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Gene Symbol | ROS1 | ||||||||||
Synonyms | c-ros-1 | MCF3 | ROS | ||||||||||
Gene Description | ROS1, ROS proto-oncogene 1, receptor tyrosine kinase, is an orphan receptor tyrosine kinase that may activates multiple pathways involved in cell survival and transformation (PMID: 23719267, PMID: 32327173). ROS1 fusion proteins frequently lead to constitutive activation of Ros1 signaling and have been identified in glioblastoma, non-small cell lung cancer, cholangiocarcinoma, ovarian cancer, gastric adenocarcinoma, colorectal cancer, inflammatory myofibroblastic tumor, angiosarcoma, glioma, and epithelioid hemangioendothelioma (PMID: 23719267, PMID: 30262706, PMID: 30171048, PMID: 3004937), and ROS1 mutations are often associated with acquired resistance to inhibition (PMID: 31256210). | ||||||||||
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Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
---|---|---|---|---|
A1186D | missense | unknown | ROS1 A1186D lies within the extracellular domain of the Ros1 protein (UniProt.org). A1186D has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
A1924_I1934del | deletion | unknown | ROS1 A1924_I1934del results in the deletion of 11 amino acids in the cytoplasmic domain of the Ros1 protein from amino acids 1924 to 1934 (UniProt.org). A1924_I1934del has been identified in the scientific literature (PMID: 34907086), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
A1964T | missense | unknown | ROS1 A1964T lies within the protein kinase domain of the Ros1 protein (UniProt.org). A1964T has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
A1998G | missense | unknown | ROS1 A1998G lies within the protein kinase domain of the Ros1 protein (UniProt.org). A1998G has been identified in the scientific literature (PMID: 34907086), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
A2081T | missense | unknown | ROS1 A2081T lies within the protein kinase domain of the Ros1 protein (UniProt.org). A2081T has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
A87T | missense | unknown | ROS1 A87T lies within the extracellular domain of the Ros1 protein (UniProt.org). A87T has been identified in sequencing studies (PMID: 29338072), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Jan 2024). | |
A887V | missense | unknown | ROS1 A887V lies within the extracellular domain of the Ros1 protein (UniProt.org). A887V has been identified in the scientific literature (PMID: 29642553), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
act mut | unknown | gain of function | ROS1 act mut indicates that this variant results in a gain of function in the Ros1 protein. However, the specific amino acid change has not been identified. | |
amp | none | no effect | ROS1 amplification indicates an increased number of copies of the ROS1 gene. However, the mechanism causing the increase is unspecified. | |
C2060G | missense | unknown | ROS1 C2060G lies within the protein kinase domain of the Ros1 protein (UniProt.org). C2060G has been demonstrated to confer resistance to Ros1 tyrosine kinase inhibitors in the context of Ros1 fusion in culture (PMID: 24218589), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | Y |
C72R | missense | unknown | ROS1 C72R lies within the extracellular domain of the Ros1 protein (UniProt.org). C72R has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
D1192V | missense | unknown | ROS1 D1192V lies within the extracellular domain of the Ros1 protein (UniProt.org). D1192V has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
D1776H | missense | unknown | ROS1 D1776H lies within fibronectin type-III domain 9 of the Ros1 protein (UniProt.org). D1776H has been identified in sequencing studies (PMID: 25589003, PMID: 26420498, PMID: 32077636), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
D2033N | missense | unknown | ROS1 D2033N lies within the protein kinase domain of the Ros1 protein (UniProt.org). D2033N has been demonstrated to confer resistance to Ros1 tyrosine kinase inhibitors and increase cell migration and invasion in the context of Ros1 fusions in culture (PMID: 36265718, PMID: 26673800), but has not been individually characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | Y |
D2058G | missense | unknown | ROS1 D2058G lies within the protein kinase domain of the Ros1 protein (UniProt.org). D2058G has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
D2113E | missense | no effect - predicted | ROS1 D2113E lies within the protein kinase domain of the Ros1 protein (UniProt.org). D2113E results in similar kinase activity to wild-type Ros1 in culture (PMID: 37587872), and therefore, is predicted to have no effect on Ros1 protein function. | |
D2113G | missense | gain of function | ROS1 D2113G lies within the protein kinase domain of the Ros1 protein (UniProt.org). D2113G results in increased Ros1 activity, phosphorylation of Shp2 and Stat3, and colony formation in culture (PMID: 37587872) and has been demonstrated to confer resistance to ROS1 tyrosine kinase inhibitors in the context of ROS1 fusions in culture (PMID: 26372962). | Y |
D2113N | missense | gain of function | 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). | Y |
D2113Y | missense | loss of function - predicted | ROS1 D2113Y lies within the protein kinase domain of the Ros1 protein (UniProt.org). D2113Y results in decreased Ros1 phosphorylation in culture (PMID: 37587872), and therefore, is predicted to lead to a loss of Ros1 protein function. | |
D2213N | missense | unknown | ROS1 D2213N lies within the protein kinase domain of the Ros1 protein (UniProt.org). D2213N has been identified in sequencing studies (PMID: 27882345, PMID: 35145582, PMID: 32069381), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
D2247Y | missense | unknown | ROS1 D2247Y lies within the cytoplasmic domain of the Ros1 protein (UniProt.org). D2247Y has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
D780Y | missense | unknown | ROS1 D780Y lies within the extracellular domain of the Ros1 protein (UniProt.org). D780Y has been identified in sequencing studies (PMID: 28069802), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
dec exp | none | no effect | ROS1 dec exp indicates decreased expression of the Ros1 protein and/or mRNA. However, the mechanism causing the decreased expression is unspecified. | |
del | deletion | loss of function | ROS1 del indicates a deletion of the ROS1 gene. | |
E1244* | nonsense | loss of function - predicted | ROS1 E1244* results in a premature truncation of the Ros1 protein at amino acid 1244 of 2347 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), E1244* is predicted to lead to a loss of Ros1 protein function. | |
E1737* | nonsense | loss of function - predicted | ROS1 E1737* results in a premature truncation of the Ros1 protein at amino acid 1737 of 2347 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), E1737* is predicted to lead to a loss of Ros1 protein function. | |
E1840* | nonsense | loss of function - predicted | ROS1 E1840* results in a premature truncation of the Ros1 protein at amino acid 1840 of 2347 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), E1840* is predicted to lead to a loss of Ros1 protein function. | |
E1902K | missense | unknown | ROS1 E1902K lies within the cytoplasmic domain of the Ros1 protein (UniProt.org). E1902K has been identified in the scientific literature (PMID: 29642553, PMID: 34271921), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
E1935G | missense | unknown | ROS1 E1935G lies within the cytoplasmic domain of the Ros1 protein (UniProt.org). E1935G has been demonstrated to confer resistance to ROS1 tyrosine kinase inhibitors in the context of ROS1 fusions in culture (PMID: 24218589), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Apr 2024). | Y |
E1974K | missense | unknown | ROS1 E1974K lies within the protein kinase domain of the Ros1 protein (UniProt.org). E1974K has been identified in the scientific literature (PMID: 26372962), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Jan 2024). | |
E1990G | missense | unknown | ROS1 E1990G lies within the protein kinase domain of the Ros1 protein (UniProt.org). E1990G has been demonstrated to confer resistance to ROS1 tyrosine kinase inhibitors in the context of a ROS1 fusion in culture (PMID: 25351743), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Apr 2024). | Y |
E2020K | missense | unknown | ROS1 E2020K lies within the protein kinase domain of the Ros1 protein (UniProt.org). E2020K has been demonstrated to enhance resistance to Ros1 tyrosine kinase inhibitors with a concurrent ROS1 G2032R in the context of a Ros1 fusion in culture (PMID: 26372962, PMID: 31395437), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | Y |
E2071K | missense | gain of function - predicted | ROS1 E2071K lies within the protein kinase domain of the Ros1 protein (UniProt.org). E2071K results in increased colony formation and tumor formation that is not statistically significant relative to wild-type Ros1 and increased Ros1 phosphorylation in culture (PMID: 37587872), and therefore, is predicted to lead to a gain of Ros1 protein function. | |
E2131D | missense | unknown | ROS1 E2131D lies within the protein kinase domain of the Ros1 protein (UniProt.org). E2131D has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
E2265D | missense | unknown | ROS1 E2265D lies within the cytoplasmic domain of the Ros1 protein (UniProt.org). E2265D has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
E2308* | nonsense | unknown | ROS1 E2308* results in a premature truncation of the Ros1 protein at amino acid 2308 of 2347 (UniProt.org). E2308* has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
E2308K | missense | unknown | ROS1 E2308K lies within the cytoplasmic domain of the Ros1 protein (UniProt.org). E2308K has been identified in sequencing studies (PMID: 25759019, PMID: 26950094, PMID: 35130390), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
E290* | nonsense | loss of function - predicted | ROS1 E290* results in a premature truncation of the Ros1 protein at amino acid 290 of 2347 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), E290* is predicted to lead to a loss of Ros1 protein function. | |
E341D | missense | unknown | ROS1 E341D lies within the extracellular domain of the Ros1 protein (UniProt.org). E341D has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
E539* | nonsense | loss of function - predicted | ROS1 E539* results in a premature truncation of the Ros1 protein at amino acid 539 of 2347 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), E539* is predicted to lead to a loss of Ros1 protein function. | |
E919K | missense | unknown | ROS1 E919K lies within the extracellular domain of the Ros1 protein (UniProt.org). E919K has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
F2004C | missense | unknown | ROS1 F2004C lies within the protein kinase domain of the Ros1 protein (UniProt.org). F2004C has been demonstrated to confer resistance to ROS1 tyrosine kinase inhibitors in the context of a ROS1 fusion in culture (PMID: 26372962), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Apr 2024). | Y |
F2004I | missense | unknown | ROS1 F2004I lies within the protein kinase domain of the Ros1 protein (UniProt.org). F2004I has been identified in the scientific literature (PMID: 34907086, PMID: 38197815), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
F2004L | missense | unknown | ROS1 F2004L lies within the protein kinase domain of the Ros1 protein (UniProt.org). F2004L has been demonstrated to confer resistance to ROS1 inhibitors in the context of ROS1 fusions in culture (PMID: 33558279), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Apr 2024). | Y |
F2004V | missense | unknown | ROS1 F2004V lies within the protein kinase domain of the Ros1 protein (UniProt.org). F2004V has been demonstrated to confer resistance to ROS1 tyrosine kinase inhibitors in the context of a ROS1 fusion (PMID: 28717217, PMID: 32914039), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Apr 2024). | Y |
F2075C | missense | unknown | ROS1 F2075C lies within the protein kinase domain of the Ros1 protein (UniProt.org). F2075C has been demonstrated to confer resistance to ROS1 tyrosine kinase inhibitors in the context of a ROS1 fusion in culture (PMID: 28717217), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Apr 2024). | Y |
F2075V | missense | unknown | ROS1 F2075V lies within the protein kinase domain of the Ros1 protein (UniProt.org). F2075V has been demonstrated to confer resistance to ROS1 tyrosine kinase inhibitors in the context of a ROS1 fusion in culture (PMID: 26372962), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Apr 2024). | Y |
F250L | missense | unknown | ROS1 F250L lies within fibronectin type-III domain 2 of the Ros1 protein (UniProt.org). F250L has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, MAr 2024). | |
F383S | missense | unknown | ROS1 F383S lies within the extracellular domain of the Ros1 protein (UniProt.org). F383S has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
F923I | missense | unknown | ROS1 F923I lies within the extracellular domain of the Ros1 protein (UniProt.org). F923I has been identified in sequencing studies (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
fusion | fusion | unknown | ROS1 fusion indicates a fusion of the ROS1 gene, but the fusion partner is unknown. | |
G1027D | missense | unknown | ROS1 G1027D lies within fibronectin type-III domain 4 of the Ros1 protein (UniProt.org). G1027D has been identified in sequencing studies (PMID: 32504289, PMID: 36713525), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
G1556R | missense | unknown | ROS1 G1556R lies within fibronectin type-III domain 6 of the Ros1 protein (UniProt.org). G1556R has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
G1915R | missense | unknown | ROS1 G1915R lies within the cytoplasmic domain of the Ros1 protein (UniProt.org). G1915R has been identified in the scientific literature (PMID: 29338072), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Apr 2024). | |
G1954R | missense | unknown | ROS1 G1954R lies within the protein kinase domain of the Ros1 protein (UniProt.org). G1954R has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
G1957A | missense | unknown | ROS1 G1957A lies within the protein kinase domain of the Ros1 protein (UniProt.org). G1957A has been associated with resistance to Ros1 tyrosine kinase inhibitors in the context of a ROS1 fusion in patients (PMID: 38416709), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | Y |
G1971E | missense | unknown | ROS1 G1971E lies within the protein kinase domain of the Ros1 protein (UniProt.org). G1971E has been demonstrated to confer resistance to ROS1 tyrosine kinase inhibitors in the context of a ROS1 fusion in culture (PMID: 24218589), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Apr 2024). | Y |
G2032K | missense | unknown | ROS1 G2032K lies within the protein kinase domain of the Ros1 protein (UniProt.org). G2032K has been associated with secondary drug resistance (PMID: 32208297), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Jan 2024). | Y |
G2032R | missense | unknown | ROS1 G2032R lies within the protein kinase domain of the Ros1 protein (UniProt.org). G2032R has been associated with resistance to Ros1 tyrosine kinase inhibitors in the context of ROS1 fusions in patients (PMID: 36135089, PMID: 25033171, PMID: 29477381), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Jan 2024). | Y |
G2066C | missense | unknown | ROS1 G2066C lies within the protein kinase domain of the Ros1 protein (UniProt.org). G2066C has been identified in the scientific literature (PMID: 29312610), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Jan 2024). | |
G2101A | missense | unknown | ROS1 G2101A lies within the protein kinase domain of the Ros1 protein (UniProt.org). G2101A has been demonstrated to confer resistance to ROS1 tyrosine kinase inhibitors in the context of a ROS1 fusion in culture (PMID: 25688157), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Apr 2024). | Y |
G2148V | missense | unknown | ROS1 G2148V lies within the protein kinase domain of the Ros1 protein (UniProt.org). G2148V has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
G365A | missense | unknown | ROS1 G365A lies within the extracellular domain of the Ros1 protein (UniProt.org). G365A has been identified in sequencing studies (PMID: 28524162), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
G514fs | frameshift | loss of function - predicted | ROS1 G514fs results in a change in the amino acid sequence of the Ros1 protein beginning at aa 514 of 2347, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), G514fs is predicted to lead to a loss of Ros1 protein function. | |
G666S | missense | unknown | ROS1 G666S lies within fibronectin type-III domain 3 of the Ros1 protein (UniProt.org). G666S has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
I2151F | missense | gain of function - predicted | ROS1 I2151F lies within the protein kinase domain of the Ros1 protein (UniProt.org). I2151F results in similar colony formation to wild-type Ros1 but increased Ros1 phosphorylation in culture (PMID: 37587872), and therefore, is predicted to lead to a gain of Ros1 protein function. | |
I2239* | nonsense | loss of function - predicted | ROS1 I2239* results in a premature truncation of the Ros1 protein at amino acid 2239 of 2347 (UniProt.org). I2239* retains autophosphorylation similar to wild-type Ros1 in the context of CD74-ROS1, but leads to decreased phosphorylation of Shp2, Erk1/2, Stat3, p70S6k, and S6 in cell culture (PMID: 34907086), and therefore, is predicted to lead to a loss of Ros1 protein function. | |
I537M | missense | unknown | ROS1 I537M lies within the extracellular domain of the Ros1 protein (UniProt.org). I537M has been identified in sequencing studies (PMID: 31346352, PMID: 18056464), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Apr 2024). | |
inact mut | unknown | loss of function | ROS1 inact mut indicates that this variant results in a loss of function of the Ros1 protein. However, the specific amino acid change has not been identified. | |
K1163N | missense | unknown | ROS1 K1163N lies within the extracellular domain of the Ros1 protein (UniProt.org). K1163N has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
K1552T | missense | unknown | ROS1 K1552T lies within fibronectin type-III domain 6 of the Ros1 protein (UniProt.org). K1552T has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
K1887Q | missense | unknown | ROS1 K1887Q lies within the cytoplasmic domain of the Ros1 protein (UniProt.org). K1887Q has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
K1980E | missense | loss of function | ROS1 K1980E lies within the protein kinase domain of the Ros1 protein (UniProt.org). K1980E results in loss of Ros1 protein function as demonstrated by decreased Ros1 phosphorylation, and failure to induce colony growth in culture or tumor formation in a mouse model (PMID: 37587872). | |
K2003I | missense | unknown | ROS1 K2003I lies within the protein kinase domain of the Ros1 protein (UniProt.org). K2003I has been identified in the scientific literature (PMID: 33489820, PMID: 25351743), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
K2099N | missense | unknown | ROS1 K2099N lies within the protein kinase domain of the Ros1 protein (UniProt.org). K2099N has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
K2228Q | missense | unknown | ROS1 K2228Q lies within the cytoplasmic domain of the Ros1 protein (UniProt.org). K2228Q has been identified in the scientific literature (PMID: 27882345, PMID: 25589003, PMID: 36422072), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
K298* | nonsense | loss of function - predicted | ROS1 K298* results in a premature truncation of the Ros1 protein at amino acid 298 of 2347 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), K298* is predicted to lead to a loss of Ros1 protein function. | |
L1947R | missense | unknown | ROS1 L1947R lies within the protein kinase domain of the Ros1 protein (UniProt.org). L1947R has been demonstrated to confer resistance to ROS1 tyrosine kinase inhibitors in the context of a ROS1 fusion in culture (PMID: 24218589), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Apr 2024). | Y |
L1949F | missense | gain of function - predicted | ROS1 L1949F lies within the protein kinase domain of the Ros1 protein (UniProt.org). L1949F results in increased colony formation that is not statistically significant relative to wild-type Ros1 and increased Ros1 phosphorylation in culture (PMID: 37587872), and therefore, is predicted to lead to a gain of Ros1 protein function. | |
L1950F | missense | unknown | ROS1 L1950F lies within the protein kinase domain of the Ros1 protein (UniProt.org). L1950F has been identified in the scientific literature (PMID: 34320493), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
L1951R | missense | unknown | ROS1 L1951R lies within the protein kinase domain of the Ros1 protein (UniProt.org). L1951R has been demonstrated to confer resistance to ROS1 tyrosine kinase inhibitors in the context of a ROS1 fusion in culture (PMID: 25351743), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Apr 2024). | Y |
L1982F | missense | unknown | ROS1 L1982F lies within the protein kinase domain of the Ros1 protein (UniProt.org). L1982F has been demonstrated to confer resistance to ROS1 tyrosine kinase inhibitors in the context of a ROS1 fusion in culture (PMID: 25351743, PMID: 24218589), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Apr 2024). | Y |
L1982V | missense | unknown | ROS1 L1982V lies within the protein kinase domain of the Ros1 protein (UniProt.org). L1982V has been associated with resistance to Ros1 tyrosine kinase inhibitors in the context of a ROS1 fusion in patients (PMID: 38416709), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | Y |
L2000V | missense | unknown | ROS1 L2000V lies within the protein kinase domain of the Ros1 protein (UniProt.org). L2000V has been demonstrated to confer resistance to ROS1 inhibitors in culture (PMID: 33685866), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Jan 2024). | Y |
L2010M | missense | unknown | ROS1 L2010M lies within the protein kinase domain of the Ros1 protein (UniProt.org). L2010M has been associated with resistance to Ros1 tyrosine kinase inhibitors in the context of a ROS1 fusion in patients (PMID: 38416709), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | Y |
L2026M | missense | unknown | ROS1 L2026M lies within the protein kinase domain of the Ros1 protein (UniProt.org). L2026M has been demonstrated to confer resistance to ROS1 inhibitors in the context of a Ros1 fusion (PMID: 25351743, PMID: 32918045), and results in increased colony formation, cell migration, and ERK/AKT signaling in the context of a ROS1 fusion in culture (PMID: 38148635), but has not been individually characterized and therefore, its effect on Ros1 protein function is unknown. | Y |
L2028M | missense | unknown | ROS1 L2028M lies within the protein kinase domain of the Ros1 protein (UniProt.org). L2028M has not been characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
L2086F | missense | unknown | ROS1 L2086F lies within the protein kinase domain of the Ros1 protein (UniProt.org). L2086F confers resistance to ROS1 inhibitors in the context of ROS1 fusion (PMID: 32591465), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Apr 2024). | Y |
L2086I | missense | unknown | ROS1 L2086I lies within the protein kinase domain of the Ros1 protein (UniProt.org). L2086I has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
L2155S | missense | unknown | ROS1 L2155S lies within the protein kinase domain of the Ros1 protein (UniProt.org). L2155S has been demonstrated to confer resistance to ROS1 tyrosine kinase inhibitors in the context of a ROS1 fusion in culture (PMID: 25688157), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Apr 2024). | Y |
L567V | missense | unknown | ROS1 L567V lies within fibronectin type-III domain 3 of the Ros1 protein (UniProt.org). L567V has been identified in sequencing studies (PMID: 27284491, PMID: 36422072), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Jan 2024). | |
M1805V | missense | unknown | ROS1 M1805V lies within fibronectin type-III domain 9 of the Ros1 protein (UniProt.org). M1805V has been identified in sequencing studies (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Jan 2024). | |
M2073T | missense | unknown | ROS1 M2073T lies within the protein kinase domain of the Ros1 protein (UniProt.org). M2073T has been identified in the scientific literature (PMID: 34907086), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
M2128V | missense | unknown | ROS1 M2128V lies within the protein kinase domain of the Ros1 protein (UniProt.org). M2128V has been demonstrated to confer resistance to ROS1 tyrosine kinase inhibitors in the context of a ROS1 fusion in culture (PMID: 25351743), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Apr 2024). | Y |
M2134I | missense | unknown | ROS1 M2134I lies within the protein kinase domain of the Ros1 protein (UniProt.org). M2134I has been identified in the scientific literature (PMID: 26372962, PMID: 32760015), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
mutant | unknown | unknown | ROS1 mutant indicates an unspecified mutation in the ROS1 gene. | |
N1534K | missense | unknown | ROS1 N1534K lies within fibronectin type-III domain 6 of the Ros1 protein (UniProt.org). N1534K has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
N1800T | missense | unknown | ROS1 N1800T lies within fibronectin type-III domain 9 of the Ros1 protein (UniProt.org). N1800T has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
N2240K | missense | unknown | ROS1 N2240K lies within the cytoplasmic domain of the Ros1 protein (UniProt.org). N2240K has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
N790S | missense | unknown | ROS1 N790S lies within the extracellular domain of the Ros1 protein (UniProt.org). N790S has been identified in the scientific literature (PMID: 27900369), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
negative | unknown | loss of function | ROS1 negative indicates a lack of the ROS1 gene, mRNA, and/or protein. | |
P1020fs | frameshift | loss of function - predicted | ROS1 P1020fs results in a change in the amino acid sequence of the Ros1 protein beginning at aa 1020 of 2347, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), P1020fs is predicted to lead to a loss of Ros1 protein function. | |
P1020H | missense | unknown | ROS1 P1020H lies within fibronectin type-III domain 4 of the Ros1 protein (UniProt.org). P1020H has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
P1020S | missense | unknown | ROS1 P1020S lies within fibronectin type-III domain 4 of the Ros1 protein (UniProt.org). P1020S has been identified in sequencing studies (PMID: 29141224), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
P1440L | missense | unknown | ROS1 P1440L lies within the extracellular domain of the Ros1 protein (UniProt.org). P1440L has been identified in sequencing studies (PMID: 22842228), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
P1440S | missense | unknown | ROS1 P1440S lies within the extracellular domain of the Ros1 protein (UniProt.org). P1440S has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
P151S | missense | unknown | ROS1 P151S lies within fibronectin type-III domain 1 of the Ros1 protein (UniProt.org). P151S has been identified in sequencing studies (PMID: 27573823, PMID: 26416732), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Jan 2024). | |
P1539S | missense | unknown | ROS1 P1539S lies within fibronectin type-III domain 6 of the Ros1 protein (UniProt.org). P1539S has been identified in sequencing studies (PMID: 28153863), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
P1721T | missense | unknown | ROS1 P1721T lies within fibronectin type-III domain 8 of the Ros1 protein (UniProt.org). P1721T has been identified in sequencing studies (PMID: 33283138), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Jan 2024). | |
P2130T | missense | unknown | ROS1 P2130T lies within the protein kinase domain of the Ros1 protein (UniProt.org). P2130T has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
P671Q | missense | unknown | ROS1 P671Q lies within fibronectin type-III domain 3 of the Ros1 protein (UniProt.org). P671Q has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
positive | unknown | unknown | ROS1 positive indicates the presence of the ROS1 gene, mRNA, and/or protein. ROS1 positive has been used alternatively to refer to presence of a ROS1 fusion or rearrangement. For related data, refer to ROS1 fusion or ROS1 rearrange in CKB. | |
Q1797H | missense | unknown | ROS1 Q1797H lies within fibronectin type-III domain 9 of the Ros1 protein (UniProt.org). Q1797H has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
Q1889P | missense | unknown | ROS1 Q1889P lies within the cytoplasmic domain of the Ros1 protein (UniProt.org). Q1889P has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
Q2012K | missense | unknown | ROS1 Q2012K lies within the protein kinase domain of the Ros1 protein (UniProt.org). Q2012K has been identified in the scientific literature (PMID: 34907086), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
Q617H | missense | unknown | ROS1 Q617H lies within fibronectin-type III domain 3 of the Ros1 protein (UniProt.org). Q617H has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
R118Q | missense | unknown | ROS1 R118Q lies within fibronectin-type III domain 1 of the Ros1 protein (UniProt.org). R118Q has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
R167Q | missense | unknown | ROS1 R167Q lies within fibronectin type-III domain 1 of the Ros1 protein (UniProt.org). R167Q has been identified in the scientific literature (PMID: 28690523, PMID: 31346352, PMID: 36422072), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
R2078W | missense | unknown | ROS1 R2078W lies within the protein kinase domain of the Ros1 protein (UniProt.org). R2078W has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
R2083G | missense | unknown | ROS1 R2083G lies within the protein kinase domain of the Ros1 protein (UniProt.org). R2083G has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
R2096L | missense | unknown | ROS1 R2096L lies within the protein kinase domain of the Ros1 protein (UniProt.org). R2096L has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
R2096Q | missense | unknown | ROS1 R2096Q lies within the protein kinase domain of the Ros1 protein (UniProt.org). R2096Q has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
R2096W | missense | unknown | ROS1 R2096W lies within the protein kinase domain of the Ros1 protein (UniProt.org). R2096W has been identified in sequencing studies (PMID: 24413735), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
R2116K | missense | unknown | ROS1 R2116K lies within the protein kinase domain of the Ros1 protein (UniProt.org). R2116K has been identified in the scientific literature (PMID: 34907086), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
R2205I | missense | unknown | ROS1 R2205I lies within the protein kinase domain of the Ros1 protein (UniProt.org). R2205I has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
R245I | missense | unknown | ROS1 R245I lies within fibronectin type-III domain 2 of the Ros1 protein (UniProt.org). R245I has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
R304I | missense | unknown | ROS1 R304I lies within the extracellular domain of the Ros1 protein (UniProt.org). R304I has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
R360I | missense | unknown | ROS1 R360I lies within the extracellular domain of the Ros1 protein (UniProt.org). R360I has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
R380I | missense | unknown | ROS1 R380I lies within the extracellular domain of the Ros1 protein (UniProt.org). R380I has been identified in sequencing studies (PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
R77W | missense | unknown | ROS1 R77W lies within the extracellular domain of the Ros1 protein (UniProt.org). R77W has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
rearrange | unknown | unknown | ROS1 rearrange indicates an unspecified rearrangement of the ROS1 gene. | |
S1109L | missense | unknown | ROS1 S1109L lies within fibronectin type-III domain 5 of the Ros1 protein (UniProt.org). S1109L has been identified in the scientific literature (PMID: 34299796, PMID: 18056464, PMID: 36422072), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
S1577Y | missense | unknown | ROS1 S1577Y lies within fibronectin type-III domain 7 of the Ros1 protein (UniProt.org). S1577Y has been identified in sequencing studies (PMID: 26960398, PMID: 34839264), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
S1581F | missense | unknown | ROS1 S1581F lies within fibronectin type-III domain 7 of the Ros1 protein (UniProt.org). S1581F has been identified in the scientific literature (PMID: 27900369), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
S1626Vfs*7 | frameshift | loss of function - predicted | ROS1 S1626Vfs*7 indicates a shift in the reading frame starting at amino acid 1626 and terminating 7 residues downstream causing a premature truncation of the 2347 amino acid Ros1 protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), S1626Vfs*7 is predicted to lead to a loss of Ros1 protein function. | |
S1986F | missense | gain of function - predicted | ROS1 S1986F lies within the protein kinase domain of the Ros1 protein (UniProt.org). S1986F results in increased colony formation that is not statistically significant relative to wild-type Ros1 and increased Ros1 phosphorylation in culture (PMID: 37587872), and has been demonstrated to occur as a secondary drug resistance mutation and increase cell migration and invasion in the context of ROS1 fusions in culture (PMID: 36265718, PMID: 27401242, PMID: 32776005), and therefore, is predicted to lead to a gain of Ros1 protein function. | Y |
S1986T | missense | unknown | ROS1 S1986T lies within the protein kinase domain of the Ros1 protein (UniProt.org). S1986T has been identified in the scientific literature (PMID: 34907086), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
S1986Y | missense | unknown | ROS1 S1986Y lies within the protein kinase domain of the Ros1 protein (UniProt.org). S1986Y has been demonstrated to occur as a secondary drug resistance mutation in the context of ROS1 fusions (PMID: 27401242), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Apr 2024). | Y |
S2229C | missense | unknown | ROS1 S2229C lies within the cytoplasmic domain of the Ros1 protein (UniProt.org). S2229C has been identified in the scientific literature (PMID: 32069381), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Jan 2024). | |
S32I | missense | unknown | ROS1 S32I lies within the extracellular domain of the Ros1 protein (UniProt.org). S32I has been identified in sequencing studies (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
S653F | missense | unknown | ROS1 S653F lies within fibronectin type-III domain 3 of the Ros1 protein (UniProt.org). S653F has been identified in the scientific literature (PMID: 29665843, PMID: 37655099), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
T145P | missense | unknown | ROS1 T145P lies within fibronectin type-III domain 1 of the Ros1 protein (UniProt.org). T145P has been identified in sequencing studies (PMID: 29981866, PMID: 36422072), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
T2195S | missense | unknown | ROS1 T2195S lies within the protein kinase domain of the Ros1 protein (UniProt.org). T2195S has been identified in sequencing studies (PMID: 34676052), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
T804N | missense | unknown | ROS1 T804N lies within the extracellular domain of the Ros1 protein (UniProt.org). T804N has been identified in sequencing studies (PMID: 30404791), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
V1729L | missense | unknown | ROS1 V1729L lies within fibronectin type-III domain 8 of the Ros1 protein (UniProt.org). V1729L has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
V1979A | missense | unknown | ROS1 V1979A lies within the protein kinase domain of the Ros1 protein (UniProt.org). V1979A has been identified in the scientific literature (PMID: 34907086), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
V1979E | missense | unknown | ROS1 V1979E lies within the protein kinase domain of the Ros1 protein (UniProt.org). V1979E has been identified in sequencing studies (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Apr 2024) | |
V2089M | missense | unknown | ROS1 V2089M lies within the protein kinase domain of the Ros1 protein (UniProt.org). V2089M has been identified in the scientific literature (PMID: 26372962), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Jan 2024). | |
V2098I | missense | unknown | ROS1 V2098I lies within the protein kinase domain of the Ros1 protein (UniProt.org). V2098I has been demonstrated to confer resistance to ROS1 tyrosine kinase inhibitors in the context of a ROS1 fusion in culture (PMID: 24218589), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Apr 2024). | Y |
V768L | missense | unknown | ROS1 V768L lies within the extracellular domain of the Ros1 protein (UniProt.org). V768L has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
V785M | missense | unknown | ROS1 V785M lies within the extracellular domain of the Ros1 protein (UniProt.org). V785M has not been characterized in the scientific literature and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
W1694* | nonsense | loss of function - predicted | ROS1 W1694* results in a premature truncation of the Ros1 protein at amino acid 1694 of 2347 (UniProt.org). Due to the loss of the protein kinase domain (UniProt), W1694* is predicted to lead to a loss of Ros1 protein function. | |
W1817* | nonsense | loss of function - predicted | ROS1 W1817* results in a premature truncation of the Ros1 protein at amino acid 1817 of 2347 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), W1817* is predicted to lead to a loss of Ros1 protein function. | |
W21* | nonsense | loss of function - predicted | ROS1 W21* results in a premature truncation of the Ros1 protein at amino acid 21 of 2347 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), W21* is predicted to lead to a loss of Ros1 protein function. | |
wild-type | none | no effect | Wild-type ROS1 indicates that no mutation has been detected within the ROS1 gene. | |
Y1700* | nonsense | loss of function - predicted | ROS1 Y1700* results in a premature truncation of the Ros1 protein at amino acid 1700 of 2347 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), Y1700* is predicted to lead to a loss of Ros1 protein function. | |
Y1960H | missense | unknown | ROS1 Y1960H lies within the protein kinase domain of the Ros1 protein (UniProt.org). Y1960H has not been characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Apr 2024). | |
Y382H | missense | unknown | ROS1 Y382H lies within the extracellular domain of the Ros1 protein (UniProt.org). Y382H has been identified in sequencing studies (PMID: 29981866, PMID: 38159331), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024). | |
Y718* | nonsense | loss of function - predicted | ROS1 Y718* results in a premature truncation of the Ros1 protein at amino acid 718 of 2347 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), Y718* is predicted to lead to a loss of Ros1 protein function. |