Born This Way: Using Intrinsic Disorder to Map the Connections between SLITRKs, TSHR, and Male Sexual Orientation

Abstract

Recently, genome-wide association study reveals a significant association between specific single nucleotide polymorphisms (SNPs) in men and their sexual orientation. These SNPs (rs9547443 and rs1035144) reside in the intergenic region between the SLITRK5 and SLITRK6 genes and in the intronic region of the TSHR gene and might affect functionality of SLITRK5, SLITRK6, and TSHR proteins that are engaged in tight control of key developmental processes, such as neurite outgrowth and modulation, cellular differentiation, and hormonal regulation. SLITRK5 and SLITRK6 are single-pass transmembrane proteins, whereas TSHR is a heptahelical G protein-coupled receptor (GPCR). Mutations in these proteins are associated with various diseases and are linked to phenotypes found at a higher rate in homosexual men. A bioinformatics analysis of SLITRK5, SLITRK6, and TSHR proteins is conducted to look at their structure, protein interaction networks, and propensity for intrinsic disorder. It is assumed that this information might improve understanding of the roles that SLITRK5, SLITRK6, and TSHR play within neuronal and thyroidal tissues and give insight into the phenotypes associated with male homosexuality.

Keywords: SLITRK5; SLITRK6; TSHR; intrinsic disorder; polymorphisms; sexual orientation; single nucleotide.