Zmym2, also known as ZNF198, is a zinc finger transcriptional regulator and a component of a transcriptional corepressor complex. It is involved in multiple biological processes such as the silencing of developmentally regulated endogenous retrovirus elements, DNA methylation patterning in early embryonic development, and the choice between DNA double-strand break repair pathways [1,2,4]. It is also associated with diseases like congenital anomalies of the kidney and urinary tract (CAKUT) and hematologic malignancies [1,5]. Mouse models have been crucial in studying Zmym2. Zmym2-deficient mice recapitulate features of CAKUT with high penetrance, establishing Zmym2 loss-of-function mutations as causes of human CAKUT [1]. Zmym2-/-mice also show embryonic lethality by E10.5, with defects in DNA methylation and silencing of germline gene promoters and active LINE element subclasses [2].

In hematologic malignancies, avadomide can induce the degradation of ZMYM2-FGFR1 and ZMYM2-FLT3 chimeric oncoproteins both in vitro and in vivo, suggesting potential treatment benefits for patients with such ZMYM2 fusion proteins [5]. Zmym2 also inhibits NANOG-mediated reprogramming of epiblast stem cells and somatic cells, and impairs embryonic stem cell self-renewal [3]. Additionally, it restricts 53BP1 at DNA double-strand breaks to favor BRCA1 loading and homologous recombination, and cells deficient for Zmym2/3 display genome instability [4].

In conclusion, Zmym2 plays essential roles in embryonic development, DNA repair, and cell reprogramming. Mouse models, especially Zmym2 KO models, have been instrumental in revealing its functions and associations with diseases like CAKUT and hematologic malignancies. These findings offer new perspectives for understanding disease pathogenesis and developing potential treatments.