Cardiomyopathy, dilated, 2j

Summary

Cardiomyopathy, dilated, 2j (MONDO:0957984) is a disease caused by FLII (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: FLII (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cardiomyopathy, dilated, 2j
Mondo ID	MONDO:0957984
OMIM	620635
UMLS	C5882725
MedGen	1846005
GARD	0026900
Is cancer (heuristic)	no

Data availability: 5 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 › cardiomyopathy, dilated, 2j

Related subtypes (28): autosomal recessive limb-girdle muscular dystrophy type 2C, Barth syndrome, histiocytoid cardiomyopathy, Kearns-Sayre syndrome, Leber hereditary optic neuropathy, autosomal recessive limb-girdle muscular dystrophy type 2F, myofibrillar myopathy 1, autosomal recessive limb-girdle muscular dystrophy type 2E, dilated cardiomyopathy 1J, hypertrophic cardiomyopathy 25, autosomal recessive limb-girdle muscular dystrophy type 2D, DK1-congenital disorder of glycosylation, autosomal recessive limb-girdle muscular dystrophy type 2M, early-onset myopathy with fatal cardiomyopathy, PGM1-congenital disorder of glycosylation, autosomal recessive limb-girdle muscular dystrophy type 2W, symptomatic form of muscular dystrophy of Duchenne and Becker in female carriers, Emery-Dreifuss muscular dystrophy, familial isolated dilated cardiomyopathy, cardiomyopathy, dilated, 1LL, cardiomyopathy, dilated, 1MM, cardiomyopathy, dilated, 100, cardiomyopathy, dilated, 2I, cardiomyopathy, dilated, 2K, cardiomyopathy, dilated, 2l, cardiomyopathy, dilated, 1QQ, cardiomyopathy, dilated, 2M, cardiomyopathy, dilated, 3C

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

5 retrieved; paginated sample, class counts are floors:

2 likely pathogenic, 2 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
2663896	NM_002018.4(FLII):c.1360C>T (p.Gln454Ter)	FLII	Pathogenic	no assertion criteria provided
2663897	NM_002018.4(FLII):c.3502C>T (p.Arg1168Trp)	FLII	Pathogenic	no assertion criteria provided
1699194	NM_002018.4(FLII):c.3718C>T (p.Arg1240Cys)	FLII	Likely pathogenic	criteria provided, single submitter
4849343	NM_002018.4(FLII):c.1382_1383+1del	FLII	Likely pathogenic	criteria provided, single submitter
2663895	NM_002018.4(FLII):c.2020C>G (p.Leu674Val)	FLII	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · 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
FLII	Strong	Autosomal recessive	cardiomyopathy, dilated, 2j	8

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
FLII	HGNC:3750	ENSG00000177731	Q13045	Protein flightless-1 homolog	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FLII	Protein flightless-1 homolog	Is a regulator of actin polymerization, required for proper myofibril organization and regulation of the length of sarcomeric thin filaments.

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)
FLII	Other/Unknown	no		Leu-rich_rpt, Leu-rich_rpt_typical-subtyp, Villin/Gelsolin

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
hindlimb stylopod muscle	1
lower esophagus mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FLII	134	ubiquitous	marker	lower esophagus mucosa, apex of heart, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FLII	2,364

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FLII	Q13045	81.20

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
actin filament severing	1	1203.7×	0.002	FLII
myofibril assembly	1	1123.5×	0.002	FLII
barbed-end actin filament capping	1	802.5×	0.002	FLII
actin polymerization or depolymerization	1	766.0×	0.002	FLII
sarcomere organization	1	383.0×	0.003	FLII

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
FLII	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	FLII

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)
FLII	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.