SRY-BOX 3

Alternative Names

  • SOX3
  • SRY-Related HMG-BOX Gene 3
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OMIM Number

313430

Gene Map Locus
Xq26.3

Description

SOX3 gene is a member of the SOX [SRY related high mobility group (HMG) box[ family of transcription factors, which were initially identified based on homology to the conserved binding motif of the HMG class, present in the mammalian sex determining gene, SRY. SOX3 is believed to be the gene from which the testis-determining gene SRY evolved. On the basis of sequence homology, SOX3 is closely related to SOX1 and SOX2, and the products of all three genes belong to the SOXB1 subfamily exhibiting the highest degree of similarity to SRY. SOX3 is implicated in the control of nervous system development and is considered to be one of the earliest neural markers. Additionally, studies on SOX3-null mice and the observations from human 46, XY male with complete loss of SOX3 suggested that SOX3 plays an important role in testis development and possibly sperm maturation.

Molecular Genetics

SOX3 is encoded by a single exon producing a transcript with a coding region of approximately 1.3 kb, mapping to chromosome Xq27. It is highly expressed in fetal brain and spinal cord throughout the developing CNS. The SOX3 protein is 446 amino acids long and weighs 45,210 Da. It consists of a short 66 amino acid N-terminal domain of unknown function, a 79 amino acid DNA-binding HMG domain, and a longer C-terminal domain, containing four polyalanine stretches, shown to be involved in transcriptional activation.

Duplications of Xq26-27, containing SOX3 gene, have been implicated in the etiology of X-linked hypopituitarism associated with mental retardation. Additionally, an expansion of a polyalanine tract (by 11 alanines) within this gene (Xq27.1) has been reported in patients with growth hormone deficiency and variable learning difficulties.

Epidemiology in the Arab World

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Other Reports

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In a consanguineous Qatari family affected with panhypopituitarism, Woods et al. (2005) identified a novel seven-alanine expansion (from 15 to 22 alanine residues) within a polyalanine tract (Ala(7)240ins241) as a result of a 21-bp duplication between nucleotides 720 and 721 of the SOX3 gene. Woods et al. (2005) also performed in vitro functional expression studies which indicated that the expansion was associated with decreased SOX3 activity and impaired nuclear localization of the mutant protein. The three affected siblings (males) of this family were found to be homozygous for this mutation, whereas the mother of these four children was heterozygous for the same mutation and did not exhibit significantly skewed X inactivation in DNA extracted from peripheral blood. The phenotype was similar in all three siblings with profound and complete panhypopituitarism in association with severe anterior pituitary hypoplasia (APH), an absent or hypoplastic infundibulum, and an ectopic/undescended posterior pituitary (EPP). All had normal neurodevelopment. Another sibling (male) also had the similar phonotype, but his DNA was unavailable for genetic testing. Woods et al. (2005) suggested that this patient may have the same mutation.

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