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Gene | ROS1 |
Variant | D2113N |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | ROS1 D2113N lies within the protein kinase domain of the Ros1 protein (UniProt.org). D2113N results in increased Ros1 activity, phosphorylation of Shp2 and Stat3, and colony formation in culture, and induces tumor formation in a mouse model (PMID: 37587872), and has been demonstrated to enhance resistance to ROS1 tyrosine kinase inhibitors with concurrent ROS1 G2032R in the context of a ROS1 fusion in culture (PMID: 26372962). |
Associated Drug Resistance | Y |
Category Variants Paths |
ROS1 mutant ROS1 act mut ROS1 D2113N |
Transcript | NM_002944.3 |
gDNA | chr6:g.117310178C>T |
cDNA | c.6337G>A |
Protein | p.D2113N |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_002944.2 | chr6:g.117310178C>T | c.6337G>A | p.D2113N | RefSeq | GRCh38/hg38 |
NM_002944 | chr6:g.117310178C>T | c.6337G>A | p.D2113N | RefSeq | GRCh38/hg38 |
NM_002944.3 | chr6:g.117310178C>T | c.6337G>A | p.D2113N | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
ROS1 D2113N | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited proliferation of transformed cells expressing ROS1 D2113N in culture and inhibited tumor growth and increased survival in a cell line xenograft model (PMID: 37587872). | 37587872 |
ROS1 D2113N | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited proliferation of transformed cells expressing ROS1 D2113N in culture and inhibited tumor growth and increased survival in a cell line xenograft model (PMID: 37587872). | 37587872 |
ROS1 D2113N | Advanced Solid Tumor | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Koselugo (selumetinib) inhibited proliferation of transformed cells expressing ROS1 D2113N in culture (PMID: 37587872). | 37587872 |
ROS1 D2113N | Advanced Solid Tumor | sensitive | Repotrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, Augtyro (repotrectinib) inhibited proliferation of transformed cells expressing ROS1 D2113N in culture (PMID: 37587872). | 37587872 |
ROS1 D2113N | Advanced Solid Tumor | sensitive | TNO155 | Preclinical - Cell culture | Actionable | In a preclinical study, TNO155 inhibited proliferation of transformed cells expressing ROS1 D2113N in culture (PMID: 37587872). | 37587872 |
ROS1 D2113N | Advanced Solid Tumor | sensitive | RMC-4550 | Preclinical - Cell culture | Actionable | In a preclinical study, RMC-4550 inhibited proliferation of transformed cells expressing ROS1 D2113N in culture (PMID: 37587872). | 37587872 |
ROS1 D2113N | Advanced Solid Tumor | sensitive | NUV-520 | Preclinical - Cell culture | Actionable | In a preclinical study, NUV-520 inhibited proliferation of transformed cells expressing ROS1 D2113N in culture (PMID: 37587872). | 37587872 |