Target intelligence / Profile preview

Nudix hydrolase 12 (NUDT12)

Target
NUDT12
Molecular classification
Enzyme, Nudix hydrolase family, Peroxisomal protein
01

Overview

Nudix hydrolase 12 (NUDT12) is a peroxisomal enzyme belonging to the Nudix hydrolase family, characterized by its ability to hydrolyze a wide range of nucleoside diphosphate derivatives. Its primary biochemical role is as a "deNADding" enzyme, specifically removing the non-canonical NAD cap from the 5’-end of a subset of mammalian mRNAs, leading to their degradation and thus regulating mRNA stability[1][5]. Beyond decapping NAD-capped RNAs, NUDT12 can hydrolyze free NAD(H) and NADPH, producing NMN(H) and 5’AMP or 2’,5’-ADP, and has a role in maintaining nucleotide pools important for mitochondrial and peroxisomal function[1][5][6]. NUDT12 activity has been linked to cellular responses to metabolic and nutrient stress, and may play a role in energetic metabolism by targeting NAD-capped mRNAs encoding mitochondrial proteins[1]. Disease associations include certain cancers and potential effects on circadian clock regulation[5]. At present, no drugs are known to target NUDT12 directly, and it is not currently a validated biomarker or a drug safety concern.

Other names
NAD-capped RNA hydrolase NUDT12DeNADding enzyme NUDT12NADH pyrophosphatase NUDT12Nudix motif 12DKFZP761I172Nucleoside diphosphate-linked moiety X motif 12Nucleoside diphosphate linked moiety X-type motif 12Peroxisomal NADH pyrophosphatase NUDT12
02

Mechanism of action

NUDT12 is not currently a therapeutic target for drugs, so mechanisms of action for drugs targeting this enzyme are not defined.

03

Biological functions

RNA metabolism (specifically, decapping/deNADding of NAD-capped RNAs)Regulation of mRNA stabilityMetabolism of nicotinamide nucleotidesRegulation of peroxisomal nucleotide cofactorsCellular energetic homeostasis
04

Disease associations

Cancer (e.g., potential links to granular cell carcinoma)[5]Thrombophilia[5]Other (implicated in metabolic regulation and, potentially, in circadian rhythm due to effects on PER/CRY genes)[5]

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