ROS1
Chr 6ROS proto-oncogene 1, receptor tyrosine kinase
Also known as: MCF3, ROS, c-ros-1
The ROS1 protein is a receptor tyrosine kinase that regulates cell differentiation, proliferation, and survival through multiple downstream signaling pathways including PI3K-mTOR and STAT3. Mutations in ROS1 cause autosomal dominant gingival fibromatosis, a condition characterized by progressive enlargement of the gums. This gene is not highly constrained against loss-of-function mutations, suggesting the pathogenic variants may act through other mechanisms.
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
Protein Context — Lollipop Plot
ROS1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions)
ACTIVE NOT RECRUITINGCanadian Profiling and Targeted Agent Utilization Trial (CAPTUR)
RECRUITINGKPMNG Study of MOlecular Profiling Guided Therapy Based on Genomic Alterations in Advanced Solid Tumors II
RECRUITINGNitroglycerin Plus Radiotherapy Versus Conventional Radiotherapy in Patients With Lung Cancer.
RECRUITINGA Study of XZP-5955 Tablets in Patients With NTRK or ROS1 Fusion Positive Locally Advanced or Metastatic Solid Tumors
RECRUITINGEarly Rebiopsy to Identify Biomarkers of Tumor Cell Survival Following EGFR, ALK, ROS1 or BRAF TKI Therapy
RECRUITINGEfficacy and Safety Analysis of First-Line ABCP Therapy in Advanced SMARCA4-Mutated NSCLC
NOT YET RECRUITINGSacituzumab Tirumotecan (MK-2870) Versus Chemotherapy in Previously Treated Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer (NSCLC) With EGFR Mutations or Other Genomic Alterations (MK-2870-004)
RECRUITINGFeasibility of Targeted Bronchial Washing for Molecular Testing by Next Generation Sequencing in Early-stage Lung Cancer
ACTIVE NOT RECRUITINGLIquid BIopsies in Patients Presenting Non-small Cell Lung Cancer
RECRUITINGStudy on the Mechanism of Acquired Resistance of Entrectinib
RECRUITINGAmivantamab With Tyrosine Kinase Inhibitors (TKI) for Advanced NSCLC With ALK, ROS1, or RET Alterations
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools