XLID_SOX3
- Gene
- SOX3
- Disease
- XLID, PHPX
- Inheritance
- XR
- Classification
- Limited
- Total Score
- 5
- Publications Reviewed
- 4
- Publication Span
- 0.88 years
- Last Updated
- 05/14/2026
- Curator(s)
- Laurel Hiatt, Macayla Weiner, Harriet Dashnow
Description
Patients have been reported with SOX3 polyalanine repeat mutations associated with X-linked pituitary hormone deficiency with or without intellectual disability, with functional studies showing altered transactivation, protein aggregation in overexpression systems, and reduced SOX3 protein levels in a mouse expansion model. 5 total patients across 2 papers and a mouse model. SOX3 has previously been curated by the ClinGen Syndromic Disorders GCEP (08/02/2023) for SOX3-related X-linked pituitary hormone deficiency with or without intellectual developmental disorder.
Genetic evidence
Total: 3
| Singular Evidence | Probands | PMID:24346842 | 1.5 | One male proband with molecularly confirmed Kabuki syndrome and CPHD carried a hemizygous 21-bp SOX3 polyalanine-tract deletion (p.Ala239_245del7A); the SOX3 deletion was maternally inherited, while a separate MLL2 variant was de novo. |
| Collective Evidence | Segregation | PMID:19654509 | 1.5 | One family with three affected males carrying a 21-bp in-frame SOX3 polyalanine expansion (+7 alanines) segregating with GH deficiency through carrier females; LOD = 2.68 and the expansion was absent from 100 control females. |
Experimental evidence
Total: 2
| Function | Regulatory impact | PMID:17127446 | 0.5 | SOX3 polyalanine expansion mutants showed impaired transcriptional activation and reduced repression of β-catenin/TCF-mediated transcription in reporter assays. |
| Function | Biochemical function | PMID:17127446 | 0.5 | SOX3 +7 and +11 alanine expansion proteins formed cytoplasmic and nuclear aggregates, including aggresome-like perinuclear aggregates, in transfected cell systems and chick neural explants. |
| Models | Non-human model organism | PMID:23505376 | 1 | Sox3-26ala mouse/ES-cell model showed markedly reduced nuclear SOX3 protein, pituitary-region developmental abnormalities, no detectable in vivo aggregates, and a partial loss-of-function mechanism. |
Note: Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.