dilated cardiomyopathy 1HH

Summary

dilated cardiomyopathy 1HH (MONDO:0013479) is a disease caused by BAG3 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: BAG3 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 1,182

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dilated cardiomyopathy 1HH
Mondo ID	MONDO:0013479
OMIM	613881
DOID	DOID:0110448
UMLS	C3151293
MedGen	462643
GARD	0015726
Is cancer (heuristic)	no

Also known as: BAG3 familial isolated dilated cardiomyopathy · cardiomyopathy, dilated, 1HH · cardiomyopathy, dilated, type 1Hh · CMD1HH · dilated cardiomyopathy type 1HH · familial isolated dilated cardiomyopathy caused by mutation in BAG3

Data availability: 1,182 ClinVar variants · 3 GenCC gene-disease records · 4 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 1HH

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 1P, 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 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

600 retrieved; paginated sample, class counts are floors:

326 uncertain significance, 163 likely benign, 48 conflicting classifications of pathogenicity, 40 pathogenic, 9 pathogenic/likely pathogenic, 7 benign/likely benign, 4 likely pathogenic, 3 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1066195	NM_004281.4(BAG3):c.1348A>T (p.Lys450Ter)	BAG3	Pathogenic	criteria provided, single submitter
1069307	NM_004281.4(BAG3):c.811C>T (p.Gln271Ter)	BAG3	Pathogenic	criteria provided, multiple submitters, no conflicts
1070601	NM_004281.4(BAG3):c.824del (p.Ser275fs)	BAG3	Pathogenic	criteria provided, single submitter
1075312	NM_004281.4(BAG3):c.351_352insTGGATGCAGCGATTCCGAACTGAGGCGGCAGCAGCGGCTCCTCAGAGGTCCCAGTCACCTCTGCGGGGCATGCCAGAAACCACTCAGCCAGATAAACAGCGTGGACAGGTGGCAGCGGCGGCGGCAGCCCAGCCCCCAGCCT (p.Gly118fs)	BAG3	Pathogenic	criteria provided, single submitter
1075572	NM_004281.4(BAG3):c.530_531del (p.Ala176_Ser177insTer)	BAG3	Pathogenic	criteria provided, single submitter
1076610	NM_004281.4(BAG3):c.654del (p.Pro219fs)	BAG3	Pathogenic	criteria provided, single submitter
1076893	NC_000010.10:g.(?121411178)(121437012_?)del	BAG3	Pathogenic	criteria provided, single submitter
1323968	NM_004281.4(BAG3):c.1353C>A (p.Tyr451Ter)	BAG3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324072	NM_004281.4(BAG3):c.457C>T (p.Gln153Ter)	BAG3	Pathogenic	criteria provided, single submitter
1324087	NM_004281.4(BAG3):c.331_332del (p.Phe111fs)	BAG3	Pathogenic	criteria provided, single submitter
1324094	NM_004281.4(BAG3):c.361C>T (p.Arg121Ter)	BAG3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324125	NM_004281.4(BAG3):c.1057del (p.Gln353fs)	BAG3	Pathogenic	criteria provided, single submitter
1324260	NM_004281.4(BAG3):c.910C>T (p.Gln304Ter)	BAG3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1362749	NM_004281.4(BAG3):c.598C>T (p.Gln200Ter)	BAG3	Pathogenic	criteria provided, single submitter
1396666	NM_004281.4(BAG3):c.165del (p.Ser56fs)	BAG3	Pathogenic	criteria provided, single submitter
1398633	NM_004281.4(BAG3):c.640C>T (p.Gln214Ter)	BAG3	Pathogenic	criteria provided, single submitter
1432977	NM_004281.4(BAG3):c.751C>T (p.Gln251Ter)	BAG3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1452208	NM_004281.4(BAG3):c.38_39dup (p.Ser14fs)	BAG3	Pathogenic	criteria provided, single submitter
1453625	NM_004281.4(BAG3):c.488del (p.Pro163fs)	BAG3	Pathogenic	criteria provided, single submitter
1455927	NC_000010.10:g.(?121411188)(121411387_?)del	BAG3	Pathogenic	criteria provided, single submitter
1456226	NM_004281.4(BAG3):c.1326dup (p.Glu443Ter)	BAG3	Pathogenic	criteria provided, single submitter
1456480	NM_004281.4(BAG3):c.766G>T (p.Glu256Ter)	BAG3	Pathogenic	criteria provided, single submitter
1457623	NC_000010.10:g.(?121435956)(121436794_?)del	BAG3	Pathogenic	criteria provided, single submitter
1494973	NM_004281.4(BAG3):c.1088_1708del (p.Glu363_Pro569del)	BAG3	Pathogenic	criteria provided, single submitter
156530	NM_004281.4(BAG3):c.626C>A (p.Pro209Gln)	BAG3	Pathogenic	criteria provided, single submitter
162769	NM_004281.4(BAG3):c.72del (p.Gly25fs)	BAG3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1675064	NM_004281.4(BAG3):c.612del (p.Tyr205fs)	BAG3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1736414	NM_004281.4(BAG3):c.394C>T (p.Gln132Ter)	BAG3	Pathogenic	criteria provided, multiple submitters, no conflicts
1797440	NM_004281.4(BAG3):c.29_35del (p.Met10fs)	BAG3	Pathogenic	criteria provided, multiple submitters, no conflicts
179764	NM_004281.4(BAG3):c.1067del (p.Pro356fs)	BAG3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · 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
BAG3	Definitive	Autosomal dominant	dilated cardiomyopathy 1HH	13

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BAG3	Orphanet:154	Familial isolated dilated cardiomyopathy
BAG3	Orphanet:199340	BAG3-related myofibrillar myopathy
DTNA	Orphanet:54260	Left ventricular noncompaction

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
BAG3	HGNC:939	ENSG00000151929	O95817	BAG family molecular chaperone regulator 3	gencc,clinvar
DTNA	HGNC:3057	ENSG00000134769	Q9Y4J8	Dystrobrevin alpha	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BAG3	BAG family molecular chaperone regulator 3	Co-chaperone and adapter protein that connects different classes of molecular chaperones including heat shock proteins 70 (HSP70s), e.g.
DTNA	Dystrobrevin alpha	May be involved in the formation and stability of synapses as well as being involved in the clustering of nicotinic acetylcholine receptors.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 0 · 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
Scaffold/PPI	1	8.6×	0.225
Transcription factor	1	4.1×	0.228

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BAG3	Scaffold/PPI	no		WW_dom, BAG_domain, WW_dom_sf
DTNA	Transcription factor	no		Znf_ZZ, EF-hand-dom_pair, EF-hand_dom_typ1

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
body of tongue	1
gastrocnemius	1
skeletal muscle tissue of rectus abdominis	1
C1 segment of cervical spinal cord	1
globus pallidus	1
medial globus pallidus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BAG3	286	ubiquitous	marker	gastrocnemius, skeletal muscle tissue of rectus abdominis, body of tongue
DTNA	266	ubiquitous	marker	medial globus pallidus, globus pallidus, C1 segment of cervical spinal cord

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BAG3	4,957
DTNA	1,738

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DTNA	Q9Y4J8	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BAG3	O95817	57.98

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Cellular response to heat stress	1	196.9×	0.016	BAG3
Formation of the dystrophin-glycoprotein complex (DGC)	1	154.3×	0.016	DTNA
Regulation of HSF1-mediated heat shock response	1	69.6×	0.024	BAG3
Cellular responses to stress	1	18.4×	0.063	BAG3
Cellular responses to stimuli	1	15.7×	0.063	BAG3

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
striated muscle cell apoptotic process	1	8426.0×	0.003	BAG3
negative regulation of striated muscle cell apoptotic process	1	2808.7×	0.003	BAG3
protein transport along microtubule	1	2808.7×	0.003	BAG3
chaperone-mediated autophagy	1	1404.3×	0.003	BAG3
aggresome assembly	1	1404.3×	0.003	BAG3
obsolete negative regulation of protein targeting to mitochondrion	1	1404.3×	0.003	BAG3
positive regulation of aggrephagy	1	1404.3×	0.003	BAG3
synaptic signaling	1	766.0×	0.004	DTNA
cellular response to unfolded protein	1	495.6×	0.006	BAG3
striated muscle contraction	1	421.3×	0.006	DTNA
positive regulation of protein export from nucleus	1	401.2×	0.006	BAG3
muscle cell cellular homeostasis	1	324.1×	0.006	BAG3
neuromuscular synaptic transmission	1	300.9×	0.006	DTNA
spinal cord development	1	255.3×	0.007	BAG3
extrinsic apoptotic signaling pathway in absence of ligand	1	234.1×	0.007	BAG3
positive regulation of protein import into nucleus	1	210.7×	0.007	BAG3
extrinsic apoptotic signaling pathway via death domain receptors	1	200.6×	0.007	BAG3
cellular response to heat	1	172.0×	0.008	BAG3
autophagosome assembly	1	112.3×	0.012	BAG3
cellular response to mechanical stimulus	1	108.0×	0.012	BAG3
protein folding	1	51.7×	0.023	BAG3
chemical synaptic transmission	1	38.6×	0.029	DTNA
protein stabilization	1	33.4×	0.032	BAG3
negative regulation of apoptotic process	1	17.4×	0.059	BAG3
signal transduction	1	8.0×	0.121	DTNA

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BAG3	0	0
DTNA	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
BAG3	8	Binding:8

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	BAG3, DTNA

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)
BAG3	8	—
DTNA	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.