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Gene ALK
Variant D1203N
Impact List missense
Protein Effect unknown
Gene Variant Descriptions 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: 35123209, PMID: 27432227, PMID: 28434515), 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 D1203N

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Transcript NM_004304.5
gDNA chr2:g.29220744C>T
cDNA c.3607G>A
Protein p.D1203N
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004304.4 chr2:g.29220744C>T c.3607G>A p.D1203N RefSeq GRCh38/hg38
NM_004304 chr2:g.29220744C>T c.3607G>A p.D1203N RefSeq GRCh38/hg38
NM_004304.5 chr2:g.29220744C>T c.3607G>A p.D1203N 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 D1203N Advanced Solid Tumor predicted - resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N Advanced Solid Tumor predicted - resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Alunbrig (brigatinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N Advanced Solid Tumor resistant TAE684 Preclinical - Cell culture Actionable In a preclinical study, transformed cells overexpressing ALK D1203N in the context of EML4-ALK were resistant to TAE684 in culture (PMID: 21948233). 21948233
EML4 - ALK ALK D1203N Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N Advanced Solid Tumor predicted - resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174C ALK D1203N Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated resistance to treatment with Xalkori (crizotinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK F1174C ALK D1203N Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C did not response to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK F1174C ALK D1203N Advanced Solid Tumor decreased response Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated a decreased response to treatment with Alunbrig (brigatinib) when compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4 - ALK ALK F1174C ALK D1203N Advanced Solid Tumor decreased response Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated a decreased response to treatment with Lorlatinib (PF-06463922) in culture compared to cells expressing wild-type EML4-ALK (PMID: 27432227). 27432227
EML4 - ALK ALK F1174C ALK D1203N Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated resistance to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
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
EML4 - ALK ALK C1156Y ALK D1203N Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK D1203N was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
ALK rearrange ALK I1171N ALK D1203N lung non-small cell carcinoma resistant Lorlatinib Case Reports/Case Series Actionable In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK I1171N and D1203N developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
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
ALK rearrange ALK D1203N lung non-small cell carcinoma predicted - resistant Brigatinib Case Reports/Case Series Actionable In a clinical case study, ALK D1203N was identified at disease progression while on Alunbrig (brigatinib) treatment in a patient with ALK-positive non-small cell lung cancer (PMID: 29935304). 29935304
ALK rearrange ALK D1203N lung non-small cell carcinoma predicted - resistant Lorlatinib Clinical Study - Cohort Actionable In a retrospective study, ALK D1203N was identified in 24% (7/29) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Lorbrena (lorlatinib) treatment (PMID: 31358542). 31358542
EML4 - ALK ALK F1174L ALK D1203N ALK G1269A lung adenocarcinoma predicted - resistant Ceritinib Case Reports/Case Series Actionable In a clinical case study, ALK D1203N were identified as a newly acquired mutation in the pleural effusion from a patient with lung adenocarcinoma after his disease progressed on Zykadia (ceritinib) treatment, in addition to the EML4-ALK, ALK F1174L, and ALK G1269A acquired after disease progression on Xalkori (crizotinib) and Belizatinib (TSR-011) sequentially (PMID: 28434515). 28434515
ALK rearrange ALK L1196M ALK D1203N lung adenocarcinoma predicted - resistant Ceritinib Case Reports/Case Series Actionable In a clinical case study, Zykadia (ceritinib) treatment resulted in disease progression after 5 months of therapy in a patient with lung adenocarcinoma harboring ALK rearrangement and an acquired ALK L1196M, ALK D1203N was detected in the biopsies at disease progression (PMID: 31585938). 31585938
ALK rearrange ALK L1196M ALK D1203N lung adenocarcinoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a clinical case study, a patient with lung adenocarcinoma harboring ALK rearrangement and acquired ALK L1196M, ALK D1203N mutations demonstrated primary resistance to Lorbrena (lorlatinib) treatment, resulted in immediate disease progression (PMID: 31585938). 31585938
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1196M and ALK D1203N compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) in culture (PMID: 31585938). 31585938
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor predicted - resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N demonstrated resistance to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor predicted - resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor predicted - resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V demonstrated resistance to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N and F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor predicted - resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N and F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N and F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
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 I1171N ALK D1203N Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and ALK D1203N were resistant to Xalkori (crizotinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK I1171N ALK D1203N Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and ALK D1203N were resistant to Alecensa (alectinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK I1171N ALK D1203N Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and ALK D1203N were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063). 35726063
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 L1196M ALK G1202R ALK D1203N large cell neuroendocrine carcinoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a clinical case study, ALK L1196M, ALK D1203N, and ALK G1202R were identified on post-progression biopsy in a patient with metastatic large cell neuroendocrine lung carcinoma harboring EML4-ALK (e20:e20), who previously achieved disease stabilization for 8 months with Lorbrena (lorlatinib) treatment (PMID: 36207130). 36207130
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
ALK F1174L ALK G1202R ALK D1203N ALK amp neuroblastoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a Phase I trial, a neuroblastoma patient harboring ALK F1174L developed progressive disease on treatment with Lorbrena (lorlatinib) and was found to have acquired ALK amplification, and ALK G1202R and D1203N each in cis with F1174L via circulating tumor DNA (PMID: 37147298; NCT03107988). 37147298