Gene Variant Detail

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Gene RET
Variant V804M
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions RET V804M lies within the protein kinase domain of the Ret protein (UniProt.org). V804M confers a gain of function on the Ret protein, resulting in increased kinase activity, cell transformation (PMID: 16469774), and is considered a gatekeeper due to lack of response to some inhibitors, including cabozantinib and vandetanib (PMID: 23811235, PMID: 27712045).
Associated Drug Resistance Y
Category Variants Paths

RET mutant RET act mut RET V804M

RET mutant RET V804X RET V804M

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Transcript NM_020975.5
gDNA chr10:g.43119548G>A
cDNA c.2410G>A
Protein p.V804M
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_020975 chr10:g.43119548G>A c.2410G>A p.V804M RefSeq GRCh38/hg38
NM_020630.5 chr10:g.43119548G>A c.2410G>A p.V804M RefSeq GRCh38/hg38
NM_020630 chr10:g.43119548G>A c.2410G>A p.V804M RefSeq GRCh38/hg38
NM_020975.5 chr10:g.43119548G>A c.2410G>A p.V804M RefSeq GRCh38/hg38

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  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET V804M Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, transformed human cell lines expressing RET V804M demonstrated sensitivity to Iclusig (ponatinib) (PMID: 23811235). 23811235
RET V804M Advanced Solid Tumor sensitive Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) inhibited RET phosphorylation and decreased growth of transformed cells expressing RET V804M in culture (PMID: 16507829). 16507829
RET V804M Advanced Solid Tumor resistant Vandetanib Preclinical Actionable In a preclinical study, transformed cells expressing RET V804M demonstrated resistance to growth inhibition by Caprelsa (vandetanib) in culture (PMID: 15184865). 15184865
RET V804M Advanced Solid Tumor predicted - sensitive Pz-1 Preclinical Actionable In a preclinical study, Pz-1 inhibited Ret phosphorylation in transformed cells expressing RET V804M (PMID: 26126987). 26126987
RET V804M thyroid gland medullary carcinoma sensitive Selpercatinib Phase I Actionable In a Phase I trial, Retevmo (selpercatinib) treatment resulted in partial response in a thyroid medullary cancer patient harboring RET V804M (J Clin Oncol 36, 2018 (suppl; abstr 102); NCT03157128). detail...
RET V804M thyroid gland medullary carcinoma sensitive Selpercatinib Case Reports/Case Series Actionable In a Phase I/II trial (LIBRETTO-001), Retevmo (selpercatinib) treatment resulted in an objective response in three patients (3/5) and stable disease in two patients (2/5) with medullary thyroid cancer harboring RET V804M or RET V804L who were previously treated (PMID: 32846061; NCT03157128). detail... 32846061
RET V804M Advanced Solid Tumor predicted - sensitive APS03118 Preclinical - Biochemical Actionable In a preclinical study, APS03118 inhibited the enzymatic activity of RET V804M in an in vitro assay, inhibited Ret phosphorylation in cells expressing RET V804M in culture, and inhibited tumor growth in cell line xenograft models expressing RET V804M (J Clin Oncol 40, no. 16_suppl (June 1, 2022)). detail...