Gene Detail

Gene Symbol MPL
Synonyms C-MPL | CD110 | MPLV | THCYT2 | TPOR
Gene Description MPL, thrombopoietin receptor, binds the cytokine, thrombopoietin, to induce signaling of JAK2 and TYK2 to activate several signal transduction pathways to control blood cell development (PMID: 16834459, PMID: 28408900). MPL mutations are often found in myeloproliferative neoplasms (PMID: 27727468).
Entrez Id 4352
Chromosome 1
Map Location 1p34.2
Canonical Transcript NM_005373

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
W515M missense gain of function - predicted MPL W515M lies within the cytoplasmic domain of the Mpl protein (UniProt.org). W515M is predicted to confer a gain of function to Mpl protein as indicated by ligand-independent activation of Jak-Stat signaling in cell culture (PMID: 26437785).
A21V missense unknown MPL A21V lies within the signal peptide of the Mpl protein (UniProt.org). A21V has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
R390C missense unknown MPL R390C lies within the extracellular domain of the Mpl protein (UniProt.org). R390C has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
R75H missense unknown MPL R75H lies within the extracellular domain of the Mpl protein (UniProt.org). R75H has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
V92M missense unknown MPL V92M lies within the extracellular domain of the Mpl protein (UniProt.org). V92M has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
W4R missense unknown MPL W4R lies within the signal peptide of the Mpl protein (UniProt.org). W4R has been identified in sequencing studies (PMID: 25801912), but has not been biochemically characterized and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
Y591D missense gain of function MPL Y591D lies within the cytoplasmic domain of the Mpl protein (UniProt.org). Y591D confers a gain of function to the Mpl protein as indicated by ligand-independent activation of Jak-Stat signaling and growth advantage in cell culture (PMID: 26423830).
R90Q missense unknown MPL R90Q lies within the extracellular domain of the Mpl protein (UniProt.org). R90Q has been identified in sequencing studies (PMID: 26214590), but has not been biochemically characterized and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
R102P missense loss of function MPL R102P lies within the Tpo-binding domain of the Mpl protein (PMID: 18422784). R102P confers a loss of function to the Mpl protein as indicated by decreased Mpl downstream STAT and PI3K/Akt signaling as compared to wild-type (PMID: 18422784, PMID: 25538044).
T487A missense gain of function MPL T487A does not lie within any known functional domains of the Mpl protein (UniProt.org). T487A results in activation of Mpl signaling as indicated by increased phosphorylation of Stat5, Erk1/2, and Akt, and is transforming in culture (PMID: 18755984).
L109H missense unknown MPL L109H lies within the extracellular domain of the Mpl protein (UniProt.org). L109H has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
R592* nonsense unknown MPL R592* results in a premature truncation of the Mpl protein at amino acid 592 of 635 (UniProt.org). R592* has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
R321W missense gain of function - predicted MPL R321W lies within the extracellular domain of the Mpl protein (UniProt.org). R321W is predicted to confer a gain of function to Mpl protein as indicated by ligand-independent activation of Jak-Stat signaling in cell culture (PMID: 26423830).
V114M missense no effect - predicted MPL V114M lies within the extracellular domain of the Mpl protein (UniProt.org). V114M has been described as non-pathogenic and demonstrates levels of Mpl receptor expression and TPO ligand-dependent proliferation similar to wild-type (PMID: 16219544) and therefore is predicted to have no effect on Mpl protein function.
V285L missense unknown MPL V285L lies within the extracellular domain of the Mpl protein (UniProt.org). V285L has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
P106L missense gain of function MPL P106L lies within the extracellular domain of the Mpl protein (UniProt.org). P106L results in constitutive activation of Mpl and ligand-independent growth of cells in culture (PMID: 25538044).
W515_F517del deletion no effect - predicted MPL W515_F517del results in the deletion of three amino acids in the cytoplasmic domain of the Mpl protein from amino acids 515 to 517 (UniProt.org). W515_F517del demonstrates activation of Jak-Stat signaling to similar level of wild-type Mpl protein in cell culture (PMID: 26437785) and therefore, is predicted to have no effect on Mpl protein function.
A554T missense unknown MPL A554T lies within the cytoplasmic domain of the Mpl protein (UniProt.org). A554T has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
S566N missense unknown MPL S566N lies within the cytoplasmic domain of the Mpl protein (UniProt.org). S566N has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
F126fs frameshift loss of function - predicted MPL F126fs results in a change in the amino acid sequence of the Mpl protein beginning at aa 126 of 635, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of all known functional domains (UniProt.org), F126fs is predicted to lead to a loss of Mpl protein function.
L406V missense unknown MPL L406V lies within the fibronectin type-III domain 2 of the Mpl protein (UniProt.org). L406V has been identified in sequencing studies (PMID: 22675565), but has not been biochemically characterized and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
P248L missense unknown MPL P248L lies within the Fibronectin type-III domain 1 of the Mpl protein (UniProt.org). P248L has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
G238D missense unknown MPL G238D lies within the fibronectin type-III domain 1 of the Mpl protein (UniProt.org). G238D has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Mpl protein function is unknown (PubMed, Sep 2018).
W515E missense gain of function - predicted MPL W515E lies within the cytoplasmic domain of the Mpl protein (UniProt.org). W515E is predicted to confer a gain of function to Mpl protein as indicated by ligand-independent activation of Jak-Stat signaling in cell culture (PMID: 26437785).
S557* nonsense unknown MPL S557* results in a premature truncation of the Mpl protein at amino acid 557 of 635 (UniProt.org). S557* has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
P195H missense unknown MPL P195H lies within the fibronectin type-III domain 1 of the Mpl protein (UniProt.org). P195H has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
T180S missense unknown MPL T180S lies within the fibronectin type-III domain 1 of the Mpl protein (UniProt.org). T180S has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
R71W missense unknown MPL R71W lies within the extracellular domain of the Mpl protein (UniProt.org). R71W has been identified in sequencing studies (PMID: 21798897), but has not been biochemically characterized and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
P200T missense unknown MPL P200T lies within the fibronectin type-III domain 1 of the Mpl protein (UniProt.org). P200T has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
W515K missense gain of function MPL W515K lies within the cytoplasmic domain of the Mpl protein (UniProt.org). W515K results in activation of Mpl signaling as indicated by constitutive activation of Jak/Stat, Ras/Mapk, and Pi3k signaling (PMID: 26450985), is transforming in cell culture (PMID: 18528423, PMID: 26437785), and induces tumor formation in mice (PMID: 18528423).
W515Q missense gain of function - predicted MPL W515Q lies within the cytoplasmic domain of the Mpl protein (UniProt.org). W515Q is predicted to confer a gain of function to Mpl protein as indicated by ligand-independent activation of Jak-Stat signaling in cell culture (PMID: 26437785).
G600E missense unknown MPL G600E lies within the cytoplasmic domain of the Mpl protein (UniProt.org). G600E has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
L498V missense unknown MPL L498V lies within the transmembrane domain of the Mpl protein (UniProt.org). L498V has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
P324H missense unknown MPL P324H lies within the extracellular domain of the Mpl protein (UniProt.org). P324H has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
over exp none no effect MPL over exp indicates an over expression of the Mpl protein. However, the mechanism causing the over expression is unspecified.
W515R missense gain of function - predicted MPL W515R lies within the cytoplasmic domain of the Mpl protein (UniProt.org). W515R is predicted to confer a gain of function to Mpl protein as indicated by ligand-independent activation of Jak-Stat signaling in cell culture (PMID: 26437785).
W515H missense gain of function - predicted MPL W515H lies within the cytoplasmic domain of the Mpl protein (UniProt.org). W515H is predicted to confer a gain of function to Mpl protein as indicated by ligand-independent activation of Jak-Stat signaling in cell culture (PMID: 26437785).
W515Y missense gain of function MPL W515Y lies within the cytoplasmic domain of the Mpl protein (UniProt.org). W515Y confers a gain of function to Mpl protein as indicated by ligand-independent activation of Jak-Stat signaling in cell culture (PMID: 26437785, PMID: 23359689).
W515A missense gain of function MPL W515A lies within the cytoplasmic domain of the Mpl protein (UniProt.org). W515A confers a gain of function to Mpl protein as indicated by ligand-independent activation of Jak-Stat signaling in cell culture (PMID: 26437785) and induces ligand-independent cell proliferation in cell culture (PMID: 19996410).
K39N missense loss of function - predicted MPL K39N does not lie within any known functional domains of the Mpl protein (UniProt.org). K39N may confer a loss of function to the Mpl protein as indicated by incomplete processing, resulting in decreased protein levels (PMID: 15269348).
L571fs frameshift unknown MPL L571fs results in a change in the amino acid sequence of the Mpl protein beginning at aa 571 of 635, likely resulting in premature truncation of the functional protein (UniProt.org). L571fs has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Sep 2018).
W515V missense gain of function - predicted MPL W515V lies within the cytoplasmic domain of the Mpl protein (UniProt.org). W515V is predicted to confer a gain of function to Mpl protein as indicated by ligand-independent activation of Jak-Stat signaling in cell culture (PMID: 26437785).
L48I missense unknown MPL L48I lies within the extracellular domain of the Mpl protein (UniProt.org). L48I has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
R170C missense unknown MPL R170C lies within the extracellular domain of the Mpl protein (UniProt.org). R170C has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
W253R missense unknown MPL W253R lies within the fibronectin type-III domain 1 of the Mpl protein (UniProt.org). W253R has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
H620fs frameshift unknown MPL H620fs results in a change in the amino acid sequence of the Mpl protein at aa 620 of 635, likely resulting in premature truncation of the functional protein (UniProt.org). H620fs has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
S204P missense unknown MPL S204P lies within the fibronectin type-III domain 1 of the Mpl protein (UniProt.org). The functional effect of S204P is conflicting, as S204P has been reported to confer a gain of function as demonstrated by ligand-independent activation of Jak-Stat signaling in cell culture (PMID: 26423830, PMID: 26450985), but does not induce cell proliferation, has cellular localization similar to wild-type and normal sensitivity to the ligand, Tpo (PMID: 26450985).
F517_P518insYIV insertion unknown MPL F517_P518insYIV results in the insertion of three amino acids in the Mpl protein between amino acids 517 and 518 (UniProt.org). F517_P518insYIV has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Sep 2018).
W515T missense gain of function - predicted MPL W515T lies within the cytoplasmic domain of the Mpl protein (UniProt.org). W515T is predicted to confer a gain of function to Mpl protein as indicated by ligand-independent activation of Jak-Stat signaling in cell culture (PMID: 26437785).
S42Y missense unknown MPL S42Y lies within the extracellular domain of the Mpl protein (UniProt.org). S42Y has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
W515P missense no effect - predicted MPL W515P lies within the cytoplasmic domain of the Mpl protein (UniProt.org). W515P demonstrates activation of Jak-Stat signaling to similar level of wild-type Mpl protein in cell culture (PMID: 26437785) and therefore, is predicted to have no effect on Mpl protein function.
Y591F missense gain of function - predicted MPL Y591F lies within the cytoplasmic domain of the Mpl protein (UniProt.org). Y591F is predicted to confer a gain of function to the Mpl protein, as demonstrated by increased Erk signaling upon ligand stimulation, as compared to wild-type Mpl in cell culture (PMID: 24607955).
G282E missense unknown MPL G282E lies within the extracellular domain of the Mpl protein (UniProt.org). G282E has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
Y591N missense gain of function MPL Y591N lies within the cytoplasmic domain of the Mpl protein (UniProt.org). Y591N confers a gain of function to the Mpl protein as demonstrated by constitutive phosphorylation of STAT3, STAT5, and ERK and is transforming in the presence of the ligand, Tpo, in cell culture (PMID: 26450985).
W515F missense gain of function MPL W515F lies within the cytoplasmic domain of the Mpl protein (UniProt.org). W515F confers a gain of function to Mpl protein as indicated by ligand-independent activation of Jak-Stat signaling in cell culture (PMID: 26437785, PMID: 23359689).
E230G missense gain of function - predicted MPL E230G lies within the Fibronectin type-III domain 1 of the Mpl protein (UniProt.org). E230G is predicted to confer a gain of function to Mpl protein as indicated by ligand-independent activation of Jak-Stat signaling in cell culture (PMID: 26423830).
W515G missense gain of function - predicted MPL W515G lies within the cytoplasmic domain of the Mpl protein (UniProt.org). W515G is predicted to confer a gain of function to Mpl protein as indicated by ligand-independent activation of Jak-Stat signaling in cell culture (PMID: 26437785).
W515N missense gain of function - predicted MPL W515N lies within the cytoplasmic domain of the Mpl protein (UniProt.org). W515N is predicted to confer a gain of function to Mpl protein as indicated by ligand-independent activation of Jak-Stat signaling in cell culture (PMID: 26437785).
wild-type none no effect Wild-type MPL indicates that no mutation has been detected within the MPL gene.
S204F missense gain of function - predicted MPL S204F lies within the Fibronectin type-III domain 1 of the Mpl protein (UniProt.org). S204F is predicted to confer a gain of function to Mpl protein as indicated by ligand-independent activation of Jak-Stat signaling in cell culture (PMID: 26423830).
V501M missense unknown MPL V501M lies within the transmembrane domain of the Mpl protein (UniProt.org). V501M has been identified in the scientific literature (PMID: 23994117), but has not been biochemically characterized and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
W515D missense gain of function - predicted MPL W515D lies within the cytoplasmic domain of the Mpl protein (UniProt.org). W515D is predicted to confer a gain of function to Mpl protein as indicated by ligand-independent activation of Jak-Stat signaling in cell culture (PMID: 26437785).
L31R missense unknown MPL L31R lies within the extracellular domain of the Mpl protein (UniProt.org). L31R has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
A286S missense unknown MPL A286S lies within the extracellular domain of the Mpl protein (UniProt.org). A286S has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
P159T missense unknown MPL P159T lies within the extracellular domain of the Mpl protein (UniProt.org). P159T has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
V285E missense gain of function - predicted MPL V285E lies within the extracellular domain of the Mpl protein (UniProt.org). V285E is predicted to confer a gain of function to Mpl protein as indicated by ligand-independent activation of Jak-Stat signaling in cell culture (PMID: 26423830).
W515L missense gain of function 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).
S505N missense gain of function MPL S505N lies within the transmembrane domain of the Mpl protein (UniProt.org). S505N results in activation of Mpl signaling as indicated by constitutive phosphorylation of Mek1/2 and Stat5b, and is transforming in cell culture (PMID: 14764528, PMID: 26437785).
W515_P518del deletion gain of function - predicted MPL W515_P518del results in the deletion of four amino acids in the cytoplasmic domain of the Mpl protein from amino acids 515 to 518 (UniProt.org). W515_P518del is predicted to confer a gain of function to Mpl protein as indicated by ligand-independent activation of Jak-Stat signaling in cell culture (PMID: 26437785).
P551L missense unknown MPL P551L lies within the cytoplasmic domain of the Mpl protein (UniProt.org). P551L has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
E338D missense unknown MPL E338D lies within the extracellular domain of the Mpl protein (UniProt.org). E338D has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
T487V missense unknown MPL T487V lies within the extracellular domain of the Mpl protein (UniProt.org). T487V has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Sep 2018).
S550N missense unknown MPL S550N lies within the cytoplasmic domain of the Mpl protein (UniProt.org). S550N has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
W515C missense no effect MPL W515C lies within the cytoplasmic domain of the Mpl protein (UniProt.org). W515C demonstrates activation of Jak-Stat signaling and cell viability to similar levels of wild-type Mpl protein in cell culture (PMID: 26437785) and therefore, has no effect on Mpl protein function.
A506G missense unknown MPL A506G lies within the transmembrane domain of the Mpl protein (UniProt.org). A506G has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
P551Q missense unknown MPL P551Q lies within the cytoplasmic domain of the Mpl protein (UniProt.org). P551Q has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
H624D missense unknown MPL H624D lies within the cytoplasmic domain of the Mpl protein (UniProt.org). H624D has been identified in sequencing studies (PMID: 27276561), but has not been biochemically characterized and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
P85S missense unknown MPL P85S lies within the extracellular domain of the Mpl protein (UniProt.org). P85S has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
T119I missense gain of function - predicted MPL T119I lies within the extracellular domain of the Mpl protein (UniProt.org). T119I is predicted to confer a gain of function to Mpl protein as indicated by ligand-independent activation of Jak-Stat signaling in cell culture (PMID: 26423830).
P217S missense unknown MPL P217S lies within the fibronectin type-III domain 1 of the Mpl protein (UniProt.org). P217S has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
S232* nonsense loss of function - predicted MPL S232* results in a premature truncation of the Mpl protein at amino acid 232 of 635 (UniProt.org). Due to the loss of the transmembrane and cytoplasmic domains (UniProt.org), S232* is predicted to lead to a loss of Mpl protein function.
G429E missense unknown MPL G429E lies within the fibronectin type-III domain 2 of the Mpl protein (UniProt.org). G429E has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
W515S missense gain of function - predicted MPL W515S lies within the cytoplasmic domain of the Mpl protein (UniProt.org). W515S is predicted to confer a gain of function to Mpl protein as indicated by ligand-independent activation of Jak-Stat signaling in cell culture (PMID: 26437785).
R321Q missense unknown MPL R321Q lies within the extracellular domain of the Mpl protein (UniProt.org). R321Q has been identified in sequencing studies (PMID: 26423830), but has not been biochemically characterized and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
R357Q missense unknown MPL R357Q lies within the extracellular domain of the Mpl protein (UniProt.org). R357Q has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
W515I missense gain of function - predicted MPL W515I lies within the cytoplasmic domain of the Mpl protein (UniProt.org). W515I is predicted to confer a gain of function to Mpl protein as indicated by ligand-independent activation of Jak-Stat signaling in cell culture (PMID: 26437785).
R593I missense unknown MPL R593I lies within the cytoplasmic domain of the Mpl protein (UniProt.org). R593I has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
P347T missense unknown MPL P347T lies within the extracellular domain of the Mpl protein (UniProt.org). P347T has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
R514L missense unknown MPL R514K lies within the cytoplasmic domain of the Mpl protein (UniProt.org). MPL R514K has not been characterized in the scientific literature and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
T601A missense unknown MPL T601A lies within the cytoplasmic domain of the Mpl protein (UniProt.org). T601A has been identified in sequencing studies (PMID: 22941188), but has not been biochemically characterized and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2018).
Molecular Profile Protein Effect Treatment Approaches
MPL W515M gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
MPL A21V unknown
MPL R390C unknown
MPL R75H unknown
MPL V92M unknown
MPL W4R unknown
MPL Y591D gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
MPL R90Q unknown
MPL R102P loss of function
MPL T487A gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
MPL L109H unknown
MPL R592* unknown
MPL R321W gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
MPL V114M no effect - predicted
MPL V285L unknown
MPL P106L gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
MPL W515_F517del no effect - predicted
MPL A554T unknown
MPL S566N unknown
MPL F126fs loss of function - predicted
MPL L406V unknown
MPL P248L unknown
MPL G238D unknown
MPL W515E gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
MPL S557* unknown
MPL P195H unknown
MPL T180S unknown
MPL R71W unknown
MPL P200T unknown
MPL W515K gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
MPL W515Q gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
MPL G600E unknown
MPL L498V unknown
MPL P324H unknown
MPL over exp no effect
JAK2 over exp MPL over exp
MPL W515R gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
MPL W515H gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
MPL W515Y gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
MPL W515A gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
MPL K39N loss of function - predicted
MPL L571fs unknown
MPL W515V gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
MPL L48I unknown
MPL R170C unknown
MPL W253R unknown
MPL H620fs unknown
MPL S204P unknown JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
MPL F517_P518insYIV unknown
MPL W515T gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
MPL S42Y unknown
MPL W515P no effect - predicted
MPL Y591F gain of function - predicted
MPL G282E unknown
MPL Y591N gain of function
MPL W515F gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
MPL E230G gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
MPL W515G gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
MPL W515N gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
CALR wild-type JAK2 wild-type MPL wild-type
MPL wild-type no effect
JAK2 V617F MPL wild-type
MPL S204F gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
MPL V501M unknown
MPL W515D gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
MPL L31R unknown
MPL A286S unknown
MPL P159T unknown
MPL V285E gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
MPL W515L gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive MK2206
MPL S505N gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
MPL W515_P518del gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
MPL P551L unknown
MPL E338D unknown
MPL T487V unknown
MPL S550N unknown
MPL W515C no effect
MPL A506G unknown
MPL P551Q unknown
MPL H624D unknown
MPL P85S unknown
MPL T119I gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
MPL P217S unknown
MPL S232* loss of function - predicted
MPL G429E unknown
MPL W515S gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
MPL R321Q unknown
MPL R357Q unknown
MPL W515I gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
MPL R593I unknown
MPL P347T unknown
MPL R514L unknown
MPL T601A unknown
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
MPL W515K myelofibrosis not applicable N/A Guideline Prognostic MPL W515K 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 W515K 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
JAK2 over exp MPL over exp 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 wild-type Mpl and Jak2 in cell culture (PMID: 24251790). 24251790
JAK2 over exp MPL over exp 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 wild-type Mpl and Jak2 in cell culture (PMID: 24251790). 24251790
JAK2 over exp MPL over exp 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 wild-type Mpl and Jak2 in cell culture (PMID: 24251790). 24251790
JAK2 over exp MPL over exp 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 wild-type Mpl and Jak2 in cell culture (PMID: 24251790). 24251790
CALR wild-type JAK2 wild-type MPL wild-type myelofibrosis not applicable N/A Guideline Prognostic The presence of concurrent wild-type JAK2, MPL, and CALR in myelofibrosis patients is associated with inferior leukemia-free survival compared to patients with JAK2 and/or CALR mutations, and is associated with inferior overall survival when compared to patients with CALR mutations (NCCN.org). detail...
JAK2 V617F MPL wild-type 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 wild-type Mpl and JAK2 V617F in cell culture (PMID: 24251790). 24251790
JAK2 V617F MPL wild-type 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 wild-type Mpl and JAK2 V617F in cell culture (PMID: 24251790). 24251790
JAK2 V617F MPL wild-type 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 wild-type Mpl and JAK2 V617F in cell culture (PMID: 24251790). 24251790
JAK2 V617F MPL wild-type 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 wild-type Mpl and JAK2 V617F in cell culture (PMID: 24251790). 24251790
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 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 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 + 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
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 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 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 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 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 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 hematologic cancer sensitive NS-108 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 myelofibrosis sensitive CHZ868 Preclinical Actionable In a preclinical study, CHZ868 demonstrated efficacy in a mouse model of MPL W515L induced myelofibrosis (PMID: 26175413). 26175413