Gene Variant Detail

Gene MPL
Variant W515L
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions MPL W515L lies within the cytoplasmic domain of the Mpl protein (UniProt.org). MPL W515L confers a gain of function to the Mpl protein, as demonstrated by constitutive activation of JAK/STAT signaling to promote cytokine-independent proliferation of hematopoietic cells (PMID: 16834459, PMID: 18528423) and induces tumor formation in mice (PMID: 18528423).
Associated Drug Resistance

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Transcript NM_005373
gDNA chr1:g.43349338G>T
cDNA c.1544G>T
Protein p.W515L
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_005373 chr1:g.43349338G>T c.1544G>T p.W515L 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"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
MPL W515L Advanced Solid Tumor sensitive Pictilisib + Ruxolitinib Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) and Pictilisib (GDC-0941) synergistically inhibited growth of transformed cell lines over expressing MPL W515L in cell culture (PMID: 24251790). 24251790
MPL W515L myelofibrosis sensitive Everolimus Phase II Actionable In a phase II study of patients with myelofibrosis, 2/2 patients with MPL W515L/K had tumor response to everolimus, with one patient displaying clinical benefit (PMID: 21725052). 21725052
MPL W515L Advanced Solid Tumor sensitive BEZ235 + Ruxolitinib Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) and BEZ235 synergistically inhibited growth of transformed cell lines over expressing MPL W515L in cell culture (PMID: 24251790). 24251790
MPL W515L myeloproliferative neoplasm sensitive BMS-911543 Preclinical - Cell culture Actionable In a preclinical study, BMS-911543 inhibited colony growth in myeloproliferative neoplasm patient-derived hematopoetic progenitor cells harboring MPL W515L in culture (PMID: 22015772). 22015772
MPL W515L Advanced Solid Tumor sensitive Ruxolitinib + TGX-221 Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) and TGX-221 synergistically inhibited growth of transformed cell lines over expressing MPL W515L in cell culture (PMID: 24251790). 24251790
MPL W515L hematologic cancer sensitive CHZ868 Preclinical Actionable In a preclinical study, CHZ868 inhibited proliferation of bone marrow cell lines expressing MPL W515L in culture, including cells with decreased response to Type I JAK inhibitors due to chronic exposure (PMID: 26175413). 26175413
MPL W515L myelofibrosis not applicable N/A Guideline Prognostic MPL W515L is associated with intermediate prognosis and higher risk of thrombosis when compared to the presence of CALR mutations in patients with primary myelofibrosis (NCCN.org). detail...
MPL W515L hematologic cancer sensitive BMS-911543 Preclinical - Cell culture Actionable In a preclinical study, BMS-911543 inhibited proliferation of transformed cells expressing MPL W515L in culture (PMID: 22015772). 22015772
MPL W515L myelofibrosis sensitive MK2206 Preclinical Actionable In a preclinical study, MK2206 treatment reduced disease burden in MPL W515L transduced mouse models of myelofibrosis (PMID: 23748344). 23748344
MPL W515L myelofibrosis sensitive CHZ868 Preclinical Actionable In a preclinical study, CHZ868 demonstrated efficacy in a mouse model of MPL W515L induced myelofibrosis (PMID: 26175413). 26175413
MPL W515L hematologic cancer sensitive NS-018 Preclinical - Cell culture Actionable In a preclinical study, cells expressing MPL W515L were sensitive to treatment with NS-108, demonstrating inhibition of cell growth in culture (PMID: 22829185). 22829185
MPL W515L Advanced Solid Tumor sensitive Ruxolitinib + ZSTK474 Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) and ZSTK474 synergistically inhibited growth of transformed cell lines over expressing MPL W515L in cell culture (PMID: 24251790). 24251790