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 FLT3
Variant D835Y
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions FLT3 D835Y lies within the protein kinase domain activation loop of the Flt3 protein (UniProt.org, PMID: 11290608). D835Y results in constitutive phosphorylation of Flt3 and activation of Stat5, Erk signaling, leading to transformation of cultured cells (PMID: 15256420, PMID: 30651561), and has been demonstrated to promote secondary drug resistance in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 22504184, PMID: 29187377).
Associated Drug Resistance Y
Category Variants Paths

FLT3 mutant FLT3 act mut FLT3 D835Y

FLT3 mutant FLT3 exon20 FLT3 D835X FLT3 D835Y

Filtering

  • Case insensitive filtering will display rows if any text in any cell matches the filter term
  • Use simple literal full or partial string matches
  • Separate multiple filter terms with a space. Any order may be used (i. e. 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 on a longer phrase with spaces (i.e. "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_004119.3
gDNA chr13:g.28018505C>A
cDNA c.2503G>T
Protein p.D835Y
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004119.2 chr13:g.28018505C>A c.2503G>T p.D835Y RefSeq GRCh38/hg38
NM_004119 chr13:g.28018505C>A c.2503G>T p.D835Y RefSeq GRCh38/hg38
NM_004119.3 chr13:g.28018505C>A c.2503G>T p.D835Y RefSeq GRCh38/hg38

Filtering

  • Case insensitive filtering will display rows if any text in any cell matches the filter term
  • Use simple literal full or partial string matches
  • Separate multiple filter terms with a space. Any order may be used (i. e. 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 on a longer phrase with spaces (i.e. "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
FLT3 D835Y Advanced Solid Tumor sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, treatment with Rydapt (midostaurin) inhibited FLT3 phosphorylation and resulted in decreased proliferation and viability of transformed cells expressing FLT3 D835Y in culture (PMID: 12124173). 12124173
FLT3 D835Y Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3 D835Y were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 D835Y leukemia sensitive E6201 Preclinical Actionable In a preclinical study, E6201 inhibited proliferation and induced apoptosis in FLT3 inhibitor-resistant leukemia cell lines over expressing FLT3 D835Y in culture (PMID: 26822154). 26822154
FLT3 D835Y acute myeloid leukemia sensitive E6201 Preclinical - Cell culture Actionable In a preclinical study, E6201 induced apoptosis in blast samples derived from acute myeloid leukemia patients harboring FLT3 D835Y in culture (PMID: 26822154). 26822154
FLT3 D835Y Advanced Solid Tumor sensitive MRX-2843 Preclinical - Cell culture Actionable In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant transformed cells over expressing FLT3 D835Y in culture (PMID: 27158668). 27158668
FLT3 D835Y acute promyelocytic leukemia predicted - sensitive Arsenic trioxide + Cytarabine + Methotrexate + Tretinoin Case Reports/Case Series Actionable In a clinical case study, a patient with acute promyelocytic leukemia harboring FLT3 D835Y demonstrated a complete molecular remission after treatment with Trisenox (arsenic trioxide) and Vesanoid (tretinoin) combined with Cytosar-U (cytarabine) and Methotrexate (PMID: 27626069). 27626069
FLT3 D835Y acute promyelocytic leukemia predicted - resistant Tretinoin Case Reports/Case Series Actionable In a clinical case study, a patient with acute promyelocytic leukemia developed meningeal relapse after maintenance therapy with Vesanoid (tretinoin), which was found to be due to a FLT3 D835Y variant (PMID: 27626069). 27626069
FLT3 D835Y hematologic cancer sensitive SKI-G-801 Preclinical - Cell culture Actionable In a preclinical study, cells expressing FLT3 D835Y were sensitive to SKI-G-801 in culture, demonstrating inhibition of cell growth and inhibition of Flt3 autophosphorylation (PMID: 24532805). 24532805
FLT3 D835Y hematologic cancer sensitive CG-806 Preclinical - Cell culture Actionable In a preclinical study, CG-806 inhibited proliferation of a cell line expressing FLT3 D835Y in culture (PMID: 35499387). 35499387
FLT3 D835Y hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib (CP-868596) decreased proliferation of transformed cells expressing FLT3 D835Y in culture (PMID: 30651561). 30651561
FLT3 D835Y hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib inhibited growth of transformed hematologic cells expressing FLT3 D835Y in culture (PMID: 31309543). 31309543
FLT3 D835Y hematologic cancer sensitive Crenolanib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Crenolanib (CP-868596) and Mekinist (trametinib) synergistically decreased proliferation of transformed cells expressing FLT3 D835Y in culture (PMID: 30651561). 30651561
FLT3 D835Y hematologic cancer sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Vanflyta (quizartinib) inhibited growth of transformed hematologic cells expressing FLT3 D835Y in culture (PMID: 31309543). 31309543
FLT3 D835Y hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited growth of transformed hematologic cells expressing FLT3 D835Y in culture (PMID: 31309543). 31309543
FLT3 D835Y hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) resulted in reduced cell viability in transformed cells expressing FLT3 D835Y in culture (PMID: 32040554). 32040554
FLT3 D835Y hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited growth of transformed hematologic cells expressing FLT3 D835Y in culture (PMID: 31309543). 31309543
FLT3 D835Y hematologic cancer resistant Sorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3 D835Y were resistant to Nexavar (sorafenib)-induced growth inhibition in culture (PMID: 31309543). 31309543
FLT3 D835Y hematologic cancer resistant Avapritinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3 D835Y were resistant to Ayvakit (avapritinib)-induced growth inhibition in culture (PMID: 31309543). 31309543
FLT3 D835Y acute myeloid leukemia predicted - sensitive LAM-003 Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived acute myeloid leukemia cells harboring FLT3 D835Y demonstrated sensitivity to LAM-003 treatment in culture (PMID: 31751472). 31751472
FLT3 D835Y hematologic cancer sensitive Palbociclib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells expressing FLT3 D835Y were sensitive to treatment with Ibrance (palbociclib), demonstrating reduced cell viability in culture and tumor growth inhibition in cell line xenograft models (PMID: 30544932). 30544932
FLT3 D835Y acute myeloid leukemia sensitive Palbociclib Preclinical - Cell culture Actionable In a preclinical study, patient-derived acute myeloid leukemia cells harboring FLT3 D835Y were sensitive to treatment with Ibrance (palbociclib) in culture, demonstrating reduced cell viability and colony formation (PMID: 30544932). 30544932
FLT3 D835Y hematologic cancer sensitive Danusertib + Palbociclib Preclinical - Cell culture Actionable In a preclinical study, the combination of Ibrance (palbociclib) and Danusertib (PHA-739358) resulted in a synergistic effect, leading to a greater decrease in cell viability of transformed cells expressing FLT3 D835Y in culture compared to either agent alone (PMID: 30544932). 30544932
FLT3 D835Y hematologic cancer sensitive Alisertib + Palbociclib Preclinical - Cell culture Actionable In a preclinical study, the combination treatment of Ibrance (palbociclib) and Alisertib (MLN8237) resulted in a synergistic effect in transformed cells expressing FLT3 D835Y, demonstrating a greater reduction in cell viability compared to either agent alone (PMID: 30544932). 30544932
FLT3 D835Y hematologic cancer sensitive Everolimus + Palbociclib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Ibrance (palbociclib) and Afinitor (everolimus) resulted in a synergistic effect in transformed cells expressing FLT3 D835Y, demonstrating a greater reduced cell viability compared to either agent alone (PMID: 30544932). 30544932
FLT3 D835Y hematologic cancer sensitive HQP1351 Preclinical - Cell culture Actionable In a preclinical study, GZD824 (HQP1351) inhibited growth of transformed cells expressing FLT3 D835Y in culture (PMID: 32247263). 32247263
FLT3 D835Y hematologic cancer sensitive Dubermatinib Preclinical - Cell culture Actionable In a preclinical study, Dubermatinib (TP-0903) inhibited growth of transformed cells expressing FLT3 D835Y in culture (PMID: 33268594). 33268594
FLT3 D835Y hematologic cancer sensitive LT-171-861 Preclinical - Cell culture Actionable In a preclinical study, LT-171-861 inhibited cell viability and decreased FLT3 phosphorylation in transformed cells expressing FLT3 D835Y in culture (PMID: 33391463). 33391463
FLT3 D835Y hematologic cancer sensitive Pacritinib Preclinical - Cell culture Actionable In a preclinical study, Vonjo (pacritinib) inhibited kinase activity and viability in a transformed cell line expressing FLT3 D835Y in culture (PMID: 31102119). 31102119