Left ventricular noncompaction 8

Summary

Left ventricular noncompaction 8 (MONDO:0014152) is a disease with 4 cohort genes.

At a glance

• Cohort genes: 4
• ClinVar variants: 1,322

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	left ventricular noncompaction 8
Mondo ID	MONDO:0014152
OMIM	615373
DOID	DOID:0081157
UMLS	C3809288
MedGen	815618
GARD	0015952
Is cancer (heuristic)	no

Also known as: familial isolated dilated cardiomyopathy caused by mutation in PRDM16 · left ventricular noncompaction 8 · left ventricular noncompaction type 8 · LVNC8 · PRDM16 familial isolated dilated cardiomyopathy

Data availability: 1,322 ClinVar variants · 3 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 › left ventricular noncompaction › left ventricular noncompaction 8

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 10, left ventricular noncompaction 9, left ventricular noncompaction 4, 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

600 retrieved; paginated sample, class counts are floors:

288 uncertain significance, 239 likely benign, 28 conflicting classifications of pathogenicity, 23 benign/likely benign, 19 benign, 2 likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1029845	NM_022114.4(PRDM16):c.534C>A (p.Cys178Ter)	PRDM16	Pathogenic	criteria provided, single submitter
1710027	NM_022114.4(PRDM16):c.2434del (p.Arg812fs)	PRDM16	Likely pathogenic	criteria provided, single submitter
2582631	NM_022114.4(PRDM16):c.3142del (p.Leu1048fs)	PRDM16	Likely pathogenic	criteria provided, single submitter
1020280	NM_022114.4(PRDM16):c.2056A>G (p.Thr686Ala)	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1042499	NM_022114.4(PRDM16):c.1525G>A (p.Ala509Thr)	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1214086	NM_022114.4(PRDM16):c.1807G>A (p.Asp603Asn)	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1307370	NM_022114.4(PRDM16):c.746A>G (p.Lys249Arg)	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1308045	NM_022114.4(PRDM16):c.2392G>A (p.Gly798Ser)	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1310240	NM_022114.4(PRDM16):c.2223G>A (p.Thr741=)	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1407377	NM_022114.4(PRDM16):c.445G>A (p.Glu149Lys)	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1419980	NM_022114.4(PRDM16):c.2169G>A (p.Ser723=)	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1805269	NM_022114.4(PRDM16):c.3271C>T (p.Arg1091Ter)	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1915212	NM_022114.4(PRDM16):c.3313G>A (p.Ala1105Thr)	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2109693	NM_022114.4(PRDM16):c.3536A>G (p.His1179Arg)	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2156407	NM_022114.4(PRDM16):c.720G>T (p.Gln240His)	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
218791	NM_022114.4(PRDM16):c.2747C>T (p.Ala916Val)	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
227024	NM_022114.4(PRDM16):c.1426C>T (p.Pro476Ser)	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
227030	NM_022114.4(PRDM16):c.2506G>A (p.Gly836Ser)	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
229156	NM_022114.4(PRDM16):c.1093G>T (p.Ala365Ser)	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
229157	NM_022114.4(PRDM16):c.1187-10G>C	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
229158	NM_022114.4(PRDM16):c.1574G>A (p.Arg525Gln)	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
229162	NM_022114.4(PRDM16):c.2290G>A (p.Val764Met)	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
229164	NM_022114.4(PRDM16):c.2576C>T (p.Ser859Leu)	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
229165	NM_022114.4(PRDM16):c.2786C>A (p.Pro929His)	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
229168	NM_022114.4(PRDM16):c.38-14G>A	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
235271	NM_022114.4(PRDM16):c.553A>G (p.Met185Val)	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
241425	NM_022114.4(PRDM16):c.2449G>A (p.Gly817Ser)	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
241427	NM_022114.4(PRDM16):c.2741T>C (p.Met914Thr)	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
241431	NM_022114.4(PRDM16):c.3621A>T (p.Glu1207Asp)	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2499448	NM_022114.4(PRDM16):c.259C>T (p.Arg87Ter)	PRDM16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 3 · 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
PRDM16	Moderate	Autosomal dominant	left ventricular noncompaction 8	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PRDM16	Orphanet:154	Familial isolated dilated cardiomyopathy
PRDM16	Orphanet:1606	1p36 deletion syndrome
PRDM16	Orphanet:54260	Left ventricular noncompaction

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PRDM16	HGNC:14000	ENSG00000142611	Q9HAZ2	Histone-lysine N-methyltransferase PRDM16	gencc,clinvar
CDK11B	HGNC:1729	ENSG00000248333	P21127	Cyclin-dependent kinase 11B	clinvar
MORN1	HGNC:25852	ENSG00000116151	Q5T089	MORN repeat-containing protein 1	clinvar
CPTP	HGNC:28116	ENSG00000224051	Q5TA50	Ceramide-1-phosphate transfer protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PRDM16	Histone-lysine N-methyltransferase PRDM16	Transcription regulator that acts both as a histone methyltransferase or chromatin adapter, depending on the context.
CDK11B	Cyclin-dependent kinase 11B	Cyclin-dependent protein kinase that acts as a regulator of transcription and pre-mRNA splicing.
CPTP	Ceramide-1-phosphate transfer protein	Mediates the intracellular transfer of ceramide-1-phosphate (C1P) between organelle membranes and the cell membrane.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.25

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
Kinase	1	6.9×	0.410
Transcription factor	1	2.1×	0.605
Other/Unknown	2	0.9×	0.769

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PRDM16	Transcription factor	no	2.1.1.367	SET_dom, Znf_C2H2_type, Znf_C2H2_sf
CDK11B	Kinase	yes	2.7.11.22	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
MORN1	Other/Unknown	no		MORN
CPTP	Other/Unknown	no		Glycolipid_transfer_prot_dom, GLTP_sf

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
sural nerve	2
ascending aorta	1
pigmented layer of retina	1
gastrocnemius	1
muscle of leg	1
olfactory bulb	1
right uterine tube	1
type B pancreatic cell	1
apex of heart	1
heart left ventricle	1
lower esophagus mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PRDM16	202	broad	marker	sural nerve, pigmented layer of retina, ascending aorta
CDK11B	134	ubiquitous	marker	sural nerve, gastrocnemius, muscle of leg
MORN1	173	ubiquitous	marker	right uterine tube, type B pancreatic cell, olfactory bulb
CPTP	278	ubiquitous	marker	apex of heart, lower esophagus mucosa, heart left ventricle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRDM16	2,633
CDK11B	1,943
MORN1	604
CPTP	512

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CPTP	Q5TA50	6
CDK11B	P21127	5
PRDM16	Q9HAZ2	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MORN1	Q5T089	75.53

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. 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
Glycosphingolipid transport	1	475.8×	0.019	CPTP
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	1	126.9×	0.030	PRDM16
Centrosome maturation	1	84.6×	0.030	CDK11B
PKMTs methylate histone lysines	1	53.6×	0.030	PRDM16
Recruitment of mitotic centrosome proteins and complexes	1	45.3×	0.030	CDK11B
Mitotic G2-G2/M phases	1	42.3×	0.030	CDK11B
G2/M Transition	1	42.3×	0.030	CDK11B
Cell Cycle, Mitotic	1	16.1×	0.069	CDK11B
Cell Cycle	1	12.0×	0.081	CDK11B

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
ceramide 1-phosphate transport	1	5617.3×	0.005	CPTP
negative regulation of white fat cell differentiation	1	2808.7×	0.005	PRDM16
beige fat cell differentiation	1	1872.4×	0.005	PRDM16
tolerance induction in gut-associated lymphoid tissue	1	1404.3×	0.005	PRDM16
mitotic sister chromatid cohesion, centromeric	1	1404.3×	0.005	CDK11B
regulation of cellular respiration	1	936.2×	0.006	PRDM16
negative regulation of granulocyte differentiation	1	702.2×	0.006	PRDM16
regulatory T cell differentiation	1	702.2×	0.006	PRDM16
regulation of centrosome cycle	1	624.1×	0.006	CDK11B
negative regulation of muscle cell differentiation	1	561.7×	0.006	PRDM16
ceramide transport	1	510.7×	0.006	CPTP
heterochromatin organization	1	432.1×	0.007	PRDM16
intermembrane lipid transfer	1	401.2×	0.007	CPTP
negative regulation of NLRP3 inflammasome complex assembly	1	330.4×	0.008	CPTP
regulation of mRNA processing	1	295.6×	0.008	CDK11B
protein localization to chromatin	1	193.7×	0.011	PRDM16
negative regulation of interleukin-1 beta production	1	170.2×	0.012	CPTP
brown fat cell differentiation	1	144.0×	0.013	PRDM16
negative regulation of autophagy	1	86.4×	0.021	CPTP
regulation of cell growth	1	73.9×	0.023	CDK11B
regulation of RNA splicing	1	73.0×	0.023	CDK11B
negative regulation of transforming growth factor beta receptor signaling pathway	1	57.9×	0.026	PRDM16
methylation	1	56.7×	0.026	PRDM16
protein maturation	1	54.5×	0.026	PRDM16
positive regulation of cold-induced thermogenesis	1	54.5×	0.026	PRDM16
mitotic cell cycle	1	44.6×	0.030	CDK11B
regulation of apoptotic process	1	27.8×	0.046	CDK11B
regulation of cell cycle	1	24.9×	0.050	CDK11B
protein phosphorylation	1	22.6×	0.053	CDK11B
regulation of DNA-templated transcription	1	10.5×	0.104	CDK11B

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 4 evidence-associated genes (50%) 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
CDK11B	PAZOPANIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CDK11B	12	4
PRDM16	0	0
MORN1	0	0
CPTP	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PAZOPANIB	4	CDK11B
CRIZOTINIB	4	CDK11B
LINIFANIB	3	CDK11B
INDIRUBIN	2	CDK11B
FORETINIB	2	CDK11B
MOLIBRESIB	2	CDK11B
DEFOSBARASERTIB	2	CDK11B
RG-547	2	CDK11B
AT-7519	2	CDK11B
TOZASERTIB	2	CDK11B
BMS-387032	1	CDK11B
AST-487	1	CDK11B

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
CDK11B	158	Binding:158
PRDM16	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PRDM16	2.1.1.367, 2.1.1.370	[histone H3]-lysine9 N-methyltransferase, [histone H3]-lysine4 N-dimethyltransferase
CDK11B	2.7.11.22	cyclin-dependent kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CDK11B	158

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

12 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)
PAZOPANIB	4	CDK11B
CRIZOTINIB	4	CDK11B
LINIFANIB	3	CDK11B
INDIRUBIN	2	CDK11B
FORETINIB	2	CDK11B
MOLIBRESIB	2	CDK11B
DEFOSBARASERTIB	2	CDK11B
RG-547	2	CDK11B
AT-7519	2	CDK11B
TOZASERTIB	2	CDK11B
BMS-387032	1	CDK11B
AST-487	1	CDK11B

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CDK11B
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	3	PRDM16, MORN1, CPTP

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PRDM16	2	—
MORN1	0	—
CPTP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.