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Target intelligence / Profile preview
Kinesin family member 12 (KIF12)
- Target
- KIF12
- Molecular classification
- Motor protein, Enzyme, Other (kinesin superfamily, microtubule-associated molecular motor)
01
Overview
Kinesin family member 12 (KIF12) is a motor protein within the kinesin superfamily that functions as a microtubule-associated molecular motor, critical for intracellular transport and cell division. It is essential for maintaining hepatocyte polarity and bile flow as well as epithelial cell polarity during kidney development. Pathogenic mutations in KIF12 cause progressive familial intrahepatic cholestasis (PFIC8) and have been implicated in various cholestatic liver phenotypes and metabolic liver disease (MASH/MAFLD). In the pancreas, KIF12 also modulates oxidative stress responses in beta cells by acting as a scaffold for the transcription factor Sp1, and its deficiency leads to beta cell dysfunction and glucose intolerance in mice[1][2][3].
- Other names
- Kinesin-like protein KIF12PFIC8KIF12Kinesin superfamily protein KIF12
02
Mechanism of action
no specific small molecule mechanisms for drugs targeting KIF12 identified; pathogenic mutations disrupt protein function
03
Biological functions
Intracellular transportMicrotubule-based movementCell divisionMaintenance of cell polarityRegulation of lipid metabolismScaffold for transcription factors
04
Disease associations
Cholestatic liver disease (including progressive familial intrahepatic cholestasis 8, PFIC8)Chronic liver diseaseSteatohepatitis (MASH/MAFLD)Kidney development abnormalitiesBeta cell dysfunction and oxidative stress
05
Safety considerations
Loss-of-function or pathogenic variation leads to cholestasis, liver fibrosis, steatohepatitis, and possible renal developmental defectsBeta cell oxidative stress and possible glucose intolerance if inhibited systemically
06
Biomarkers
KIF12 mutation/variant for PFIC8 and other cholestatic diseasesKIF12 expression for hepatocyte polarity and kidney development status
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