Ventricular tachycardia, familial

Summary

Ventricular tachycardia, familial (MONDO:0008648) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ventricular tachycardia, familial
Mondo ID	MONDO:0008648
OMIM	192605
SNOMED CT	233906007
UMLS	C0340485
MedGen	83309
GARD	0002263
Is cancer (heuristic)	no

Also known as: familial ventricular tachycardia · hereditary ventricular tachycardia · ventricular tachycardia, familial · ventricular tachycardia, idiopathic

Data availability: 1 ClinVar variant · 3 GenCC gene-disease records.

Disease family

An umbrella term covering 1 Mondo subtype.

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

Related subtypes (2): torsades de pointes, polymorphic ventricular tachycardia

Subtypes (1): catecholaminergic polymorphic ventricular tachycardia

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

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
3893134	NM_002070.4(GNAI2):c.385C>T (p.Arg129Trp)	GNAI2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 1 · 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
GNAI2	Moderate	Autosomal dominant	ventricular tachycardia, familial	2
ABCA5	Limited	Unknown	ventricular tachycardia, familial	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ABCA5	Orphanet:2026	Gingival fibromatosis-hypertrichosis 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
GNAI2	HGNC:4385	ENSG00000114353	P04899	Guanine nucleotide-binding protein G(i) subunit alpha-2	gencc,clinvar
ABCA5	HGNC:35	ENSG00000154265	Q8WWZ7	Cholesterol transporter ABCA5	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GNAI2	Guanine nucleotide-binding protein G(i) subunit alpha-2	Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades.
ABCA5	Cholesterol transporter ABCA5	Cholesterol efflux transporter in macrophages that is responsible for APOAI/high-density lipoproteins (HDL) formation at the plasma membrane under high cholesterol levels and participates in reverse cholesterol transport.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Transporter	1	38.9×	0.051
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GNAI2	Other/Unknown	no		Gprotein_alpha_su, Gprotein_alpha_I, GproteinA_insert
ABCA5	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC2_TM

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
granulocyte	1
monocyte	1
right lung	1
adrenal tissue	1
body of pancreas	1
calcaneal tendon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GNAI2	291	ubiquitous	marker	granulocyte, monocyte, right lung
ABCA5	289	ubiquitous	marker	adrenal tissue, body of pancreas, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GNAI2	3,311
ABCA5	817

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GNAI2	P04899	34

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ABCA5	Q8WWZ7	77.12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. 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
Adenylate cyclase inhibitory pathway	1	380.7×	0.015	GNAI2
ABC transporters in lipid homeostasis	1	300.5×	0.015	ABCA5
ADP signalling through P2Y purinoceptor 12	1	248.3×	0.015	GNAI2
Adrenaline,noradrenaline inhibits insulin secretion	1	196.9×	0.015	GNAI2
ADORA2B mediated anti-inflammatory cytokines production	1	126.9×	0.015	GNAI2
GPER1 signaling	1	124.1×	0.015	GNAI2
G alpha (z) signalling events	1	116.5×	0.015	GNAI2
Regulation of insulin secretion	1	109.8×	0.015	GNAI2
Extra-nuclear estrogen signaling	1	85.2×	0.017	GNAI2
ABC-family protein mediated transport	1	60.7×	0.021	ABCA5
G alpha (s) signalling events	1	36.6×	0.032	GNAI2
G alpha (i) signalling events	1	19.5×	0.055	GNAI2
Transport of small molecules	1	12.6×	0.078	ABCA5

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
positive regulation of reverse cholesterol transport	1	4213.0×	0.005	ABCA5
G protein-coupled adenosine receptor signaling pathway	1	1203.7×	0.005	GNAI2
regulation of cholesterol efflux	1	1203.7×	0.005	ABCA5
negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway	1	1203.7×	0.005	GNAI2
negative regulation of calcium ion-dependent exocytosis	1	936.2×	0.005	GNAI2
negative regulation of synaptic transmission	1	842.6×	0.005	GNAI2
negative regulation of adenylate cyclase activity	1	702.2×	0.005	GNAI2
negative regulation of macrophage derived foam cell differentiation	1	648.1×	0.005	ABCA5
positive regulation of urine volume	1	648.1×	0.005	GNAI2
G protein-coupled acetylcholine receptor signaling pathway	1	526.6×	0.006	GNAI2
reverse cholesterol transport	1	468.1×	0.006	ABCA5
positive regulation of superoxide anion generation	1	443.5×	0.006	GNAI2
high-density lipoprotein particle remodeling	1	401.2×	0.006	ABCA5
regulation of calcium ion transport	1	401.2×	0.006	GNAI2
positive regulation of neural precursor cell proliferation	1	383.0×	0.006	GNAI2
negative regulation of apoptotic signaling pathway	1	280.9×	0.007	GNAI2
gamma-aminobutyric acid signaling pathway	1	271.8×	0.007	GNAI2
cholesterol efflux	1	263.3×	0.007	ABCA5
positive regulation of vascular associated smooth muscle cell proliferation	1	216.1×	0.008	GNAI2
response to nutrient	1	147.8×	0.011	GNAI2
lipid transport	1	131.7×	0.012	ABCA5
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1	109.4×	0.013	GNAI2
cholesterol metabolic process	1	98.0×	0.014	ABCA5
cholesterol homeostasis	1	78.0×	0.017	ABCA5
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1	56.5×	0.023	GNAI2
cell population proliferation	1	51.4×	0.024	GNAI2
positive regulation of ERK1 and ERK2 cascade	1	42.6×	0.028	GNAI2
positive regulation of cell migration	1	30.9×	0.037	GNAI2
cell division	1	23.1×	0.047	GNAI2
G protein-coupled receptor signaling pathway	1	18.1×	0.058	GNAI2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GNAI2	2	3
ABCA5	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ALISERTIB	3	GNAI2
MOLIBRESIB	2	GNAI2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
GNAI2	9	Binding:9

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

2 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)
ALISERTIB	3	GNAI2
MOLIBRESIB	2	GNAI2

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	1	GNAI2
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	ABCA5
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)
ABCA5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.