- Tools
- Downloads
- Links
- Community
- About
- Help
FB2026_03
,
released September 17, 2026
This reports describes panhypopituitarism, X-linked, with or without intellectual disability. The human gene implicated in this disease is SOX3, a member of the SOX (SRY-related HMG-box) family of transcription factors. There is a single orthologous gene in Drosophila, SoxN, for which classical loss-of-function alleles and RNAi-targeting constructs have been generated. Dmel\SoxN is also orthologous to SOX1 and SOX2.
None of the orthologous human SOX genes (SOX3, SOX1, SOX2) has been introduced into flies.
The SOX3 protein has several small polyalanine runs; expansion of the longest (normally 15 alanine residues) to 22 or 26 has been implicated in this disease. The human SOX1 gene has a shorter polyalanine tract in the analogous position, however, expansion of that poly-Ala tract has not been implicated in disease.
A UAS construct carrying an expansion of the analogous Ala-repeat tract in Dmel\SoxN (from 12 alanine residues to 34) has been used to model this disease in flies. When expressed in the developing eye, the expanded A34 protein results in a rough eye phenotype; the wild-type A12 protein does not. Work in Drosophila has concentrated on the mislocalization of the expanded-Ala-repeat protein to the cytoplasm. An A12-SoxN-EGFP protein was found to localize in the nucleus, whereas A34-SoxN-EGFP predominantly localizes in the cytoplasm and forms protein aggregates. The gene Dmel\eEF1α1 has been identified as a having a role in the nuclear export of the SoxN expanded-Ala-repeat protein.
[updated Apr. 2021 by FlyBase; FBrf0222196]
[INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, WITH PANHYPOPITUITARISM](https://omim.org/entry/300123)
[SRY-BOX 3; SOX3](https://omim.org/entry/313430)
A variant of the X-linked SOX3 gene was implicated in a large family in which affected individuals have mental retardation and growth hormone deficiency (Laumonnier et al., 2002; pubmed:12428212).
Panhypopituitarism is a hypopituitarism characterized by deficiency in growth hormone and at least one other pituitary hormone. [Disease Ontology; DOID:9410]
OMIM describes two allelic disorders: Mental retardation, X-linked, with panhypopituitarism (MIM:300123) and Panhypopituitarism, X-linked (MIM:312000).
In the initial characterized family, it was determined that affected individuals carried a mutation that results in an in-frame duplication of 33 bp encoding for 11 alanines in a polyalanine tract of the SOX3 gene (Laumonnier et al., 2002; pubmed:12428212).
An expansion of a poly-Ala track in the SOX3 protein from 15 alanine residues to 22 is implicated in Panhypopituitarism, X-linked (MIM:312000); an expansion of the same poly-Ala track from 15 alanine residues to 26 is implicated in Mental retardation, X-linked, with panhypopituitarism (MIM:300123). [from MIM:313430; 2021.04.22]
SOX3 encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins. [Gene Cards, SOX3; 2021.04.22]
It is postulated that expansion of a polyalanine tract in SOX3 and other transcription factors results in impaired nuclear localization of the mutant protein (FBrf0235213 and references cited therein).
Many to one: 3 human genes to 1 Drosophila gene; additional related genes in both species.
Low- to moderate-scoring ortholog of human SOX1, SOX2, and SOX3 (1 Drosophila to 3 human; additional related genes in both species). Dmel\SoxN shares 35-42% identity and 44-49% similarity with the human genes.