ROS1
Chr 6ROS proto-oncogene 1, receptor tyrosine kinase
Also known as: MCF3, ROS, c-ros-1
This proto-oncogene, highly-expressed in a variety of tumor cell lines, belongs to the sevenless subfamily of tyrosine kinase insulin receptor genes. The protein encoded by this gene is a type I integral membrane protein with tyrosine kinase activity. The protein may function as a growth or differentiation factor receptor. [provided by RefSeq, Jul 2008]
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
ROS1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Early Rebiopsy to Identify Biomarkers of Tumor Cell Survival Following EGFR, ALK, ROS1 or BRAF TKI Therapy
RECRUITINGPHOENIX: QL1706 Plus Chemotherapy and Bevacizumab in AGA-Resistant, PD-L1 ≥50% Non-Squamous NSCLC
NOT YET RECRUITINGSurvival Outcomes of Lung Cancer
RECRUITINGA Phase II Clinical Study to Evaluate the Safety, Pharmacokinetic Profile, and Preliminary Efficacy of IMM2510 in Combination with Chemotherapy As First-line Treatment in Subjects with Non-small Cell Lung Cancer or Triple-negative Breast Cancer
NOT YET RECRUITINGPhase I Study of JYP0322 in ROS1 Fusion-Positive Solid Tumors
RECRUITINGCabozantinib in Patients With RET Fusion-Positive Advanced Non-Small Cell Lung Cancer and Those With Other Genotypes: ROS1 or NTRK Fusions or Increased MET or AXL Activity
RECRUITINGFirst-line Therapy With Nivolumab Plus Ipilimumab in Combination With Chemotherapy for Metatastatic NSCLC (NICReWo Trial)
RECRUITINGStudy on the Mechanism of Acquired Resistance of Entrectinib
RECRUITINGMYLUNG Consortium Study Protocol 2
ACTIVE NOT RECRUITINGLIquid BIopsies in Patients Presenting Non-small Cell Lung Cancer
RECRUITINGPhase II Efficacy Study of Repotrectinib in Frail and/or Elderly Patients With ROS1-rearranged Advanced NSCLC
RECRUITINGREPotrectinib in ROS1-positive Non-small Cell Lung Cancer Patients With Active Brain mEtastasis
RECRUITINGExternal Resources
Links to major genomics databases and tools