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Gene Symbol | DDR2 | ||||||||||
Synonyms | MIG20a | NTRKR3 | TKT | TYRO10 | WRCN | ||||||||||
Gene Description | DDR2, discoidin domain receptor tyrosine kinase 2, is a tyrosine kinase receptor activated by collagen, promoting cell migration, proliferation, and survival (PMID: 22328973, PMID: 27398168). Altered expression and mutations of DDR2 have been identified in a variety of solid tumors, including ovarian (PMID: 27398168), lung (PMID: 28161936), gastric (PMID: 27350126), and HNSCC (PMID: 27434411). | ||||||||||
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Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
---|---|---|---|---|
A21G | missense | unknown | DDR2 A21G lies within the signal peptide of the Ddr2 protein (UniProt.org). A21G has been identified in sequencing studies (PMID: 29129434), but has not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Feb 2021). | |
A695D | missense | unknown | DDR2 A695D lies within the protein kinase domain of the Ddr2 protein (UniProt.org). A695D has been identified in sequencing studies (PMID: 29129434), but has not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Oct 2020). | |
act mut | unknown | gain of function | DDR2 act mut indicates that this variant results in a gain of function in the Ddr2 protein. However, the specific amino acid change has not been identified. | |
amp | none | no effect | DDR2 amplification indicates an increased number of copies of the DDR2 gene. However, the mechanism causing the increase is unspecified. | |
C177F | missense | unknown | DDR2 C177F lies within the F5/8 type C domain of the Ddr2 protein (UniProt.org). C177F has not been characterized in the scientific literature and therefore, its effect on Ddr2 protein function is unknown (PubMed, Feb 2021). | |
C580Y | missense | unknown | DDR2 C580Y lies within the protein kinase domain of the Ddr2 protein (UniProt.org). C580Y has been identified in the scientific literature (PMID: 28161936), but has not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Feb 2021). | |
C784_P788dup | duplication | unknown | DDR2 C784_P788dup indicates the insertion of five duplicate amino acids, cysteine (C)-784 through proline (P)-788, in the protein kinase domain of the Ddr2 protein (UniProt.org). C784_P788dup has not been characterized in the scientific literature and therefore, its effect on Ddr2 protein function is unknown (PubMed, Dec 2020). | |
D241Y | missense | unknown | DDR2 D241Y lies within the extracellular domain of the Ddr2 protein (UniProt.org). D241Y has been identified in sequencing studies (PMID: 29129434), but has not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Oct 2020). | |
D613N | missense | unknown | DDR2 D613N lies within the protein kinase domain of the Ddr2 protein (UniProt.org). D613N has been identified in sequencing studies (PMID: 25056374), but has not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Sep 2020). | |
D648_Y656dup | duplication | unknown | DDR2 D648_Y656dup indicates the insertion of 9 duplicate amino acids, aspartic acid (D)-648 through tyrosine (Y)-656, in the protein kinase domain of the Ddr2 protein (UniProt.org). D648_Y656dup has not been characterized in the scientific literature and therefore, its effect on Ddr2 protein function is unknown (PubMed, Feb 2021). | |
D661V | missense | unknown | DDR2 D661V lies within the protein kinase domain of the Ddr2 protein (UniProt.org). D661V has not been characterized in the scientific literature and therefore, its effect on Ddr2 protein function is unknown (PubMed, Jan 2021). | |
D661Y | missense | unknown | DDR2 D661Y lies within the protein kinase domain of the Ddr2 protein (UniProt.org). D661Y has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Feb 2021). | |
E113K | missense | loss of function - predicted | DDR2 E113K lies within the F5/8 type C domain of the Ddr2 protein (UniProt.org). E113K demonstrates localization similar to wild-type Ddr2, but results in a loss of ligand binding and concomitant loss of collagen-induced phosphorylation of Ddr2 in culture (PMID: 20223752), and therefore, is predicted to lead to a loss of Ddr2 protein function. | |
E181K | missense | unknown | DDR2 E181K lies within the F5/8 type C domain of the Ddr2 protein (UniProt.org). E181K has not been characterized in the scientific literature and therefore, its effect on Ddr2 protein function is unknown (PubMed, Feb 2021). | |
E625K | missense | unknown | DDR2 E625K lies within the protein kinase domain of the Ddr2 protein (UniProt.org). E625K has not been characterized in the scientific literature and therefore, its effect on Ddr2 protein function is unknown (PubMed, Sep 2020). | |
E655K | missense | no effect | DDR2 E655K lies within the protein kinase domain of the Ddr2 protein (UniProt.org). E655K demonstrates phosphorylation levels similar to wild-type Ddr2 and is not transforming, and leads to increased binding of the the E3 ubiquitin ligase, Cbl-b, rendering the cells resistant to collagen-induced growth inhibition in culture (PMID: 26826182). | |
E66G | missense | unknown | DDR2 E66G lies within the F5/8 type C domain of the Ddr2 protein (UniProt.org). E66G has not been characterized in the scientific literature and therefore, its effect on Ddr2 protein function is unknown (PubMed, Feb 2021). | |
E85* | nonsense | loss of function - predicted | DDR2 E85* results in a premature truncation of the Ddr2 protein at amino acid 85 of 855 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), E85* is predicted to result in a loss of Ddr2 protein function. | |
E85D | missense | unknown | DDR2 E85D lies within the F5/8 type C domain of the Ddr2 protein (UniProt.org). E85D has not been characterized in the scientific literature and therefore, its effect on Ddr2 protein function is unknown (PubMed, Oct 2020). | |
G126D | missense | unknown | DDR2 G126D lies within the F5/8 type C domain of the Ddr2 protein (UniProt.org). G126D has not been characterized in the scientific literature and therefore, its effect on Ddr2 protein function is unknown (PubMed, Feb 2021). | |
G253C | missense | gain of function - predicted | DDR2 G253C lies within the extracellular domain of the Ddr2 protein (UniProt.org). G253C results in transforming activity in cell culture (PMID: 22328973), and therefore, is predicted to result in a gain of Ddr2 protein function. | |
G466R | missense | unknown | DDR2 G466R lies within the cytoplasmic domain of the Ddr2 protein (UniProt.org). G466R has been identified in sequencing studies (PMID: 29129434), but has not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Oct 2020). | |
G505S | missense | gain of function - predicted | DDR2 G505S lies within the cytoplasmic domain of the Ddr2 protein (UniProt.org). G505S results in tyrosine phosphorylation and phosphorylation of Shp2 similar to wild-type Ddr2 and variable Ddr2 phosphorylation, but is transforming in cell culture (PMID: 22328973, PMID: 23822953), and therefore, is predicted to result in a gain of Ddr2 protein function. | |
G575R | missense | unknown | DDR2 G575R lies within the protein kinase domain of the Ddr2 protein (UniProt.org). G575R has been identified in the scientific literature (PMID: 29129434), but has not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Oct 2020). | |
G660E | missense | unknown | DDR2 G660E lies within the protein kinase domain of the Ddr2 protein (UniProt.org). G660E has not been characterized in the scientific literature and therefore, its effect on Ddr2 protein function is unknown (PubMed, Feb 2021). | |
G774E | missense | unknown | DDR2 G774E lies within the protein kinase domain of the Ddr2 protein (UniProt.org). G774E has been identified in the scientific literature (PMID: 28161936), but has not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Dec 2020). | |
G774V | missense | gain of function - predicted | DDR2 G774V lies within the protein kinase domain of the Ddr2 protein (PMID: 22328973). G774V is transforming in cell culture (PMID: 22328973), and therefore, is predicted to result in a gain of Ddr2 protein function. | |
H246R | missense | no effect | DDR2 H246R lies within the extracellular domain of the Ddr2 protein (UniProt.org). H246R demonstrates phosphorylation levels similar to wild-type Ddr2 and is not transforming in culture (PMID: 26826182). | |
H249Q | missense | unknown | DDR2 H249Q lies within the extracellular domain of the Ddr2 protein (UniProt.org). H249Q has not been characterized in the scientific literature and therefore, its effect on Ddr2 protein function is unknown (PubMed, Feb 2021). | |
I159T | missense | unknown | DDR2 I159T lies within the F5/8 type C domain of the Ddr2 protein (UniProt.org). I159T has been identified in sequencing studies (PMID: 28590426), but has not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Oct 2020). | |
I638F | missense | gain of function | DDR2 I638F lies within the protein kinase domain of the Ddr2 protein (UniProt.org). I638F confers a gain of function to the Ddr2 protein, as demonstrated by increased Ddr2 phosphorylation (PMID: 28161936) and Stat5 activation and transformation of cultured cells, and induced tumor formation in mouse xenograft models (PMID: 22328973). | |
I653_M657dup | duplication | unknown | DDR2 I653_M657dup indicates the insertion of five duplicate amino acids, isoleucine (I)-653 through methionine (M)-657, in the protein kinase domain of the Ddr2 protein (UniProt.org). I653_M657dup has not been characterized in the scientific literature and therefore, its effect on Ddr2 protein function is unknown (PubMed, Dec 2020). | |
I726R | missense | loss of function | DDR2 I726R lies within the protein kinase domain of the Ddr2 protein (UniProt.org). I726R results in aberrant Ddr2 localization and decreased collagen-induced Ddr2 phosphorylation in culture (PMID: 20223752). | |
inact mut | unknown | loss of function | DDR2 inact mut indicates that this variant results in a loss of function of the Ddr2 protein. However, the specific amino acid change has not been identified. | |
K608M | missense | loss of function - predicted | DDR2 K608M lies within the protein kinase domain of the Ddr2 protein (UniProt.org). K608M results in a loss of kinase activity as demonstrated by reduced Shp2 phosphorylation upon collagen induction in culture (PMID: 23822953), and therefore, is predicted to lead to a loss of Ddr2 protein function. | |
L239P | missense | unknown | DDR2 L239P lies within the extracellular domain of the Ddr2 protein (UniProt.org). L239P has been identified in sequencing studies (PMID: 32699558), but has not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Sep 2020). | |
L239R | missense | gain of function - predicted | DDR2 L239R lies within the extracellular domain of the Ddr2 protein (UniProt.org). L239R results in transforming activity in cell culture (PMID: 22328973), and therefore, is predicted to result in a gain of Ddr2 protein function. | |
L595P | missense | gain of function | DDR2 L595P lies within the protein kinase domain of the Ddr2 protein (UniProt.org). L595P results in increased cell proliferation and is transforming in culture (PMID: 28161936). | |
L610P | missense | gain of function - predicted | DDR2 L610P lies within the protein kinase domain of the Ddr2 protein (UniProt.org). L610P results in increased Ddr2 autophosphorylation in culture (PMID: 30449416), and therefore, is predicted to result in a gain of Ddr2 protein function. | |
L63V | missense | gain of function | DDR2 L63V lies within the discoidin domain of the Ddr2 protein (PMID: 22328973). L63V confers a gain of function to the Ddr2 protein, as demonstrated by increased Stat5 and Src phosphorylation (PMID: 22328973), elevated phosphorylation of Ddr2, and transformation activity in cell culture (PMID: 28161936). | |
M117I | missense | unknown | DDR2 M117I lies within the F5/8 type C domain of the Ddr2 protein (UniProt.org). M117I has been identified in sequencing studies (PMID: 27573823), but has not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Feb 2021). | |
M272T | missense | unknown | DDR2 M272T lies within the extracellular domain of the Ddr2 protein (UniProt.org). M272T has not been characterized in the scientific literature and therefore, its effect on Ddr2 protein function is unknown (PubMed, Oct 2020). | |
M441I | missense | unknown | DDR2 M441I lies within the cytoplasmic domain of the Ddr2 protein (UniProt.org). M441I has been identified in sequencing studies (PMID: 27882345), but has not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Feb 2021). | |
mutant | unknown | unknown | DDR2 mutant indicates an unspecified mutation in the DDR2 gene. | |
N134K | missense | unknown | DDR2 N134K lies within the F5/8 type C domain of the Ddr2 protein (UniProt.org). N134K has been identified in sequencing studies (PMID: 29129434), but has not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Oct 2020). | |
over exp | none | no effect | DDR2 over exp indicates an over expression of the Ddr2 protein and/or mRNA. However, the mechanism causing the over expression is unspecified. | |
P168_S173dup | duplication | unknown | DDR2 P168_S173dup indicates the insertion of six duplicate amino acids, proline (P)-168 through serine (S)-173, in the F5/8 type C domain of the Ddr2 protein (UniProt.org). P168_S173dup has not been characterized in the scientific literature and therefore, its effect on Ddr2 protein function is unknown (PubMed, Dec 2020). | |
P476S | missense | unknown | DDR2 P476S lies within the cytoplasmic domain of the Ddr2 protein (UniProt.org). P476S has been identified in sequencing studies (PMID: 30545397), but has not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Feb 2021). | |
P492S | missense | unknown | DDR2 P492S lies within the cytoplasmic domain of the Ddr2 protein (UniProt.org). P492S has been identified in sequencing studies (PMID: 25801821, PMID: 29129434), but has not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Oct 2020). | |
P840S | missense | unknown | DDR2 P840S lies within the protein kinase domain of the Ddr2 protein (UniProt.org). P840S has been identified in sequencing studies (PMID: 30205045), but has not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Feb 2021). | |
Q808H | missense | unknown | DDR2 Q808H lies within the protein kinase domain of the Ddr2 protein (UniProt.org). Q808H has been identified in the scientific literature (PMID: 30048458), but has not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Oct 2020). | |
R135H | missense | unknown | DDR2 R135H lies within the F5/8 type C domain of the Ddr2 protein (UniProt.org). R135H has been identified in sequencing studies (PMID: 31534501), but has not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Dec 2020). | |
R179G | missense | unknown | DDR2 R179G lies within the F5/8 type C domain of the Ddr2 protein (UniProt.org). R179G has not been characterized in the scientific literature and therefore, its effect on Ddr2 protein function is unknown (PubMed, Oct 2020). | |
R489fs | frameshift | loss of function - predicted | DDR2 R489fs results in a change in the amino acid sequence of the Ddr2 protein beginning at aa 489 of 855, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), R489fs is predicted to result in a loss of Ddr2 protein function. | |
R611* | nonsense | loss of function - predicted | DDR2 R611* results in a premature truncation of the Ddr2 protein at amino acid 611 of 855 (UniProt.org). Due to the disruption of the protein kinase domain (UniProt.org), R611* is predicted to result in a loss of Ddr2 protein function. | |
R619S | missense | unknown | DDR2 R619S lies within the protein kinase domain of the Ddr2 protein (UniProt.org). R619S has been identified in the scientific literature (PMID: 25348954, PMID: 29129434), but has not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Oct 2020). | |
R62M | missense | unknown | DDR2 R62M lies within the F5/8 type C domain of the Ddr2 protein (UniProt.org). R62M has not been characterized in the scientific literature and therefore, its effect on Ddr2 protein function is unknown (PubMed, Feb 2021). | |
R709* | nonsense | unknown | DDR2 R709* results in a premature truncation of the Ddr2 protein at amino acid 709 of 855 (UniProt.org). R709* has been identified in the scientific literature (PMID: 26619122), but not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Oct 2020). | |
R752C | missense | loss of function | DDR2 R752C lies within the protein kinase domain of the Ddr2 protein (UniProt.org). R752C results in aberrant Ddr2 localization and decreased collagen-induced Ddr2 phosphorylation in culture (PMID: 20223752). | |
R752H | missense | unknown | DDR2 R752H lies within the protein kinase domain of the Ddr2 protein (UniProt.org). R752H has been identified in sequencing studies (PMID: 27170661, PMID: 29129434), but has not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Oct 2020). | |
R839H | missense | unknown | DDR2 R839H lies within the protein kinase domain of the Ddr2 protein (UniProt.org). R839H has been identified in sequencing studies (PMID: 23917401), but not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Sep 2020). | |
S123I | missense | unknown | DDR2 S123I lies within the F5/8 type C domain of the Ddr2 protein (UniProt.org). S123I has been identified in sequencing studies (PMID: 28069802), but has not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Feb 2021). | |
S50N | missense | unknown | DDR2 S50N lies within the F5/8 type C domain of the Ddr2 protein (UniProt.org). S50N has been identified in sequencing studies (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Feb 2021). | |
S768R | missense | gain of function | DDR2 S768R lies within the protein kinase domain of the Ddr2 protein (PMID: 22328973). S768R confers a gain of function to the Ddr2 protein, as demonstrated by increased Ddr2 phosphorylation and transforming activity in cultured cells (PMID: 26826182). | |
T654I | missense | unknown | DDR2 T654I is a gatekeeper mutation that lies within the protein kinase domain of the Ddr2 protein (UniProt.org). T654I has been associated with secondary drug resistance (PMID: 24296828), but has not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Dec 2020). | Y |
T654M | missense | unknown | DDR2 T654M lies within the protein kinase domain of the Ddr2 protein (UniProt.org). T654M has been demonstrated to occur as a "gatekeeper" mutation and is associated with secondary drug resistance (PMID: 22328973), but has not been biochemically characterized, and therefore, its effect on Ddr2 protein function is unknown (PubMed, Feb 2021). | Y |
T713I | missense | loss of function | DDR2 T713I lies within the protein kinase domain of the Ddr2 protein (UniProt.org). T713I results in aberrant Ddr2 localization and decreased collagen-induced Ddr2 phosphorylation in culture (PMID: 20223752). | |
T765P | missense | unknown | DDR2 T765P lies within the protein kinase domain of the Ddr2 protein (UniProt.org). T765P has been identified in the scientific literature (PMID: 28161936), but has not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Dec 2020). | |
V302I | missense | unknown | DDR2 V302I lies within the extracellular domain of the Ddr2 protein (UniProt.org). V302I has not been characterized in the scientific literature and therefore, its effect on Ddr2 protein function is unknown (PubMed, Feb 2021). | |
V582E | missense | gain of function | DDR2 V582E lies within the protein kinase domain of the Ddr2 protein (UniProt.org). V582E results in increased Ddr2 phosphorylation, and leads to increased cell proliferation and transformation in culture (PMID: 28161936). | |
V605M | missense | unknown | DDR2 V605M lies within the protein kinase domain of the Ddr2 protein (UniProt.org). V605M has been identified in sequencing studies (PMID: 25122428), but has not been biochemically characterized and therefore, its effect on Ddr2 protein function is unknown (PubMed, Feb 2021). | |
W72L | missense | unknown | DDR2 W72L lies within the F5/8 type C domain of the Ddr2 protein (UniProt.org). W72L has not been characterized in the scientific literature and therefore, its effect on Ddr2 protein function is unknown (PubMed, Feb 2021). | |
wild-type | none | no effect | Wild-type DDR2 indicates that no mutation has been detected within the DDR2 gene. | |
Y122C | missense | unknown | DDR2 Y122C lies within the F5/8 type C domain of the Ddr2 protein (UniProt.org). Y122C has not been characterized in the scientific literature and therefore, its effect on Ddr2 protein function is unknown (PubMed, Feb 2021). | |
Y740C | missense | gain of function - predicted | DDR2 Y740C lies within the protein kinase domain of the Ddr2 protein (UniProt.org). Y740C results in increased Ddr2 autophosphorylation in culture (PMID: 30449416), and therefore, is predicted to result in a gain of Ddr2 protein function. |