dilated cardiomyopathy 1O

Summary

dilated cardiomyopathy 1O (MONDO:0012062) is a disease caused by ABCC9 (GenCC Strong), with 3 cohort genes.

At a glance

• Causal gene: ABCC9 (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 1,663

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dilated cardiomyopathy 1O
Mondo ID	MONDO:0012062
MeSH	C563906
OMIM	608569
DOID	DOID:0110451
UMLS	C1837839
MedGen	325268
GARD	0015434
Is cancer (heuristic)	no

Also known as: ABCC9 familial isolated dilated cardiomyopathy · cardiomyopathy, dilated, 1O · cardiomyopathy, dilated, type 1O · CMD1O · dilated cardiomyopathy type 1O · familial isolated dilated cardiomyopathy caused by mutation in ABCC9

Data availability: 1,663 ClinVar variants · 4 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 1O

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 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 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

600 retrieved; paginated sample, class counts are floors:

260 uncertain significance, 260 likely benign, 34 conflicting classifications of pathogenicity, 21 pathogenic, 11 benign, 8 likely pathogenic, 5 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1000443	NM_020297.4(ABCC9):c.2721T>G (p.Tyr907Ter)	ABCC9	Pathogenic	criteria provided, single submitter
1022992	NM_020297.4(ABCC9):c.2371C>T (p.Gln791Ter)	ABCC9	Pathogenic	criteria provided, single submitter
1026876	NM_020297.4(ABCC9):c.2422_2423del (p.Arg808fs)	ABCC9	Pathogenic	criteria provided, single submitter
1035485	NM_020297.4(ABCC9):c.438del (p.Thr147fs)	ABCC9	Pathogenic	criteria provided, single submitter
1044828	NM_020297.4(ABCC9):c.2826T>G (p.Tyr942Ter)	ABCC9	Pathogenic	criteria provided, single submitter
1057737	NM_020297.4(ABCC9):c.2529_2530del (p.Ile844fs)	ABCC9	Pathogenic	criteria provided, single submitter
1395006	NM_020297.4(ABCC9):c.1022_1032dup (p.Lys345fs)	ABCC9	Pathogenic	criteria provided, single submitter
1402291	NM_020297.4(ABCC9):c.3269del (p.Gly1090fs)	ABCC9	Pathogenic	criteria provided, single submitter
1409851	NM_020297.4(ABCC9):c.1319del (p.Gln440fs)	ABCC9	Pathogenic	criteria provided, single submitter
1446144	NM_020297.4(ABCC9):c.1600del (p.Leu534fs)	ABCC9	Pathogenic	criteria provided, single submitter
1482842	NM_020297.4(ABCC9):c.1867G>T (p.Glu623Ter)	ABCC9	Pathogenic	criteria provided, single submitter
1486684	NM_020297.4(ABCC9):c.1057_1073dup (p.Phe359_Leu360insTerPhe)	ABCC9	Pathogenic	criteria provided, multiple submitters, no conflicts
1705465	NM_020297.4(ABCC9):c.2506-1G>A	ABCC9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2004320	NM_020297.4(ABCC9):c.2625T>A (p.Tyr875Ter)	ABCC9	Pathogenic	criteria provided, single submitter
2008293	NM_020297.4(ABCC9):c.2828C>G (p.Ser943Ter)	ABCC9	Pathogenic	criteria provided, single submitter
2018281	NM_020297.4(ABCC9):c.1320+2T>G	ABCC9	Pathogenic	criteria provided, single submitter
2018500	NM_020297.4(ABCC9):c.729del (p.Ile243fs)	ABCC9	Pathogenic	criteria provided, single submitter
2022414	NM_020297.4(ABCC9):c.2589_2590del (p.Arg864fs)	ABCC9	Pathogenic	criteria provided, single submitter
2023230	NM_020297.4(ABCC9):c.3586C>T (p.Gln1196Ter)	ABCC9	Pathogenic	criteria provided, single submitter
2059714	NM_020297.4(ABCC9):c.565C>T (p.Arg189Ter)	ABCC9	Pathogenic	criteria provided, multiple submitters, no conflicts
2081678	NM_020297.4(ABCC9):c.259dup (p.Ile87fs)	ABCC9	Pathogenic	criteria provided, single submitter
2128352	NM_020297.4(ABCC9):c.3388_3389insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNGAAAACTGGCTAGCCATATGTAGAAAGCTGAAACTGGATCCCTTCCTTACACCTTATACAAAAATCAAATCAATTCAAGATGGGATGATTTCTT (p.Tyr1130delinsPhePhePhePhePhePhePheXaaXaaXaaXaaLysLeuAlaSerHisMetTer)	ABCC9	Pathogenic	criteria provided, single submitter
1355082	NM_020297.4(ABCC9):c.4211+2T>C	ABCC9	Likely pathogenic	criteria provided, single submitter
1366444	NM_020297.4(ABCC9):c.1619-2A>G	ABCC9	Likely pathogenic	criteria provided, single submitter
1381567	NM_020297.4(ABCC9):c.1803-1G>A	ABCC9	Likely pathogenic	criteria provided, single submitter
1404740	NM_020297.4(ABCC9):c.620A>C (p.Asp207Ala)	ABCC9	Likely pathogenic	criteria provided, single submitter
1418960	NM_020297.4(ABCC9):c.2199-1G>A	ABCC9	Likely pathogenic	criteria provided, single submitter
1465409	NM_020297.4(ABCC9):c.2237+1G>C	ABCC9	Likely pathogenic	criteria provided, single submitter
1485362	NM_020297.4(ABCC9):c.1321-2A>G	ABCC9	Likely pathogenic	criteria provided, single submitter
1499130	NM_020297.4(ABCC9):c.1164+1G>T	ABCC9	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 18 · Orphanet: 4 · 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
ABCC9	Strong	Autosomal dominant	dilated cardiomyopathy 1O	18

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ABCC9	Orphanet:130	Brugada syndrome
ABCC9	Orphanet:1517	Cantú syndrome
ABCC9	Orphanet:154	Familial isolated dilated cardiomyopathy
ABCC9	Orphanet:334	Hereditary atrial fibrillation

Cohort genes → proteins

3 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ABCC9	HGNC:60	ENSG00000069431	O60706	ATP-binding cassette sub-family C member 9	gencc,clinvar
SPX	HGNC:28139	ENSG00000134548	Q9BT56	Spexin	clinvar
KCNJ8-AS1	HGNC:58193	ENSG00000256615		KCNJ8 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ABCC9	ATP-binding cassette sub-family C member 9	Subunit of ATP-sensitive potassium channels (KATP).
SPX	Spexin	Plays a role as a central modulator of cardiovascular and renal function and nociception.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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
Transporter	1	25.9×	0.076
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ABCC9	Transporter	yes		ABCC8/9, ABCC9, ABC_transporter-like_ATP-bd
SPX	Other/Unknown	no		Spexin
KCNJ8-AS1	Other/Unknown	no

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gastrocnemius	1
hindlimb stylopod muscle	1
muscle of leg	1
body of pancreas	1
globus pallidus	1
medial globus pallidus	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
small intestine	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ABCC9	195	broad	marker	gastrocnemius, muscle of leg, hindlimb stylopod muscle
SPX	208	broad	marker	body of pancreas, medial globus pallidus, globus pallidus
KCNJ8-AS1	83		yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, small intestine

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ABCC9	1,728
SPX	527
KCNJ8-AS1	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SPX	Q9BT56	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ABCC9	O60706	81.72

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 3 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective ABCC9 causes CMD10, ATFB12 and Cantu syndrome	1	5710.0×	0.002	ABCC9
ATP sensitive Potassium channels	1	2855.0×	0.002	ABCC9
Inwardly rectifying K+ channels	1	713.8×	0.006	ABCC9
ABC transporter disorders	1	439.2×	0.007	ABCC9
Ion homeostasis	1	203.9×	0.013	ABCC9
Disorders of transmembrane transporters	1	139.3×	0.013	ABCC9
Potassium Channels	1	134.3×	0.013	ABCC9
ABC-family protein mediated transport	1	121.5×	0.013	ABCC9
Cardiac conduction	1	108.8×	0.013	ABCC9
Muscle contraction	1	77.2×	0.017	ABCC9
Neuronal System	1	44.3×	0.027	ABCC9
Transport of small molecules	1	25.1×	0.043	ABCC9
Disease	1	13.1×	0.076	ABCC9

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
negative regulation of renal sodium excretion	1	8426.0×	0.003	SPX
positive regulation of gastro-intestinal system smooth muscle contraction	1	8426.0×	0.003	SPX
response to hydrogen sulfide	1	4213.0×	0.004	ABCC9
oxygen metabolic process	1	2106.5×	0.005	ABCC9
cellular response to chemical stress	1	1404.3×	0.005	ABCC9
reactive oxygen species biosynthetic process	1	936.2×	0.005	ABCC9
long-chain fatty acid import into cell	1	842.6×	0.005	SPX
cardiac conduction	1	842.6×	0.005	ABCC9
cardiac muscle cell contraction	1	842.6×	0.005	ABCC9
negative regulation of appetite	1	766.0×	0.005	SPX
positive regulation of systemic arterial blood pressure	1	702.2×	0.005	SPX
negative regulation of heart rate	1	648.1×	0.005	SPX
response to peptide	1	561.7×	0.005	ABCC9
fatty acid oxidation	1	526.6×	0.005	ABCC9
cellular response to potassium ion	1	526.6×	0.005	ABCC9
response to ATP	1	495.6×	0.005	ABCC9
regulation of sensory perception of pain	1	495.6×	0.005	SPX
obsolete inorganic cation transmembrane transport	1	468.1×	0.005	ABCC9
cellular response to ATP	1	443.5×	0.005	ABCC9
negative regulation of blood pressure	1	324.1×	0.006	ABCC9
coronary vasculature development	1	312.1×	0.006	ABCC9
monoatomic cation transmembrane transport	1	312.1×	0.006	ABCC9
regulation of potassium ion transmembrane transport	1	312.1×	0.006	ABCC9
response to hydrogen peroxide	1	234.1×	0.008	ABCC9
ATP metabolic process	1	234.1×	0.008	ABCC9
cellular respiration	1	216.1×	0.008	ABCC9
fibroblast proliferation	1	195.9×	0.008	ABCC9
heart morphogenesis	1	187.2×	0.008	ABCC9
vasodilation	1	183.2×	0.008	ABCC9
potassium ion import across plasma membrane	1	183.2×	0.008	ABCC9

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ABCC9	PINACIDIL ANHYDROUS

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ABCC9	5	4
SPX	0	0
KCNJ8-AS1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PINACIDIL ANHYDROUS	4	ABCC9
GLYBURIDE	4	ABCC9
PROPAFENONE	4	ABCC9
CROMAKALIM	2	ABCC9
CLAMIKALANT	2	ABCC9

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ABCC9	61	Functional:46, Binding:15

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

5 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.

Compound	Max phase	Cohort target (bioactivity)
PINACIDIL ANHYDROUS	4	ABCC9
GLYBURIDE	4	ABCC9
PROPAFENONE	4	ABCC9
CROMAKALIM	2	ABCC9
CLAMIKALANT	2	ABCC9

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ABCC9
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	SPX, KCNJ8-AS1

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)
SPX	0	—
KCNJ8-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.