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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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DDR1
discoidin domain receptor tyrosine kinase 1
Chromosome 6 · 6p21.33
NCBI Gene: 780Ensembl: ENSG00000137332.19HGNC: HGNC:2730UniProt: A0A024RCQ1
233PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
KinaseReceptor
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
plasma membraneGO:0005615collagen bindingextracellular exosomeneurodegenerative diseaseAlzheimer diseasemultiple sclerosisParkinson disease
✦AI Summary

DDR1 is a collagen-binding receptor tyrosine kinase that serves as a key sensor of extracellular matrix (ECM) composition and state 1. Upon collagen binding, DDR1 activates signaling cascades involving autophosphorylation and downstream kinases to regulate cell adhesion, migration, differentiation, and matrix remodeling 2. DDR1 upregulates matrix metalloproteinases (MMP2, MMP7, MMP9) to facilitate ECM remodeling and promote wound healing in normal physiology. In disease contexts, DDR1 dysregulation contributes to multiple pathologies. In vitiligo, reduced DDR1 expression compromises melanocyte-epithelial adhesion, facilitating autoimmune attack 3. In cancer, DDR1 plays multifaceted roles: it promotes immune exclusion by organizing collagen fiber alignment, obstructing T cell infiltration in triple-negative breast cancer 4; regulates tumor metabolism through collagen-dependent macropinocytosis 1; and drives gastric cancer progression via the DDR1-HIF-1α axis, enhancing angiogenesis and metastatic capacity 5. DDR1 expression correlates with an immune-exclusion signature in colorectal cancer progression 6. Clinically, DDR1 represents a therapeutic target for cancer, fibrosis, atherosclerosis, and neurodegenerative diseases 7. DDR1 inhibitors show promise in preclinical models 8, though drug development faces challenges including selectivity and complex ECM interactions.

Sources cited
1
DDR1 is a collagen sensor controlling tumor metabolism, growth, and therapy response
PMID: 37709651
2
Collagen remodeling through DDR1 signaling affects tumor bioenergetics and progression
PMID: 37400314
3
DDR1 expression reduction in vitiligo facilitates melanocyte damage and autoimmunity
PMID: 35643735
4
DDR1 promotes collagen alignment to cause immune exclusion in triple-negative breast cancer
PMID: 34732895
5
DDR1 drives gastric cancer progression through HIF-1α stabilization and enhanced angiogenesis
PMID: 39024501
6
DDR1 is part of an immune-exclusion signature in colorectal cancer progression
PMID: 38065082
7
DDR1 is implicated in cancer, fibrosis, atherosclerosis, and neurodegenerative diseases as therapeutic target
PMID: 38580164
8
DDR1 kinase inhibitors can be identified using deep learning with favorable pharmacokinetics
PMID: 31477924
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.45Moderate
Alzheimer diseaseOpen Targets
0.26Weak
multiple sclerosisOpen Targets
0.26Weak
Parkinson diseaseOpen Targets
0.24Weak
lysosomal storage diseaseOpen Targets
0.23Weak
ankylosing spondylitisOpen Targets
0.16Weak
neoplasmOpen Targets
0.12Weak
cancerOpen Targets
0.11Weak
gastric cancerOpen Targets
0.11Weak
breast cancerOpen Targets
0.11Weak
hepatocellular carcinomaOpen Targets
0.11Weak
colorectal carcinomaOpen Targets
0.11Weak
attention deficit hyperactivity disorderOpen Targets
0.10Weak
colon carcinomaOpen Targets
0.10Suggestive
osteosarcomaOpen Targets
0.10Suggestive
melanomaOpen Targets
0.10Suggestive
oral squamous cell carcinomaOpen Targets
0.10Suggestive
ovarian cancerOpen Targets
0.10Suggestive
non-small cell lung carcinomaOpen Targets
0.10Suggestive
cervical cancerOpen Targets
0.09Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
COL3A1Protein interaction100%COL5A1Protein interaction99%TM4SF1Protein interaction87%LTKShared pathway25%ALKAL1Shared pathway20%ALKAL2Shared pathway20%
Tissue Expression6 tissues
Brain
100%
Ovary
53%
Heart
34%
Lung
31%
Liver
7%
Bone Marrow
6%
Gene Interaction Network
Click a node to explore
DDR1COL3A1COL5A1TM4SF1LTKALKAL1ALKAL2
PROTEIN STRUCTURE
Preparing viewer…
PDB6FEX · 1.29 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.81LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.65 [0.53–0.81]
RankingsWhere DDR1 stands among ~20K protein-coding genes
  • #1,712of 20,598
    Most Researched233 · top 10%
  • #6,762of 17,882
    Most Constrained (LOEUF)0.81
Genes detectedDDR1
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Update on the pathogenesis of vitiligo.
PMID: 35643735
An Bras Dermatol · 2022
1.00
2
Multifaceted collagen-DDR1 signaling in cancer.
PMID: 37709651
Trends Cell Biol · 2024
0.90
3
Tumour DDR1 promotes collagen fibre alignment to instigate immune exclusion.
PMID: 34732895
Nature · 2021
0.80
4
Modulating tumor collagen fiber alignment for enhanced lung cancer immunotherapy via inhaled RNA.
PMID: 40885724
Nat Commun · 2025
0.72
5
Collagen architecture and signaling orchestrate cancer development.
PMID: 37400314
Trends Cancer · 2023
0.70