Curation HFG HOXA13-III

Gene HOXA13

Disease HFG-III

Inheritance AD

Score

2 + 2.5 = 4.5 / 18

Genetic + experimental = total

Classification

Limited

Refuted

Moderate

Definitive

Last Updated 08/18/2025

Pubs Reviewed 3

Publication Span 7.46 years

Publication Interval 7.46 years

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.

All criTRia Curations Locus Page

Genetic evidence

Total: 2

Per page

Category	Type	Citation	Score	Details
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

Per page

Category	Type	Citation	Score	Details
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.

Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.