Kinetochore scaffold 1 (KNL1) (KNL1)

Kinetochore scaffold 1 (KNL1), frequently referred to as D40 or CASC5, is a large protein essential for the assembly of the kinetochore and the regulation of the spindle assembly checkpoint during mitosis. It acts as a primary scaffold for the assembly of the KMN (KNL1-Mis12-Ndc80) network and the recruitment of checkpoint proteins like Bub1 and BubR1, ensuring high-fidelity chromosome segregation. KNL1 is classified as a cancer/testis (CT) antigen, characterized by high expression in the testis and various human cancers—including lung, colorectal, and bladder cancers—while remaining largely absent in normal somatic tissues. This restricted expression profile makes it an attractive therapeutic target; experimental studies have demonstrated that silencing KNL1 using siRNA can selectively inhibit tumor growth and induce apoptosis regardless of p53 status. Additionally, germline mutations in the KNL1 gene are associated with autosomal recessive primary microcephaly, highlighting its critical role in the division of neural progenitor cells.

Other names

D40Cancer susceptibility candidate 5 (CASC5)AF15q14BlinkinSpc7hSpc105Cancer/testis antigen 29 (CT29)PPP1R55

Inhibition of KNL1 expression or function disrupts kinetochore assembly and the spindle assembly checkpoint, leading to mitotic arrest and apoptosis in cancer cells.