Molecular Characteristics
ANKLE2 is located at chromosome 12q24.33 and encodes for Ankyrin Repeat and Lem Domain-Containing Protein 2. The gene localizes to the nuclear envelope and plays an essential role in the nuclear enevolpe reassembly during the onset of anaphase by interacting directly with VRK1 and inhibiting its kinase activity against BAF.
Mutations and pathophysiology
Drosophila knockout models for ANKLE2 affected asymmetric protein localization, spindle alignment, and cell division of Drosophila neuroblasts. Pathogenic ANKLE2 variants in humans lead to autosomal recessive primary microcephaly-16 (MCPH16).
Shaheen et al. (2019) reported two homozygous truncating variants in ANKLE2 (NM_015114.2):
1) c.1754G>T, p.(Gly585Val) in a Sudanese girl with MCPH16
2) c.601G>T, p.(Gly201Trp) in a 15 year-old boy with MCPH16
3) c.601G>T, p.(Gly201Trp) in a 14 year-old boy with MCPH16
ANKLE2