ANK2

ankyrin 2

4 disorders 2 disputed 1 causative 1 untyped 4q25-q26 gene with protein product

HGNC:493 Monarch NCBI Gene 287 ENSG00000145362 UniProt Q01484 OMIM 106410

Previous symbols: LQT4. Aliases: FAP87, CFAP87.

Normal function · from ai-gene-review (Q01484, commit 79fe13b38970) · AI-generated, not KB evidence

Ankyrin-B is a membrane-associated adaptor that binds spectrins and organizes ion channels, transporters and other membrane proteins. In cardiac cells it positions calcium-handling proteins and supports electrical activity; in muscle it contributes to dystrophin-associated membrane organization. A 220-kDa form also couples PI3P-bearing organelles to dynactin and recruits RabGAP1L during endosomal trafficking. The giant neuronal form contains an insertion that binds and bundles microtubules to constrain axonal branching. It also maintains L1CAM-neuropilin receptor complexes at the neuronal surface for Sema3A responses, through a mechanism separable from its microtubule-binding and betaII-spectrin interactions.

Couples membrane proteins to spectrin-based and associated cytoskeletal assemblies, positioning transporters, channels and dystrophin-associated machinery. This anchoring organizes cardiac calcium-handling proteins and muscle membrane complexes. The giant isoform also organizes Sema3A receptor targeting through a membrane-organizing mechanism separable from its microtubule binding and betaII-spectrin interaction.

molecular function: cytoskeletal adaptor activity · directly involved in: protein localization to plasma membrane; cytoskeleton organization · locations: plasma membrane; M band

The neurospecific giant ankyrin-B domain directly binds and bundles microtubules through tandem repeats and an adjacent conserved segment. Human recombinant fragments establish the molecular activity; human full-length construct rescue in mouse neurons links this activity to restricting microtubule entry into nascent axon branches. This function is distinct from the spectrin-associated membrane-adaptor mechanism.

molecular function: microtubule binding

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
ANK2-Related Complex Neurodevelopmental Disorder	causative	mechanism: ANK2 Haploinsufficiency in Neurons; Developmental Forebrain Ank2 Loss; Giant Ankyrin-B Axonal Membrane-Microtubule Coupling Failure
Cardiac Arrhythmia, Ankyrin-B-Related	disputed	mechanism: ANK2-Dependent Cardiac Membrane-Targeting Failure
Familial Long QT Syndrome	disputed	subtype: Type 4 scoped to subtype: Type 4
Familial Sick Sinus Syndrome	untyped Causative

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
long QT syndrome MONDO:0002442	AD	Disputed 2020-12-15	no dismech entry
catecholaminergic polymorphic ventricular tachycardia MONDO:0017990	AD	Disputed 2021-01-20	RYR2 CPVT not named
complex neurodevelopmental disorder MONDO:0100038	AD	Definitive 2020-10-21	no dismech entry

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.