DKK1 (Dickkopf WNT Signaling Pathway Inhibitor 1)
A key inhibitor of Wnt signaling with roles in development, cancer, and bone metabolism.
Gene Information Card
| Symbol | DKK1 |
|---|---|
| Full Name | Dickkopf WNT Signaling Pathway Inhibitor 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q21.1 |
| NCBI Gene ID | 22943 ncbi.nlm.nih.gov/gene/22943 |
| Ensembl ID | ENSG00000107984 |
| UniProt ID | O94907 |
| OMIM ID | 605189 |
| HGNC ID | 2891 |
| Aliases | DKK-1, Dickkopf-1, SK |
Description
DKK1 encodes Dickkopf-1, a secreted protein that functions as a potent inhibitor of the canonical Wnt signaling pathway. It binds to LRP5/6 co-receptors and the Kremen proteins, leading to receptor internalization and degradation, thereby blocking Wnt/β-catenin signaling. DKK1 plays critical roles in embryonic development, particularly in head formation and limb patterning, and is involved in adult tissue homeostasis, including bone metabolism and cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | DKK1 is often overexpressed in tumors, promoting proliferation and metastasis by modulating Wnt signaling and immune evasion. | High expression in multiple myeloma, lung, breast, and liver cancers (COSMIC, literature). |
| Osteolytic bone lesions (multiple myeloma) | DKK1 secreted by myeloma cells inhibits osteoblast differentiation, leading to bone destruction. | Elevated DKK1 levels in myeloma patients correlate with bone lesions (OMIM, literature). |
| Osteoporosis | Increased DKK1 expression reduces bone formation, contributing to low bone mass. | Association studies and animal models (OMIM, literature). |
| Alzheimer's disease | DKK1 is upregulated in the brain and may contribute to neurodegeneration by inhibiting Wnt signaling. | Expression studies in human brain tissue (literature). |
| Osteoarthritis | DKK1 dysregulation affects cartilage homeostasis and subchondral bone remodeling. | Expression and functional studies (literature). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Placenta | High | High expression in placental tissue. |
| Bone marrow | Medium | Expressed in bone marrow, relevant to hematopoiesis and myeloma. |
| Liver | Medium | Moderate expression in liver. |
| Lung | Low | Low expression in lung. |
| Brain | Low | Low expression in brain, but upregulated in disease. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | Low | Cervical cancer cell line. |
| MCF7 | Medium | Breast cancer cell line. |
| HepG2 | Medium | Liver cancer cell line. |
| A549 | Low | Lung cancer cell line. |
| U2OS | Low | Osteosarcoma cell line. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.106C>T (p.Arg36Cys) | Missense | Rare | Potential impact on protein function; reported in ClinVar. |
| c.346G>A (p.Val116Met) | Missense | Rare | Uncertain significance; not well characterized. |
| c.−29C>T (5' UTR) | Regulatory | Rare | May affect gene expression; clinical significance unknown. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in DKK1 are rare and may lead to increased Wnt signaling, potentially contributing to developmental defects or cancer progression.
Gain of Function (GOF)
Gain-of-function (overexpression) is more common in cancer, leading to excessive Wnt inhibition and promoting tumor growth and metastasis.
Dominant Negative (DN)
No dominant-negative mutations have been reported for DKK1.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005109 (frizzled binding) | • GO:0005125 (cytokine activity) |
| • GO:0005515 (protein binding) | • GO:0005615 (extracellular space) |
| • GO:0005576 (extracellular region) | • GO:0016055 (Wnt signaling pathway) |
| • GO:0030178 (negative regulation of Wnt signaling pathway) | • GO:0007165 (signal transduction) |
Pathways
• Wnt signaling pathway (KEGG: hsa04310)
• Regulation of beta-catenin signaling by Wnt (Reactome: R-HSA-4641263)
• Signaling by WNT (Reactome: R-HSA-195721)
Protein Summary
DKK1 is a secreted glycoprotein of approximately 266 amino acids (35 kDa) that contains two cysteine-rich domains. It is synthesized as a precursor with a signal peptide and is processed to the mature form. DKK1 binds to LRP6 and Kremen1/2, forming a ternary complex that triggers endocytosis and degradation of LRP6, thereby preventing Wnt ligand-induced activation of the canonical pathway. This inhibition is crucial for regulating cell proliferation, differentiation, and apoptosis. DKK1 is also involved in bone formation by inhibiting osteoblast differentiation, and its dysregulation is linked to various cancers and bone diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DKK1 Knockout HEK293T Cell Line | EDJ-KQ153 | Human | 22943 | Details Get a Quote |
| DKK1 Knockout HEK293 Cell Line | EDJ-KQ294 | Human | 22943 | Details Get a Quote |
| DKK1 Knockout A-549 Cell Line | EDJ-KQ17964 | Human | 22943 | Details Get a Quote |
| DKK1 Knockout HCT 116 Cell Line | EDJ-KQ18409 | Human | 22943 | Details Get a Quote |
| DKK1 Knockout HeLa Cell Line | EDJ-KQ18410 | Human | 22943 | Details Get a Quote |
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