Cmtr2, also known as HMTR2, is an mRNA cap methyltransferase. It catalyzes 2'-O-ribose methylation of the second transcribed nucleotide of mRNAs. This modification potentially marks RNAs as "self" to avoid the cellular innate immune response, and is involved in pathways related to mRNA processing, translation, and stability [1,3,4].

Gene knockout (KO) mouse models have been crucial in understanding Cmtr2's functions. Constitutive deletion of Cmtr2 in mice leads to mid-gestation embryonic death, with defects in embryo size, placental malformation, and yolk sac vascularization [1]. Endothelial cell-specific deletion (conditional knockout, CKO) results in vascular and hematopoietic defects and perinatal lethality [1]. The KO phenotype shows activation of the p53 pathway and decreased proliferation, without interferon pathway activation [1]. In addition, gene-based burden tests suggest an association of CMTR2 with increased risk of lung cancer and cutaneous melanoma [2].

In summary, Cmtr2 is essential for mammalian embryonic development, playing key roles in processes like embryo growth, placental and yolk sac development, as well as in hematopoiesis and vascular development. The KO and CKO mouse models have revealed its significance in these biological processes and its potential links to cancer, enhancing our understanding of the underlying molecular mechanisms and providing insights into related disease areas.