SMYD1
The murine Smyd1 gene, also known as Bop , was described in the ‘90s (Hwang and Gottlieb 1995). The Smyd1 gene was linked to T lymphocytes, and the authors demonstrated that this gene produces a presumably non-coding cDNA and a protein variant expressed in cytotoxic T lymphocytes that derives from alternative splicing, as well as another protein variant expressed in cardiac and skeletal muscle, the transcription of which is activated by a different promoter (Hwang and Gottlieb 1997).
Since then, other not-so-obvious relations of Smyd1 with the immune system have been described. Due to its key role in cardiac and skeletal muscle development and regeneration (Du, Tan, and Zhang 2014), muscle-specific Smyd1 KO mice exhibited multiple defects of skeletal muscle, that finally led to perinatal death. Interestingly, trunk muscles were substituted with brown adipose tissue (BAT), and downregulation of key adaptive and innate immune transcription factors for BAT development and functionality, such as interleukin-6 (Il-6), tumour necrosis factor-alpha (TNFα), chemokine (C-C motif) ligand 6 (Ccl6), chemokine (C-C motif) ligand 7 (Ccl7), chemokine (C-C motif) ligand 9 (Ccl9), forkhead box P3 (Foxp3), BAF chromatin remodelling complex subunit BCL11A(Bcl11A), RUNX family transcription factor 1 (RunX1) and core binding factor β (Cbfβ) , was observed (Rasmussen and Tucker 2018). Furthermore, whole-genome resequencing of yak populations (Bos grunniens, ruminant animals that are evolutionarily adapted to high altitudes and, therefore, hypoxia) identified copy number variations in SMYD1 , which may be involved in immune responses, as well as hypoxia adaptation (H. Wang et al. 2019). A cluster of patients with AnWj-negative blood group antigen, which is associated with lymphoid malignancies, immunologic disorders and autoimmune haemolytic anaemia, presented a R320Q substitution in SMYD1 . This gene variant seems to be the base of an inherited form of the AnWJ-negative blood group phenotype, although the molecular mechanism is unknown (Yahalom et al. 2018). It has also been suggested thatSMYD1 is involved in the pathogenesis of velocardiofacial syndrome, a disease with heterogeneous genotypes and phenotypes, which could include immune deficiency (Wu et al. 2019). Regarding immune cell-related cancer, recurrent mutations in SMYD1 were found in a group of patients with splenic marginal zone lymphoma, which is a type of B-cell non-Hodgkin lymphoma (Peveling-Oberhag et al. 2015).