Ventricular fibrillation, paroxysmal familial, 2

Summary

Ventricular fibrillation, paroxysmal familial, 2 (MONDO:0013063) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ventricular fibrillation, paroxysmal familial, 2
Mondo ID	MONDO:0013063
MeSH	C567841
OMIM	612956
UMLS	C2751829
MedGen	442823
GARD	0015596
Is cancer (heuristic)	no

Also known as: DPP6 ventricular fibrillation (disease) · ventricular fibrillation (disease) caused by mutation in DPP6 · ventricular fibrillation, paroxysmal familial, 2 · ventricular fibrillation, paroxysmal familial, type 2 · VF2

Data availability: 10 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › cardiac rhythm disease › ventricular fibrillation › paroxysmal familial ventricular fibrillation › ventricular fibrillation, paroxysmal familial, 2

Related subtypes (1): ventricular fibrillation, paroxysmal familial, type 1

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

10 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 2 conflicting classifications of pathogenicity, 2 benign, 1 pathogenic; risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
16794	NM_130797.4(DPP6):c.244-141059C>T	DPP6	Pathogenic; risk factor	no assertion criteria provided
1049455	NM_130797.4(DPP6):c.58G>A (p.Ala20Thr)	DPP6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
810229	NM_130797.4(DPP6):c.167GCG[8] (p.Gly62dup)	DPP6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1049266	NM_130797.4(DPP6):c.1621G>A (p.Ala541Thr)	DPP6	Uncertain significance	criteria provided, single submitter
3594439	NM_130797.4(DPP6):c.685C>A (p.Pro229Thr)	DPP6	Uncertain significance	criteria provided, multiple submitters, no conflicts
3594440	NM_130797.4(DPP6):c.965G>A (p.Arg322His)	DPP6	Uncertain significance	criteria provided, single submitter
3594441	NM_130797.4(DPP6):c.1578G>C (p.Gln526His)	DPP6	Uncertain significance	criteria provided, single submitter
3731513	NM_130797.4(DPP6):c.1667-4A>G	DPP6	Uncertain significance	criteria provided, single submitter
1174770	NM_130797.4(DPP6):c.723A>G (p.Lys241=)	DPP6	Benign	criteria provided, multiple submitters, no conflicts
1297169	NM_130797.4(DPP6):c.813G>A (p.Gln271=)	DPP6	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
DPP6	Supportive	Autosomal dominant	paroxysmal familial ventricular fibrillation	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DPP6	Orphanet:228140	Idiopathic ventricular fibrillation
DPP6	Orphanet:2514	Autosomal dominant primary microcephaly

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
DPP6	HGNC:3010	ENSG00000130226	P42658	A-type potassium channel modulatory protein DPP6	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DPP6	A-type potassium channel modulatory protein DPP6	Promotes cell surface expression of the potassium channel KCND2.

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)
DPP6	Protease	yes		Peptidase_S9_cat, Peptidase_S9B_N, AB_hydrolase_fold

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
Brodmann (1909) area 23	1
endothelial cell	1
middle temporal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DPP6	221	broad	marker	middle temporal gyrus, Brodmann (1909) area 23, endothelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DPP6	2,224

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DPP6	P42658	8

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
regulation of potassium ion transmembrane transport	1	624.1×	0.005	DPP6
protein localization to plasma membrane	1	108.7×	0.014	DPP6
proteolysis	1	34.2×	0.029	DPP6

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
DPP6	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	1	DPP6
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
DPP6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.