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Gene | KIT |
Variant | K642E |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | KIT K642E lies within the tyrosine kinase domain 1 (exon 13) of the Kit protein (PMID: 15990278). K642E results in constitutive phosphorylation of Kit and activation of downstream signaling (PMID: 15990278, PMID: 19802003), as well as transformation of cultured cells (PMID: 11073817). |
Associated Drug Resistance | |
Category Variants Paths |
KIT mutant KIT act mut KIT K642E KIT mutant KIT exon13 KIT K642E |
Transcript | NM_000222.3 |
gDNA | chr4:g.54728055A>G |
cDNA | c.1924A>G |
Protein | p.K642E |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_000222.3 | chr4:g.54728055A>G | c.1924A>G | p.K642E | RefSeq | GRCh38/hg38 |
NM_000222.2 | chr4:g.54728055A>G | c.1924A>G | p.K642E | RefSeq | GRCh38/hg38 |
XM_017008178.1 | chr4:g.54728055A>G | c.1924A>G | p.K642E | RefSeq | GRCh38/hg38 |
NM_000222 | chr4:g.54728055A>G | c.1924A>G | p.K642E | RefSeq | GRCh38/hg38 |
XM_017008178 | chr4:g.54728055A>G | c.1924A>G | p.K642E | RefSeq | GRCh38/hg38 |
NM_001385285.1 | chr4:g.54728055A>G | c.1924A>G | p.K642E | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
KIT K642E KIT C809G KIT N822H | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, an acquired KIT C809G mutation was identified in a gastrointestinal stromal tumor (GIST) patient harboring KIT K642E and KIT N822H at the time of progression on Gleevec (imatinib) (PMID: 16954519). | 16954519 |
KIT K642E KIT N822K | 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 K642E and KIT N822K (PMID: 32350132). | 32350132 |
KIT K642E KIT N822K | gastrointestinal stromal tumor | sensitive | Regorafenib | Preclinical - Pdx | Actionable | In a preclinical study, Stivarga (regorafenib) suppressed tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT K642E and KIT N822K, but was less potent in comparison to treatment with AZD3229 (PMID: 32350132). | 32350132 |
KIT K642E KIT N822Y | gastrointestinal stromal tumor | predicted - resistant | Ripretinib | Case Reports/Case Series | Actionable | In a retrospective study, a patient with a gastrointestinal stromal tumor harboring KIT N822Y progressed on sixth-line treatment with Qinlock (ripretinib) after 7.3 months and was found to have acquired KIT K642E in the metastatic lesion (PMID: 38408285). | 38408285 |