NEK11, a member of the never in mitosis gene A (NIMA) family of serine/threonine kinases, is involved in multiple biological processes. It plays a crucial role in the DNA damage response, enforcing the G2/M cell cycle checkpoint. Specifically, it controls the degradation of CDC25A, a key CDK activator, by directly phosphorylating it, which is essential for the cell to prevent division when DNA lesions are present. Additionally, it may be associated with cell cycle-related processes during meiosis and DNA replication [3,4,5].

In a Dutch family with melanoma, a rare, nonsense variant in the NEK11 gene (c.1120C>T, p.Arg374Ter) was identified. This variant cosegregated in all five affected members, and somatic loss of the wild-type allele was demonstrated in a melanoma from a variant carrier. Functional analyses showed that this mutation led to loss-of-function through protein instability, suggesting NEK11 as a melanoma susceptibility gene [1]. In mouse oocytes, knockdown of Nek11 by siRNA microinjection did not affect germinal vesicle breakdown (GVBD) and the first polar body extrusion but caused the formation of 2-cell-like eggs, indicating its role in regulating asymmetric cell division during oocyte meiotic maturation [2]. In HCT116 colorectal cancer cells, RNAi-mediated depletion of Nek11 prevented the G2/M arrest induced by genotoxic agents like ionizing radiation or irinotecan and promoted p53-dependent apoptosis, with Nek11S having an important role in the DNA damage response [6].

In conclusion, NEK11 is essential in processes such as the DNA damage response, cell cycle regulation during meiosis, and may be involved in disease conditions like melanoma and colorectal cancer. Studies using gene-knockdown models in cells and identification of disease-associated variants in families have provided insights into its role in these biological processes and diseases.