long QT syndrome 4

Summary

long QT syndrome 4 (MONDO:0800323) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	long QT syndrome 4
Mondo ID	MONDO:0800323
UMLS	C1833154
MedGen	331449
GARD	0026501
Is cancer (heuristic)	no

Also known as: LQT4

Data availability: 4 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › long QT syndrome › familial long QT syndrome › long QT syndrome 4

Related subtypes (18): Jervell and Lange-Nielsen syndrome, Andersen-Tawil syndrome, cardiac arrhythmia, ankyrin-B-related, Timothy syndrome, long QT syndrome 3, long QT syndrome 9, long QT syndrome 10, long QT syndrome 11, long QT syndrome 12, long QT syndrome 13, long QT syndrome 2, long QT syndrome 6, long QT syndrome 5, long QT syndrome 14, long QT syndrome 15, long QT syndrome 8, long QT syndrome 16, long QT syndrome 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

4 retrieved; paginated sample, class counts are floors:

3 conflicting classifications of pathogenicity, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
18056	NM_001148.6(ANK2):c.4373A>G (p.Glu1458Gly)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
18059	NM_001148.6(ANK2):c.11716C>T (p.Arg3906Trp)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190570	NM_001148.6(ANK2):c.4016C>T (p.Pro1339Leu)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
526950	NM_001148.6(ANK2):c.4673A>G (p.Asp1558Gly)	ANK2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ANK2	Orphanet:101016	Romano-Ward syndrome

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
ANK2	HGNC:493	ENSG00000145362	Q01484	Ankyrin-2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ANK2	Ankyrin-2	Plays an essential role in the localization and membrane stabilization of ion transporters and ion channels in several cell types, including cardiomyocytes, as well as in striated muscle cells.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ANK2	Scaffold/PPI	no		Death_dom, ZU5_dom, Ankyrin_rpt

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
lateral nuclear group of thalamus	1
substantia nigra pars compacta	1
substantia nigra pars reticulata	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ANK2	281	ubiquitous	marker	substantia nigra pars compacta, lateral nuclear group of thalamus, substantia nigra pars reticulata

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ANK2	6,423

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ANK2	Q01484	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. 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
Interaction between L1 and Ankyrins	1	368.4×	0.025	ANK2
ER to Golgi Anterograde Transport	1	132.8×	0.025	ANK2
L1CAM interactions	1	120.2×	0.025	ANK2
COPI-mediated anterograde transport	1	109.8×	0.025	ANK2
Transport to the Golgi and subsequent modification	1	102.9×	0.025	ANK2
Asparagine N-linked glycosylation	1	60.1×	0.036	ANK2
Axon guidance	1	45.1×	0.037	ANK2
Nervous system development	1	42.9×	0.037	ANK2
Membrane Trafficking	1	37.1×	0.037	ANK2
Vesicle-mediated transport	1	34.8×	0.037	ANK2
Post-translational protein modification	1	19.2×	0.062	ANK2
Developmental Biology	1	14.5×	0.075	ANK2
Metabolism of proteins	1	12.4×	0.081	ANK2

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
protein localization to T-tubule	1	16852.0×	7e-04	ANK2
atrial cardiac muscle cell to AV node cell communication	1	16852.0×	7e-04	ANK2
SA node cell to atrial cardiac muscle cell communication	1	16852.0×	7e-04	ANK2
protein localization to M-band	1	8426.0×	0.001	ANK2
regulation of atrial cardiac muscle cell action potential	1	5617.3×	0.001	ANK2
sarcoplasmic reticulum calcium ion transport	1	3370.4×	0.001	ANK2
membrane depolarization during SA node cell action potential	1	3370.4×	0.001	ANK2
positive regulation of potassium ion import across plasma membrane	1	3370.4×	0.001	ANK2
paranodal junction assembly	1	2808.7×	0.001	ANK2
T-tubule organization	1	2808.7×	0.001	ANK2
SA node cell action potential	1	2808.7×	0.001	ANK2
regulation of SA node cell action potential	1	2808.7×	0.001	ANK2
response to methylmercury	1	2407.4×	0.001	ANK2
atrial septum development	1	2106.5×	0.001	ANK2
protein localization to endoplasmic reticulum	1	2106.5×	0.001	ANK2
atrial cardiac muscle cell action potential	1	1685.2×	0.001	ANK2
regulation of cardiac muscle contraction by calcium ion signaling	1	1296.3×	0.002	ANK2
regulation of cardiac muscle cell contraction	1	1123.5×	0.002	ANK2
ventricular cardiac muscle cell action potential	1	991.3×	0.002	ANK2
regulation of release of sequestered calcium ion into cytosol	1	936.2×	0.002	ANK2
regulation of cardiac muscle contraction	1	887.0×	0.002	ANK2
regulation of ventricular cardiac muscle cell membrane repolarization	1	842.6×	0.002	ANK2
regulation of calcium ion transport	1	802.5×	0.002	ANK2
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	1	674.1×	0.002	ANK2
positive regulation of calcium ion transport	1	581.1×	0.002	ANK2
protein localization to cell surface	1	495.6×	0.003	ANK2
regulation of heart rate	1	468.1×	0.003	ANK2
regulation of heart rate by cardiac conduction	1	374.5×	0.003	ANK2
intracellular calcium ion homeostasis	1	145.3×	0.009	ANK2
regulation of protein stability	1	125.8×	0.010	ANK2

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
ANK2	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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	ANK2

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)
ANK2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.