ANK1 Gene: Ankyrin 1 – Function, Mutations, and Associated Diseases

The ANK1 gene encodes ankyrin 1 (ankyrin-R), a member of the ankyrin family of adaptor proteins that link integral membrane proteins to the spectrin-actin cytoskeleton. In erythrocytes, ankyrin 1 attaches the membrane protein band 3 (SLC4A1) to the spectrin-based skeleton, maintaining red cell membrane integrity and deformability. Mutations in ANK1 are a common cause of hereditary spherocytosis (SPH1). The gene undergoes extensive alternative splicing, producing multiple isoforms expressed in erythroid, muscle, and neuronal tissues.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Erythrocyte membrane skeleton (Reactome: R-HSA-5621480)

• Band 3-ankyrin-spectrin complex (Reactome: R-HSA-5621481)

• Cell junction organization (Reactome: R-HSA-446728)

Ankyrin 1 (UniProt P16157) is a 1881-amino-acid protein with three major domains: an N-terminal membrane-binding domain (containing 24 ankyrin repeats), a central spectrin-binding domain, and a C-terminal regulatory domain. It anchors the erythrocyte membrane skeleton by binding to the cytoplasmic tail of band 3 (SLC4A1) and to β-spectrin. Isoforms lacking the spectrin-binding domain are expressed in brain and muscle. The protein is essential for red cell membrane stability and deformability.