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Gene Symbol ALK
Synonyms CD246 | NBLST3
Gene Description ALK, anaplastic lymphoma kinase, is a receptor in the insulin receptor superfamily and is a key regulator of neuronal development (PMID: 21502284) and also promotes cell proliferation through activation of MAPK and PI3K signaling pathways (PMID: 27573755). Alk activating mutations, rearrangements, and fusions have been identified in various cancers (PMID: 22649787), including EML4-ALK in non-small cell lung cancer (PMID: 30108712, PMID: 30194140), and a number of mutations confer resistance in the context of Alk fusions (PMID: 25749034, PMID: 21948233).

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
A1047T missense unknown ALK A1047T lies within the transmembrane domain of the Alk protein (UniProt.org). A1047T has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Jul 2020).
A1200V missense no effect - predicted ALK A1200V lies within the protein kinase domain of the Alk protein (UniProt.org). A1200V demonstrates kinase activity comparable to wild-type Alk in culture (PMID: 25517749) and therefore, is predicted to have no effect on Alk protein function.
A1266D missense unknown ALK A1266D lies within the protein kinase domain of the Alk protein (UniProt.org). A1266D has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
A1266V missense no effect - predicted ALK A1266V lies within the protein kinase domain of the Alk protein (UniProt.org). A1266V has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
A195V missense no effect - predicted ALK A195V lies within the extracellular domain of the Alk protein (UniProt.org). A195V has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
A348D missense gain of function ALK A348D lies within the MAM domain 1 of the Alk protein (UniProt.org). A384D confers a gain of function to the Alk protein as demonstrated by increased cell proliferation in the absence of growth factor and colony formation in culture (PMID: 26032424).
A585T missense no effect - predicted ALK A585T lies within the MAM domain 2 of the Alk protein (UniProt.org). A585T has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
act mut unknown gain of function ALK act mut indicates that this variant results in a gain of function in the Alk protein. However, the specific amino acid change has not been identified.
amp none no effect ALK amplification indicates an increased number of copies of the ALK gene. However, the mechanism causing the increase is unspecified.
C1156F missense unknown ALK C1156F lies within the protein kinase domain of the Alk protein (UniProt.org). C1156F has been demonstrated to occur as a secondary drug resistance mutation in the context of NPM1-ALK (PMID: 25749034, PMID: 30322862), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Mar 2020). Y
C1156Y missense unknown ALK C1156Y lies within the protein kinase domain of the Alk protein (UniProt.org). C1156Y has been demonstrated to occur as a secondary drug resistance mutation in the context of ALK fusions (PMID: 21613408, PMID: 20979473, PMID: 27490033, PMID: 27045755), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020). Y
C990R missense unknown ALK C990R lies within the extracellular domain of the Alk protein (UniProt.org). C990R increased cell proliferation and cell viability compared to wild-type Alk in one of two cell lines in culture (PMID: 29533785), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020).
D1091N missense unknown ALK D1091N lies within the cytoplasmic domain of the Alk protein (UniProt.org). D1091N was observed to increase ERK activation in the presence of agonist antibodies (PMID: 23104988), but is unable to transform cultured cells (PMID: 23104988), and therefore, its effect on Alk protein function is unknown.
D1203fs frameshift loss of function - predicted ALK D1203fs results in a change in the amino acid sequence of the Alk protein beginning at aa 1203 of 1620, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the ATP binding site, D1203fs is predicted to lead to a loss of Alk protein function (UniProt.org).
D1203N missense unknown ALK D1203N lies within the protein kinase domain of the Alk protein (UniProt.org). D1203N has been demonstrated to occur as a secondary drug resistance mutation in the context of ALK fusions (PMID: 25421750, PMID: 27432227, PMID: 28434515), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020). Y
D1249fs frameshift loss of function - predicted ALK D1249fs results in a change in the amino acid sequence of the Alk protein beginning at aa 1249 of 1620, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the ATP binding site, D1249fs is predicted to lead to a loss of Alk protein function (UniProt.org).
D1529E missense no effect - predicted ALK D1529E lies within the cytoplasmic domain of the Alk protein (UniProt.org). D1529E has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
D1529G missense unknown ALK D1529G lies within the cytoplasmic domain of the Alk protein (UniProt.org). D1529G has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
D94N missense unknown ALK D94N lies within the extracellular domain of the Alk protein (UniProt.org). D94N has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
E1154K missense unknown ALK E1154K lies within the protein kinase domain of the Alk protein (UniProt.org). E1154K has been identified in the scientific literature (PMID: 31585938), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jul 2020).
E1210K missense unknown ALK E1210K lies within the protein kinase domain of the Alk protein (UniProt.org). E1210K has been demonstrated to occur as a secondary drug resistance mutation in the context of ALK fusions (PMID: 29650534, PMID: 25914136, PMID: 27432227), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020). Y
E1303K missense unknown ALK E1303K lies within the protein kinase domain of the Alk protein (UniProt.org). E1303K has been identified in the scientific literature (PMID: 29978950), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020).
E717K missense unknown ALK E717K lies within the extracellular domain of the Alk protein (UniProt.org). E717K has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020).
E862D missense unknown ALK E862D lies within the extracellular domain of the Alk protein (UniProt.org). E862D has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020).
E994K missense no effect - predicted ALK E994K lies within the extracellular domain of the Alk protein (UniProt.org). E994K has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
F1174C missense gain of function ALK F1174C lies within the protein kinase domain of the Alk protein (UniProt.org). F1174C confers a gain of function to Alk, as indicated by constitutive Alk phosphorylation in cell culture (PMID: 24509625, PMID: 22072639).
F1174I missense gain of function ALK F1174I lies within the protein kinase domain of the Alk protein (UniProt.org). F1174I results in ligand-independent phosphorylation of the Alk protein, activation of Erk, Stat3 pathways, and is transforming in cell culture (PMID: 23104988).
F1174L missense gain of function ALK F1174L lies within the protein kinase domain of the Alk protein (UniProt.org). F1174L confers a gain of function to the Alk protein as indicated by transformation activity and increased cell proliferation in culture (PMID: 18923525, PMID: 29533785, PMID: 29907598), and has been demonstrated to occur as a secondary resistance mutation in the context of ALK fusions in culture and in vivo (PMID: 21030459, PMID: 31452835). Y
F1174S missense gain of function ALK F1174S lies within the protein kinase domain of the Alk protein (UniProt.org). F1174S results in ligand-independent activation of the Alk protein, increased Erk phosphorylation, and transformation of cells in culture (PMID: 21059859).
F1174V missense gain of function - predicted ALK F1174V lies within the protein kinase domain of the Alk protein (UniProt.org). F1174V is predicted to confer a gain of function to the Alk protein as indicated by constitutive activation of the Alk protein in cell culture (PMID: 21242967) and has been demonstrated to occur as a secondary resistance mutation in the context of ALK fusions (PMID: 24675041). Y
F1174X missense unknown ALK F1174X indicates any Alk missense mutation that results in replacement of the phenylalanine (F) at amino acid 1174 by a different amino acid.
F1245C missense gain of function ALK F1245C lies within the protein kinase domain of the Alk protein (UniProt.org). Alk F1245C results in increased downstream signalling and is transforming in cell culture (PMID: 21838707).
F1245I missense unknown ALK F1245I lies within the protein kinase domain of the Alk protein (UniProt.org). F1245I has been identified in the scientific literature (PMID: 30778092), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
F1245L missense unknown ALK F1245L lies within the protein kinase domain of the Alk protein (UniProt.org). F1245L has been identified in the scientific literature (PMID: 30867766, PMID: 18923524), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
F1245Q missense unknown ALK F1245Q lies within the protein kinase domain of the Alk protein (UniProt.org). F1245Q has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
F1245V missense gain of function ALK F1245V lies within the protein kinase domain of the Alk protein (UniProt.org). F1245V confers a gain of function to the Alk protein, as it results in increased Alk kinase activity in vitro and leads to transformation activity in cell culture (PMID: 25517749).
F457L missense no effect - predicted ALK F457L lies within the LDL-receptor class A domain of the Alk protein (UniProt.org). F457L has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
F856S missense gain of function ALK F856S lies within the extracellular domain of the Alk protein (UniProt.org). F856S confers a gain of function to the Alk protein as demonstrated by increased cell proliferation in the absence of growth factor and colony formation in culture (PMID: 26032424).
fusion fusion unknown ALK fusion indicates a fusion of the ALK gene, but the fusion partner is unknown.
G1123D missense unknown ALK G1123D lies within the protein kinase domain of the Alk protein (UniProt.org). G1123D has been demonstrated to confer drug resistance in cell culture (PMID: 21948233), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020). Y
G1123S missense unknown ALK G1123S lies within the protein kinase domain of the Alk protein (UniProt.org). G1123S has been demonstrated to confer drug resistance in culture (PMID: 26134233, PMID: 21948233), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020). Y
G1128A missense gain of function ALK G1128A lies within the protein kinase domain of the Alk protein (UniProt.org). G1128A confers a gain of function to the Alk protein as demonstrated by increased downstream signaling in vitro and transformation in cultured cells (PMID: 21838707).
G1128S missense unknown ALK G1128S lies within the protein kinase domain of the Alk protein (UniProt.org). G1128S has been demonstrated to occur as a secondary drug resistance mutation in the context of NPM1-ALK (PMID: 25749034), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020). Y
G1137R missense no effect - predicted ALK G1137R lies within the protein kinase domain of the Alk protein (UniProt.org). G1137R has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
G1201E missense gain of function ALK G1201E lies within the protein kinase domain of the Alk protein (UniProt.org). G1201E confers a gain of function to the Alk protein as demonstrated by increased Alk kinase activity and downstream Pi3k and Mapk pathway activation in culture (PMID: 21596819).
G1202del deletion unknown ALK G1202del results in the deletion of an amino acid in the protein kinase domain of the Alk protein at amino acid 1202 (UniProt.org). G1202del has been demonstrated to occur as a secondary drug resistance mutation in the context of EML4-ALK (PMID: 27432227), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020). Y
G1202R missense unknown ALK G1202R lies within the protein kinase domain of the Alk protein (UniProt.org). G1202R has been demonstrated to confer drug resistance in the context of ALK fusions (PMID: 22277784, PMID: 24736079), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020). Y
G1202X missense unknown ALK G1202X indicates any Alk missense mutation that results in replacement of the glycine (G) at amino acid 1202 by a different amino acid.
G1269A missense unknown ALK G1269A lies within the protein kinase domain of the Alk protein (UniProt.org). G1269A has been demonstrated to occur as a secondary resistance mutation in the context of ALK rearrangement (PMID: 30675302, PMID: 28434515, PMID: 29872693), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020). Y
G1269E missense unknown ALK G1269E lies within the protein kinase domain of the Alk protein (UniProt.org). G1269E has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
G1269S missense gain of function - predicted ALK G1269S lies within the protein kinase domain of the Alk protein (UniProt.org). G1269S is predicted to confer a gain of function on the Alk protein as indicated by increased phosphorylation of Alk (PMID: 21948233) and has been demonstrated to confer resistance to Alk inhibitors in the context of EML4-ALK (PMID: 21948233, PMID: 22034911). Y
G1552R missense no effect - predicted ALK G1552R lies within the cytoplasmic domain of the Alk protein (UniProt.org). G1552R has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
G689V missense unknown ALK G689V lies within the extracellular domain of the Alk protein (UniProt.org). G689V has been identified in sequencing studies (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
G746C missense unknown ALK G746C lies within the extracellular domain of the Alk protein (UniProt.org). G746C has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020).
G875R missense no effect - predicted ALK G875R lies within the extracellular domain of the Alk protein (UniProt.org). G875R has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
G922R missense unknown ALK G922R lies within the extracellular domain of the Alk protein (UniProt.org). G922R has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
H1030P missense unknown ALK H1030P lies within the extracellular domain of the ALK protein (UniProt.org). H1030P has been identified in sequencing studies (PMID: 25275298), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
H354Q missense no effect - predicted ALK H354Q lies within the MAM domain 1 of the Alk protein (UniProt.org). H354Q has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
I1171N missense gain of function ALK I1171N lies within the protein kinase domain of the Alk protein (UniProt.org). I1171N results in increased ligand-independent Alk phosphorylation, activation of the Stat pathway, and is transforming in cell culture (PMID: 23239810, PMID: 21838707), and has been demonstrated to occur as a secondary resistance mutation in the context of ALK fusions (PMID: 27565911). Y
I1171S missense unknown ALK I1171S lies within the protein kinase domain of the Alk protein (UniProt.org). I1171S has been demonstrated to confer drug resistance in the context of ALK fusions in culture (PMID: 27009859, PMID: 25393796, PMID: 26464158), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020). Y
I1171T missense gain of function ALK I1171T lies within the protein kinase domain of the Alk protein (UniProt.org). I1171T confers a gain of function on the Alk protein as indicated by ligand-independent autophosphorylation, activation of Erk1/2, and cell transformation (PMID: 29907598), and has been demonstrated to confer drug resistance in the context of ALK fusions in culture (PMID: 27009859). Y
I1171X missense unknown ALK I1171X indicates any Alk missense mutation that results in replacement of the isoleucine (I) at amino acid 1171 by a different amino acid.
I1179V missense unknown ALK I1179V lies within the protein kinase domain of the Alk protein (UniProt.org). I1179V has been demonstrated to occur as a secondary drug resistance mutation in the context of ALK compound mutations (PMID: 29650534), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020). Y
I1250T missense loss of function ALK I1250T lies within the protein kinase domain of the Alk protein (UniProt.org). I1250T confers a loss of function on Alk as indicated by loss of kinase activity and loss of the ability to activate downstream signaling pathways in cell culture (PMID: 21804922).
I1268V missense unknown ALK I1268V lies within the protein kinase domain of the Alk protein (UniProt.org). I1268V has been identified in the scientific literature (PMID: 31585938), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jul 2020).
I1461V missense unknown ALK I1461V lies within the cytoplasmic domain of the Alk protein (UniProt.org). I1461V has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020).
inact mut unknown loss of function ALK inact mut indicates that this variant results in a loss of function of the Alk protein. However, the specific amino acid change has not been identified.
K1062M missense gain of function ALK K1062M lies within the cytoplasmic domain of the Alk protein (UniProt.org). K1062M confers a gain of function to the Alk protein as demonstrated by increased Alk kinase activity (PMID: 28199182) and increased AKT and ERK phosphorylation in in vitro assays (PMID: 21596819).
K1491R missense no effect - predicted ALK K1491R lies within the cytoplasmic domain of the Alk protein (UniProt.org). K1491R has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
K894T missense unknown ALK K894T lies within the extracellular domain of the Alk protein (UniProt.org). K894T has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
L1122V missense unknown ALK L1122V lies within the protein kinase domain of the Alk protein (UniProt.org). L1122V has been demonstrated to occur as a secondary drug resistance mutation in the context of ALK fusions (PMID: 29650534, PMID: 25421750), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020). Y
L1152P missense unknown ALK L1152P lies within the protein kinase domain of the Alk protein (UniProt.org). L1152P has been demonstrated to confer drug resistance in in the context of ALK rearrangement in culture (PMID: 24675041), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020). Y
L1152R missense unknown ALK L1152R lies within the protein kinase domain of the Alk protein (UniProt.org). L1152R has been demonstrated to occur as a secondary drug resistance mutation in the context of ALK fusions (PMID: 21791641, PMID: 27091190), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020). Y
L1152V missense unknown ALK L1152V lies within the protein kinase domain of the Alk protein (UniProt.org). L1152P is associated with decreased ALK inhibitor sensitivity in the context of an ALK fusion in culture (PMID: 22034911), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jul 2020).
L1196M missense gain of function - predicted ALK L1196M lies within the protein kinase domain of the Alk protein (UniProt.org). L1196M is predicted to confer a gain of function to the Alk protein as demonstrated by transformation activity and modest autophosphorylation of Alk in culture (PMID: 25517749), and confers resistance to Alk inhibitors in the context of ALK rearrangements in culture and in vivo (PMID: 21613408, PMID: 25421750, PMID: 31452835). Y
L1196Q missense gain of function - predicted ALK L1196Q lies within the protein kinase domain of the Alk protein (UniProt.org). L1196Q is predicted to confer a gain of function on the Alk protein as indicated by increased phosphorylation of Alk (PMID: 25749034) and has been demonstrated to confer resistance to Alk inhibitors in the context of NPM1-ALK in culture (PMID: 25749034, PMID: 23239810). Y
L1196X missense unknown ALK L1196X indicates any Alk missense mutation that results in replacement of the leucine (L) at amino acid 1196 by a different amino acid.
L1198F missense gain of function ALK L1198F lies within the protein kinase domain of the Alk protein (UniProt.org). L1198F confers a gain of function to the Alk protein as demonstrated by increased Alk kinase activity and downstream Pi3k and Mapk pathway activation (PMID: 21596819).
L1198H missense unknown ALK L1198H lies within the protein kinase domain of the Alk protein (UniProt.org). L1198H has been demonstrated to occur as a secondary drug resistance mutation in the context of ALK compound mutations (PMID: 29650534), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020). Y
L1198P missense gain of function - predicted ALK L1198P lies within the protein kinase domain of the Alk protein (UniProt.org). L1198P is predicted to confer a gain of function on the Alk protein as indicated by increased phosphorylation of Alk and has been demonstrated to confer resistance to Alk inhibitors in the context of EML4-ALK in culture (PMID: 21948233). Y
L1198V missense unknown ALK L1198V lies within the protein kinase domain of the Alk protein (UniProt.org). L1198V has been demonstrated to confer resistance to ALK inhibitors in vivo in the context of EML4-ALK and ALK F1174L (PMID: 29636358), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020). Y
L1198X missense unknown ALK L1198X indicates any Alk missense mutation that results in replacement of the leucine (L) at amino acid 1198 by a different amino acid.
L1204V missense unknown ALK L1204V lies within the protein kinase domain of the Alk protein (UniProt.org). L1204V has been demonstrated to occur as a secondary drug resistance mutation in the context of ALK compound mutations (PMID: 29650534), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020). Y
L1256F missense unknown ALK L1256F lies within the protein kinase domain of the Alk protein (UniProt.org). L1256F demonstrates transforming and tumorigenic activity and confers drug resistance in the context of ALK fusions (PMID: 29650534, PMID: 30662002), but has not been individually characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020). Y
L560F missense no effect - predicted ALK L560F lies within the MAM domain 2 of the Alk protein (UniProt.org). L560F has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
L868Q missense unknown ALK L868Q lies within the extracellular domain of the Alk protein (UniProt.org). L868Q has not been characterized and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
M1166R missense gain of function ALK M1166R lies within the protein kinase domain of the Alk protein (UniProt.org). M1166R confers a gain of function to the Alk protein, as indicated by ligand-independent activation of the Alk protein and increased Erk and Stat3 phosphorylation in cell culture (PMID: 23104988).
M1166V missense unknown ALK M1166V lies within the protein kinase domain of the Alk protein (UniProt.org). M1166V has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
M1478T missense unknown ALK M1478T lies within the cytoplasmic domain of the Alk protein (UniProt.org). M1478T has been identified in sequencing studies (PMID: 27852271), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
M301I missense no effect - predicted ALK M301I lies within the MAM domain 1 of the Alk protein (UniProt.org). M301I has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
M552I missense no effect - predicted ALK M552I lies within the MAM domain 2 of the Alk protein (UniProt.org). M552I has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
mutant unknown unknown ALK mutant indicates an unspecified mutation in the ALK gene.
N1178H missense unknown ALK N1178H lies within the protein kinase domain of the Alk protein (UniProt.org). N1178H has been demonstrated to occur as a secondary drug resistance mutation in the context of NPM1-ALK (PMID: 25749034), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020). Y
negative unknown loss of function ALK negative indicates a lack of the ALK gene, mRNA, and/or protein.
over exp none no effect ALK over exp indicates an over expression of the Alk protein and/or mRNA. However, the mechanism causing the over expression is unspecified.
P1112Q missense unknown ALK P1112Q lies within the cytoplasmic domain of the Alk protein (UniProt.org). P1112Q has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
P1139S missense unknown ALK P1139S lies within the protein kinase domain of the Alk protein (UniProt.org). P1139S has been demonstrated to occur as a secondary drug resistance mutation in the context of NPM1-ALK (PMID: 25421750), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020). Y
P1298S missense unknown ALK P1298S lies within the protein kinase domain of the Alk protein (UniProt.org). P1298S has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
P1543S missense unknown ALK P1543S lies within the cytoplasmic domain of the Alk protein (UniProt.org). P1543S has not been characterized and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
P1599S missense unknown ALK P1599S lies within the cytoplasmic domain of the Alk protein (UniProt.org). P1599S has been identified in sequencing studies (PMID: 29684080), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
P336S missense no effect - predicted ALK P336S lies within the MAM domain 1 of the Alk protein (UniProt.org). P336S has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
P36S missense unknown ALK P36S lies within the extracellular domain of the Alk protein (UniProt.org). P36S has been identified in sequencing studies (PMID: 20579941), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
P40L missense unknown ALK P40L lies within the extracellular domain of the Alk protein (UniProt.org). P40L has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020).
P858S missense no effect - predicted ALK P858S lies within the extracellular domain of the Alk protein (UniProt.org). P858S has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
positive unknown unknown ALK positive indicates the presence of the ALK gene, mRNA, and/or protein. ALK positive has been used alternatively to refer to presence of an ALK fusion or rearrangement. For related data, refer to ALK fusion or ALK rearrange in CKB.
R1113Q missense unknown ALK R1113Q lies within the cytoplasmic domain of the Alk protein (UniProt.org). R1113Q has has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
R1192P missense gain of function ALK R1192P lies within the protein kinase domain of the Alk protein (UniProt.org). R1192P confers a gain of function to the Alk protein as demonstrated by transformed cells and increased downstream signalling, although less robustly than other activating mutants (PMID: 21838707).
R1209Q missense loss of function - predicted ALK R1209Q lies within the protein kinase domain of the Alk protein (UniProt.org). R1209Q has not been biochemically characterized, but in one of two cell lines, R1209Q had decreased cell proliferation and cell viability as compared to wild-type Alk (PMID: 29533785) and therefore, is predicted to result in a loss of Alk protein function.
R1212H missense unknown ALK R1212H lies within the protein kinase domain of the Alk protein (UniProt.org). R1212H has been identified in sequencing studies (PMID: 21499247, PMID: 28912153, PMID: 28581676), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
R1275L missense unknown ALK R1275L is a hotspot mutation that lies within the protein kinase domain of the Alk protein (UniProt.org, PMID: 18923525, PMID: 21242967). R1275L has been identified in in the scientific literature (PMID: 27888620), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
R1275Q missense gain of function ALK R1275Q lies within the protein kinase domain of the Alk protein (UniProt.org). R1275Q confers a gain of function to the Alk protein as demonstrated by transformation activity in cell culture and increased downstream signalling in in vitro assays (PMID: 21838707, PMID: 29533785).
R133H missense no effect - predicted ALK R133H lies within the extracellular domain of the Alk protein (UniProt.org). R133H has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
R284K missense unknown ALK R284K lies within the MAM domain 1 of the Alk protein (UniProt.org). R284K has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020).
R291C missense unknown ALK R291C lies within the MAM domain 1 of the Alk protein (UniProt.org). R291C has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jun 2020).
R311H missense unknown ALK R311H lies within the MAM domain 1 of the Alk protein (UniProt.org). R311H has been identified in sequencing studies (PMID: 23202128, PMID: 25344691), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jun 2020).
R395H missense unknown ALK R395H lies within the MAM domain 1 of the Alk protein (UniProt.org). R395H has been identified in sequencing studies (PMID: 22877736), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jun 2020).
R401* nonsense loss of function - predicted ALK R401* results in a premature truncation of the Alk protein at amino acid 401 of 1620 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), R401* is predicted to lead to a loss of Alk protein function.
R401Q missense no effect - predicted ALK R401Q lies within the MAM domain 1 of the Alk protein (UniProt.org). R401Q has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted have no effect on Alk protein function.
R753Q missense unknown ALK R753Q lies within the extracellular domain of the Alk protein (UniProt.org). R753Q has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
rearrange unknown unknown ALK rearrangement indicates an unspecified rearrangement of the ALK gene.
S1053F missense unknown ALK S1053F lies within the transmembrane domain of the Alk protein (UniProt.org). S1053F has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
S1206C missense unknown ALK S1206C lies within the protein kinase domain of the Alk protein (UniProt.org). S1206C has been demonstrated to occur as a secondary drug resistance mutation in the context of ALK compound mutations (PMID: 25421750), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020). Y
S1206F missense unknown ALK S1206F lies within the protein kinase domain of the Alk protein (UniProt.org). S1206F has been identified in the scientific literature (PMID: 27565908), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
S1206Y missense unknown ALK S1206Y lies within the protein kinase domain of the Alk protein (UniProt.org). S1206Y has been demonstrated to occur as a secondary drug resistance mutation in the context of ALK rearrangements (PMID: 22277784, PMID: 24675041, PMID: 25727400), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020). Y
S529Y missense no effect - predicted ALK S529Y lies within the MAM domain 2 of the Alk protein (UniProt.org). S529Y has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
S711R missense no effect - predicted ALK S711R lies within the extracellular domain of the Alk protein (UniProt.org). S711R has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
S865P missense no effect - predicted ALK S865P lies within the extracellular domain of the Alk protein (UniProt.org). S865P has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
T1151dup duplication unknown ALK T1151dup indicates the insertion of the duplicate amino acid, threonine (T)-1151, in the protein kinase domain of the Alk protein (UniProt.org). T1151dup has been demonstrated to occur as a secondary drug resistance mutation in the context of EML4-ALK (PMID: 22277784, PMID: 20695522), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020). Y
T1151M missense unknown ALK T1151M lies within the protein kinase domain and inhibitor binding region of the Alk protein (UniProt.org). T1151M has been demonstrated to occur as a secondary drug resistance mutation in the context of ALK fusions (PMID: 28676215, PMID: 27009859), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020). Y
T429I missense unknown ALK T429I lies within the extracellular domain of the Alk protein (UniProt.org). T429I has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
T680I missense no effect - predicted ALK T680I lies within the MAM domain 2 of the Alk protein (UniProt.org). T680I has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
V1180L missense unknown ALK V1180L lies within the protein kinase domain of the Alk protein (UniProt.org). V1180L has been demonstrated to occur as a secondary resistance mutation in the context of EML4-ALK (PMID: 25228534, PMID: 27432227), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020). Y
V1180X missense unknown ALK V1180X indicates any Alk missense mutation that results in replacement of the valine (V) at amino acid 1180 by a different amino acid.
V1413G missense unknown ALK V1413G lies within the cytoplasmic domain of the Alk protein (UniProt.org). V1413G has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
V1545I missense no effect - predicted ALK V1545I lies within the cytoplasmic domain of the Alk protein (UniProt.org). V1545I has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
V163L missense unknown ALK V163L lies within the extracellular domain of the Alk protein (UniProt.org). V163L has been identified in sequencing studies (PMID: 24728327), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
V198M missense unknown ALK V198M lies within the extracellular domain of the Alk protein (UniProt.org). V198M has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020).
V476A missense no effect - predicted ALK V476A lies within the extracellular domain of the Alk protein (UniProt.org). V476A has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
V66A missense unknown ALK V66A lies within the extracellular domain of the Alk protein (UniProt.org). V66A has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020).
V66G missense unknown ALK V66G lies within the extracellular domain of the Alk protein (UniProt.org). V66G has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, May 2020).
W501* nonsense loss of function - predicted ALK W501* results in a premature truncation of the Alk protein at amino acid 501 of 1620 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), W501* is predicted to lead to a loss of Alk protein function.
wild-type none no effect Wild-type ALK indicates that no mutation has been detected within the ALK gene.
Y1278S missense gain of function ALK Y1278S is a hotspot mutation that lies within the activation loop of the Alk protein (PMID: 24060861, PMID: 25071110). Y1278S results in constitutive activation of Alk and is transforming in cell culture (PMID: 25517749, PMID: 29084134).
NPM1 - ALK fusion gain of function NPM1-ALK (NPM-ALK) results from the fusion of NPM1 and ALK, and leads to constitutive tyrosine kinase activity (PMID: 8122112, PMID: 9121481). NPM1-ALK fusions have been identified in anaplastic large cell lymphoma (PMID: 17488663, PMID: 25961700)
ETV6 - ALK fusion gain of function - predicted ETV6-ALK results from the fusion of ETV6 and ALK (PMID: 29327718), which is transforming in culture (PMID: 21572589) and therefore, is predicted to confer a gain of function. ETV6-ALK fusion has been identified in epithelioid fibrous histiocytoma (PMID: 29327718).
EML4 - ALK fusion gain of function EML4-ALK results from the fusion of EML4 and ALK, resulting in constitutive kinase activity, transformation in cultured cells, and tumor activity in mouse models (PMID: 19064915, PMID: 17625570). EML4-ALK fusions have been associated with non-small cell lung cancer (PMID: 26755435).