DKK3 (Dickkopf WNT Signaling Pathway Inhibitor 3)
A secreted glycoprotein involved in Wnt signaling regulation, tumor suppression, and neuroprotection.
Gene Information Card
| Symbol | DKK3 |
|---|---|
| Full Name | Dickkopf WNT Signaling Pathway Inhibitor 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 11p15.3 |
| NCBI Gene ID | 27122 ncbi.nlm.nih.gov/gene/27122 |
| Ensembl ID | ENSG00000096384 |
| UniProt ID | Q9UBP4 |
| OMIM ID | 605416 |
| HGNC ID | 2892 |
| Aliases | REIC, RIG, dkk-3, Dickkopf-3 |
Description
DKK3 (Dickkopf-3) is a member of the Dickkopf family of secreted glycoproteins. Unlike other Dickkopf proteins, DKK3 does not directly inhibit canonical Wnt signaling but modulates various cellular processes including proliferation, differentiation, and apoptosis. It is widely expressed in adult tissues and is frequently downregulated in multiple cancers, suggesting a tumor suppressor role. DKK3 is also implicated in neuroprotection and cardiovascular development.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prostate cancer | Downregulation of DKK3 leads to increased Wnt/β-catenin signaling and tumor progression. | NCBI Gene, OMIM |
| Non-small cell lung cancer | Promoter hypermethylation silences DKK3 expression, contributing to oncogenesis. | NCBI Gene, COSMIC |
| Breast cancer | Reduced DKK3 expression correlates with poor prognosis and metastasis. | NCBI Gene, OMIM |
| Alzheimer's disease | DKK3 levels are altered in brain tissue; potential role in amyloid-beta toxicity. | NCBI Gene |
| Cardiovascular disease | DKK3 modulates cardiac fibrosis and angiogenesis. | NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Lung | 6.1 | Low |
| Liver | 4.7 | Low |
| Kidney | 9.2 | Low |
| Prostate | 15.8 | Medium |
| Breast | 7.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 10.2 | Embryonic kidney cells |
| HeLa | 6.8 | Cervical cancer cells |
| A549 | 4.5 | Lung cancer cells |
| MCF7 | 3.1 | Breast cancer cells |
| LNCaP | 2.0 | Prostate cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G | Missense | <0.01% | Unknown |
| c.214C>T | Nonsense | <0.01% | Premature truncation |
| c.487G>A | Missense | <0.01% | Unknown |
Mutation functional classification
Loss of Function (LOF)
Promoter hypermethylation and nonsense mutations reduce DKK3 expression or protein function, contributing to tumorigenesis.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
| • Wnt signaling pathway | • negative regulation of canonical Wnt signaling pathway |
| • extracellular space | • protein binding |
| • cell differentiation | • apoptotic process |
Pathways
• Wnt signaling pathway (Reactome R-HSA-195721)
• DKK-mediated Wnt inhibition (Reactome R-HSA-4641262)
Protein Summary
DKK3 is a 350-amino acid secreted glycoprotein containing two cysteine-rich domains. It is involved in modulating Wnt signaling, though its mechanism differs from other Dickkopf proteins. It is frequently silenced by promoter methylation in cancers and is considered a tumor suppressor. In the nervous system, DKK3 may protect against amyloid-beta toxicity. Its expression is regulated by various transcription factors and epigenetic modifications.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DKK3 Knockout HEK293 Cell Line | EDJ-KQ408 | Human | 27122 | Details Get a Quote |
| DKK3 Knockout A-549 Cell Line | EDJ-KQ19983 | Human | 27122 | Details Get a Quote |
| DKK3 Knockout HeLa Cell Line | EDJ-KQ19984 | Human | 27122 | Details Get a Quote |
| DKK3 Knockout HCT 116 Cell Line | EDJ-KQ72951 | Human | 27122 | Details Get a Quote |
