Thioredoxin-related transmembrane protein 2 (TMX2)

Thioredoxin-related transmembrane protein 2 (TMX2) is a transmembrane enzyme belonging to the protein disulfide isomerase (PDI) family, which is part of the thioredoxin superfamily[2][3][5]. TMX2 contains a thioredoxin-like domain with an atypical SNDC motif, localizes mainly to the endoplasmic reticulum (ER) membrane—including regions closely associated with mitochondria (mitochondria-associated membrane) and the nuclear envelope—and is expressed broadly in human tissues[3][5]. Unlike classic PDIs, TMX2 lacks canonical oxidoreductase activity but is implicated in the regulation of protein folding and redox homeostasis, mitochondrial function, and nucleocytoplasmic protein transport, in part via regulation of Ran GTPase compartmentalization at the nuclear envelope[1][3][5]. TMX2 is essential for early embryonic development (embryonic lethal in knockout mice) and for proper mitochondrial maintenance. Pathogenic loss-of-function mutations in TMX2 cause recessive microlissencephaly, with global developmental delay, intellectual disability, and epilepsy[2][3]. TMX2 is also reported to contribute to cell survival and chemotherapy resistance in certain cancers[3]. No drugs targeting TMX2 are known, and it is not currently considered a direct therapeutic target[2][3][5].

Other names

TXNDC14PDIA12CGI-31My009PIG26PSEC0045UNQ237/PRO270Cell proliferation-inducing gene 26 proteinThioredoxin domain-containing protein 14protein disulfide isomerase family A member 12growth-inhibiting gene 11NEDMCMS