771	NM_001281740.3(FHOD3):c.1972C>T (p.Arg658Ter)	FHOD3	Uncertain significance	criteria provided, single submitter
3254772	NM_001281740.3(FHOD3):c.4090T>G (p.Cys1364Gly)	FHOD3	Uncertain significance	criteria provided, single submitter
3255140	NM_001281740.3(FHOD3):c.1271G>C (p.Cys424Ser)	FHOD3	Uncertain significance	criteria provided, single submitter
3255380	NM_001281740.3(FHOD3):c.3362C>T (p.Thr1121Ile)	FHOD3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
FHOD3	Definitive	Autosomal dominant	hypertrophic cardiomyopathy	5

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
FHOD3	HGNC:26178	ENSG00000134775	Q2V2M9	FH1/FH2 domain-containing protein 3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FHOD3	FH1/FH2 domain-containing protein 3	Actin-organizing protein that may cause stress fiber formation together with cell elongation.

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)
FHOD3	Other/Unknown	no		ARM-like, DAD_dom, GBD/FH3_dom

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
apex of heart	1
left ventricle myocardium	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FHOD3	244	ubiquitous	marker	apex of heart, left ventricle myocardium, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FHOD3	407

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FHOD3	Q2V2M9	64.62

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
cardiac myofibril assembly	1	1296.3×	0.003	FHOD3
sarcomere organization	1	383.0×	0.004	FHOD3
positive regulation of stress fiber assembly	1	312.1×	0.004	FHOD3
actin filament organization	1	118.7×	0.008	FHOD3

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
FHOD3	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	FHOD3

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)
FHOD3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.