Sex-determining region Y protein (SRY) (SRY)

The Sex-determining region Y protein (SRY), also known as the testis-determining factor (TDF), is a pivotal transcription factor encoded by the SRY gene located on the Y chromosome (UniProt). Its primary biological function is to initiate male sex determination in therian mammals by triggering the differentiation of the bipotential embryonic gonad into testes (MedlinePlus). SRY acts by binding to specific DNA sequences via its high-mobility group (HMG) box domain, inducing a sharp bend in the DNA that facilitates the recruitment of other factors and the upregulation of downstream targets such as SOX9 (Wikipedia). Beyond its role in development, SRY is expressed in the adult male brain, specifically in the substantia nigra, where it regulates dopamine biosynthesis and contributes to the male-specific susceptibility to neurodegeneration (NIH). Mutations in the SRY gene are associated with disorders of sex development, including Swyer syndrome (46,XY gonadal dysgenesis), while translocations can result in 46,XX testicular disorder (MedlinePlus). Although there are currently no approved drugs targeting SRY, experimental approaches such as antisense oligonucleotides are being explored to modulate its expression in the context of Parkinson's disease and certain male-biased cancers (NIH).

Other names

Testis-determining factorTDFTDYSex-determining region of Y-chromosomeSRXX1SRXY1

Suppression of SRY protein expression or activity via gene-silencing techniques