Transcription factor required during the formation of the hypothalamo-pituitary axis. May function as a switch in neuronal development. Keeps neural cells undifferentiated by counteracting the activity of proneural proteins and suppresses neuronal differentiation. Required also within the pharyngeal epithelia for craniofacial morphogenesis. Controls a genetic switch in male development. Is necessary for initiating male sex determination by directing the development of supporting cell precursors (pre-Sertoli cells) as Sertoli rather than granulosa cells.
Involvement in disease
Defects in SOX3 are a cause of panhypopituitarism X-linked (PHPX) [MIM:312000]. Affected individuals have absent infundibulum, anterior pituitary hypoplasia, and ectopic posterior pituitary. Defects in SOX3 are the cause of mental retardation X-linked with isolated growth hormone deficiency (MRXGH) [MIM:300123]. Defects in SOX3 are the cause of 46,XX sex reversal type 3 (SRXX3) [MIM:300833]. A condition in which male gonads develop in a genetic female (female to male sex reversal). Note=Copy number variations (CNV) encompassing or in close proximity to SOX3 are responsible for XX male reversal. These variations include two duplications of approximately 123 kb and 85 kb, the former of which spans the entire SOX3 gene; a 343 kb deletion immediately upstream of SOX3 that is probably responsible of altered regulation (and not increased dosage) of SOX3; a large (approximately 6 Mb) duplication that encompasses SOX3 and at least 18 additional distally located genes. Its proximal breakpoint falls within the SOX3 regulatory region. This large rearrangement has been found in a patient with XX male reversal and a complex phenotype that also includes a scrotal hypoplasia, microcephaly, developmental delay, and growth retardation.