DCC
Chr 18ARADDCC netrin 1 receptor
Also known as: CRC18, CRCR1, HGPPS2, IGDCC1, MRMV1, NTN1R1
DCC encodes a netrin 1 receptor that mediates axon guidance by attracting neuronal growth cones toward netrin sources and can induce apoptosis in the absence of ligand. Mutations cause familial horizontal gaze palsy with progressive scoliosis, mirror movements, and/or agenesis of the corpus callosum, with both autosomal recessive and autosomal dominant inheritance patterns reported. The gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.28), reflecting its critical role in nervous system development.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
409 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 30 | 7 | 50 | 0 | 87 |
Likely Pathogenic | 14 | 2 | 4 | 0 | 20 |
VUS | 4 | 180 | 20 | 2 | 206 |
Likely Benign | 0 | 18 | 8 | 26 | 52 |
Benign | 0 | 7 | 6 | 6 | 19 |
Conflicting | — | 5 | |||
| Total | 48 | 214 | 88 | 34 | 389 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
DCC · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Testing MK-3475 (Pembrolizumab) as Adjuvant Therapy for Triple Receptor-Negative Breast Cancer
ACTIVE NOT RECRUITINGGenetic Testing in Screening Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been or Will Be Removed by Surgery (The ALCHEMIST Screening Trial)
ACTIVE NOT RECRUITINGErlotinib Hydrochloride in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been Completely Removed by Surgery (An ALCHEMIST Treatment Trial)
ACTIVE NOT RECRUITINGTrametinib and Docetaxel in Treating Patients With Recurrent or Stage IV KRAS Mutation Positive Non-small Cell Lung Cancer
ACTIVE NOT RECRUITINGTamoxifen Citrate or Z-Endoxifen Hydrochloride in Treating Patients With Locally Advanced or Metastatic, Estrogen Receptor-Positive, HER2-Negative Breast Cancer
ACTIVE NOT RECRUITINGPhysician/Patient Choice of Either High-Dose Recombinant Interferon Alfa-2B or Ipilimumab, Versus Pembrolizumab in Treating Patients With Stage III-IV High Risk Melanoma That Has Been Removed by Surgery
ACTIVE NOT RECRUITINGTesting the Combination of Olaparib and Durvalumab, Cediranib and Durvalumab, Olaparib and Capivasertib, and Cediranib Alone in Recurrent or Refractory Endometrial Cancer Following the Earlier Phase of the Study That Tested Olaparib and Cediranib in Comparison to Cediranib Alone, and Olaparib Alone
ACTIVE NOT RECRUITINGNivolumab and Ipilimumab in Treating Patients With Rare Tumors
ACTIVE NOT RECRUITINGPhase 2A/B Efficacy and Safety of Dabogratinib in Participants With Low Grade Upper Tract Urothelial Carcinoma
RECRUITINGTargeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
ACTIVE NOT RECRUITINGLeveraging Pharmacogenomics in Asthma for Predication, Mechanism and Endotyping
RECRUITINGNivolumab After Surgery and Chemotherapy in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer (An ALCHEMIST Treatment Trial)
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools