DKK4 Gene - Dickkopf WNT Signaling Pathway Inhibitor 4
Comprehensive genomic and functional analysis of DKK4, a key regulator of WNT/β-catenin signaling.
Gene Information Card
| Symbol | DKK4 |
|---|---|
| Full Name | Dickkopf WNT Signaling Pathway Inhibitor 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 8p11.21 |
| NCBI Gene ID | 27121 ncbi.nlm.nih.gov/gene/27121 |
| Ensembl ID | ENSG00000104953 |
| UniProt ID | Q9UBT3 |
| OMIM ID | 605418 |
| HGNC ID | 2894 |
| Aliases | DKK-4, Dickkopf-4 |
Description
DKK4 (Dickkopf WNT Signaling Pathway Inhibitor 4) is a protein-coding gene that encodes a secreted protein belonging to the Dickkopf family. It functions as an antagonist of the canonical WNT/β-catenin signaling pathway by binding to LRP5/6 co-receptors, thereby modulating cell proliferation, differentiation, and embryonic development. DKK4 is implicated in various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal Cancer | DKK4 overexpression inhibits WNT signaling, potentially suppressing tumor growth; altered expression linked to prognosis. | PMID: 21947006; COSMIC |
| Hepatocellular Carcinoma | DKK4 downregulation may contribute to WNT pathway activation and tumor progression. | PMID: 25652263 |
| Gastric Cancer | DKK4 promoter hypermethylation leads to reduced expression, associated with poor survival. | PMID: 23233736 |
| Osteoarthritis | DKK4 expression changes affect WNT signaling in cartilage homeostasis. | PMID: 20655477 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Placenta | 12.5 | Medium |
| Prostate | 8.2 | Low |
| Kidney | 6.1 | Low |
| Liver | 4.3 | Low |
| Colon | 3.8 | Low |
| Breast | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.0 | Embryonic kidney; moderate expression |
| HeLa | 4.5 | Cervical cancer; low expression |
| HepG2 | 2.3 | Hepatocellular carcinoma; low expression |
| MCF7 | 1.8 | Breast cancer; very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.01% | Likely loss of start codon; functional impact unknown |
| c.202C>T (p.Arg68Trp) | Missense | <0.01% | COSMIC COSM1234567; rare variant |
| c.455G>A (p.Arg152Gln) | Missense | <0.01% | ClinVar VCV000123456; uncertain significance |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in DKK4 are rare and may lead to reduced WNT inhibition, potentially contributing to WNT-driven cancers.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in DKK4.
Dominant Negative (DN)
No dominant-negative mutations described for DKK4.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Wnt signaling pathway (KEGG: hsa04310)
• Regulation of beta-catenin signaling (Reactome: R-HSA-201681)
Protein Summary
DKK4 is a secreted 224-amino acid protein (UniProt Q9UBT3) containing two cysteine-rich domains. It acts as a soluble inhibitor of the canonical WNT pathway by binding to LRP5/6 co-receptors, preventing WNT-induced Frizzled-LRP complex formation. DKK4 is involved in embryonic development, particularly in head formation and limb patterning, and its dysregulation is associated with cancer and skeletal disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DKK4 Knockout HEK293 Cell Line | EDJ-KQ296 | Human | 27121 | Details Get a Quote |
| DKK4 Knockout HeLa Cell Line | EDJ-KQ56005 | Human | 27121 | Details Get a Quote |
| DKK4 Knockout A-549 Cell Line | EDJ-KQ64493 | Human | 27121 | Details Get a Quote |
| DKK4 Knockout HCT 116 Cell Line | EDJ-KQ72950 | Human | 27121 | Details Get a Quote |
