HFG_HOXA13-III
- Gene
- HOXA13
- Disease
- HFG-III
- Inheritance
- AD
- Classification
- Limited
- Total Score
- 4.5
- Publications Reviewed
- 3
- Publication Span
- 7.46 years
- Last Updated
- 08/18/2025
- Curator(s)
- Macayla Weiner, Laurel Hiatt
Description
Autosomal dominant hand-foot-genital syndrome type III (HFG-III) is associated with expansions of the third N-terminal polyalanine tract in HOXA13. PMID 10839976 reported an HFGS family with a 24-bp in-frame insertion in exon 1 that expands HOXA13 polyalanine tract III from 18 to 26 alanines and segregates across multiple affected relatives. PMID 17935235 reported a father-daughter family with a 42-bp insertion adding 14 alanines to the same tract and showed that expanded HOXA13 proteins mislocalize to cytoplasmic aggregates, show reduced steady-state abundance, and can sequester wild-type HOXA13/HOXD13 in transfected cells.
Genetic evidence
Total: 2
| Singular Evidence | Probands | PMID:10839976 | 0.5 | One HFGS family (family 4) had a HOXA13 tract III 24-bp in-frame insertion after base 387, expanding the third N-terminal polyalanine tract from 18 to 26 alanines, with typical limb and genitourinary abnormalities. |
| Collective Evidence | Segregation | PMID:10839976 | 1.5 | The HOXA13 tract III expansion was detected in multiple affected relatives in family 4 (I.2, III.1, III.3, and III.5) and was reported as stable over at least three generations. |
Experimental evidence
Total: 2.5
| Function | Protein interaction | PMID:17935235 | 0.5 | In transfected COS-7 cells, +10 and +14 HOXA13 polyalanine expansion proteins sequestered wild-type HOXA13 and wild-type HOXD13 into cytoplasmic aggregates in a length-dependent manner. |
| Models | Non-human model organism | PMID:15385446 | 2 | Engineered Hoxa13 tract-III polyalanine-expansion mice (Hoxa13Ala28) showed limb phenotypes indistinguishable from Hoxa13 null mice and no homozygote survival to birth, supporting loss of function for HOXA13 polyalanine expansions. |
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.