Ankyrin repeat and sterile alpha motif domain-containing protein 6 (ANKS6)

Ankyrin repeat and sterile alpha motif domain-containing protein 6 (ANKS6) is a cytoplasmic scaffold protein characterized by an N-terminal region containing multiple ankyrin repeats and a C-terminal sterile alpha motif (SAM) domain[2][6]. ANKS6 localizes to the primary cilium, particularly the proximal ciliary region, where it is essential for renal and cardiovascular development[1][4][5]. It acts as a central organizing hub that links components of the nephronophthisis (NPH) module, specifically connecting NEK8 (a serine/threonine kinase), INVS (inversin), and NPHP3, thereby governing ciliary signaling processes critical for left-right symmetry, kidney morphogenesis, and heart development[1][2][3][6]. Loss-of-function mutations in ANKS6 cause nephronophthisis 16, an autosomal recessive cystic kidney disease that often presents as infantile or juvenile renal failure with associated extrarenal abnormalities, including congenital heart defects, laterality disorders (such as situs inversus), and periportal liver fibrosis[1][5]. The protein can be regulated by asparaginyl hydroxylation (via the oxygen sensor HIF1AN), which modulates complex assembly and ciliary localization[1]. ANKS6 is not known to be a direct receptor, enzyme, transporter, or common therapeutic target, and there are currently no drugs directly interacting with it in clinical practice. Its role is primarily as an adaptor/scaffold facilitating multi-protein complex formation in cilia-associated pathways underlying specific developmental and cystic diseases[2][3][5].

Other names

Ankyrin repeat and SAM domain-containing protein 6ANKS6ANKRD14PKDR1SAMD6SAM domain-containing protein 6FLJ36928NPHP16Ankyrin repeat domain-containing protein 14SamCystinSterile alpha motif domain-containing protein 6ankyrin repeat domain 14samCystin