DLX4: Distal-Less Homeobox 4 – A Key Regulator in Development and Cancer
Comprehensive genomic and functional overview of DLX4, a homeobox transcription factor implicated in embryogenesis and oncogenesis.
Gene Information Card
| Symbol | DLX4 |
|---|---|
| Full Name | distal-less homeobox 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 17q21.33 |
| NCBI Gene ID | 1748 ncbi.nlm.nih.gov/gene/1748 |
| Ensembl ID | ENSG00000108821 |
| UniProt ID | O60481 |
| OMIM ID | 601911 |
| HGNC ID | 2917 |
| Aliases | DLX7, DLX8, DLX9, BP1, HOXC4 |
Description
DLX4 (distal-less homeobox 4) encodes a homeobox transcription factor belonging to the DLX family, which is essential for embryonic development, particularly in craniofacial, limb, and placental morphogenesis. DLX4 regulates gene expression by binding to DNA as a homodimer or heterodimer with other homeobox proteins. Aberrant DLX4 expression is associated with several cancers, including breast cancer, acute myeloid leukemia, and neuroblastoma, where it can promote proliferation, invasion, and chemoresistance.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast Cancer | DLX4 overexpression promotes epithelial-mesenchymal transition (EMT) and invasion via upregulation of SNAI1 and TWIST1. | PMID: 23454724; NCBI GeneRIF |
| Acute Myeloid Leukemia (AML) | DLX4 is highly expressed in AML blasts and associated with poor prognosis; may block differentiation. | PMID: 15692067; NCBI GeneRIF |
| Neuroblastoma | DLX4 expression correlates with MYCN amplification and aggressive tumor behavior. | PMID: 19029980; NCBI GeneRIF |
| Ovarian Cancer | DLX4 upregulation linked to cisplatin resistance and increased cell survival. | PMID: 21804532; NCBI GeneRIF |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Placenta | 45.2 | High |
| Bone Marrow | 12.8 | Medium |
| Breast | 8.5 | Low |
| Brain | 3.1 | Low |
| Kidney | 2.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 18.3 | High expression; associated with EMT |
| K562 (leukemia) | 22.1 | High expression; blocks differentiation |
| SH-SY5Y (neuroblastoma) | 14.7 | Moderate expression; MYCN co-expression |
| HEK293 (embryonic kidney) | 6.2 | Low baseline expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | missense | Rare | Potential loss of start codon; functional impact unknown |
| c.365C>T (p.Pro122Leu) | missense | 0.01% (gnomAD) | Located in homeodomain; may alter DNA binding |
| c.512G>A (p.Arg171Gln) | missense | 0.005% (gnomAD) | Reported in COSMIC; possible gain-of-function in cancer |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations reported; knockdown studies show reduced proliferation in cancer cells.
Gain of Function (GOF)
Overexpression and certain missense variants (e.g., p.Arg171Gln) are associated with increased transcriptional activity and oncogenic potential.
Dominant Negative (DN)
Not described for DLX4; heterodimerization with other DLX family members may be disrupted by some mutations.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Homeobox transcription factor pathway (Reactome: R-HSA-5619507)
• Developmental biology (Reactome: R-HSA-1266738)
• Transcriptional regulation by DLX4 (GeneCards)
Protein Summary
The DLX4 protein (UniProt O60481) is a 240-amino-acid homeobox transcription factor containing a conserved DNA-binding homeodomain. It localizes to the nucleus and regulates target genes involved in cell proliferation, differentiation, and migration. DLX4 can form homodimers or heterodimers with other DLX proteins (e.g., DLX2) to modulate transcriptional activity. In cancer, DLX4 is frequently overexpressed and contributes to EMT, stemness, and chemoresistance.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DLX4 Knockout HEK293 Cell Line | EDJ-KQ4449 | Human | 1748 | Details Get a Quote |
| DLX4 Knockout A-549 Cell Line | EDJ-KQ27001 | Human | 1748 | Details Get a Quote |
| DLX4 Knockout HCT 116 Cell Line | EDJ-KQ27002 | Human | 1748 | Details Get a Quote |
| DLX4 Knockout HeLa Cell Line | EDJ-KQ25737 | Human | 1748 | Details Get a Quote |
