On this page
DDR2
discoidin domain receptor tyrosine kinase 2
The *DDR2* gene provides instructions for making a protein that acts as a receptor on the cell surface, primarily involved in detecting and responding to collagen. The *DDR2* gene encodes Discoidin Domain Receptor Tyrosine Kinase 2, a crucial protein in cellular signalling pathways.
DDR2 is located on the long (q) arm of chromosome 1, at band 1q23.3. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 1 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The *DDR2* gene is responsible for producing the DDR2 protein, a type of receptor tyrosine kinase. This protein is located on the surface of cells and acts as a sensor for collagen, a key component of the extracellular matrix. By binding to collagen, DDR2 initiates intracellular signalling pathways that influence cell adhesion, migration, proliferation, and differentiation.
Dysregulation of DDR2 function is emerging as a factor in the development of certain diseases, particularly those affecting connective tissues and involving abnormal cell proliferation. Understanding its role provides insights into tissue maintenance and disease mechanisms.
What the gene does
The DDR2 protein functions as an important cell surface receptor that specifically recognises and binds to collagen, a major structural protein in connective tissues. Upon binding collagen, DDR2 undergoes autophosphorylation - adding phosphate groups to itself - which then activates downstream signalling cascades within the cell. This signalling is critical for regulating various cellular behaviours including cell adhesion to the extracellular matrix, cell migration, and processes involved in cell growth and differentiation.
The protein's ability to sense collagen changes allows cells to adapt to their microenvironment. Through these mechanisms, DDR2 contributes to maintaining tissue integrity and plays roles in tissue repair and modelling. Its activity influences various physiological and pathological processes.
Video: Genetics 101
Chromosome location
The *DDR2* gene is situated on chromosome 1, specifically at position 1q23.3. This chromosomal location indicates where the gene can be found within the human genome.
Protein structure
The DDR2 protein has a length of 855 amino acids and features several distinct functional regions. It contains an F5/8 type C domain spanning amino acids 30-185, which is typically involved in binding to other molecules. A Disordered region is located between amino acids 452-471, suggesting flexibility and potential involvement in protein-protein interactions. Furthermore, a Protein kinase domain from amino acids 563-849 is essential for its tyrosine kinase activity, mediating intracellular signal transduction.
Key variants
Variations within the *DDR2* gene can alter the structure or function of the DDR2 protein, potentially affecting its ability to bind collagen or to initiate downstream signalling pathways. These genetic changes can range from single nucleotide substitutions to larger deletions or insertions within the gene sequence. The predicted impact of a variant on protein function can vary, leading to a spectrum of potential clinical effects, from benign to pathogenic.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1829T>C | p.Leu610Pro | Pathogenic/Likely pathogenic | ★★☆☆ | Warburg-cinotti syndrome |
g.(?_162740256)_(162757423_?)del | - | Pathogenic | ★☆☆☆ | not provided |
g.162775664_162775665insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNACCTCATGATCCACCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCGGAATGATTTTCTT | - | Pathogenic | ★☆☆☆ | not provided |
c.1021C>T | p.Arg341Ter | Pathogenic | ★☆☆☆ | not provided |
c.1045C>T | p.Gln349Ter | Pathogenic | ★☆☆☆ | not provided |
c.1711G>T | p.Glu571Ter | Pathogenic | ★☆☆☆ | not provided |
c.2125C>T | p.Arg709Ter | Pathogenic | ★☆☆☆ | not provided |
c.2408_2409del | p.Glu803fs | Pathogenic | ★☆☆☆ | not provided |
c.681del | p.Gly228_Leu229insTer | Pathogenic | ★☆☆☆ | not provided |
c.768T>A | p.Tyr256Ter | Pathogenic | ★☆☆☆ | not provided |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
While no specific conditions are currently listed as directly associated with the *DDR2* gene for this catalogue, variations in this gene have been explored in the context of conditions affecting growth and development. Research continues to investigate how DDR2 dysregulation may contribute to the pathology of diseases involving connective tissue remodelling or abnormal cell proliferation.
No disease links recorded for this gene in our reference set.
UK clinical status
The *DDR2* gene is recognised within the UK's National Health Service (NHS) Genomic Medicine Service. It is listed on the DDG2P panel, indicating its association with developmental disorders. Additionally, it is part of the Foetal anomalies panel (R21) and the Skeletal dysplasia panel (R104), highlighting its relevance in the genetic investigation of these conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the DDR2 gene do?
The *DDR2* gene produces a protein that acts as a receptor on the surface of cells. This protein specifically recognises and binds to collagen, triggering signals inside the cell that are important for cell growth, movement, and tissue development.
What is the function of the DDR2 protein?
The DDR2 protein detects collagen in the extracellular matrix and initiates a cascade of intracellular signals. This signalling helps regulate various cellular processes, including cell adhesion, migration, proliferation, and differentiation, which are vital for maintaining tissue structure and function.
Is the DDR2 gene associated with any conditions?
While no specific conditions are listed directly, changes in the *DDR2* gene are recognised by the NHS Genomic Medicine Service. It is included on panels for developmental disorders, foetal anomalies, and skeletal dysplasias, indicating its potential relevance in these areas.