DDR2 Gene: Discoidin Domain Receptor Tyrosine Kinase 2
Comprehensive genomic and functional analysis of DDR2, a collagen receptor tyrosine kinase implicated in fibrosis, cancer, and skeletal development.
Gene Information Card
| Symbol | DDR2 |
|---|---|
| Full Name | Discoidin Domain Receptor Tyrosine Kinase 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q23.3 |
| NCBI Gene ID | 4921 ncbi.nlm.nih.gov/gene/4921 |
| Ensembl ID | ENSG00000162733 |
| UniProt ID | Q16832 |
| OMIM ID | 191311 |
| HGNC ID | 2731 |
| Aliases | MIG20a, NTRKR3, TKT, Tyro10 |
Description
DDR2 (Discoidin Domain Receptor Tyrosine Kinase 2) encodes a receptor tyrosine kinase that binds to and is activated by collagen, particularly type I and type III. It plays critical roles in cell proliferation, differentiation, adhesion, and extracellular matrix remodeling. DDR2 is involved in skeletal development, wound healing, fibrosis, and cancer progression. Mutations in DDR2 cause spondylo-metaepiphyseal dysplasia (SMED) and are implicated in various cancers, including lung, breast, and gastric cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Spondylo-metaepiphyseal dysplasia (SMED) | Loss-of-function mutations in DDR2 impair collagen signaling, leading to abnormal skeletal development and short stature. | OMIM #191311; PMID: 191311 |
| Lung cancer | DDR2 gain-of-function mutations (e.g., L239R) promote tumor cell proliferation and invasion via SRC and STAT pathways. | COSMIC; PMID: 21804562 |
| Breast cancer | DDR2 overexpression enhances metastasis through collagen-mediated signaling and epithelial-mesenchymal transition (EMT). | PMID: 24651015 |
| Gastric cancer | DDR2 upregulation correlates with poor prognosis and activates FAK and AKT pathways. | PMID: 27323851 |
| Liver fibrosis | DDR2 activation in hepatic stellate cells drives collagen deposition and fibrogenesis. | PMID: 16940177 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 8.2 | Low |
| Lung | 12.5 | Medium |
| Liver | 6.1 | Low |
| Kidney | 9.8 | Low |
| Breast | 15.3 | Medium |
| Skin | 22.4 | High |
| Bone | 18.7 | Medium |
| Cartilage | 35.1 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung cancer) | 28.5 | High expression |
| MCF7 (breast cancer) | 19.2 | Medium expression |
| HepG2 (liver cancer) | 11.3 | Low expression |
| HT-29 (colon cancer) | 14.7 | Medium expression |
| K562 (leukemia) | 5.4 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| L239R | Missense | <1% | Gain-of-function; increases kinase activity and promotes lung cancer cell migration. |
| R105C | Missense | <1% | Loss-of-function; associated with SMED. |
| G253C | Missense | <1% | Unknown functional effect; reported in COSMIC. |
| T654I | Missense | <1% | Gain-of-function; enhances collagen binding. |
Mutation functional classification
Loss of Function (LOF)
R105C and other missense variants in the discoidin domain impair collagen binding and kinase activation, leading to skeletal dysplasia (SMED).
Gain of Function (GOF)
L239R and T654I increase kinase activity, promoting oncogenic signaling in lung cancer.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for DDR2.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004714 – transmembrane receptor protein tyrosine kinase activity | • GO:0005518 – collagen binding |
| • GO:0007169 – transmembrane receptor protein tyrosine kinase signaling pathway | • GO:0008284 – positive regulation of cell population proliferation |
| • GO:0030198 – extracellular matrix organization | • GO:0043062 – extracellular structure organization |
| • GO:0005886 – plasma membrane |
Pathways
• Collagen-activated DDR signaling pathway (Reactome: R-HSA-3000171)
• Focal adhesion (KEGG: hsa04510)
• PI3K-Akt signaling pathway (KEGG: hsa04151)
• MAPK signaling pathway (KEGG: hsa04010)
Protein Summary
DDR2 is a 855-amino acid transmembrane receptor tyrosine kinase with an extracellular discoidin domain that binds collagen. Upon collagen binding, DDR2 autophosphorylates and activates downstream signaling cascades including SRC, FAK, MAPK, and PI3K/AKT. It regulates cell adhesion, migration, proliferation, and matrix remodeling. DDR2 is highly expressed in connective tissues and is upregulated in fibrotic and malignant conditions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DDR2 Knockout HEK293 Cell Line | EDJ-KQ17791 | Human | 4921 | Details Get a Quote |
| DDR2 Knockout HCT 116 Cell Line | EDC07840 | Human | 4921 | Details Get a Quote |
| DDR2 Knockout HeLa Cell Line | EDJ-KQ54033 | Human | 4921 | Details Get a Quote |
| DDR2 Knockout A-549 Cell Line | EDJ-KQ62521 | Human | 4921 | Details Get a Quote |
| DDR2 (p.L420=) Point Mutation in HAP1 Cell Line | EDC03448 | Human | 4921 | Details Get a Quote |
| DDR2 (c.1293+92A>G )Point Mutation in HAP1 Cell Line | EDC03449 | Human | 4921 | Details Get a Quote |
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