dilated cardiomyopathy 1FF

Summary

dilated cardiomyopathy 1FF (MONDO:0013211) is a disease caused by TNNI3 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: TNNI3 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 38

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dilated cardiomyopathy 1FF
Mondo ID	MONDO:0013211
MeSH	C567654
OMIM	613286
DOID	DOID:0110459
UMLS	C2750091
MedGen	412876
GARD	0015643
Is cancer (heuristic)	no

Also known as: cardiomyopathy, dilated, 1FF · cardiomyopathy, dilated, type 1Ff · CMD1FF · dilated cardiomyopathy type 1FF

Data availability: 38 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 › dilated cardiomyopathy › familial dilated cardiomyopathy › familial isolated dilated cardiomyopathy › dilated cardiomyopathy 1FF

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 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

38 retrieved; paginated sample, class counts are floors:

15 uncertain significance, 7 conflicting classifications of pathogenicity, 4 likely pathogenic, 4 pathogenic/likely pathogenic, 4 pathogenic, 2 likely benign, 1 benign/likely benign, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
694066	NM_001730.5(KLF5):c.1100T>A (p.Leu367Ter)	KLF5	Pathogenic	no assertion criteria provided
12422	NM_000363.5(TNNI3):c.586G>A (p.Asp196Asn)	TNNI3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12426	NM_000363.5(TNNI3):c.433C>T (p.Arg145Trp)	TNNI3	Pathogenic	criteria provided, multiple submitters, no conflicts
12430	NM_000363.5(TNNI3):c.106A>C (p.Lys36Gln)	TNNI3	Pathogenic	no assertion criteria provided
12431	NM_000363.5(TNNI3):c.555C>G (p.Asn185Lys)	TNNI3	Pathogenic	no assertion criteria provided
43381	NM_000363.5(TNNI3):c.422G>A (p.Arg141Gln)	TNNI3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
43384	NM_000363.5(TNNI3):c.434G>A (p.Arg145Gln)	TNNI3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
43392	NM_000363.5(TNNI3):c.544G>A (p.Glu182Lys)	TNNI3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1175200	NM_000363.5(TNNI3):c.536A>G (p.Glu179Gly)	TNNI3	Likely pathogenic	criteria provided, single submitter
165510	NM_000363.5(TNNI3):c.574C>T (p.Arg192Cys)	TNNI3	Likely pathogenic	reviewed by expert panel
4072018	NM_000363.5(TNNI3):c.470C>A (p.Ala157Glu)	TNNI3	Likely pathogenic	criteria provided, single submitter
43389	NM_000363.5(TNNI3):c.485G>A (p.Arg162Gln)	TNNI3	Likely pathogenic	reviewed by expert panel
165517	NM_000363.5(TNNI3):c.508C>G (p.Arg170Gly)	TNNI3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
181573	NM_000363.5(TNNI3):c.114A>T (p.Lys38Asn)	TNNI3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
181575	NM_000363.5(TNNI3):c.292C>T (p.Arg98Ter)	TNNI3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
181599	NM_000363.5(TNNI3):c.302A>G (p.His101Arg)	TNNI3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3234113	NM_000363.5(TNNI3):c.184G>T (p.Glu62Ter)	TNNI3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
378932	NM_000363.5(TNNI3):c.108+2T>G	TNNI3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
419596	NM_000363.5(TNNI3):c.114dup (p.Ser39fs)	TNNI3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1171378	NM_000363.5(TNNI3):c.220C>T (p.Arg74Cys)	TNNI3	Uncertain significance	criteria provided, multiple submitters, no conflicts
161396	NM_000363.5(TNNI3):c.484C>T (p.Arg162Trp)	TNNI3	Uncertain significance	reviewed by expert panel
165526	NM_000363.5(TNNI3):c.167T>C (p.Ile56Thr)	TNNI3	Uncertain significance	criteria provided, multiple submitters, no conflicts
181579	NM_000363.5(TNNI3):c.356C>T (p.Thr119Ile)	TNNI3	Uncertain significance	criteria provided, multiple submitters, no conflicts
181600	NM_000363.5(TNNI3):c.331A>G (p.Arg111Gly)	TNNI3	Uncertain significance	criteria provided, multiple submitters, no conflicts
188674	NM_000363.5(TNNI3):c.439G>C (p.Val147Leu)	TNNI3	Uncertain significance	criteria provided, multiple submitters, no conflicts
237688	NM_000363.5(TNNI3):c.108+4G>T	TNNI3	Uncertain significance	criteria provided, multiple submitters, no conflicts
264048	NM_000363.5(TNNI3):c.221G>C (p.Arg74Pro)	TNNI3	Uncertain significance	criteria provided, multiple submitters, no conflicts
3075666	NM_000363.5(TNNI3):c.23C>G (p.Ala8Gly)	TNNI3	Uncertain significance	criteria provided, single submitter
43375	NM_000363.5(TNNI3):c.356C>A (p.Thr119Asn)	TNNI3	Uncertain significance	criteria provided, multiple submitters, no conflicts
454401	NM_000363.5(TNNI3):c.104C>T (p.Ala35Val)	TNNI3	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 2 · 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
TNNI3	Definitive	Autosomal recessive	dilated cardiomyopathy 2A	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TNNI3	Orphanet:154	Familial isolated dilated cardiomyopathy
TNNI3	Orphanet:75249	Familial isolated restrictive cardiomyopathy

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
TNNI3	HGNC:11947	ENSG00000129991	P19429	Troponin I, cardiac muscle	gencc,clinvar
KLF5	HGNC:6349	ENSG00000102554	Q13887	Krueppel-like factor 5	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TNNI3	Troponin I, cardiac muscle	Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.
KLF5	Krueppel-like factor 5	Transcription factor that binds to GC box promoter elements.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TNNI3	Other/Unknown	no		Troponin, Troponin-I_N, Troponin_sf
KLF5	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf

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
apex of heart	1
left ventricle myocardium	1
right atrium auricular region	1
epithelium of nasopharynx	1
gingival epithelium	1
lower esophagus mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TNNI3	169	broad	marker	apex of heart, left ventricle myocardium, right atrium auricular region
KLF5	261	ubiquitous	marker	lower esophagus mucosa, epithelium of nasopharynx, gingival epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KLF5	2,723
TNNI3	1,836

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TNNI3	P19429	39
KLF5	Q13887	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Striated Muscle Contraction	1	154.3×	0.019	TNNI3
Ion homeostasis	1	102.0×	0.019	TNNI3
Adipogenesis	1	78.2×	0.019	KLF5
Transcriptional regulation of white adipocyte differentiation	1	64.9×	0.019	KLF5
Transcriptional regulation of granulopoiesis	1	62.8×	0.019	KLF5
Developmental Biology	1	7.2×	0.134	KLF5

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
regulation of systemic arterial blood pressure by ischemic conditions	1	4213.0×	0.003	TNNI3
positive regulation of transcription by transcription factor localization	1	4213.0×	0.003	KLF5
satellite cell activation involved in skeletal muscle regeneration	1	2106.5×	0.004	KLF5
myotube differentiation involved in skeletal muscle regeneration	1	1685.2×	0.004	KLF5
regulation of microvillus assembly	1	1203.7×	0.004	KLF5
skeletal muscle satellite cell differentiation	1	1053.2×	0.004	KLF5
microvillus assembly	1	936.2×	0.004	KLF5
negative regulation of ATP-dependent activity	1	842.6×	0.004	TNNI3
intestinal epithelial cell development	1	766.0×	0.004	KLF5
cellular response to endothelin	1	702.2×	0.004	KLF5
regulation of cardiac muscle contraction by calcium ion signaling	1	648.1×	0.004	TNNI3
regulation of smooth muscle contraction	1	601.9×	0.004	TNNI3
muscle filament sliding	1	526.6×	0.004	TNNI3
heart contraction	1	383.0×	0.005	TNNI3
ventricular cardiac muscle tissue morphogenesis	1	351.1×	0.005	TNNI3
skeletal muscle contraction	1	255.3×	0.007	TNNI3
cardiac muscle contraction	1	200.6×	0.008	TNNI3
positive regulation of fat cell differentiation	1	150.5×	0.010	KLF5
vasculogenesis	1	127.7×	0.011	TNNI3
cellular response to leukemia inhibitory factor	1	79.5×	0.017	KLF5
intracellular calcium ion homeostasis	1	72.6×	0.018	TNNI3
heart development	1	39.4×	0.031	TNNI3
angiogenesis	1	31.2×	0.037	KLF5
positive regulation of cell population proliferation	1	16.8×	0.066	KLF5
negative regulation of transcription by RNA polymerase II	1	8.9×	0.118	KLF5
positive regulation of transcription by RNA polymerase II	1	7.4×	0.135	KLF5
regulation of transcription by RNA polymerase II	1	5.8×	0.164	KLF5

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TNNI3	0	0
KLF5	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
KLF5	3	Binding:2, Functional:1
TNNI3	2	Binding:2

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	TNNI3, KLF5

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)
TNNI3	2	—
KLF5	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.