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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
DCC
DCC netrin 1 receptor
Chromosome 18 Β· 18q21.2
NCBI Gene: 1630Ensembl: ENSG00000187323.13HGNC: HGNC:2701UniProt: P43146
156PubMed Papers
22Diseases
0Drugs
49Pathogenic Variants
FUNCTIONAL ROLE
ReceptorTumor Suppressor
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingneuron migrationcell surfaceaxon guidancemirror movements 1horizontal gaze palsy with progressive scoliosismirror movements 1 and/or agenesis of the corpus callosumgenetic disorder
✦AI Summary

DCC (Deleted in Colorectal Cancer) encodes a transmembrane receptor protein of the immunoglobulin-CAM family that serves dual functions in neural development and tumor suppression 1. As a netrin-1 receptor, DCC mediates axon guidance by promoting chemoattraction of commissural axons to the midline during nervous system development 2. The receptor's cytoplasmic tail contains a conserved WAVE regulatory complex-interacting receptor sequence (WIRS) motif that is essential for netrin-1-mediated axon guidance through actin dynamics regulation 3. DCC can also mediate axon repulsion when associated with UNC5 proteins 2. Beyond neural development, DCC functions as a tumor suppressor gene, with frequent loss of expression observed in colorectal cancers and other malignancies including lung cancer and hematological malignancies 145. The protein shows an inverse relationship between differentiation and tumorigenesis, being expressed in differentiated intestinal cells but lost in dedifferentiated tumors 1. Genetic variants in DCC are associated with congenital mirror movements, with one variant (R1343H) disrupting the DCC-WAVE regulatory complex interaction and impairing axon guidance 3. Additionally, DCC-mediated netrin-1 signaling appears to play protective roles in precancerous lesions by modulating sympathetic neuroplasticity 6.

Sources cited
1
DCC encodes a membrane-bound protein of the immunoglobulin-CAM family and functions as a tumor suppressor with inverse relationship to differentiation
PMID: 7926722
2
DCC mediates netrin-1 chemoattraction and can mediate repulsion when associated with UNC5 proteins
PMID: 18269208
3
DCC contains a WIRS motif essential for WAVE regulatory complex interaction and axon guidance, with R1343H variant causing mirror movements
PMID: 39353037
4
DCC expression varies in lung cancer cell lines with infrequent mutations but altered expression patterns
PMID: 11005564
5
DCC expression is reduced or absent in various hematological malignancies
PMID: 7696919
6
DCC mediates netrin-1 signaling that promotes sympathetic axon growth and plays protective roles in precancerous lesions
PMID: 40753071
Disease Associationsβ“˜22
mirror movements 1Open Targets
0.79Strong
horizontal gaze palsy with progressive scoliosisOpen Targets
0.69Moderate
mirror movements 1 and/or agenesis of the corpus callosumOpen Targets
0.64Moderate
genetic disorderOpen Targets
0.52Moderate
Agenesis of corpus callosumOpen Targets
0.51Moderate
smoking initiationOpen Targets
0.46Moderate
autism spectrum disorderOpen Targets
0.46Moderate
attention deficit hyperactivity disorderOpen Targets
0.43Moderate
corneal dystrophyOpen Targets
0.40Weak
Fuchs' endothelial dystrophyOpen Targets
0.40Weak
colorectal cancerOpen Targets
0.40Weak
intelligenceOpen Targets
0.39Weak
major depressive disorderOpen Targets
0.38Weak
familial congenital mirror movementsOpen Targets
0.38Weak
esophageal carcinomaOpen Targets
0.38Weak
COVID-19Open Targets
0.38Weak
obesityOpen Targets
0.38Weak
substance abuseOpen Targets
0.37Weak
Kallmann syndromeOpen Targets
0.37Weak
colon carcinomaOpen Targets
0.36Weak
Gaze palsy, familial horizontal, with progressive scoliosis, 2, with impaired intellectual developmentUniProt
Mirror movements 1UniProt
Pathogenic Variants49
NM_005215.4(DCC):c.3061C>T (p.Arg1021Ter)Pathogenic
Inborn genetic diseases|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 1021
NM_005215.4(DCC):c.823C>T (p.Arg275Ter)Pathogenic
Mirror movements 1|Corpus callosum, agenesis of|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 275
NM_005215.4(DCC):c.437_440del (p.Thr146fs)Pathogenic
not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 146
NM_005215.4(DCC):c.1789C>T (p.Arg597Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 597
NM_005215.4(DCC):c.788_794del (p.Val263fs)Pathogenic
Gaze palsy, familial horizontal, with progressive scoliosis, 2|Mirror movements 1
β˜…β˜†β˜†β˜†2025β†’ Residue 263
NM_005215.4(DCC):c.2635C>T (p.Arg879Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 879
NM_005215.4(DCC):c.3073C>T (p.Arg1025Ter)Likely pathogenic
Mirror movements 1|not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1025
NM_005215.4(DCC):c.278C>A (p.Ser93Ter)Pathogenic
Mirror movements 1
β˜…β˜†β˜†β˜†2025β†’ Residue 93
NM_005215.4(DCC):c.2216_2217dup (p.Cys740fs)Likely pathogenic
Mirror movements 1
β˜…β˜†β˜†β˜†2024β†’ Residue 740
NM_005215.4(DCC):c.2205_2207delinsATGAT (p.Pro736Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 736
NM_005215.4(DCC):c.2551C>T (p.Gln851Ter)Likely pathogenic
Mirror movements 1
β˜…β˜†β˜†β˜†2023β†’ Residue 851
NM_005215.4(DCC):c.2280_2286del (p.Ile760fs)Pathogenic
Mirror movements 1
β˜…β˜†β˜†β˜†2023β†’ Residue 760
NM_005215.4(DCC):c.3577C>T (p.Gln1193Ter)Pathogenic
Mirror movements 1
β˜…β˜†β˜†β˜†2023β†’ Residue 1193
NM_005215.4(DCC):c.3778C>T (p.Gln1260Ter)Likely pathogenic
Mirror movements 1
β˜…β˜†β˜†β˜†2023β†’ Residue 1260
NM_005215.4(DCC):c.1501C>T (p.Arg501Ter)Likely pathogenic
DCC-related disorder
β˜…β˜†β˜†β˜†2023β†’ Residue 501
NM_005215.4(DCC):c.1140+1G>APathogenic
Mirror movements 1|not provided
β˜…β˜†β˜†β˜†2023
NM_005215.4(DCC):c.1573+2T>GPathogenic
Mirror movements 1 and/or agenesis of the corpus callosum
β˜…β˜†β˜†β˜†2023
NM_005215.4(DCC):c.1534G>T (p.Glu512Ter)Likely pathogenic
DCC-related disorder
β˜…β˜†β˜†β˜†2023β†’ Residue 512
NM_005215.4(DCC):c.2828-1G>ALikely pathogenic
DCC-related disorder
β˜…β˜†β˜†β˜†2023
NM_005215.4(DCC):c.2540del (p.Pro847fs)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2023β†’ Residue 847
View on ClinVar β†—
Related Genes
UNC5AProtein interaction100%DSCAMProtein interaction100%UNC5BProtein interaction100%UNC5CProtein interaction100%NTN1Protein interaction100%MYO10Protein interaction99%
Tissue Expression6 tissues
Brain
100%
Lung
13%
Ovary
5%
Bone Marrow
2%
Liver
2%
Heart
0%
Gene Interaction Network
Click a node to explore
DCCUNC5ADSCAMUNC5BUNC5CNTN1MYO10
PROTEIN STRUCTURE
Preparing viewer…
PDB3AU4 Β· 1.90 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.41Moderately Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.32 [0.25–0.41]
RankingsWhere DCC stands among ~20K protein-coding genes
  • #2,884of 20,598
    Most Researched156 Β· top quartile
  • #1,350of 5,498
    Most Pathogenic Variants49 Β· top quartile
  • #2,150of 17,882
    Most Constrained (LOEUF)0.41 Β· top quartile
Genes detectedDCC
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
The DCC gene product in cellular differentiation and colorectal tumorigenesis.
PMID: 7926722
Genes Dev Β· 1994
1.00
2
Genetic Susceptibility of DCC Gene in Gallbladder Cancer in Kashmir and Meta-Analysis.
PMID: 34259111
Nutr Cancer Β· 2022
0.90
3
DCC and SMAD4 alterations in human colorectal and pancreatic tumor dissemination.
PMID: 10698524
Oncogene Β· 2000
0.88
4
Mutation and expression of the DCC gene in human lung cancer.
PMID: 11005564
Neoplasia Β· 2000
0.80
5
Neural function of Netrin-1 in precancerous lesions of the pancreas.
PMID: 40753071
Nat Commun Β· 2025
0.70