DLX5: A Key Regulator of Craniofacial and Limb Development
Homeobox transcription factor involved in skeletal patterning and associated with split-hand/foot malformation
Gene Information Card
| Symbol | DLX5 |
|---|---|
| Full Name | Distal-less homeobox 5 |
| Gene Type | Protein-coding |
| Chromosomal Location | 7q21.3 |
| NCBI Gene ID | 1749 ncbi.nlm.nih.gov/gene/1749 |
| Ensembl ID | ENSG00000105880 |
| UniProt ID | P56178 |
| OMIM ID | 600028 |
| HGNC ID | 2918 |
| Aliases | SHFM1D, DLX5 homeobox |
Description
DLX5 encodes a homeobox transcription factor belonging to the distal-less family. It plays a critical role in craniofacial patterning, limb development, and osteoblast differentiation. DLX5 is essential for proper formation of the mandible, maxilla, and appendicular skeleton. Mutations in DLX5 are associated with split-hand/foot malformation type 1 (SHFM1) and other developmental anomalies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Split-hand/foot malformation 1 (SHFM1) | Loss-of-function mutations in DLX5 disrupt limb bud patterning, leading to ectrodactyly | OMIM #600028; ClinVar |
| Craniofacial abnormalities | DLX5 haploinsufficiency impairs mandibular and maxillary development | NCBI Gene; OMIM |
| Osteoporosis (susceptibility) | DLX5 variants may alter bone density regulation | UniProt; NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone | 12.5 | Medium |
| Brain | 8.3 | Low |
| Lung | 6.1 | Low |
| Kidney | 4.7 | Low |
| Skin | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Osteoblasts | 15.0 | High expression in differentiated osteoblasts |
| Fibroblasts | 5.2 | Moderate expression |
| HEK293 | 2.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.571C>T (p.Arg191*) | Nonsense | Rare | Loss of function; associated with SHFM1 |
| c.2T>C (p.Met1?) | Missense | Rare | Loss of function; disrupts translation initiation |
| c.470G>A (p.Arg157Gln) | Missense | Rare | Likely loss of function; reduced DNA binding |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations that truncate or impair DLX5 protein function are linked to SHFM1 and craniofacial defects.
Gain of Function (GOF)
No gain-of-function mutations reported in DLX5.
Dominant Negative (DN)
Some missense variants may act in a dominant-negative manner by interfering with wild-type DLX5 activity, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Hedgehog signaling pathway (Reactome R-HSA-5358351)
• BMP signaling pathway (Reactome R-HSA-201451)
• Osteoclast differentiation (KEGG hsa04380)
Protein Summary
DLX5 is a 290-amino acid homeobox transcription factor that binds DNA via a conserved homeodomain. It regulates target genes involved in cell proliferation, differentiation, and morphogenesis during embryonic development. DLX5 interacts with other homeobox proteins and is modulated by BMP and Hedgehog signaling. Its expression is enriched in developing limb buds, branchial arches, and osteogenic tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DLX5 Knockout HEK293 Cell Line | EDJ-KQ4452 | Human | 1749 | Details Get a Quote |
| DLX5 Knockout HeLa Cell Line | EDJ-KQ27006 | Human | 1749 | Details Get a Quote |
| DLX5 Knockout A-549 Cell Line | EDJ-KQ61563 | Human | 1749 | Details Get a Quote |
| DLX5 Knockout HCT 116 Cell Line | EDJ-KQ70054 | Human | 1749 | Details Get a Quote |
