Left ventricular noncompaction 4

Summary

Left ventricular noncompaction 4 (MONDO:0800350) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	left ventricular noncompaction 4
Mondo ID	MONDO:0800350
UMLS	C3150682
MedGen	462032
GARD	0026515
Is cancer (heuristic)	no

Also known as: LVNC4

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › cardiomyopathy › intrinsic cardiomyopathy › left ventricular noncompaction › left ventricular noncompaction 4

Related subtypes (12): dilated cardiomyopathy 1C, dilated cardiomyopathy 1D, left ventricular noncompaction 1, left ventricular noncompaction 2, dilated cardiomyopathy 1Y, dilated cardiomyopathy 1R, dilated cardiomyopathy 1S, left ventricular noncompaction 7, left ventricular noncompaction 8, left ventricular noncompaction 10, left ventricular noncompaction 9, left ventricular noncompaction 5

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

2 retrieved; paginated sample, class counts are floors:

1 not provided, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
18331	NM_005159.5(ACTC1):c.301G>A (p.Glu101Lys)	ACTC1	Pathogenic	reviewed by expert panel
1177490	NM_004380.3(CREBBP):c.383C>A (p.Ser128Tyr)	CREBBP	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 7 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ACTC1	Orphanet:154	Familial isolated dilated cardiomyopathy
ACTC1	Orphanet:54260	Left ventricular noncompaction
ACTC1	Orphanet:99103	Atrial septal defect, ostium secundum type
CREBBP	Orphanet:353277	Rubinstein-Taybi syndrome due to CREBBP mutations
CREBBP	Orphanet:353281	Rubinstein-Taybi syndrome due to 16p13.3 microdeletion
CREBBP	Orphanet:370026	Acute myeloid leukemia with t(8;16)(p11;p13) translocation
CREBBP	Orphanet:592574	Menke-Hennekam syndrome

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
ACTC1	HGNC:143	ENSG00000159251	P68032	Actin, alpha cardiac muscle 1	clinvar
CREBBP	HGNC:2348	ENSG00000005339	Q92793	CREB-binding protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ACTC1	Actin, alpha cardiac muscle 1	Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
CREBBP	CREB-binding protein	Acetylates histones, giving a specific tag for transcriptional activation.

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)
ACTC1	Other/Unknown	no		Actin, Actin_CS, Actin/actin-like_CS
CREBBP	Transcription factor	no	2.3.1.48	Znf_TAZ, Znf_ZZ, Bromodomain

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
heart right ventricle	1
left ventricle myocardium	1
myocardium	1
amniotic fluid	1
sural nerve	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ACTC1	224	broad	marker	left ventricle myocardium, heart right ventricle, myocardium
CREBBP	297	ubiquitous	marker	sural nerve, tibia, amniotic fluid

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CREBBP	6,959
ACTC1	996

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CREBBP	Q92793	144
ACTC1	P68032	16

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 137. 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
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production	1	1142.0×	0.015	CREBBP
NFE2L2 regulating inflammation associated genes	1	1142.0×	0.015	CREBBP
NFE2L2 regulating ER-stress associated genes	1	1142.0×	0.015	CREBBP
RUNX1 regulates transcription of genes involved in differentiation of myeloid cells	1	713.8×	0.015	CREBBP
NFE2L2 regulates pentose phosphate pathway genes	1	713.8×	0.015	CREBBP
NFE2L2 regulating MDR associated enzymes	1	713.8×	0.015	CREBBP
Regulation of NFE2L2 gene expression	1	713.8×	0.015	CREBBP
Regulation of FOXO transcriptional activity by acetylation	1	571.0×	0.015	CREBBP
Regulation of gene expression by Hypoxia-inducible Factor	1	475.8×	0.015	CREBBP
Activation of the TFAP2 (AP-2) family of transcription factors	1	475.8×	0.015	CREBBP
Regulation of CDH1 Function	1	475.8×	0.015	ACTC1
NFE2L2 regulating tumorigenic genes	1	475.8×	0.015	CREBBP
Cellular response to hypoxia	1	439.2×	0.015	CREBBP
Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters	1	439.2×	0.015	CREBBP
RUNX3 regulates NOTCH signaling	1	407.9×	0.015	CREBBP
TRAF3-dependent IRF activation pathway	1	380.7×	0.015	CREBBP
R-HSA-1368082	1	356.9×	0.015	CREBBP
Regulation of beta-cell development	1	356.9×	0.015	CREBBP
Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells	1	356.9×	0.015	CREBBP
FOXO-mediated transcription of cell death genes	1	356.9×	0.015	CREBBP
Maternal to zygotic transition (MZT)	1	356.9×	0.015	CREBBP
The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CLOCK) complex	1	356.9×	0.015	CREBBP
Zygotic genome activation (ZGA)	1	335.9×	0.015	CREBBP
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1	317.2×	0.015	CREBBP
NOTCH4 Intracellular Domain Regulates Transcription	1	285.5×	0.015	CREBBP
Transcriptional Regulation by NPAS4	1	285.5×	0.015	CREBBP
TP53 Regulates Transcription of Cell Death Genes	1	271.9×	0.015	CREBBP
TP53 Regulates Transcription of Genes Involved in Cytochrome C Release	1	271.9×	0.015	CREBBP
NFE2L2 regulating anti-oxidant/detoxification enzymes	1	271.9×	0.015	CREBBP
CD209 (DC-SIGN) signaling	1	259.6×	0.015	CREBBP

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
actin-myosin filament sliding	1	4213.0×	0.005	ACTC1
N-terminal peptidyl-lysine acetylation	1	2808.7×	0.005	CREBBP
cytoplasmic actin-based contraction involved in cell motility	1	1685.2×	0.005	ACTC1
mesenchyme migration	1	1685.2×	0.005	ACTC1
skeletal muscle thin filament assembly	1	1404.3×	0.005	ACTC1
negative regulation of transcription by RNA polymerase I	1	1203.7×	0.005	CREBBP
homeostatic process	1	842.6×	0.005	CREBBP
protein acetylation	1	702.2×	0.005	CREBBP
cardiac muscle tissue morphogenesis	1	702.2×	0.005	ACTC1
cAMP/PKA signal transduction	1	702.2×	0.005	CREBBP
cardiac myofibril assembly	1	648.1×	0.005	ACTC1
regulation of cellular response to heat	1	526.6×	0.006	CREBBP
actin filament-based movement	1	401.2×	0.007	ACTC1
heart contraction	1	383.0×	0.007	ACTC1
stimulatory C-type lectin receptor signaling pathway	1	366.4×	0.007	CREBBP
regulation of smoothened signaling pathway	1	312.1×	0.008	CREBBP
actomyosin structure organization	1	280.9×	0.008	ACTC1
positive regulation of transforming growth factor beta receptor signaling pathway	1	263.3×	0.008	CREBBP
cellular response to nutrient levels	1	234.1×	0.009	CREBBP
cardiac muscle contraction	1	200.6×	0.009	ACTC1
positive regulation of protein localization to nucleus	1	195.9×	0.009	CREBBP
positive regulation of double-strand break repair via homologous recombination	1	191.5×	0.009	CREBBP
canonical NF-kappaB signal transduction	1	183.2×	0.009	CREBBP
embryonic digit morphogenesis	1	150.5×	0.010	CREBBP
cellular response to UV	1	147.8×	0.010	CREBBP
protein destabilization	1	145.3×	0.010	CREBBP
rhythmic process	1	125.8×	0.011	CREBBP
response to ethanol	1	73.3×	0.019	ACTC1
actin filament organization	1	59.3×	0.023	ACTC1
protein-containing complex assembly	1	56.9×	0.023	CREBBP

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 evidence-associated genes (100%) 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
CREBBP	COLCHICINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CREBBP	13	4
ACTC1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
COLCHICINE	4	CREBBP
ALTRETAMINE	4	CREBBP
CURCUMIN	3	CREBBP
PAPAVERINE	3	CREBBP
EPIGALOCATECHIN GALLATE	3	CREBBP
MOLIBRESIB	2	CREBBP
FISETIN	2	CREBBP
ETAZOLATE	2	CREBBP
LUNRESERTIB	2	CREBBP
TRACAZOLATE	2	CREBBP
NOCODAZOLE	2	CREBBP
INOBRODIB	1	CREBBP
AZD-5153	1	CREBBP

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CREBBP	687	Binding:644, Functional:43
ACTC1	6	Binding:6

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CREBBP	2.3.1.48	histone acetyltransferase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CREBBP	687

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

13 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)
COLCHICINE	4	CREBBP
ALTRETAMINE	4	CREBBP
CURCUMIN	3	CREBBP
PAPAVERINE	3	CREBBP
EPIGALOCATECHIN GALLATE	3	CREBBP
MOLIBRESIB	2	CREBBP
FISETIN	2	CREBBP
ETAZOLATE	2	CREBBP
LUNRESERTIB	2	CREBBP
TRACAZOLATE	2	CREBBP
NOCODAZOLE	2	CREBBP
INOBRODIB	1	CREBBP
AZD-5153	1	CREBBP

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CREBBP
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	ACTC1

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)
ACTC1	6	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.