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Gene ALK
Variant E1210K
Impact List missense
Protein Effect unknown
Gene Variant Descriptions 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: 35123209, PMID: 27432227), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Nov 2023).
Associated Drug Resistance Y
Category Variants Paths

ALK mutant ALK E1210K

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Transcript NM_004304.5
gDNA chr2:g.29220723C>T
cDNA c.3628G>A
Protein p.E1210K
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004304 chr2:g.29220723C>T c.3628G>A p.E1210K RefSeq GRCh38/hg38
NM_004304.4 chr2:g.29220723C>T c.3628G>A p.E1210K RefSeq GRCh38/hg38
NM_004304.5 chr2:g.29220723C>T c.3628G>A p.E1210K RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
EML4 - ALK ALK E1210K Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK E1210K Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, a cell line expressing EML4-ALK with ALK E1210K was resistant to Alecensa (alectinib) in culture (PMID: 31446141). 31446141
EML4 - ALK ALK E1210K Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK E1210K Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Alunbrig (brigatinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK E1210K Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a cell line expressing EML4-ALK with ALK E1210K in culture (PMID: 31446141). 31446141
EML4 - ALK ALK E1210K Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK E1210K lung non-small cell carcinoma resistant Crizotinib Case Reports/Case Series Actionable In a clinical study, a patient with non-small cell lung carcinoma harboring EML4-ALK progressed on treatment with Xalkori (crizotinib) and was subsequently found to harbor a secondary resistance mutation, ALK E1210K (PMID: 29636358). 29636358
EML4 - ALK ALK E1210K Advanced Solid Tumor resistant Ensartinib Preclinical - Cell culture Actionable In a preclinical study, a cell line expressing EML4-ALK with ALK E1210K was resistant to Ensartinib (X-396) in culture (PMID: 31446141). 31446141
EML4 - ALK ALK D1203N ALK E1210K Advanced Solid Tumor decreased response Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N ALK E1210K Advanced Solid Tumor decreased response Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated a decreased response to treatment with Zykadia (ceritinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N ALK E1210K Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K did not response to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N ALK E1210K Advanced Solid Tumor decreased response Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated a decreased response to treatment with Alunbrig (brigatinib) when compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N ALK E1210K Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
ALK rearrange ALK D1203N ALK E1210K ALK G1269A lung non-small cell carcinoma resistant Lorlatinib Case Reports/Case Series Actionable In a clinical study, ALK G1269A was identified as an acquired mutation in an ALK-positive non-small cell lung cancer patient harboring ALK E1210K and D1203N, who developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
EML4 - ALK ALK S1206C ALK E1210K lung non-small cell carcinoma resistant Brigatinib Case Reports/Case Series Actionable In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK and ALK E1210K eventually progressed on treatment with Alunbrig (brigatinib) and was subsequently found to have acquired another resistance mutation, ALK S1206C in cis (PMID: 29636358). 29636358
ALK rearrange ALK E1210K lung non-small cell carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with ALK-rearranged non-small cell lung cancer demonstrated disease progression when treated with Xalkori (crizotinib) due to a secondary acquired resistance mutation, ALK E1210K (PMID: 27432227). 27432227
ALK S1206C ALK E1210K Advanced Solid Tumor predicted - sensitive TPX-0131 Preclinical - Biochemical Actionable In a preclinical study, TPX-0131 inhibited kinase activity of ALK S1206C and ALK E1210K compound mutation in an in vitro assay (PMID: 34158340). 34158340
ALK D1203N ALK E1210K Advanced Solid Tumor decreased response TPX-0131 Preclinical - Biochemical Actionable In a preclinical study, ALK D1203N and E1210K compound mutation demonstrated reduced sensitivity to TPX-0131 in an in vitro kinase assay (PMID: 34158340). 34158340
EML4 - ALK ALK F1174C ALK E1210K lung adenocarcinoma predicted - sensitive Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a patient with metastatic lung adenocarcinoma harboring EML4-ALK, ALK F1174C, and ALK E1210K (PMID: 34378333). 34378333
ALK fusion ALK D1203N ALK E1210K ALK G1269A lung non-small cell carcinoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a clinical case study, ALK G1269A was identified as an acquired mutation in a non-small cell lung cancer patient harboring an ALK fusion with ALK D1203N and ALK E1210K who developed resistance to Lorbrena (lorlatinib) after initial response (PMID: 35726063). 35726063
EML4 - ALK ALK F1174L ALK E1210K ALK G1269A lung adenocarcinoma predicted - sensitive Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a patient with lung adenocarcinoma harboring EML4-ALK (e13:e20), ALK G1269A, ALK F1174L, and ALK E1210K (PMID: 35123209). 35123209
EML4 - ALK ALK I1171T ALK F1174L ALK L1196M ALK D1203N ALK E1210K ALK G1269A lung adenocarcinoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a clinical case study, ALK L1196M, D1203N, and I1171T were identified at the time of progression on Lorbrena (lorlatinib) treatment in a patient with lung adenocarcinoma harboring EML4-ALK (e13:e20), ALK G1269A, ALK F1174L, and ALK E1210K (PMID: 35123209). 35123209
EML4 - ALK ALK F1174L ALK E1210K lung adenocarcinoma predicted - resistant Brigatinib Case Reports/Case Series Actionable In a clinical case study, ALK E1210K was identified at the time of progression on Alunbrig (brigatinib) treatment in a patient with lung adenocarcinoma who initially harbored EML4-ALK (e13:e20) and ALK G1269A, and also acquired ALK F1174L and lost ALK G1269A during Alunbrig (brigatinib) treatment (PMID: 35123209). 35123209