**9. RPL3L and MYZAP gene polymorphisms**

A polygenic process involving transcription factors, cardiac ion channels, myocardial and cytoskeletal proteins plays an important role in AF pathogenesis. Based on the entire genome sequence, GWAS has shown that three low-frequency coding variants are effective in the development of AF. The myosin sarcomeric genes MYH6 and MYL4, the cytoskeletal gene PLEC, are these variants. MYH6, MYL4 and PLEC genes also encode cardiomyocyte structural components such as MYZAP. Ribosome activity can be specifically regulated in the cell via changes in the ribozyme protein composition. The eukaryotic ribosome consists of 4 different ribosomal RNAs and about 80 ribosomal proteins. This ribosome plays an important role in translating the messenger mRNA into a protein. Ribosomal proteins or genes encoding ribosome biogenesis factors may result in mutations leading to ribosomopathy, a hereditary disease. It is known that RPL3L-containing ribosomes may cause translational activity changes. Among RPL3L missense mutations, a negative regulator of muscle growth, p.Ala75Val and p.Gly12Arg mutations are important. Apart from these mutations, the RPL3L c.1167+1G>A mutation is involved in the impairment of the interaction of RPL3L with endoplasmic reticulum. As a result of these mutations, the risk of developing AF is increasing. Human Myozap mRNA is expressed primarily in the heart. Myozap regulates serum response factor signaling in the nucleus. This is why it plays an important role in cardiac signal transduction. Mutations in intercalated disk genes result in cardiomyopathies and sudden cardiac deaths that are a significant risk for AF. AF variants are defined in the genes coding for components of intercalated discs and in the vicinity of these genes. Seeger et al. found the MYZAP gene in the components of intercalated discs. Intercalated discs are a cell-cell contact structure that provides mechanical, electrical and chemical communication between cardiomyocytes. The risk of AF is also increasing as a result of MYZAP p.Gln254Pro gene polymorphism. In a previous study, there was a significant relationship between four lowfrequency coding variants in the RPL3L and MYZAP genes and the risk of developing AF. The missense variant in MYZAP was identified as a genetic risk factor in the development of AF [26].
