Gene Variant Detail

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Gene KIT
Variant N822K
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions KIT N822K lies within the activation loop in the protein kinase domain of the Kit protein (PMID: 24205792). N822K results in constitutive activation of Kit, increased Erk1/2 and Stat3 phosphorylation, is transforming in culture (PMID: 24205792, PMID: 31484543), leads to mislocalization of Kit to endolysosomes (PMID: 31484543), and has been identified as a secondary mutation associated with imatinib resistance (PMID: 18488160).
Associated Drug Resistance Y
Category Variants Paths

KIT mutant KIT act mut KIT N822K

KIT mutant KIT exon17 KIT N822K

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Transcript NM_000222.3
gDNA chr4:g.54733174T>G
cDNA c.2466T>G
Protein p.N822K
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_000222.3 chr4:g.54733174T>G c.2466T>G p.N822K RefSeq GRCh38/hg38
NM_001385290.1 chr4:g.54733174T>G c.2466T>G p.N822K RefSeq GRCh38/hg38
NM_000222.2 chr4:g.54733174T>G c.2466T>G p.N822K RefSeq GRCh38/hg38
XM_005265741.1 chr4:g.54733174T>G c.2466T>G p.N822K RefSeq GRCh38/hg38
NM_000222 chr4:g.54733174T>G c.2466T>G p.N822K RefSeq GRCh38/hg38
XM_005265741 chr4:g.54733174T>G c.2466T>G p.N822K RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
KIT N822K gastrointestinal stromal tumor predicted - resistant Imatinib Case Reports/Case Series Actionable In a clinical case study, KIT N822K was identified in the tumor of a gastrointestinal stromal tumor patient who was resistant to Gleevec (imatinib) treatment (PMID: 26316776). 26316776
KIT N822K leukemia sensitive Ponatinib Preclinical - Cell culture Actionable In a preclinical study, Iclusig (ponatinib) inhibited Kit signaling and viability in leukemia cells harboring KIT N822K in culture (PMID: 21482694). 21482694
KIT N822K acute myeloid leukemia sensitive Ripretinib Preclinical - Pdx Actionable In a preclinical study, Qinlock (ripretinib) induced tumor regression in a patient-derived xenograft (PDX) model of acute myeloid leukemia harboring KIT N822K (Cancer Res 2015;75(15 Suppl):Abstract nr 2690). detail...
KIT N822K acute myeloid leukemia sensitive Ripretinib Preclinical - Cell culture Actionable In a preclinical study, Qinlock (ripretinib) inhibited proliferation of acute myeloid leukemia cells harboring KIT N822K in culture (PMID: 31085175). 31085175
KIT N822K acute myeloid leukemia sensitive BPR1J373 Preclinical - Cell line xenograft Actionable In a preclinical study, an acute myeloid leukemia cell line harboring KIT N822K demonstrated sensitivity to treatment with BPR1J373, showing inhibition of Kit phosphorylation and apoptotic induction in culture, and tumor regression in xenograft models (PMID: 27512117). 27512117
KIT N822K acute myeloid leukemia sensitive Avapritinib Preclinical - Cell culture Actionable In a preclinical study, Ayvakit (avapritinib) inhibited Kit phosphorylation and proliferation of acute myeloid leukemia cells harboring KIT N822K in culture (PMID: 29093181). 29093181
KIT N822K Advanced Solid Tumor resistant Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT N822K were resistant to treatment with Gleevec (imatinib) in culture (PMID: 24205792). 24205792
KIT N822K Advanced Solid Tumor predicted - sensitive Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT N822K were more sensitive to treatment with Flumatinib in culture compared to Gleevec (imatinib), demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT N822K Advanced Solid Tumor predicted - sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT N822K were more sensitive to treatment with Sutent (sunitinib) in culture compared to Gleevec (imatinib), demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT N822K acute myeloid leukemia predicted - sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, an acute myeloid leukemia cell line harboring KIT N822K demonstrated increased sensitivity to Sutent (sunitinib) compared to cells with wild-type KIT, resulting in increased inhibition of colony formation, and induction of cell-cycle arrest, apoptosis, and autophagy in culture (PMID: 31217744). 31217744
KIT N822K acute myeloid leukemia predicted - sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, Sutent (sunitinib) inhibited proliferation of acute myeloid leukemia cells harboring KIT N822K in culture (PMID: 31085175). 31085175
KIT N822K acute myeloid leukemia decreased response Imatinib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring KIT N822K demonstrated reduced response to growth inhibition by Gleevec (imatinib) compared to GIST cells harboring KIT exon 11 deletion in culture (PMID: 31085175). 31085175
KIT N822K acute myeloid leukemia sensitive Regorafenib Preclinical - Cell culture Actionable In a preclinical study, Stivarga (regorafenib) inhibited proliferation of acute myeloid leukemia cells harboring KIT N822K in culture (PMID: 31085175). 31085175
KIT N822K acute myeloid leukemia sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited proliferation of acute myeloid leukemia cells harboring KIT N822K in culture (PMID: 31085175). 31085175
KIT N822K hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT N822K were sensitive to treatment with Crenolanib in culture, demonstrating reduced cell survival (PMID: 31182436). 31182436
KIT N822K hematologic cancer sensitive Dasatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT N822K were sensitive to treatment with Sprycel (dasatinib) in culture, demonstrating reduced cell survival (PMID: 31182436). 31182436
KIT N822K mucosal melanoma predicted - sensitive Avapritinib Case Reports/Case Series Actionable In a clinical case study, Ayvakit (avapritinib) resulted in a partial response in extracranial lesions and stable disease in the central nervous lesions that lasted for 11 months in a patient with mucosal melanoma harboring KIT N822K (PMID: 35820244). 35820244
KIT N822K thymus squamous cell carcinoma predicted - sensitive Avapritinib Case Reports/Case Series Actionable In a clinical case study, Ayvakit (avapritinib) resulted in stable disease in a patient with thymus squamous cell carcinoma harboring KIT N822K (PMID: 35820244). 35820244
KIT N822K acute myeloid leukemia decreased response RMC-4550 Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cell lines harboring KIT N822K demonstrated decreased sensitivity to RMC-4550 treatment compared to cell lines harboring FLT3 ITD in culture (PMID: 37992684). 37992684
KIT N822K acute myeloid leukemia sensitive RMC-4550 + Venetoclax Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of RMC-4550 and Venclexta (venetoclax) synergistically inhibited viability and induced apoptosis in an acute myeloid leukemia cell line harboring KIT N822K in culture, and reduced tumor burden and improved survival in a cell line xenograft model (PMID: 37992684). 37992684
KIT N822K acute myeloid leukemia sensitive Trametinib + Venetoclax Preclinical - Cell culture Actionable In a preclinical study, the combination of Venclexta (venetoclax) and Mekinist (trametinib) synergistically inhibited proliferation in acute myeloid leukemia cell lines harboring KIT N822K in culture (PMID: 37992684). 37992684