Gene Variant Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Gene RET
Variant Y791F
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions RET Y791F lies within the protein kinase domain of the Ret protein (UniProt.org). Y791F confers a gain of function on the Ret protein, resulting in ligand independent kinase activity and activation of Stat3 signaling through Src, Jak1, and Jak2-dependent pathways in cell culture (PMID: 15753368).
Associated Drug Resistance

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • 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"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Transcript NM_020975
gDNA chr10:g.43118460A>T
cDNA c.2372A>T
Protein p.Y791F
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_020975 chr10:g.43118460A>T c.2372A>T p.Y791F RefSeq GRCh38/hg38
NM_020630 chr10:g.43118460A>T c.2372A>T p.Y791F RefSeq GRCh38/hg38

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • 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"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET Y791F Advanced Solid Tumor sensitive Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited Ret autophosphorylation in transformed cells expressing RET Y791F in culture (PMID: 15184865). 15184865
RET Y791F Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) inhibited phosphorylation of Ret in transformed human cells expressing RET Y971F in culture (PMID: 23526464). 23526464
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET act mut lung non-small cell carcinoma sensitive Ponatinib Preclinical - Cell culture Actionable In a preclinical study, Iclusig (ponatinib) inhibited RET phosphorylation and reduced viability of non-small cell lung cancer cells with RET activating mutations (Cancer Res April 15, 2013 73; 2084). detail...
RET mutant colorectal cancer sensitive Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) demonstrated efficacy in RET mutant positive colorectal cancer cell lines (PMID: 23811235). 23811235
RET mutant cancer sensitive Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) inhibited wild-type RET and RET mutations to prevent cell proliferation in cell culture (PMID: 17664273). 17664273
RET mutant Advanced Solid Tumor sensitive Ponatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Iclusig (ponatinib) inhibited proliferation of cancer cell lines harboring RET mutations in cultured and in cell line xenograft models (PMID: 23526464). 23526464
RET mutant thyroid gland medullary carcinoma sensitive Selpercatinib Phase I Actionable In a Phase I trial, Retevmo (selpercatinib) treatment resulted in partial response in 14% (2/14) and tumor reduction in 79% (11/14) of RET mutant thyroid medullary cancer patients (J Clin Oncol 36, 2018 (suppl; abstr 102); NCT03157128). detail...
RET mutant thyroid gland medullary carcinoma sensitive Selpercatinib FDA approved Actionable In a Phase I/II trial (LIBRETTO-001) that supported FDA approval, Retevmo (selpercatinib) treatment resulted in an objective response rate of 56% (31/55) in adult and pediatric patients of 12 years and older with medullary thyroid cancer harboring RET mutations (Ann Oncol, Oct 2019, 30 (Suppl 5): v933, Abstract LBA93; NCT03157128). detail... detail...
RET mutant thyroid gland medullary carcinoma sensitive Everolimus Phase II Actionable In a Phase II clinical trial, Afinitor (everolimus) treatment resulted in stable disease in 71% (5/7) of medullary thyroid cancer patients, including patients harboring RET mutations, with median progression-free survival of 33 weeks (PMID: 26294908). 26294908
RET mutant thyroid gland medullary carcinoma sensitive Cabozantinib Phase III Actionable In a Phase III trial, Cometriq (cabozantinib) treatment resulted in improved progression free survival (60 vs 20 weeks) compared to placebo in thyroid medullary carcinoma patients harboring RET mutations (PMID: 27525386). 27525386
RET Y791X thyroid gland medullary carcinoma not applicable N/A Guideline Risk Factor Germline RET Y791X mutations result in multiple endocrine neoplasia, type 2A (MEN 2A), which is associated with increased risk of developing thyroid medullary carcinoma (NCCN.org). detail...
Molecular Profile Protein Effect Treatment Approaches
RET Y791F gain of function RET Inhibitor