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SOX3

Domain

The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.

Function

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 (By similarity).

Involvement in disease

Panhypopituitarism X-linked

PHPX

Affected individuals have absent infundibulum, anterior pituitary hypoplasia, and ectopic posterior pituitary.

None

The disease is caused by variants affecting the gene represented in this entry.

Intellectual developmental disorder, X-linked, with isolated growth hormone deficiency

MRXGH

A disorder characterized by the association of variable degrees of intellectual disability with panhypopituitarism, variable combinations of hypothyroidism, delayed pubertal development, and short stature due to growth hormone deficiency.

None

The disease is caused by variants affecting the gene represented in this entry.

46,XX sex reversal 3

SRXX3

A condition in which male gonads develop in a genetic female (female to male sex reversal).

None

The disease is caused by variants affecting the gene represented in this entry. 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.

Hypoparathyroidism, X-linked

HYPX

An X-linked form of true hypoparathyroidism characterized by neonatal or infantile onset and absence of parathyroid glands. Clinical features are hypocalcemia, hyperphosphatemia, seizures, tetany and cramps.

None

The gene represented in this entry may be involved in disease pathogenesis. A disease causing, complex chromosomal rearrangement [del(X)(q27.1)inv ins(X;2)(q27.1;p25.3)] has been found in a family with X-linked hypoparathyroidism. This chromosomal abnormality is located 67 kb downstream of SOX3 and likely results in altered SOX3 expression with pathological consequences.

Cellular localization

Alternative names

Transcription factor SOX-3, SOX3

swissprot:P41225 omim:313430 entrezGene:6658