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Gene Symbol MPL
Synonyms C-MPL | CD110 | MPLV | THCYT2 | THPOR | TPOR
Gene Description MPL, MPL proto-oncogene, 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, PMID: 31858134, PMID: 31750750).
NCBI Gene ID Chromosome Map Location Canonical Transcript Gene Role
4352 1 1p34.2 NM_005373 Oncogene (PMID: 30606230)

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
A21V missense unknown MPL A21V lies within the signal peptide region 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, Mar 2020).
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, Mar 2020).
A506G missense unknown MPL A506G lies within the cytoplasmic 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, Mar 2020).
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, Mar 2020).
act mut unknown gain of function MPL act mut indicates that this variant results in a gain of function in the Mpl protein. However, the specific amino acid change has not been identified.
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).
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, Mar 2020).
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.
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, Jul 2020).
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, Jul 2020).
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, Mar 2020).
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, Mar 2020).
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, Mar 2020).
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, Mar 2020).
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, Mar 2020).
inact mut unknown loss of function MPL inact mut indicates that this variant results in a loss of function of the Mpl protein. However, the specific amino acid change has not been identified.
K39N missense loss of function - predicted MPL K39N lies within the extracellular domain 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).
L109H missense unknown MPL L109H lies within the extracellular domain of the Mpl protein (UniProt.org). L109H has been identified in sequencing studies (PMID: 24121792), but has not been biochemically characterized and therefore, its effect on Mpl protein function is unknown (PubMed, Mar 2020).
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, Mar 2020).
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 2020).
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 2020).
L498V missense unknown MPL L498V lies within the transmembrane domain of the Mpl protein (UniProt.org). L498V has not been characterized and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2020).
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, Jul 2020).
mutant unknown unknown MPL mutant indicates an unspecified mutation in the MPL gene.
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.
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).
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 2020).
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 2020).
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 2020).
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 2020).
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 2020).
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 2020).
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 2020).
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 2020).
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 2020).
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 2020).
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).
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 2020).
R321Q missense unknown MPL R321Q lies within the extracellular domain of the Mpl protein (UniProt.org). R321Q has been identified in sequencing studies (PMID: 30214228, PMID: 26423830, PMID: 28466600), but has not been biochemically characterized and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2020).
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).
R357Q missense unknown MPL R357Q lies within the extracellular domain of the Mpl protein (UniProt.org). R357Q has been identified in sequencing studies (PMID: 25589618), but has not been biochemically characterized and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2020).
R390C missense unknown MPL R390C lies within the fibronectin type-III domain 2 of the Mpl protein (UniProt.org). R390C has been identified in sequencing studies (PMID: 24755471, PMID: 31555481), but has not been biochemically characterized and therefore, its effect on Mpl protein function is unknown (PubMed, Mar 2020).
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 2020).
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 2020).
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 2020).
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 2020).
R75H missense unknown MPL R75H lies within the extracellular domain of the Mpl protein (UniProt.org). R75H has been identified in sequencing studies (PMID: 27997549), but has not been biochemically characterized and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2020).
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 2020).
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).
S204P missense gain of function - predicted MPL S204P lies within the fibronectin type-III domain 1 of the Mpl protein (UniProt.org). S204P is not transforming and does not promote cell proliferation, but results in ligand-independent activation of Jak-Stat signaling in cell culture (PMID: 26423830, PMID: 26450985), and therefore, is predicted to lead to a gain of Mpl protein function.
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.
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 2020).
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).
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 2020).
S557* nonsense unknown MPL S557* results in a premature truncation of the Mpl protein at amino acid 557 of 635 (UniProt.org). S557* 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 2020).
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 2020).
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).
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 2020).
T487A missense gain of function MPL T487A lies within the extracellular domain 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).
T487V missense unknown MPL T487V lies within the extracellular domain of the Mpl protein (UniProt.org). T487V is not transforming in cell culture (PMID: 18755984), but has not been fully biochemically characterized and therefore, its effect on Mpl protein function is unknown (PubMed, Mar 2020).
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 2020).
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.
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).
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 2020).
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 2020).
V92M missense unknown MPL V92M lies within the extracellular domain of the Mpl protein (UniProt.org). V92M has been identified in sequencing studies (PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Mpl protein function is unknown (PubMed, Apr 2020).
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 2020).
W4R missense unknown MPL W4R lies within the signal peptide region 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 2020).
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).
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.
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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.
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).
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).
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).
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).
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).
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).
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.
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).
wild-type none no effect Wild-type MPL indicates that no mutation has been detected within the MPL gene.
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).
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).
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).