cardiac arrhythmia, ankyrin-B-related

Summary

cardiac arrhythmia, ankyrin-B-related (MONDO:0010958) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 506

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cardiac arrhythmia, ankyrin-B-related
Mondo ID	MONDO:0010958
OMIM	600919
DOID	DOID:0111700, DOID:0111701
SNOMED CT	764457005
UMLS	C1970119
MedGen	370181
GARD	0013294
Is cancer (heuristic)	no

Also known as: ankyrin-B syndrome · cardiac arrhythmia, ankyrin-b-related · LQT4

Data availability: 506 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › long QT syndrome › familial long QT syndrome › cardiac arrhythmia, ankyrin-B-related

Related subtypes (18): Jervell and Lange-Nielsen syndrome, Andersen-Tawil syndrome, 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, long QT syndrome 4

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

506 retrieved; paginated sample, class counts are floors:

183 uncertain significance, 175 conflicting classifications of pathogenicity, 90 benign/likely benign, 28 benign, 24 likely benign, 3 likely pathogenic, 2 pathogenic/likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2576605	NM_001148.6(ANK2):c.3262C>T (p.Arg1088Ter)	ANK2	Pathogenic	criteria provided, multiple submitters, no conflicts
985692	NM_001148.6(ANK2):c.11761C>T (p.Gln3921Ter)	ANK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
985758	NM_001148.6(ANK2):c.3019C>T (p.Arg1007Ter)	ANK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3383192	NM_001148.6(ANK2):c.64_65del (p.Arg22fs)	ANK2	Likely pathogenic	criteria provided, single submitter
3897593	NM_001148.6(ANK2):c.4892_4893del (p.Lys1631fs)	ANK2	Likely pathogenic	criteria provided, single submitter
4278327	NM_001148.6(ANK2):c.11137T>G (p.Ser3713Ala)	ANK2	Likely pathogenic	criteria provided, single submitter
1005220	NM_001148.6(ANK2):c.8423A>G (p.Tyr2808Cys)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1010772	NM_001148.6(ANK2):c.229G>A (p.Val77Met)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1024600	NM_001148.6(ANK2):c.1993C>T (p.Pro665Ser)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1033338	NM_001148.6(ANK2):c.7985C>T (p.Ser2662Phe)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1042920	NM_001148.6(ANK2):c.9242A>T (p.Asp3081Val)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1047560	NM_001148.6(ANK2):c.5431C>T (p.Pro1811Ser)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1188715	NM_001148.6(ANK2):c.7265G>A (p.Ser2422Asn)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1206823	NM_001148.6(ANK2):c.6977A>G (p.Asp2326Gly)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1211590	NM_001148.6(ANK2):c.8176A>G (p.Thr2726Ala)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1318748	NM_001148.6(ANK2):c.11807A>G (p.Tyr3936Cys)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
136380	NM_001148.6(ANK2):c.-39G>T	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
136384	NM_001148.6(ANK2):c.1899A>G (p.Leu633=)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1367968	NM_001148.6(ANK2):c.2761G>A (p.Val921Met)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1393809	NM_001148.6(ANK2):c.9967A>G (p.Ser3323Gly)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1416687	NM_001148.6(ANK2):c.7082A>G (p.His2361Arg)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1444516	NM_001148.6(ANK2):c.4259C>T (p.Thr1420Met)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
18056	NM_001148.6(ANK2):c.4373A>G (p.Glu1458Gly)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
18057	NM_001148.6(ANK2):c.11231C>A (p.Thr3744Asn)	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
188143	NM_001148.6(ANK2):c.7132G>A (p.Glu2378Lys)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190529	NM_001148.6(ANK2):c.10703G>A (p.Arg3568Gln)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190561	NM_001148.6(ANK2):c.3067G>A (p.Gly1023Arg)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190562	NM_001148.6(ANK2):c.3074G>C (p.Gly1025Ala)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190565	NM_001148.6(ANK2):c.3526G>T (p.Val1176Leu)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · 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
ANK2	Limited	Autosomal dominant	cardiac arrhythmia, ankyrin-B-related	11

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	gencc,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.