Nuclear protein in testis (NUTM1)

Nuclear protein in testis (NUTM1) is a nuclear protein normally expressed in post-meiotic germ cells of the testis and ovary, critical for chromatin remodeling during spermatogenesis by facilitating EP300-mediated histone acetylation[3][5]. The wild-type protein allows regulated nucleocytoplasmic shuttling. In cancer, chromosomal rearrangements involving NUTM1 create fusion proteins (most commonly with BRD4, but also with BRD3, NSD3, ZNF532, ZNF592, MGA, and others) that aberrantly tether NUTM1 to chromatin via bromodomain-containing partners, leading to massive histone hyperacetylation ("megadomains"), blocked differentiation, and malignant cell proliferation[1][2][5][6]. NUTM1 fusion–driven neoplasms (especially NUT carcinoma) are typically aggressive and resistant to standard therapies, for which bromodomain (BET) inhibitors are under clinical investigation as targeted therapies[1][5].

Other names

NUT family member 1C15orf55NUTDKFZp434O192FAM22Hnuclear protein in testisNAP1L4/NUTM1D fusionnuclear protein in testis geneNUTM1 fusion proteinNUT carcinoma family member 1

Inhibition of BRD4/NUTM1 chromatin binding (BET inhibitor mechanism) Disruption of megadomain formation and global histone hyperacetylation Reactivation of differentiation pathways in NUTM1 fusion-driven tumors