DCC

Chr 18

DCC netrin 1 receptor

Also known as: CRC18, CRCR1, HGPPS2, IGDCC1, MRMV1, NTN1R1

This gene encodes a netrin 1 receptor. The transmembrane protein is a member of the immunoglobulin superfamily of cell adhesion molecules, and mediates axon guidance of neuronal growth cones towards sources of netrin 1 ligand. The cytoplasmic tail interacts with the tyrosine kinases Src and focal adhesion kinase (FAK, also known as PTK2) to mediate axon attraction. The protein partially localizes to lipid rafts, and induces apoptosis in the absence of ligand. The protein functions as a tumor suppressor, and is frequently mutated or downregulated in colorectal cancer and esophageal carcinoma. [provided by RefSeq, Oct 2009]

GeneReviewsResearchGenerating clinical summary…
LOFmechanismLOEUF 0.28
Clinical SummaryDCC
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Gene-Disease Validity (ClinGen)
mirror movements 1 and/or agenesis of the corpus callosum · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
57 unique Pathogenic / Likely Pathogenic· 192 VUS of 345 total submissions
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — DCC
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint?
0.28LOEUF
pLI 0.994
Z-score 6.83
OE 0.18 (0.120.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
0.37Z-score
OE missense 0.96 (0.911.02)
752 obs / 781.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.18 (0.120.28)
00.351.4
Missense OE?0.96 (0.911.02)
00.61.4
Synonymous OE?1.16
01.21.6
LoF obs/exp: 15 / 81.6Missense obs/exp: 752 / 781.3Syn Z: -2.18
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongDCC-related midline-bridging neuronal commissure disruption, horizontal gaze palsy, scoliosis, and intellectual disabilityLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.4983th %ile
GOF
0.5268th %ile
LOF
0.69top 10%

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

LOFHere, the identification of a large four-generational family that carries a mutation to the axon guidance molecule receptor gene, DCC, enabled us to demonstrate effects on mesocorticolimbic anatomical connectivity, striatal volumes, and personality traits. Reductions in striatal volumes were replica1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

  1. 1.PMID 29712788

ClinVar Variant Classifications

345 submitted variants in ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic19
VUS192
Likely Benign52
Benign19
Conflicting5
38
Pathogenic
19
Likely Pathogenic
192
VUS
52
Likely Benign
19
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
30
7
1
0
38
Likely Pathogenic
17
2
0
0
19
VUS
4
180
6
2
192
Likely Benign
0
18
8
26
52
Benign
0
7
6
6
19
Conflicting
5
Total512142134325

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

55 pathogenic / likely-pathogenic (of 70) ClinVar copy-number / structural variants overlap DCC — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

DCC · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

KRAS Gene MutationRecurrent Lung Non-Small Cell CarcinomaStage IV Lung Non-Small Cell Cancer AJCC v7

Trametinib and Docetaxel in Treating Patients With Recurrent or Stage IV KRAS Mutation Positive Non-small Cell Lung Cancer

ACTIVE NOT RECRUITING
NCT02642042Phase PHASE2National Cancer Institute (NCI)Started 2016-07-18
DocetaxelLaboratory Biomarker AnalysisTrametinib
Previously Treated Non-Small Cell Lung Cancer

Lung-MAP: A Master Screening Protocol for Previously-Treated Non-Small Cell Lung Cancer

RECRUITING
NCT03851445Phase PHASE2, PHASE3SWOG Cancer Research NetworkStarted 2019-02-06
Screening Platform
Endometrial AdenocarcinomaEndometrial Mixed Cell AdenocarcinomaEndometrial Serous Adenocarcinoma

Testing 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 RECRUITING
NCT03660826Phase PHASE2National Cancer Institute (NCI)Started 2018-09-27
Biospecimen CollectionBone Marrow AspirateBone Marrow Biopsy
Advanced LymphomaAdvanced Malignant Solid NeoplasmBladder Carcinoma

Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

ACTIVE NOT RECRUITING
NCT02465060Phase PHASE2National Cancer Institute (NCI)Started 2015-08-17
AdavosertibAfatinibAfatinib Dimaleate
Lung Non-Squamous Non-Small Cell CarcinomaStage IB Lung Non-Small Cell Carcinoma AJCC v7Stage II Lung Non-Small Cell Cancer AJCC v7

Erlotinib 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 RECRUITING
NCT02193282Phase PHASE3National Cancer Institute (NCI)Started 2015-02-11
Clinical ObservationErlotinib HydrochlorideLaboratory Biomarker Analysis
Stage IB Lung Non-Small Cell Carcinoma AJCC v7Stage II Lung Non-Small Cell Cancer AJCC v7Stage IIA Lung Cancer AJCC v8

Genetic 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 RECRUITING
NCT02194738Phase NANational Cancer Institute (NCI)Started 2014-09-26
Biospecimen CollectionCarboplatinCisplatin
Breast Adenocarcinoma

Doxorubicin Hydrochloride, Cyclophosphamide, and Paclitaxel With or Without Bevacizumab in Treating Patients With Lymph Node-Positive or High-Risk, Lymph Node-Negative Breast Cancer

ACTIVE NOT RECRUITING
NCT00433511Phase PHASE3National Cancer Institute (NCI)Started 2007-11-02
BevacizumabCyclophosphamideDoxorubicin Hydrochloride
Lupus Erythematosus, Systemic

A Study of Nipocalimab in Adults With Moderate to Severe Systemic Lupus Erythematosus

RECRUITING
NCT07438496Phase PHASE3Janssen Research & Development, LLCStarted 2026-03-05
NipocalimabPlaceboStandard of care treatment
Low Grade Upper Tract Urothelial Carcinoma

Phase 2A/B Efficacy and Safety of Dabogratinib in Participants With Low Grade Upper Tract Urothelial Carcinoma

RECRUITING
NCT07265947Phase PHASE2Tyra Biosciences, IncStarted 2025-12-22
Dabogratinib (TYRA-300) 60mgDabogratinib (TYRA-300) 80mgDabogratinib (TYRA-300) TBD
Acinar Cell CarcinomaAdenoid Cystic CarcinomaAdrenal Cortical Carcinoma

Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

ACTIVE NOT RECRUITING
NCT02834013Phase PHASE2National Cancer Institute (NCI)Started 2017-01-30
Biospecimen CollectionComputed TomographyEchocardiography Test
Recurrent Breast CarcinomaStage III Breast Cancer AJCC v7Stage IIIA Breast Cancer AJCC v7

Tamoxifen Citrate or Z-Endoxifen Hydrochloride in Treating Patients With Locally Advanced or Metastatic, Estrogen Receptor-Positive, HER2-Negative Breast Cancer

ACTIVE NOT RECRUITING
NCT02311933Phase PHASE2National Cancer Institute (NCI)Started 2015-05-28
Endoxifen HydrochlorideLaboratory Biomarker AnalysisPharmacological Study
Breast Carcinoma In SituInvasive Breast CarcinomaStage I Breast Cancer AJCC v7

Testing MK-3475 (Pembrolizumab) as Adjuvant Therapy for Triple Receptor-Negative Breast Cancer

ACTIVE NOT RECRUITING
NCT02954874Phase PHASE3National Cancer Institute (NCI)Started 2017-01-18
Biospecimen CollectionLaboratory Biomarker AnalysisPatient Observation