SOX3

Transcription factor SOX-3 is a protein that in humans is encoded by the SOX3 gene. This gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic brain development and in determination of cell fate. The encoded protein acts as a transcriptional activator.

Mutations in this gene have been associated with X-linked hypopituitarism (XH) and X-linked mental retardation. Patients with XH are male, have short stature, exhibit a mild form of mental retardation and present pan-hypopituitarism. A duplication of the SOX3 gene has also been discovered to cause XX male sex reversal.

SRY-box transcription factor 3, SOX3, is a transcription factor that is encoded by the SOX3 gene. This gene is responsible for ensuring proper embryonic development and determining the fate of different cells. Regarding its developmental facet, SOX3, alongside other SOX transcription factors, ensures the proper formation of the hypothalamo-pituitary axis. The proper development of the hypothalamo-pituitary axis is necessary as it serves to ensure proper systemic hormonal function. When SOX3 expression is affected, the development of different structures can be affected as well. Specifically, both the hypothalamus and the pituitary gland can suffer in accomplishing proper growth. Due to this, conditions such as hypopituitarism and mental retardation are found in cases with a lack of SOX3. Also, craniofacial abnormalities can be seen as a result of a lack of the SOX3 gene. To aid in the further understanding of the SOX3 gene, mice have been used as knockout models to study the effects of the gene’s absence.

Function
SOX3 belongs to the family of SRY-related HMG-box containing genes which behave as transcription factors. SOX3 has been found to be involved in the regulation of embryonic brain development, the determination of cell fate and in XX male sex reversal.

SOX3 contains a single exon and is found in a highly conserved region of the X chromosome. The SOX3 gene shares some conservation with the SRY gene, and encodes a protein that is similar, sharing 67% amino acid identity across the DNA-binding HMG domain. This has led to the hypothesis that the SRY gene arose from SOX3 through a gain of function mutation within the proto-Y chromosome. Evidence to support this hypothesis arose from the discovery of a rare human case of XX sex reversal, that is thought to have occurred through a de novo duplication of the SOX3 gene. Such a duplication is thought to result in a gain of function expression of SOX3 in the genital ridge of the developing embryo leading to XX male sex reversal.