HFG_HOXA13-I
- Gene
- HOXA13
- Disease
- HFG-I
- Inheritance
- AD
- Classification
- Limited
- Total Score
- 3.5
- Publications Reviewed
- 2
- Publication Span
- 3.08 years
- Last Updated
- 08/18/2025
- Curator(s)
- Macayla Weiner, Laurel Hiatt, Elbay Aliyev
Description
This HFG-I HOXA13 curation is based on experimental evidence from PMID 17935235 and primary mouse-model evidence from PMID 15385446. PMID 17935235 reports a father and daughter with hand-foot-genital syndrome carrying a heterozygous +14 alanine expansion in HOXA13 polyalanine tract III and shows, in COS-7 cells, length-dependent cytoplasmic aggregation of HOXA13 polyalanine expansion proteins, altered steady-state abundance after geldanamycin treatment, and sequestration of wild-type HOXA13/HOXD13. PMID 15385446 reports human HOXA13 polyalanine expansions in all three large tracts and a Hoxa13Ala28 knock-in mouse model with a +10 alanine expansion in tract III, showing a Hoxa13 loss-of-function-like phenotype with normal RNA expression/splicing but reduced steady-state HOXA13 protein abundance. Evidence is primarily experimental and supports a loss-of-function mechanism through post-transcriptional reduction/degradation of expanded HOXA13 protein.
Genetic evidence
Total: 0
No genetic evidence details available.
Experimental evidence
Total: 3.5
| Function | Biochemical function | PMID:17935235 PMID:15385446 | 0.5 | HOXA13 polyalanine expansion proteins showed misfolding/cytoplasmic aggregation and reduced steady-state protein abundance; mouse Hoxa13Ala28 data showed normal RNA expression/splicing but reduced HOXA13 protein abundance, supporting post-transcriptional protein loss. |
| Function | Protein interaction | PMID:17935235 | 0.5 | Co-expression assays showed polyalanine-expanded HOXA13 sequestered wild-type HOXA13 and wild-type HOXD13 proteins into cytoplasmic aggregates; this is locus-relevant protein interaction evidence from non-patient cell assays. |
| Function | Regulatory impact | PMID:17935235 PMID:15385446 | Western blot and immunohistochemistry data showed reduced steady-state HOXA13 protein abundance for the expanded allele despite normal RNA expression and splicing, indicating post-transcriptional protein reduction rather than altered transcription, epigenetic regulation, or splicing. | |
| Functional Alteration | Non-patient cells | PMID:17935235 | 0.5 | COS-7 transfection/immunocytochemistry assays showed wild-type HOXA13 localized to the nucleus, while +10 and +14 HOXA13 polyalanine expansion proteins formed cytoplasmic aggregates, with greater aggregation for longer expansions. |
| Models | Non-human model organism | PMID:15385446 | 2 | Mouse Hoxa13Ala28 knock-in model with a +10 alanine expansion in polyalanine tract III showed a phenotype indistinguishable from Hoxa13 null mice. Mutant limb buds had normal Hoxa13 RNA expression and splicing but reduced steady-state HOXA13 protein by immunohistochemistry and Western blot, supporting loss of function through in vivo degradation of the expanded protein. |
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.