Gene Variant Detail

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Gene KIT
Variant Y823D
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions KIT Y823D lies within the protein kinase domain of the Kit protein (UniProt.org). Y823D confers a gain of function on Kit, as indicated by constitutive phosphorylation of Kit in cultured cells (PMID: 14695343, PMID: 20633291).
Associated Drug Resistance
Category Variants Paths

KIT mutant KIT act mut KIT Y823D

KIT mutant KIT exon17 KIT Y823D

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Transcript NM_000222.3
gDNA chr4:g.54733175T>G
cDNA c.2467T>G
Protein p.Y823D
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
XM_005265741 chr4:g.54733175T>G c.2467T>G p.Y823D RefSeq GRCh38/hg38
XM_005265741.1 chr4:g.54733175T>G c.2467T>G p.Y823D RefSeq GRCh38/hg38
NM_000222.2 chr4:g.54733175T>G c.2467T>G p.Y823D RefSeq GRCh38/hg38
NM_000222 chr4:g.54733175T>G c.2467T>G p.Y823D RefSeq GRCh38/hg38
NM_001385290.1 chr4:g.54733175T>G c.2467T>G p.Y823D RefSeq GRCh38/hg38
NM_000222.3 chr4:g.54733175T>G c.2467T>G p.Y823D RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
KIT W557_K558del KIT Y823D gastrointestinal stromal tumor sensitive Ponatinib Preclinical - Pdx & cell culture Actionable In a preclinical study, a patient derived GIST cell line co-harboring KIT W557_K558del and KIT Y823D demonstrated sensitivity to Iclusig (ponatinib) in a PDX model, resulting in complete tumor regression (PMID: 25239608). 25239608
KIT W557_K558del KIT Y823D gastrointestinal stromal tumor sensitive Ripretinib Preclinical - Pdx Actionable In a preclinical study, Qinlock (ripretinib) induced tumor regression in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT W557_K558del and KIT Y823D (PMID: 31085175). 31085175
KIT W557_K558del KIT Y823D gastrointestinal stromal tumor sensitive Avapritinib Preclinical - Pdx Actionable In a preclinical study, Ayvakit (avapritinib) inhibited Kit phosphorylation and resulted in tumor regression in patient-derived xenograft models of Gleevec (imatinib mesylate)-resistant gastrointestinal stromal tumor harboring KIT W557_K558del and Y823D (PMID: 29093181). 29093181
KIT W557_K558del KIT Y823D gastrointestinal stromal tumor sensitive AZD3229 Preclinical - Pdx Actionable In a preclinical study, AZD3229 inhibited Kit signaling and tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT W557_K558del and KIT Y823D (PMID: 32350132). 32350132
KIT W557_K558del KIT Y823D gastrointestinal stromal tumor sensitive Regorafenib Preclinical - Pdx Actionable In a preclinical study, Stivarga (regorafenib) inhibited tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT W557_K558del and KIT Y823D (PMID: 32350132). 32350132
KIT W557_K558del KIT Y823D Advanced Solid Tumor decreased response Ripretinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT W557_K558del and KIT Y823D demonstrated a decreased response to treatment with Qinlock (ripretinib) compared to cells expressing KIT W557_K558del alone in culture (PMID: 32350132). 32350132
KIT W557_K558del KIT Y823D Advanced Solid Tumor predicted - sensitive Regorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT W557_K558del and KIT Y823D demonstrated sensitivity to treatment with Stivarga (regorafenib), but was decreased compared to cells expressing KIT W557_K558del alone in culture (PMID: 32350132). 32350132
KIT W557_K558del KIT Y823D Advanced Solid Tumor decreased response Avapritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT W557_K558del and KIT Y823D demonstrated a decreased response to treatment with Ayvakit (avapritinib) compared to cells expressing KIT W557_K558del alone in culture (PMID: 32350132). 32350132
KIT W557_K558del KIT Y823D Advanced Solid Tumor resistant Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT W557_K558del and KIT Y823D demonstrated resistance to Sutent (sunitinib) in culture (PMID: 32350132). 32350132
KIT W557_K558del KIT Y823D Advanced Solid Tumor resistant Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT W557_K558del and KIT Y823D demonstrated resistance to Gleevec (imatinib) in culture (PMID: 32350132). 32350132
KIT W557_K558del KIT Y823D Advanced Solid Tumor sensitive AZD3229 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT W557_K558del and KIT Y823D demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). 32350132
KIT W557_K558del KIT Y823D gastrointestinal stromal tumor sensitive PLX9486 Preclinical - Pdx Actionable In a preclinical study, PLX9486 treatment decreased Mapk phosphorylation, inhibited proliferation, and reduced tumor growth and induced regression in a Gleevec (imatinib)-resistant patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT W557_K558del and Y823D (PMID: 30523507). 30523507
KIT W557_K558del KIT Y823D gastrointestinal stromal tumor predicted - resistant Imatinib Case Reports/Case Series Actionable In a clinical case study, two patients with gastrointestinal stromal tumors harboring KIT W557_K558del progressed following an initial response to Gleevec (imatinib), and were found to have acquired the secondary resistance mutation KIT Y823D in one lesion (PMID: 18294292). 18294292
KIT V559D KIT Y823D Advanced Solid Tumor no benefit Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT Y823D and KIT V559D were insensitive to Sutent (sunitinib) in culture and in mouse models (PMID: 24205792). 24205792
KIT V559D KIT Y823D Advanced Solid Tumor sensitive Flumatinib Preclinical Actionable In a preclinical study, Flumatinib treatment in transformed cells co-expressing KIT Y823D and KIT V559D resulted in decreased cell proliferation and inhibition of Kit, Erk1/2, and Stat3 phosphorylation in culture, and led to improved survival in mouse models (PMID: 24205792). 24205792
KIT V559D KIT Y823D Advanced Solid Tumor no benefit Imatinib Preclinical Actionable In a preclinical study, Gleevec (imatinib) treatment in a mouse model with cells expressing KIT V559D and KIT Y823D resulted in shortened survival (PMID: 24205792). 24205792
KIT exon 11 del KIT Y823D Advanced Solid Tumor predicted - sensitive THE-630 Preclinical - Cell culture Actionable In a preclinical study, THE-630 treatment inhibited growth of cells co-expressing a KIT exon 11 deletion and KIT Y823D in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1292). detail...
KIT P551I KIT M552_V559del KIT Y823D gastrointestinal stromal tumor predicted - resistant Imatinib Case Reports/Case Series Actionable In a clinical case study, a patient with gastrointestinal stromal tumor harboring KIT M552_V559del and KIT P551I progressed following an initial response to Gleevec (imatinib), and was found to have acquired the secondary resistance mutation KIT Y823D (PMID: 18294292). 18294292