dilated cardiomyopathy 1V

Summary

dilated cardiomyopathy 1V (MONDO:0013373) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 79

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dilated cardiomyopathy 1V
Mondo ID	MONDO:0013373
MeSH	C566856
OMIM	613697
DOID	DOID:0110427
UMLS	C3150958
MedGen	462308
GARD	0015690
Is cancer (heuristic)	no

Also known as: cardiomyopathy, dilated, 1V · cardiomyopathy, dilated, type 1V · CMD1V · dilated cardiomyopathy type 1V · familial isolated dilated cardiomyopathy caused by mutation in PSEN2 · PSEN2 familial isolated dilated cardiomyopathy

Data availability: 79 ClinVar variants.

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 1V

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 1FF, dilated cardiomyopathy 1R, dilated cardiomyopathy 1S, dilated cardiomyopathy 1GG, dilated cardiomyopathy 1U, 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

79 retrieved; paginated sample, class counts are floors:

34 uncertain significance, 16 benign/likely benign, 15 conflicting classifications of pathogenicity, 12 benign, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
180476	NM_000447.3(PSEN2):c.149A>G (p.Gln50Arg)	PSEN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191771	NM_000447.3(PSEN2):c.205C>G (p.Pro69Ala)	PSEN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
295988	NM_000447.3(PSEN2):c.222C>G (p.Gly74=)	PSEN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
295989	NM_000447.3(PSEN2):c.336C>T (p.Tyr112=)	PSEN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
295991	NM_000447.3(PSEN2):c.690C>G (p.Ala230=)	PSEN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
295994	NM_000447.3(PSEN2):c.954C>T (p.Pro318=)	PSEN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
295995	NM_000447.3(PSEN2):c.1077C>T (p.Gly359=)	PSEN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
295999	NM_000447.3(PSEN2):c.*120G>A	PSEN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
296002	NM_000447.3(PSEN2):c.*306G>A	PSEN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
448149	NM_000447.3(PSEN2):c.415G>A (p.Val139Met)	PSEN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
448151	NM_000447.3(PSEN2):c.712C>T (p.Leu238Phe)	PSEN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
705974	NM_000447.3(PSEN2):c.754G>A (p.Ala252Thr)	PSEN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
706267	NM_000447.3(PSEN2):c.300C>T (p.Ile100=)	PSEN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
721218	NM_000447.3(PSEN2):c.100G>A (p.Gly34Ser)	PSEN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
874474	NM_000447.3(PSEN2):c.711G>A (p.Ala237=)	PSEN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1054623	NM_000447.3(PSEN2):c.203T>C (p.Val68Ala)	PSEN2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1338977	NM_000447.3(PSEN2):c.584A>G (p.Tyr195Cys)	PSEN2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1446296	NM_000447.3(PSEN2):c.85C>T (p.Arg29Cys)	PSEN2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1678339	NM_000447.3(PSEN2):c.902C>T (p.Thr301Met)	PSEN2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1802211	NM_000447.3(PSEN2):c.250G>A (p.Gly84Arg)	PSEN2	Uncertain significance	criteria provided, multiple submitters, no conflicts
295982	NM_000447.3(PSEN2):c.-278C>T	PSEN2	Uncertain significance	criteria provided, single submitter
295984	NM_000447.3(PSEN2):c.-144A>G	PSEN2	Uncertain significance	criteria provided, single submitter
295985	NM_000447.3(PSEN2):c.-82T>C	PSEN2	Uncertain significance	criteria provided, single submitter
295987	NM_000447.3(PSEN2):c.38T>C (p.Val13Ala)	PSEN2	Uncertain significance	criteria provided, multiple submitters, no conflicts
295990	NM_000447.3(PSEN2):c.410A>G (p.Asn137Ser)	PSEN2	Uncertain significance	criteria provided, multiple submitters, no conflicts
295993	NM_000447.3(PSEN2):c.937G>A (p.Gly313Ser)	PSEN2	Uncertain significance	criteria provided, multiple submitters, no conflicts
295996	NM_000447.3(PSEN2):c.*20G>A	PSEN2	Uncertain significance	criteria provided, multiple submitters, no conflicts
295997	NM_000447.3(PSEN2):c.*72T>C	PSEN2	Uncertain significance	criteria provided, single submitter
295998	NM_000447.3(PSEN2):c.*103C>T	PSEN2	Uncertain significance	criteria provided, single submitter
296000	NM_000447.3(PSEN2):c.*132T>C	PSEN2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PSEN2	Orphanet:1020	Early-onset autosomal dominant Alzheimer disease
PSEN2	Orphanet:154	Familial isolated dilated cardiomyopathy

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
PSEN2	HGNC:9509	ENSG00000143801	P49810	Presenilin-2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PSEN2	Presenilin-2	Catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein).

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PSEN2	Protease	yes		Peptidase_A22A, Pept_A22A_PS2, Preselin/SPP

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
body of pancreas	1
male germ line stem cell (sensu Vertebrata) in testis	1
pancreas	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PSEN2	134	ubiquitous	marker	body of pancreas, male germ line stem cell (sensu Vertebrata) in testis, pancreas

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PSEN2	2,338

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PSEN2	P49810	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. Enrichment computed across 1 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
Noncanonical activation of NOTCH3	1	1427.5×	0.003	PSEN2
Regulated proteolysis of p75NTR	1	1038.2×	0.003	PSEN2
NOTCH4 Activation and Transmission of Signal to the Nucleus	1	1038.2×	0.003	PSEN2
TGFBR3 PTM regulation	1	951.7×	0.003	PSEN2
NRIF signals cell death from the nucleus	1	713.8×	0.003	PSEN2
NOTCH3 Activation and Transmission of Signal to the Nucleus	1	475.8×	0.004	PSEN2
NOTCH2 Activation and Transmission of Signal to the Nucleus	1	439.2×	0.004	PSEN2
Activated NOTCH1 Transmits Signal to the Nucleus	1	356.9×	0.004	PSEN2
Nuclear signaling by ERBB4	1	346.1×	0.004	PSEN2
EPH-ephrin mediated repulsion of cells	1	219.6×	0.005	PSEN2
Constitutive Signaling by NOTCH1 PEST Domain Mutants	1	196.9×	0.005	PSEN2
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	1	196.9×	0.005	PSEN2

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
regulation of calcium import into the mitochondrion	1	5617.3×	0.001	PSEN2
obsolete mitochondrion-endoplasmic reticulum membrane tethering	1	2106.5×	0.001	PSEN2
Notch receptor processing	1	1872.4×	0.001	PSEN2
amyloid-beta formation	1	1872.4×	0.001	PSEN2
amyloid precursor protein catabolic process	1	1203.7×	0.002	PSEN2
membrane protein ectodomain proteolysis	1	648.1×	0.003	PSEN2
calcium ion homeostasis	1	443.5×	0.004	PSEN2
protein processing	1	170.2×	0.008	PSEN2
Notch signaling pathway	1	141.6×	0.009	PSEN2
response to hypoxia	1	95.8×	0.011	PSEN2
intracellular signal transduction	1	38.1×	0.026	PSEN2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
PSEN2	NIROGACESTAT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PSEN2	8	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NIROGACESTAT	4	PSEN2
TARENFLURBIL	3	PSEN2
SEMAGACESTAT	3	PSEN2
AVAGACESTAT	2	PSEN2
RG-4733	2	PSEN2
BEGACESTAT	2	PSEN2
E-2212	1	PSEN2
MK-0752	1	PSEN2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
PSEN2	479	Binding:460, Functional:12, ADMET:6, Unclassified:1

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PSEN2	479

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

8 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)
NIROGACESTAT	4	PSEN2
TARENFLURBIL	3	PSEN2
SEMAGACESTAT	3	PSEN2
AVAGACESTAT	2	PSEN2
RG-4733	2	PSEN2
BEGACESTAT	2	PSEN2
E-2212	1	PSEN2
MK-0752	1	PSEN2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PSEN2
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.