SRY

The SRY gene, short for the Sex-determining Region Y, is a gene located on the Y chromosome that encodes a transcription factor involved in initiating male sex development in therian mammals. In humans, SRY is typically expressed in the developing gonads during early embryogenesis and functions as a key trigger for the male pathway.

The SRY protein contains a DNA-binding domain known as the HMG box, which allows it to bind specific DNA sequences and influence chromatin structure. Its expression in the bipotential gonad promotes the differentiation of Sertoli cells and activates a network of genes, including SOX9, that drive testis formation. The activity of SRY biases the gonad toward male development; in the absence of SRY activity, gonadal development often proceeds along a female pathway.

Genetic variation in SRY can have pronounced effects on sex development. Deletions or loss-of-function mutations can lead to 46,XY gonadal dysgenesis or sex reversal, where an individual with a typical male karyotype develops female or ambiguous characteristics. Duplications, rearrangements, or translocations involving SRY can also disrupt normal development and contribute to disorders of sex development. In rare cases, relocation of SRY to the X chromosome or other genetic contexts can result in XY individuals developing as females.

Evolutionarily, SRY is characteristic of therian mammals, though other species may use different sex-determination mechanisms. The regulatory network surrounding SRY is complex and continues to be an active area of research.