NKD2 (Naked Cuticle Homolog 2)
A negative regulator of Wnt/β-catenin signaling involved in development and cancer
Gene Information Card
| Symbol | NKD2 |
|---|---|
| Full Name | Naked Cuticle Homolog 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q35.3 |
| NCBI Gene ID | 85409 ncbi.nlm.nih.gov/gene/85409 |
| Ensembl ID | ENSG00000145592 |
| UniProt ID | Q9BQB4 |
| OMIM ID | 607158 |
| HGNC ID | 17045 |
| Aliases | NKD2A, NKD2B, FLJ20321 |
Description
NKD2 (naked cuticle homolog 2) encodes a cytoplasmic protein that functions as a negative regulator of the canonical Wnt/β-catenin signaling pathway. It is a homolog of the Drosophila naked cuticle (nkd) gene. NKD2 binds to Dishevelled (DVL) proteins, inhibiting Wnt signal transduction. The gene is involved in embryonic development, cell differentiation, and has been implicated in several cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Loss of NKD2 expression leads to aberrant Wnt/β-catenin activation, promoting tumorigenesis. | PMID: 19151757 |
| Gastric cancer | NKD2 promoter hypermethylation reduces expression, correlating with poor prognosis. | PMID: 22351686 |
| Hepatocellular carcinoma | Downregulation of NKD2 contributes to β-catenin nuclear accumulation. | PMID: 25636873 |
| Breast cancer | NKD2 expression is reduced in invasive ductal carcinoma; associated with Wnt pathway activation. | PMID: 23593055 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 9.7 | Low |
| Testis | 15.2 | Medium |
| Colon | 11.4 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.2 | Embryonic kidney cells; moderate expression |
| HeLa | 8.5 | Cervical carcinoma; low expression |
| HCT116 | 6.3 | Colorectal carcinoma; reduced expression |
| MCF7 | 5.1 | Breast cancer; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G | Missense | <0.1% | p.Met1?; start codon loss, likely loss of function |
| c.256C>T | Nonsense | <0.1% | p.Arg86*; premature truncation, loss of function |
| c.487_488insA | Frameshift | <0.1% | p.Thr163Asnfs*2; loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations in NKD2 result in truncated proteins lacking the DVL-binding domain, impairing Wnt inhibition.
Gain of Function (GOF)
No gain-of-function mutations reported in NKD2.
Dominant Negative (DN)
No dominant-negative mutations described for NKD2.
View complete mutation data：
Gene Ontology (GO)
| • cytoplasm (GO:0005737) | • protein binding (GO:0005515) |
| • Wnt signaling pathway (GO:0016055) | • signal transduction (GO:0007165) |
| • nucleus (GO:0005634) |
Pathways
• Wnt signaling pathway (KEGG: hsa04310)
• Regulation of β-catenin signaling (Reactome: R-HSA-201681)
Protein Summary
NKD2 is a 473-amino-acid protein containing a zinc finger domain and a conserved NKD domain. It localizes to the cytoplasm and interacts with Dishevelled (DVL) proteins to inhibit Wnt/β-catenin signaling. The protein is involved in negative feedback regulation of Wnt pathway activity during development and tissue homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NKD2 Knockout HEK293 Cell Line | EDJ-KQ318 | Human | 85409 | Details Get a Quote |
| NKD2 Knockout A-549 Cell Line | EDJ-KQ18463 | Human | 85409 | Details Get a Quote |
| NKD2 Knockout HCT 116 Cell Line | EDJ-KQ18464 | Human | 85409 | Details Get a Quote |
| NKD2 Knockout HeLa Cell Line | EDJ-KQ57709 | Human | 85409 | Details Get a Quote |
