NKD1 (Naked Cuticle Homolog 1)
A negative regulator of Wnt/β-catenin signaling involved in development and cancer
Gene Information Card
| Symbol | NKD1 |
|---|---|
| Full Name | Naked Cuticle Homolog 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 16q12.1 |
| NCBI Gene ID | 85407 ncbi.nlm.nih.gov/gene/85407 |
| Ensembl ID | ENSG00000140807 |
| UniProt ID | Q969G9 |
| OMIM ID | 607158 |
| HGNC ID | 17045 |
| Aliases | NKD, hNkd, FLJ20321 |
Description
NKD1 (Naked Cuticle Homolog 1) encodes a cytoplasmic protein that acts as a negative regulator of the canonical Wnt/β-catenin signaling pathway. It is induced by Wnt signaling and participates in a negative feedback loop by binding to and inhibiting Dishevelled (DVL) proteins. NKD1 is involved in embryonic development, cell differentiation, and has been implicated in colorectal and other cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Loss of NKD1 expression leads to aberrant Wnt/β-catenin activation, promoting tumorigenesis. | PMID: 19151757; COSMIC |
| Gastric cancer | Epigenetic silencing of NKD1 via promoter methylation contributes to Wnt pathway hyperactivation. | PMID: 22198284 |
| Hepatocellular carcinoma | Reduced NKD1 expression correlates with poor prognosis and increased β-catenin nuclear accumulation. | PMID: 23541953 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 5.2 | Low |
| Colon | 12.8 | Medium |
| Kidney | 8.1 | Low |
| Liver | 3.4 | Low |
| Lung | 6.7 | Low |
| Placenta | 15.3 | Medium |
| Small intestine | 14.1 | Medium |
| Stomach | 11.5 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 10.2 | Embryonic kidney; moderate expression |
| HeLa | 7.8 | Cervical carcinoma; low expression |
| HCT 116 | 5.1 | Colorectal carcinoma; reduced due to methylation |
| MCF7 | 4.3 | Breast cancer; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.1% | Likely loss of start codon; predicted loss of function |
| c.103C>T (p.Arg35*) | Nonsense | <0.1% | Premature stop; loss of function |
| c.487_488insA | Frameshift | <0.1% | Frameshift; loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and missense mutations that disrupt the NKD1 protein structure or expression lead to loss of negative regulation of Wnt signaling, contributing to oncogenesis.
Gain of Function (GOF)
No documented gain-of-function mutations in NKD1.
Dominant Negative (DN)
No documented dominant-negative mutations in NKD1.
View complete mutation data：
Gene Ontology (GO)
| • cytoplasm (GO:0005737) | • Wnt signaling pathway (GO:0016055) |
| • negative regulation of Wnt signaling pathway (GO:0030178) | • protein binding (GO:0005515) |
| • metal ion binding (GO:0046872) |
Pathways
• Wnt signaling pathway (KEGG: hsa04310)
• Negative regulation of canonical Wnt signaling (Reactome: R-HSA-4641262)
Protein Summary
The NKD1 protein (UniProt Q969G9) is 470 amino acids long and contains an N-terminal EF-hand domain and a C-terminal histidine-rich region. It localizes to the cytoplasm and interacts with Dishevelled (DVL) proteins to inhibit Wnt/β-catenin signaling. NKD1 is itself transcriptionally induced by Wnt signaling, forming a negative feedback loop. Post-translational modifications include phosphorylation and ubiquitination, which regulate its stability and function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NKD1 Knockout HEK293 Cell Line | EDJ-KQ317 | Human | 85407 | Details Get a Quote |
| NKD1 Knockout HCT 116 Cell Line | EDJ-KQ17969 | Human | 85407 | Details Get a Quote |
| NKD1 Knockout HeLa Cell Line | EDJ-KQ57708 | Human | 85407 | Details Get a Quote |
| NKD1 Knockout A-549 Cell Line | EDJ-KQ66211 | Human | 85407 | Details Get a Quote |
