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…

Primary Disease Associations & Inheritance

UniProtMirror movements 1
UniProtGaze palsy, familial horizontal, with progressive scoliosis, 2, with impaired intellectual development

Clinical highlights

Gene-disease validity (ClinGen)
mirror movements 1 and/or agenesis of the corpus callosum · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
12
Active trials
395
Pubs (1 yr)
P/LP submissions
P/LP missense
0.28
LOEUF· LoF intol.
LOF
Mechanism· G2P
📖
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

ClinVar Variant Classifications

0 submitted variants 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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Moderate to Severe Asthma

Leveraging Pharmacogenomics in Asthma for Predication, Mechanism and Endotyping

RECRUITING
NCT06385236Phase PHASE4University of California, San DiegoStarted 2024-02-19
DupilumabBenralizumab
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
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
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
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
Clinical Stage III Cutaneous Melanoma AJCC v8Clinical Stage IV Cutaneous Melanoma AJCC v8Metastatic Cutaneous Melanoma

Physician/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 RECRUITING
NCT02506153Phase PHASE3National Cancer Institute (NCI)Started 2015-11-10
Biospecimen CollectionComputed TomographyIpilimumab
Stage IB Lung Non-Small Cell Carcinoma AJCC v7Stage II Lung Non-Small Cell Cancer AJCC v7Stage IIIA Lung Non-Small Cell Cancer AJCC v7

Nivolumab After Surgery and Chemotherapy in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer (An ALCHEMIST Treatment Trial)

ACTIVE NOT RECRUITING
NCT02595944Phase PHASE3National Cancer Institute (NCI)Started 2016-07-22
Biospecimen CollectionComputed TomographyEchocardiography Test
Low-grade NMIBCFGFR Gene AmplificationFGFR Gene Alterations

Efficacy and Safety of TYRA-300 in Participants With FGFR3 Altered Low Grade, Intermediate Risk Non-Muscle Invasive Bladder Cancer

RECRUITING
NCT06995677Phase PHASE2Tyra Biosciences, IncStarted 2025-06-27
TYRA-300 60mgTYRA-300 50mgTYRA-300 Dose 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
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