Gene: MPL

Alternate names for this Gene: C-MPL|CD110|MPLV|THCYT2|THPOR|TPOR

Gene Summary: In 1990 an oncogene, v-mpl, was identified from the murine myeloproliferative leukemia virus that was capable of immortalizing bone marrow hematopoietic cells from different lineages. In 1992 the human homologue, named, c-mpl, was cloned. Sequence data revealed that c-mpl encoded a protein that was homologous with members of the hematopoietic receptor superfamily. Presence of anti-sense oligodeoxynucleotides of c-mpl inhibited megakaryocyte colony formation. The ligand for c-mpl, thrombopoietin, was cloned in 1994. Thrombopoietin was shown to be the major regulator of megakaryocytopoiesis and platelet formation. The protein encoded by the c-mpl gene, CD110, is a 635 amino acid transmembrane domain, with two extracellular cytokine receptor domains and two intracellular cytokine receptor box motifs . TPO-R deficient mice were severely thrombocytopenic, emphasizing the important role of CD110 and thrombopoietin in megakaryocyte and platelet formation. Upon binding of thrombopoietin CD110 is dimerized and the JAK family of non-receptor tyrosine kinases, as well as the STAT family, the MAPK family, the adaptor protein Shc and the receptors themselves become tyrosine phosphorylated.

Gene is located in Chromosome: 1

Location in Chromosome : 1p34.2

Description of this Gene: MPL proto-oncogene, thrombopoietin receptor

Type of Gene: protein-coding

rs1057519752 in MPL gene and Chronic myeloproliferative disorder PMID 21228032 2011 Deep sequencing reveals double mutations in cis of MPL exon 10 in myeloproliferative neoplasms.

PMID 23970983 2013 The diagnosis and clinical course of a case of MPL S505N-positive MPN are presented with diagnostic features and treatment response resembling typical ET but with evidence of increasing bone marrow fibrosis.

PMID 18528423 2008 New mutations of MPL in primitive myelofibrosis: only the MPL W515 mutations promote a G1/S-phase transition.

PMID 18451306 2008 MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort.

rs1448812001 in MPL gene and Congenital amegakaryocytic thrombocytopenia PMID 25538044 2015 The thrombopoietin receptor P106L mutation functionally separates receptor signaling activity from thrombopoietin homeostasis.

PMID 16470591 2006 MPL mutations in 23 patients suffering from congenital amegakaryocytic thrombocytopenia: the type of mutation predicts the course of the disease.

PMID 21489838 2011 A founder mutation in the MPL gene causes congenital amegakaryocytic thrombocytopenia (CAMT) in the Ashkenazi Jewish population.

PMID 11133753 2001 c-mpl mutations are the cause of congenital amegakaryocytic thrombocytopenia.

PMID 8073287 1994 Thrombocytopenia in c-mpl-deficient mice.

PMID 24728327 2014 Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing.

PMID 11972523 2002 Three parameters, plasma thrombopoietin levels, plasma glycocalicin levels and megakaryocyte culture, distinguish between different causes of congenital thrombocytopenia.

PMID 18240171 2008 Congenital amegakaryocytic thrombocytopenia: the diagnostic importance of combining pathology with molecular genetics.

PMID 21659346 2011 Genetic analysis of inherited bone marrow failure syndromes from one prospective, comprehensive and population-based cohort and identification of novel mutations.

PMID 10971406 2000 Mutations in the thrombopoietin receptor, Mpl, in children with congenital amegakaryocytic thrombocytopenia.

PMID 28859041 2018 Case Report: Clinical Variation in Children With Thrombopoietin Receptor (C-MPL) Mutations: Report of 2 Cases.

PMID 18422784 2008 In a previous study, we identified four missense mutations in CAMT patients, predicting Arg102Pro, Pro136His, Arg257Cys and Pro635Leu.

PMID 19302922 2009 Compound heterozygous c-Mpl mutations in a child with congenital amegakaryocytic thrombocytopenia: functional characterization and a review of the literature.

PMID 17666371 2007 Congenital amegakaryocytic thrombocytopenia: clinical and biological consequences of five novel mutations.

PMID 27418648 2016 Genetic features of myelodysplastic syndrome and aplastic anemia in pediatric and young adult patients.

PMID 19036112 2009 Familial thrombocytosis caused by the novel germ-line mutation p.Pro106Leu in the MPL gene.

PMID 23625800 2013 Congenital amegakaryocytic thrombocytopenia (CAMT) presenting as severe pancytopenia in the first month of life.

rs121913615 in MPL gene and Hematologic Neoplasms PMID 16834459 2006 MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia.

rs121913615 in MPL gene and Myelofibrosis PMID 16868251 2006 MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients.

PMID 16834459 2006 DNA sequence analysis of the exons encoding the transmembrane and juxtamembrane domains of EPOR, MPL, and GCSFR, and comparison with germline DNA derived from buccal swabs, identified a somatic activating mutation in the transmembrane domain of MPL (W515L) in 9% (4/45) of JAKV617F-negative MF.

PMID 16834459 2006 MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia.

rs121913614 in MPL gene and Primary Myelofibrosis PMID 20151976 2010 Clinical utility of routine MPL exon 10 analysis in the diagnosis of essential thrombocythaemia and primary myelofibrosis.

PMID 18528423 2008 New mutations of MPL in primitive myelofibrosis: only the MPL W515 mutations promote a G1/S-phase transition.

rs121913614 in MPL gene and THROMBOCYTHEMIA 1 PMID 18451306 2008 MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort.

PMID 20151976 2010 Clinical utility of routine MPL exon 10 analysis in the diagnosis of essential thrombocythaemia and primary myelofibrosis.

PMID 18528423 2008 New mutations of MPL in primitive myelofibrosis: only the MPL W515 mutations promote a G1/S-phase transition.

PMID 19608689 2009 Evidence for a founder effect of the MPL-S505N mutation in eight Italian pedigrees with hereditary thrombocythemia.

rs121913614 in MPL gene and THROMBOCYTHEMIA 2 PMID 25538044 2015 The thrombopoietin receptor P106L mutation functionally separates receptor signaling activity from thrombopoietin homeostasis.

PMID 23441089 2013 MPL W515L mutation in pediatric essential thrombocythemia.

PMID 14764528 2004 Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin.

PMID 19483125 2009 The Asn505 mutation of the c-MPL gene, which causes familial essential thrombocythemia, induces autonomous homodimerization of the c-Mpl protein due to strong amino acid polarity.

rs146249964 in MPL gene and Thrombocythemia, Essential PMID 8073287 1994 Thrombocytopenia in c-mpl-deficient mice.

PMID 11133753 2001 c-mpl mutations are the cause of congenital amegakaryocytic thrombocytopenia.

PMID 16470591 2006 MPL mutations in 23 patients suffering from congenital amegakaryocytic thrombocytopenia: the type of mutation predicts the course of the disease.

PMID 18240171 2008 Congenital amegakaryocytic thrombocytopenia: the diagnostic importance of combining pathology with molecular genetics.

PMID 18422784 2008 Functional analysis of single amino-acid mutations in the thrombopoietin-receptor Mpl underlying congenital amegakaryocytic thrombocytopenia.

PMID 21659346 2011 Genetic analysis of inherited bone marrow failure syndromes from one prospective, comprehensive and population-based cohort and identification of novel mutations.

PMID 28859041 2018 Case Report: Clinical Variation in Children With Thrombopoietin Receptor (C-MPL) Mutations: Report of 2 Cases.

PMID 10971406 2000 Mutations in the thrombopoietin receptor, Mpl, in children with congenital amegakaryocytic thrombocytopenia.

PMID 19302922 2009 Compound heterozygous c-Mpl mutations in a child with congenital amegakaryocytic thrombocytopenia: functional characterization and a review of the literature.

PMID 11972523 2002 Three parameters, plasma thrombopoietin levels, plasma glycocalicin levels and megakaryocyte culture, distinguish between different causes of congenital thrombocytopenia.

PMID 17666371 2007 Congenital amegakaryocytic thrombocytopenia: clinical and biological consequences of five novel mutations.

PMID 25538044 2015 The thrombopoietin receptor P106L mutation functionally separates receptor signaling activity from thrombopoietin homeostasis.

PMID 19036112 2009 Familial thrombocytosis caused by the novel germ-line mutation p.Pro106Leu in the MPL gene.

rs146249964 in MPL gene and Thrombocytopenia PMID 31064749 2019 Diagnostic high-throughput sequencing of 2396 patients with bleeding, thrombotic, and platelet disorders.