dilated cardiomyopathy 1BB

Summary

dilated cardiomyopathy 1BB (MONDO:0013030) is a disease with 4 cohort genes. The dominant Reactome pathway is Formation of the cornified envelope (3 cohort genes).

At a glance

• Cohort genes: 4
• ClinVar variants: 125

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dilated cardiomyopathy 1BB
Mondo ID	MONDO:0013030
MeSH	C567877
OMIM	612877
DOID	DOID:0110458
UMLS	C2752072
MedGen	414552
GARD	0015588
Is cancer (heuristic)	no

Also known as: cardiomyopathy, dilated, 1BB · cardiomyopathy, dilated, type 1Bb · CMD1BB · dilated cardiomyopathy type 1BB · DSG2 familial isolated dilated cardiomyopathy · familial isolated dilated cardiomyopathy caused by mutation in DSG2

Data availability: 125 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 › dilated cardiomyopathy › familial dilated cardiomyopathy › familial isolated dilated cardiomyopathy › dilated cardiomyopathy 1BB

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 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 1HH, 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

125 retrieved; paginated sample, class counts are floors:

52 uncertain significance, 48 conflicting classifications of pathogenicity, 8 benign/likely benign, 7 likely benign, 6 pathogenic/likely pathogenic, 4 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
16812	NM_001943.5(DSG2):c.137G>A (p.Arg46Gln)	DSG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
585217	NM_001943.5(DSG2):c.1826dup (p.Leu610fs)	DSG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
585218	NM_001943.5(DSG2):c.512_516del (p.Leu171fs)	DSG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
666600	NM_001943.5(DSG2):c.1319_1320del (p.Val440fs)	DSG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
691669	NM_001943.5(DSG2):c.882dup (p.Val295fs)	DSG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1701778	NM_001943.5(DSG2):c.2990del (p.Gly997fs)	DSG2-AS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1066747	NM_001943.5(DSG2):c.1423+1G>T	DSG2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3382030	NM_001943.5(DSG2):c.1765dup (p.Thr589fs)	DSG2	Likely pathogenic	criteria provided, single submitter
4849207	NM_001943.5(DSG2):c.2349C>G (p.Tyr783Ter)	DSG2	Likely pathogenic	criteria provided, single submitter
653370	NM_001943.5(DSG2):c.523+1_523+2del	DSG2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
44278	NM_001943.5(DSG2):c.1003A>G (p.Thr335Ala)	DSC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1003548	NM_001943.5(DSG2):c.3283C>A (p.His1095Asn)	DSG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1057654	NM_001943.5(DSG2):c.1811A>G (p.His604Arg)	DSG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1171153	NM_001943.5(DSG2):c.355C>T (p.Arg119Ter)	DSG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1359573	NM_001943.5(DSG2):c.2375_2379dup (p.Asp794fs)	DSG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
161224	NM_001943.5(DSG2):c.1912G>A (p.Gly638Arg)	DSG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
163204	NM_001943.5(DSG2):c.806T>C (p.Ile269Thr)	DSG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
163212	NM_001943.5(DSG2):c.1478A>G (p.Asn493Ser)	DSG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
163217	NM_001943.5(DSG2):c.2305G>A (p.Glu769Lys)	DSG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
16811	NM_001943.5(DSG2):c.918G>A (p.Trp306Ter)	DSG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
16818	NM_001943.5(DSG2):c.166G>A (p.Val56Met)	DSG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
177961	NM_001943.5(DSG2):c.2368C>T (p.His790Tyr)	DSG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178021	NM_001943.5(DSG2):c.2033G>C (p.Gly678Ala)	DSG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
179294	NM_001943.5(DSG2):c.2096G>T (p.Ser699Ile)	DSG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
179849	NM_001943.5(DSG2):c.3281_3283delinsTTA (p.Gly1094_His1095delinsValAsn)	DSG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
179897	NM_001943.5(DSG2):c.98A>C (p.Asn33Thr)	DSG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
188450	NM_001943.5(DSG2):c.523+1G>C	DSG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191626	NM_001943.5(DSG2):c.430G>A (p.Glu144Lys)	DSG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191629	NM_001943.5(DSG2):c.1063G>A (p.Ala355Thr)	DSG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
199801	NM_001943.5(DSG2):c.2923del (p.Leu974_Val975insTer)	DSG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 8 · 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
DSG2	Supportive	Autosomal dominant	familial isolated dilated cardiomyopathy	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DSG2	Orphanet:154	Familial isolated dilated cardiomyopathy
DSG2	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
DSG2	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
DSG2	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
DSC2	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
DSC2	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
DSC2	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
DSC3	Orphanet:217407	Hereditary hypotrichosis with recurrent skin vesicles

Cohort genes → proteins

4 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DSG2	HGNC:3049	ENSG00000046604	Q14126	Desmoglein-2	gencc,clinvar
DSC2	HGNC:3036	ENSG00000134755	Q02487	Desmocollin-2	clinvar
DSC3	HGNC:3037	ENSG00000134762	Q14574	Desmocollin-3	clinvar
DSG2-AS1	HGNC:51311	ENSG00000264859		DSG2 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DSG2	Desmoglein-2	A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion.
DSC2	Desmocollin-2	A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion.
DSC3	Desmocollin-3	A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 4 · 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	4	1.8×	0.097

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DSG2	Other/Unknown	no		Cadherin-like_dom, Desmosomal_cadherin, Cadherin-like_sf
DSC2	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Desmosomal_cadherin
DSC3	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Desmosomal_cadherin
DSG2-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

4 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gingiva	2
gingival epithelium	2
colonic mucosa	1
jejunal mucosa	1
mucosa of sigmoid colon	1
oral cavity	1
upper leg skin	1
buccal mucosa cell	1
oocyte	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DSG2	238	ubiquitous	marker	mucosa of sigmoid colon, colonic mucosa, jejunal mucosa
DSC2	256	ubiquitous	marker	gingival epithelium, gingiva, oral cavity
DSC3	177	broad	marker	upper leg skin, gingival epithelium, gingiva
DSG2-AS1	124		marker	oocyte, buccal mucosa cell, sperm

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DSG2	2,033
DSC2	1,659
DSC3	1,474
DSG2-AS1	0

Intra-cohort edges

A	B	Sources
DSC2	DSG2	intact, string_interaction
DSC3	DSG2	intact, string_interaction

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DSG2	Q14126	12
DSC2	Q02487	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DSC3	Q14574	75.53

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 4 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of the cornified envelope	3	87.8×	9e-06	DSG2, DSC2, DSC3
Keratinization	3	55.7×	2e-05	DSG2, DSC2, DSC3
Apoptotic cleavage of cell adhesion proteins	1	346.1×	0.006	DSG2
RHOG GTPase cycle	1	49.4×	0.025	DSG2
RAC2 GTPase cycle	1	42.3×	0.025	DSG2
RAC3 GTPase cycle	1	39.6×	0.025	DSG2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
bundle of His cell-Purkinje myocyte adhesion involved in cell communication	2	1605.0×	6e-06	DSG2, DSC2
homophilic cell-cell adhesion	3	140.4×	6e-06	DSG2, DSC2, DSC3
cell-cell adhesion	3	101.5×	8e-06	DSG2, DSC2, DSC3
regulation of ventricular cardiac muscle cell action potential	2	936.2×	9e-06	DSG2, DSC2
regulation of heart rate by cardiac conduction	2	249.7×	9e-05	DSG2, DSC2
cell adhesion	3	37.5×	9e-05	DSG2, DSC2, DSC3
Purkinje myocyte development	1	2808.7×	0.001	DSG2
cardiac muscle cell-cardiac muscle cell adhesion	1	2808.7×	0.001	DSC2
positive regulation of protein localization to cell-cell junction	1	1872.4×	0.001	DSG2
negative regulation of endothelial cell differentiation	1	1123.5×	0.002	DSG2
desmosome organization	1	702.2×	0.003	DSG2
negative regulation of inflammatory response to wounding	1	561.7×	0.004	DSG2
mesenchymal to epithelial transition	1	510.7×	0.004	DSG2
maternal process involved in female pregnancy	1	312.1×	0.006	DSG2
positive regulation of sprouting angiogenesis	1	224.7×	0.007	DSG2
positive regulation of p38MAPK cascade	1	208.1×	0.007	DSC2
response to progesterone	1	165.2×	0.009	DSG2
negative regulation of epithelial to mesenchymal transition	1	137.0×	0.010	DSG2
positive regulation of stem cell population maintenance	1	114.6×	0.011	DSG2
stem cell proliferation	1	104.0×	0.012	DSG2
positive regulation of cell adhesion	1	90.6×	0.013	DSG2
cellular response to starvation	1	64.6×	0.018	DSC2
in utero embryonic development	1	24.0×	0.045	DSC3
protein stabilization	1	22.3×	0.046	DSC3
negative regulation of apoptotic process	1	11.6×	0.084	DSG2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 4 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
DSG2	0	0
DSC2	0	0
DSC3	0	0
DSG2-AS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	4	DSG2, DSC2, DSC3, DSG2-AS1

Undrugged target profiles

4 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
DSG2	0	—
DSC2	0	—
DSC3	0	—
DSG2-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.