NUDT12 Gene: Function, Expression, and Disease Associations

NUDT12 encodes a member of the Nudix hydrolase family, characterized by a conserved Nudix box motif (GX5EX7REUXEEXGU, where U is a hydrophobic residue). The protein localizes to peroxisomes and catalyzes the hydrolysis of NADH, NADPH, and Coenzyme A (CoA) derivatives, including CoA esters and oxidized CoA (CoAS-SG). It plays a role in peroxisomal nucleotide and cofactor homeostasis, potentially regulating NAD+/NADH ratios and CoA levels. NUDT12 is also implicated in cellular stress responses and has been linked to ciliopathies and cancer.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Peroxisomal NAD metabolism

• Coenzyme A biosynthesis and recycling

• Purine nucleotide metabolism

NUDT12 is a 45 kDa peroxisomal protein containing a Nudix hydrolase domain. It preferentially hydrolyzes NADH, NADPH, and CoA derivatives, releasing nicotinamide mononucleotide (NMN) or 4'-phosphopantetheine. The enzyme is essential for maintaining peroxisomal redox balance and cofactor homeostasis. Structural studies reveal a conserved catalytic core with a metal-binding site (typically Mg2+ or Mn2+). Post-translational modifications include phosphorylation at Ser-123, which may regulate activity. NUDT12 interacts with peroxisomal membrane proteins and is involved in ciliary signaling.