HOXD13: Homeobox D13 Gene in Limb Development and Synpolydactyly
A key transcription factor in digit patterning and congenital limb malformations
Gene Information Card
| Symbol | HOXD13 |
|---|---|
| Full Name | Homeobox D13 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q31.1 |
| NCBI Gene ID | 3239 ncbi.nlm.nih.gov/gene/3239 |
| Ensembl ID | ENSG00000128714 |
| UniProt ID | P35453 |
| OMIM ID | 142989 |
| HGNC ID | 5136 |
| Aliases | SPD, HOX4I, HOX4.8 |
Description
HOXD13 is a member of the HOXD cluster of homeobox transcription factors, critical for limb development and digit patterning. It regulates anterior-posterior axis formation and digit identity. Mutations in HOXD13 cause synpolydactyly (SPD) and other limb malformations. The gene encodes a protein with a homeobox DNA-binding domain that activates downstream targets involved in chondrogenesis and joint formation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Synpolydactyly (SPD) | Expansion of polyalanine tract in HOXD13 disrupts protein function, leading to abnormal digit separation and fusion. | OMIM #186000; ClinVar; multiple case studies |
| Brachydactyly type D | Missense mutations in HOXD13 impair digit development, causing shortened thumbs. | OMIM #113200; ClinVar |
| Clinodactyly | HOXD13 variants alter finger joint formation, resulting in curved digits. | ClinVar; literature reports |
| Split-hand/foot malformation (SHFM) | Rare HOXD13 deletions or rearrangements disrupt limb bud signaling. | OMIM #183600; case reports |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 0.8 | Low |
| Skeletal muscle | 0.5 | Low |
| Adipose tissue | 0.3 | Low |
| Lung | 0.2 | Low |
| Brain | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Fibroblasts | 0.6 | Low expression in dermal fibroblasts |
| Chondrocytes | 1.2 | Moderate expression in developing cartilage |
| Mesenchymal stem cells | 0.9 | Low to moderate during differentiation |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.180_182dupGCG (polyalanine expansion) | Insertion | Common in SPD | Expanded polyalanine tract causes protein aggregation and loss of function |
| c.112A>G (p.Asn38Asp) | Missense | Rare | Altered DNA binding affinity |
| c.214C>T (p.Arg72Trp) | Missense | Rare | Reduced transcriptional activity |
| c.1A>G (p.Met1Val) | Missense | Rare | Loss of start codon, likely null |
Mutation functional classification
Loss of Function (LOF)
Polyalanine expansions and missense mutations (e.g., p.Arg72Trp) reduce DNA binding and transactivation, leading to haploinsufficiency in limb development.
Gain of Function (GOF)
Not well documented; some polyalanine expansions may confer toxic gain-of-function via aggregation.
Dominant Negative (DN)
Polyalanine expansions in HOXD13 can interfere with wild-type HOXD13 and other HOX proteins, causing dominant-negative effects in digit patterning.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Hox gene regulation in limb development (Reactome: R-HSA-5617472)
• HOXD13 targets in digit patterning (KEGG: hsa05226)
Protein Summary
HOXD13 is a 335-amino acid transcription factor containing a homeobox domain (residues 270-329) that binds DNA as a monomer. It is expressed in developing limb buds, particularly in the autopod, and regulates genes involved in chondrogenesis, apoptosis, and joint formation. The protein localizes to the nucleus and interacts with other HOX proteins and co-factors like PBX and MEIS. Mutations, especially polyalanine expansions, cause protein misfolding and aggregation, leading to synpolydactyly.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HOXD13 Knockout HEK293 Cell Line | EDJ-KQ3371 | Human | 3239 | Details Get a Quote |
| HOXD13 Knockout HeLa Cell Line | EDJ-KQ53563 | Human | 3239 | Details Get a Quote |
| HOXD13 Knockout A-549 Cell Line | EDJ-KQ62030 | Human | 3239 | Details Get a Quote |
| HOXD13 Knockout HCT 116 Cell Line | EDJ-KQ70510 | Human | 3239 | Details Get a Quote |
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