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).