DCC Netrin 1 Receptor
DCC (Deleted in Colorectal Carcinoma) is a transmembrane receptor for netrin 1 involved in axon guidance, cell migration, and tumor suppression.
Gene Information Card
| Symbol | DCC |
|---|---|
| Full Name | DCC netrin 1 receptor |
| Gene Type | protein-coding |
| Chromosomal Location | 18q21.2 |
| NCBI Gene ID | 1630 ncbi.nlm.nih.gov/gene/1630 |
| Ensembl ID | ENSG00000187323 |
| UniProt ID | P43146 |
| OMIM ID | 120470 |
| HGNC ID | 2701 |
| Aliases | CRC18, HNPCC7, MRMV1, NTN1R1 |
Description
DCC (Deleted in Colorectal Carcinoma) encodes a transmembrane receptor for netrin 1. It functions as a tumor suppressor and plays a critical role in axon guidance, cell migration, and apoptosis. Loss of DCC expression is frequently observed in colorectal and other cancers, often due to loss of heterozygosity at 18q21. The receptor mediates both attractive and repulsive cues during neural development and regulates cell survival through dependence receptor signaling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer (CRC) | Loss of heterozygosity at 18q21 leads to reduced DCC expression, impairing tumor suppression and promoting metastasis. | NCBI Gene, OMIM, COSMIC |
| Hereditary non-polyposis colorectal cancer (HNPCC) | Germline mutations in DCC are associated with increased colorectal cancer risk in some families. | OMIM, ClinVar |
| Mirror movements (MRMV1) | Biallelic loss-of-function mutations in DCC cause congenital mirror movements due to defective axon guidance across the midline. | OMIM, NCBI Gene |
| Pancreatic cancer | DCC downregulation is associated with poor prognosis and metastatic progression. | COSMIC, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Spinal cord | 8.3 | Medium |
| Colon | 2.1 | Low |
| Small intestine | 1.8 | Low |
| Liver | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | High expression |
| HCT116 (colorectal carcinoma) | 0.8 | Low expression |
| HeLa (cervical carcinoma) | 1.1 | Low expression |
| MCF7 (breast carcinoma) | 0.6 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2441G>A (p.Arg814His) | Missense | <1% | Loss of netrin binding; associated with mirror movements |
| c.1603C>T (p.Arg535*) | Nonsense | <0.5% | Truncation; loss of function in colorectal cancer |
| c.2077delA (p.Thr693Profs*12) | Frameshift | <0.1% | Loss of function; reported in HNPCC |
| Loss of heterozygosity (18q21) | Copy number loss | ~50% in CRC | Reduced DCC expression; promotes metastasis |
Mutation functional classification
Loss of Function (LOF)
Most DCC mutations in cancer and mirror movements are loss-of-function, including nonsense, frameshift, and missense variants that impair netrin binding or receptor signaling.
Gain of Function (GOF)
No well-established gain-of-function mutations are reported for DCC.
Dominant Negative (DN)
Some missense mutations in the extracellular domain may exert dominant-negative effects by disrupting receptor dimerization, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • netrin receptor activity (GO:0005042) | • axon guidance (GO:0007411) |
| • apoptotic process (GO:0006915) | • signal transduction (GO:0007165) |
| • plasma membrane (GO:0005886) | • cell migration (GO:0016477) |
Pathways
• Netrin-1 signaling (P00009)
• Axon guidance (hsa04360)
• DCC-mediated attractive signaling
• UNC5-mediated repulsive signaling
Protein Summary
DCC is a 1447-amino acid transmembrane protein with four immunoglobulin-like domains and six fibronectin type III repeats in the extracellular region, and a cytoplasmic domain that interacts with downstream signaling molecules. It functions as a dependence receptor: in the presence of netrin 1, it promotes cell survival and axon attraction; in the absence of netrin 1, it induces apoptosis. Loss of DCC expression is a hallmark of many cancers, particularly colorectal carcinoma, where it contributes to tumor progression and metastasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DCC Knockout HEK293 Cell Line | EDJ-KQ2466 | Human | 1630 | Details Get a Quote |
| DCC Knockout HeLa Cell Line | EDJ-KQ53074 | Human | 1630 | Details Get a Quote |
| DCC Knockout A-549 Cell Line | EDJ-KQ61539 | Human | 1630 | Details Get a Quote |
| DCC Knockout HCT 116 Cell Line | EDJ-KQ70032 | Human | 1630 | Details Get a Quote |
