DCC

Chr 18ARAD

DCC netrin 1 receptor

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

NCBI Gene: 1630ENSG00000187323UniProt: P43146

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]

Primary Disease Associations & Inheritance

Colorectal cancer, somaticMIM #114500
Esophageal carcinoma, somaticMIM #133239
Gaze palsy, familial horizontal, with progressive scoliosis, 2MIM #617542
AR
Mirror movements 1 and/or agenesis of the corpus callosumMIM #157600
AD
382
ClinVar variants
104
Pathogenic / LP
0.99
pLI score· haploinsufficient
3
Active trials
Clinical Summary— DCC
🧬
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.
📋
ClinVar Variants
104 Pathogenic / Likely Pathogenic· 203 VUS of 382 total submissions
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.28LOEUF
pLI 0.994
Z-score 6.83
OE 0.18 (0.12–0.28)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.37Z-score
OE missense 0.96 (0.91–1.02)
752 obs / 781.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.18 (0.12–0.28)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.96 (0.91–1.02)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.16
0≤1.21.6
LoF obs/exp: 15 / 81.6Missense obs/exp: 752 / 781.3Syn Z: -2.18

ClinVar Variant Classifications

382 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic84
Likely Pathogenic20
VUS203
Likely Benign51
Benign19
Conflicting5
84
Pathogenic
20
Likely Pathogenic
203
VUS
51
Likely Benign
19
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
8
59
0
84
Likely Pathogenic
7
2
11
0
20
VUS
4
176
21
2
203
Likely Benign
0
18
7
26
51
Benign
0
7
6
6
19
Conflicting
—5
Total2821110434382

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.

Gene2Phenotype Curations

DCC-related midline-bridging neuronal commissure disruption, horizontal gaze palsy, scoliosis, and intellectual disability

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Colorectal cancer, somatic

MIM #114500

Molecular basis of disorder known

Esophageal carcinoma, somatic

MIM #133239

Molecular basis of disorder known

Gaze palsy, familial horizontal, with progressive scoliosis, 2

MIM #617542

Molecular basis of disorder known

Autosomal recessive

Mirror movements 1 and/or agenesis of the corpus callosum

MIM #157600

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — DCC
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Respiratory viral infections awaken metastatic breast cancer cells in lungs.
Chia SB et al.·Nature
2025
Effects of delayed cord clamping at different time intervals in late preterm and term neonates: a randomized controlled trial.
Chaudhary P et al.·Eur J Pediatr
2023
Deferred Cord Clamping With High Oxygen in Extremely Preterm Infants: A Randomized Clinical Trial.
Katheria AC et al.·JAMA Pediatr
2025
Effect of timing of umbilical cord clamping and other strategies to influence placental transfusion at preterm birth on maternal and infant outcomes.
Rabe H et al.·Cochrane Database Syst Rev
2019
The NIDDK Diabetic Foot Consortium.
Jones TLZ et al.·J Diabetes Sci Technol
2023
MacroH2A impedes metastatic growth by enforcing a discrete dormancy program in disseminated cancer cells.
Sun D et al.·Sci Adv
2022
Prenatal Diagnosed Agenesis of the Corpus Callosum: Identifying the Underlying Genetic Etiologies.
Wei X et al.·Prenat Diagn
2024
A human DCC variant causing mirror movement disorder reveals that the WAVE regulatory complex mediates axon guidance by netrin-1-DCC.
Chaudhari K et al.·Sci Signal
2024
Defining the Genetic Landscape of Congenital Mirror Movements in 80 Affected Individuals.
Collins Hutchinson ML et al.·Mov Disord
2024
Identification of Novel, Replicable Genetic Risk Loci for Suicidal Thoughts and Behaviors Among US Military Veterans.
Kimbrel NA et al.·JAMA Psychiatry
2023Meta-analysis
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
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
Moderate to Severe Asthma

Leveraging Pharmacogenomics in Asthma for Predication, Mechanism and Endotyping

RECRUITING
NCT06385236Phase PHASE4University of California, San DiegoStarted 2024-02-19
DupilumabBenralizumab
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

External Resources

Links to major genomics databases and tools