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Aliases for MPL Gene

Aliases for MPL Gene

  • MPL Proto-Oncogene, Thrombopoietin Receptor 2 3 5
  • Myeloproliferative Leukemia Virus Oncogene 2 3
  • Myeloproliferative Leukemia Protein 3 4
  • Proto-Oncogene C-Mpl 3 4
  • TPO-R 3 4
  • TPOR 3 4
  • Thrombopoietin Receptor 3
  • CD110 Antigen 4
  • THCYT2 3
  • C-MPL 3
  • CD110 3
  • MPLV 3

External Ids for MPL Gene

Previous GeneCards Identifiers for MPL Gene

  • GC01P043746
  • GC01P042803
  • GC01P043233
  • GC01P043216
  • GC01P043472
  • GC01P043576
  • GC01P043803
  • GC01P041923

Summaries for MPL Gene

Entrez Gene Summary for MPL Gene

  • 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. [provided by RefSeq, Jul 2008]

GeneCards Summary for MPL Gene

MPL (MPL Proto-Oncogene, Thrombopoietin Receptor) is a Protein Coding gene. Diseases associated with MPL include Thrombocytopenia, Congenital Amegakaryocytic and Myelofibrosis With Myeloid Metaplasia, Somatic. Among its related pathways are Response to elevated platelet cytosolic Ca2+ and NF-kappaB Signaling. GO annotations related to this gene include transmembrane signaling receptor activity and thrombopoietin receptor activity. An important paralog of this gene is EPOR.

UniProtKB/Swiss-Prot for MPL Gene

  • Receptor for thrombopoietin. May represent a regulatory molecule specific for TPO-R-dependent immune responses.

Gene Wiki entry for MPL Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MPL Gene

Genomics for MPL Gene

Regulatory Elements for MPL Gene

Enhancers for MPL Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH01G043293 1.7 FANTOM5 Ensembl ENCODE dbSUPER 11.3 -42.3 -42346 3.8 HDGF TBP KLF17 RAD21 YY1 FOS RELB ETV6 IKZF2 ZNF362 MED8 EBNA1BP2 MPL LOC105378687 CDC20 ELOVL1 ENSG00000229431 SZT2 FAM183A ATP6V0B
GH01G043371 1.6 FANTOM5 Ensembl ENCODE dbSUPER 11.2 +35.6 35625 3.3 GTF2F1 JUN BRCA1 FOSL1 ZNF316 GATA2 RCOR1 NFE2 FOS TCF7L2 MED8 MPL EBNA1BP2 CFAP57 ELOVL1 SZT2
GH01G043283 1.4 Ensembl ENCODE dbSUPER 11.3 -52.1 -52122 3.2 FOXA2 SIN3A RAD21 RARA ZNF121 EGR1 SP5 CEBPB ZNF592 SMARCA4 CFAP57 SZT2 MPL ENSG00000229431 MED8 CDC20 LOC105378687 ELOVL1 TMEM125 C1orf210
GH01G043365 1.4 ENCODE dbSUPER 11.2 +29.8 29801 4.2 HDGF PKNOX1 CREB3L1 ARNT ZFP64 WRNIP1 ARID4B SIN3A DMAP1 ZNF2 MED8 MPL HYI ELOVL1 MIR6734
GH01G043471 1.4 Ensembl ENCODE dbSUPER 10.5 +137.1 137149 6.8 ATF1 SIN3A ARID4B GATA2 FOS YY2 REST KAT8 SMARCA4 MXD3 MED8 SZT2 KDM4A-AS1 PTPRF ELOVL1 CDC20 LOC105378687 MPL PPIH ST3GAL3
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around MPL on UCSC Golden Path with GeneCards custom track

Transcription factor binding sites by QIAGEN in the MPL gene promoter:

Genomic Location for MPL Gene

Chromosome:
1
Start:
43,337,418 bp from pter
End:
43,354,464 bp from pter
Size:
17,047 bases
Orientation:
Plus strand

Genomic View for MPL Gene

Genes around MPL on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MPL Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MPL Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MPL Gene

Proteins for MPL Gene

  • Protein details for MPL Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P40238-TPOR_HUMAN
    Recommended name:
    Thrombopoietin receptor
    Protein Accession:
    P40238
    Secondary Accessions:
    • Q5JUZ0

    Protein attributes for MPL Gene

    Size:
    635 amino acids
    Molecular mass:
    71245 Da
    Quaternary structure:
    • Homodimer (PubMed:25538044). Interacts with ATXN2L.

    Alternative splice isoforms for MPL Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MPL Gene

Post-translational modifications for MPL Gene

  • Ubiquitination at Lys-553 and Lys-573 targets MPL for degradation by both the lysosomal and proteasomal pathways. The E3 ubiquitin-protein ligase CBL significantly contributes to this ubiquitination.
  • Ubiquitination at Lys553 and Lys573
  • Glycosylation at Asn117, Asn178, Asn298, and posLast=358358
  • Modification sites at PhosphoSitePlus

Other Protein References for MPL Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • R&D Systems Antibodies for MPL (Thrombopoietin R/Tpo R)
  • Cell Signaling Technology (CST) Antibodies for MPL (MPL)
  • Santa Cruz Biotechnology (SCBT) Antibodies for MPL

Protein Products

No data available for DME Specific Peptides for MPL Gene

Domains & Families for MPL Gene

Suggested Antigen Peptide Sequences for MPL Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P40238

UniProtKB/Swiss-Prot:

TPOR_HUMAN :
  • The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.
  • Belongs to the type I cytokine receptor family. Type 1 subfamily.
Domain:
  • The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.
  • The box 1 motif is required for JAK interaction and/or activation.
Family:
  • Belongs to the type I cytokine receptor family. Type 1 subfamily.
genes like me logo Genes that share domains with MPL: view

Function for MPL Gene

Molecular function for MPL Gene

GENATLAS Biochemistry:
myeloproliferative leukemia virus oncogene homolog,hematopoietic growth factor receptor superfamily
UniProtKB/Swiss-Prot Function:
Receptor for thrombopoietin. May represent a regulatory molecule specific for TPO-R-dependent immune responses.

Gene Ontology (GO) - Molecular Function for MPL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004888 transmembrane signaling receptor activity TAS 8020956
GO:0004896 cytokine receptor activity IEA --
GO:0005515 protein binding IPI 24931576
GO:0038164 thrombopoietin receptor activity IMP 25538044
genes like me logo Genes that share ontologies with MPL: view
genes like me logo Genes that share phenotypes with MPL: view

Human Phenotype Ontology for MPL Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for MPL Gene

MGI Knock Outs for MPL:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for MPL
  • Applied Biological Materials Clones for MPL
  • R&D Systems cDNA Clones for MPL (Thrombopoietin R/Tpo R)

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for MPL Gene

Localization for MPL Gene

Subcellular locations from UniProtKB/Swiss-Prot for MPL Gene

Cell membrane; Single-pass type I membrane protein. Golgi apparatus. Cell surface.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for MPL gene
Compartment Confidence
plasma membrane 5
golgi apparatus 5
extracellular 3
cytoskeleton 1
peroxisome 1
nucleus 1
cytosol 1
lysosome 1

Gene Ontology (GO) - Cellular Components for MPL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005794 Golgi apparatus IDA,IEA 25538044
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane TAS 8020956
GO:0009986 cell surface IEA,IDA 25538044
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with MPL: view

Pathways & Interactions for MPL Gene

genes like me logo Genes that share pathways with MPL: view

Pathways by source for MPL Gene

SIGNOR curated interactions for MPL Gene

Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for MPL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007166 cell surface receptor signaling pathway TAS 8020956
GO:0008283 cell proliferation TAS 8020956
GO:0019221 cytokine-mediated signaling pathway IEA --
GO:0038163 thrombopoietin-mediated signaling pathway IEA --
genes like me logo Genes that share ontologies with MPL: view

Drugs & Compounds for MPL Gene

(18) Drugs for MPL Gene - From: DrugBank, ApexBio, DGIdb, IUPHAR, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Eltrombopag Approved Pharma agonist, Target 0
Romiplostim Approved Pharma inhibitor, Target, agonist 0
SB-559448 Investigational Pharma agonist, Target 0
thrombopoietin Pharma Agonist, agonist 0
Eltrombopag Olamine Pharma C-mpl agonist 0

(10) Additional Compounds for MPL Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs

(2) ApexBio Compounds for MPL Gene

Compound Action Cas Number
Eltrombopag 496775-61-2
Eltrombopag Olamine C-mpl agonist 496775-62-3
genes like me logo Genes that share compounds with MPL: view

Drug Products

Transcripts for MPL Gene

mRNA/cDNA for MPL Gene

(2) REFSEQ mRNAs :
(3) Additional mRNA sequences :
(4) Selected AceView cDNA sequences:
(3) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for MPL Gene

Myeloproliferative leukemia virus oncogene:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for MPL
  • Applied Biological Materials Clones for MPL
  • R&D Systems cDNA Clones for MPL (Thrombopoietin R/Tpo R)

Alternative Splicing Database (ASD) splice patterns (SP) for MPL Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10a · 10b ^ 11 ^ 12
SP1: -
SP2: - -
SP3:

Relevant External Links for MPL Gene

GeneLoc Exon Structure for
MPL
ECgene alternative splicing isoforms for
MPL

Expression for MPL Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for MPL Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for MPL Gene

This gene is overexpressed in Peripheral blood mononuclear cells (35.6), Heart (23.0), and Platelet (10.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for MPL Gene



Protein tissue co-expression partners for MPL Gene

NURSA nuclear receptor signaling pathways regulating expression of MPL Gene:

MPL

SOURCE GeneReport for Unigene cluster for MPL Gene:

Hs.82906

mRNA Expression by UniProt/SwissProt for MPL Gene:

P40238-TPOR_HUMAN
Tissue specificity: Expressed at a low level in a large number of cells of hematopoietic origin. Isoform 1 and isoform 2 are always found to be coexpressed.

Evidence on tissue expression from TISSUES for MPL Gene

  • Blood(3)
  • Bone marrow(2.9)

Phenotype-based relationships between genes and organs from Gene ORGANizer for MPL Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • lymphatic
  • nervous
  • respiratory
  • skeleton
Organs:
Head and neck:
  • brain
  • cerebellum
  • ear
  • eye
  • face
  • head
  • jaw
  • lip
  • mandible
  • maxilla
  • mouth
  • neck
  • nose
  • skull
Thorax:
  • chest wall
  • clavicle
  • heart
  • lung
  • rib
  • rib cage
  • scapula
  • sternum
Abdomen:
  • intestine
  • large intestine
  • liver
  • small intestine
  • spleen
  • stomach
Pelvis:
  • pelvis
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
General:
  • blood
  • blood vessel
  • bone marrow
  • coagulation system
  • peripheral nerve
  • peripheral nervous system
  • red blood cell
  • skin
  • spinal column
  • sweat gland
  • vertebrae
  • white blood cell
genes like me logo Genes that share expression patterns with MPL: view

Primer Products

No data available for mRNA differential expression in normal tissues for MPL Gene

Orthologs for MPL Gene

This gene was present in the common ancestor of chordates.

Orthologs for MPL Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia MPL 34 35
  • 86.78 (n)
mouse
(Mus musculus)
Mammalia Mpl 34 16 35
  • 85.15 (n)
rat
(Rattus norvegicus)
Mammalia Mpl 34
  • 84.38 (n)
dog
(Canis familiaris)
Mammalia MPL 35
  • 83 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia MPL 35
  • 48 (a)
OneToOne
chicken
(Gallus gallus)
Aves MPL 34 35
  • 52.94 (n)
lizard
(Anolis carolinensis)
Reptilia MPL 35
  • 30 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii mpl 34 35
  • 41.17 (n)
Species where no ortholog for MPL was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chimpanzee (Pan troglodytes)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • oppossum (Monodelphis domestica)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for MPL Gene

ENSEMBL:
Gene Tree for MPL (if available)
TreeFam:
Gene Tree for MPL (if available)

Paralogs for MPL Gene

Paralogs for MPL Gene

genes like me logo Genes that share paralogs with MPL: view

Variants for MPL Gene

Sequence variations from dbSNP and Humsavar for MPL Gene

SNP ID Clin Chr 01 pos Sequence Context AA Info Type
rs121913614 Pathogenic, Thrombocythemia 2 (THCYT2) [MIM:601977] 43,349,308(+) CCTCA(A/G)CGCCG reference, missense
rs121913615 Pathogenic, Myelofibrosis with myeloid metaplasia (MMM) [MIM:254450], Thrombocythemia 2 (THCYT2) [MIM:601977] 43,349,338(+) GAGGT(C/G/T)GCAGT reference, missense
rs121913616 Myelofibrosis with myeloid metaplasia (MMM) [MIM:254450]
rs28928907 Pathogenic, Congenital amegakaryocytic thrombocytopenia (CAMT) [MIM:604498] 43,338,634(+) AGTGC(C/G)TCTCT reference, missense
rs28928908 Pathogenic, Congenital amegakaryocytic thrombocytopenia (CAMT) [MIM:604498] 43,340,096(+) CCCTC(A/C)CTGTG reference, missense

Structural Variations from Database of Genomic Variants (DGV) for MPL Gene

Variant ID Type Subtype PubMed ID
esv3585866 CNV loss 21293372
nsv546128 CNV loss 21841781

Variation tolerance for MPL Gene

Residual Variation Intolerance Score: 79.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.49; 55.27% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for MPL Gene

Human Gene Mutation Database (HGMD)
MPL
SNPedia medical, phenotypic, and genealogical associations of SNPs for
MPL

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MPL Gene

Disorders for MPL Gene

MalaCards: The human disease database

(32) MalaCards diseases for MPL Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
thrombocytopenia, congenital amegakaryocytic
  • amegakaryocytic thrombocytopenia, congenital
myelofibrosis with myeloid metaplasia, somatic
  • myelofibrosis, somatic
polycythemia vera, somatic
  • polycythemia vera
dyskeratosis congenita, autosomal dominant 6
  • dyskeratosis congenita, autosomal recessive 7
essential thrombocythemia
  • essential thrombocythaemia
- elite association - COSMIC cancer census association via MalaCards
Search MPL in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

TPOR_HUMAN
  • Congenital amegakaryocytic thrombocytopenia (CAMT) [MIM:604498]: Disease characterized by isolated thrombocytopenia and megakaryocytopenia with no physical anomalies. {ECO:0000269 PubMed:16470591, ECO:0000269 PubMed:25538044}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Myelofibrosis with myeloid metaplasia (MMM) [MIM:254450]: A chronic myeloproliferative disorder characterized by replacement of the bone marrow by fibrous tissue, extramedullary hematopoiesis, anemia, leukoerythroblastosis and hepatosplenomegaly. {ECO:0000269 PubMed:16834459, ECO:0000269 PubMed:16868251}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Thrombocythemia 2 (THCYT2) [MIM:601977]: A myeloproliferative disorder characterized by excessive platelet production, resulting in increased numbers of circulating platelets. It can be associated with spontaneous hemorrhages and thrombotic episodes. {ECO:0000269 PubMed:14764528, ECO:0000269 PubMed:19483125, ECO:0000269 PubMed:23441089, ECO:0000269 PubMed:25538044}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for MPL

Genetic Association Database (GAD)
MPL
Human Genome Epidemiology (HuGE) Navigator
MPL
Tumor Gene Database (TGDB):
MPL
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
MPL
genes like me logo Genes that share disorders with MPL: view

No data available for Genatlas for MPL Gene

Publications for MPL Gene

  1. Mpl Baltimore: a thrombopoietin receptor polymorphism associated with thrombocytosis. (PMID: 15269348) Moliterno A.R. … Spivak J.L. (Proc. Natl. Acad. Sci. U.S.A. 2004) 3 4 22 46 64
  2. Screening for MPL mutations in essential thrombocythemia and primary myelofibrosis: normal Mpl expression and absence of constitutive STAT3 and STAT5 activation in MPLW515L-positive platelets. (PMID: 20113333) Glembotsky A.C. … Heller P.G. (Eur. J. Haematol. 2010) 3 22 46 64
  3. 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. (PMID: 19483125) Ding J. … Ueda R. (Blood 2009) 3 4 22 64
  4. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. (PMID: 16834459) Pikman Y. … Levine R.L. (PLoS Med. 2006) 3 4 22 64
  5. MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. (PMID: 16868251) Pardanani A.D. … Tefferi A. (Blood 2006) 3 4 46 64

Products for MPL Gene

  • Addgene plasmids for MPL

Sources for MPL Gene

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