ANK3 Gene (Ankyrin-3): Function, Mutations, and Disease Associations | NCBI Ensembl UniProt

ANK3 encodes ankyrin-G, a member of the ankyrin family that links integral membrane proteins to the spectrin-actin cytoskeleton. Ankyrin-G is essential for the clustering of voltage-gated sodium channels at axon initial segments and nodes of Ranvier, and plays critical roles in neuronal polarity, synaptic plasticity, and cardiac excitability. Variants in ANK3 are strongly associated with bipolar disorder, schizophrenia, and autism spectrum disorders.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• REACTOME: R-HSA-5576892 – Phase 0 – rapid depolarisation

• REACTOME: R-HSA-5576893 – Phase 1 – inactivation of fast Na+ channels

• REACTOME: R-HSA-112316 – Neuronal System

• KEGG: hsa05414 – Dilated cardiomyopathy (ankyrin-G role in cardiac conduction)

Ankyrin-G (UniProt Q12955) is a 4801-amino acid protein with multiple isoforms. It contains an N-terminal membrane-binding domain (MBD) that interacts with ion channels and cell adhesion molecules, a spectrin-binding domain (SBD) that links to the cytoskeleton, and a C-terminal regulatory domain. Ankyrin-G is critical for the assembly and maintenance of the axon initial segment and nodes of Ranvier, where it clusters voltage-gated sodium channels (Nav1.2, Nav1.6) and neurofascin. It also organizes the cardiac intercalated disc and is implicated in bipolar disorder, autism, and cardiac arrhythmias.