Sickle tail protein homolog (KIAA1217)

Sickle tail protein homolog (KIAA1217, also known as SKT or ETL4) is a large, predominantly cytoplasmic protein required for the normal development of intervertebral disks and embryonic skeletal system development in humans and mice[2][3][4]. It encodes a protein with a curly helix region and actin-interaction domain involved in cell migration, substrate adhesion, and proliferation, as well as regulation of dendritic spine morphogenesis and multicellular developmental processes[2][3]. Mutations in KIAA1217 are linked to malformations of the vertebral column in humans (e.g., sacral defect with anterior meningocele, Klippel-Feil syndrome) and tail defects in mice[2][3][5]. In cancer biology, KIAA1217 is upregulated in hepatocellular carcinoma and drives epithelial-mesenchymal transition (EMT), invasion, and metastasis through a mechanism involving physical interaction with and activation of JAK1/2 and STAT3, leading to downstream activation of Notch and Wnt/β-catenin pathways[6]. KIAA1217 can also form gene fusions with the RET tyrosine kinase (e.g., KIAA1217-RET) which act as oncogenic drivers, particularly in non-small cell lung cancer (NSCLC)[4]. Currently, there are no approved drugs directly targeting KIAA1217, and it is best characterized as a scaffold or adaptor protein rather than an enzyme or receptor. Nonetheless, its function as a molecular hub suggests potential as a novel therapeutic target, especially in certain cancers[4][6].

Other names

KIAA1217SKTETL4sickle tailDKFZP761L0424sickle tail protein homologenhancer trap locus 4 (likely orthologue of Mus musculus enhancer trap locus 4)

Not drug-targeted directly; acts via protein–protein interactions to facilitate activation of signaling pathways (notably JAK/STAT3, Notch, and Wnt/β-catenin pathways) in cancer[6][4].