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    THPO thrombopoietin [ Homo sapiens (human) ]

    Gene ID: 7066, updated on 27-Nov-2024

    Summary

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    Official Symbol
    THPOprovided by HGNC
    Official Full Name
    thrombopoietinprovided by HGNC
    Primary source
    HGNC:HGNC:11795
    See related
    Ensembl:ENSG00000090534 MIM:600044; AllianceGenome:HGNC:11795
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    ML; TPO; MGDF; THC9; CAMT2; MKCSF; MPLLG; THCYT1
    Summary
    Megakaryocytopoiesis is the cellular development process that leads to platelet production. The main functional protein encoded by this gene is a humoral growth factor that is necessary for megakaryocyte proliferation and maturation, as well as for thrombopoiesis. This protein is the ligand for MLP/C_MPL, the product of myeloproliferative leukemia virus oncogene. Mutations in this gene are the cause of thrombocythemia 1. Alternative promoter usage and differential splicing result in multiple transcript variants differing in the 5' UTR and/or coding region. Multiple AUG codons upstream of the main open reading frame (ORF) have been identified, and these upstream AUGs inhibit translation of the main ORF at different extent. [provided by RefSeq, Feb 2014]
    Annotation information
    Note: TPO (Gene ID: 7173) and THPO (Gene ID: 7066) share the TPO symbol/alias in common. TPO is a widely used alternative name for thrombopoietin (THPO), which can be confused with the official symbol for TPO, thyroid peroxidase. [27 Jun 2018]
    Expression
    Biased expression in liver (RPKM 4.4), testis (RPKM 1.1) and 9 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See THPO in Genome Data Viewer
    Location:
    3q27.1
    Exon count:
    7
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (184371935..184379688, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (187181188..187188943, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (184089723..184097476, complement)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene chloride voltage-gated channel 2 Neighboring gene uncharacterized LOC124906311 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14964 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14965 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14966 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14967 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20910 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20911 Neighboring gene RNA polymerase II, I and III subunit H Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:184103787-184104288 Neighboring gene chordin Neighboring gene long intergenic non-protein coding RNA 2054 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:184134067-184134568

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Hereditary thrombocythemia due to splicing donor site mutation of THPO in a Japanese family. Kimura H, et al. Ann Hematol, 2024 Jan. PMID 37962621
    2. Thrombopoietin concentrations in peripheral blood correlated with platelet numbers in two patients with thrombocytopenia by chronic graft-versus-host disease. Hirayama Y, et al. Am J Hematol, 2003 Aug. PMID 12879435
    3. Serum thrombopoietin levels in patients with reactive thrombocytosis due to lung cancer and in patients with essential thrombocythemia. Werynska B, et al. Neoplasma, 2003. PMID 14689068
    4. Structure of the receptor-binding domain of human thrombopoietin determined by complexation with a neutralizing antibody fragment. Feese MD, et al. Proc Natl Acad Sci U S A, 2004 Feb 17. PMID 14769915, Free PMC Article
    5. A case of familial thrombocytosis: possible role of altered thrombopoietin production. Fujiwara T, et al. Am J Hematol, 2004 Aug. PMID 15282677

    See all (149) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Hereditary thrombocythemia due to splicing donor site mutation of THPO in a Japanese family.
      Title: Hereditary thrombocythemia due to splicing donor site mutation of THPO in a Japanese family.
    2. Defective binding of ETS1 and STAT4 due to a mutation in the promoter region of THPO as a novel mechanism of congenital amegakaryocytic thrombocytopenia.
      Title: Defective binding of ETS1 and STAT4 due to a mutation in the promoter region of THPO as a novel mechanism of congenital amegakaryocytic thrombocytopenia.
    3. Novel THPO variant in hereditary thrombocytopenia: A potential candidate variant for predisposition to myeloid neoplasm.
      Title: Novel THPO variant in hereditary thrombocytopenia: A potential candidate variant for predisposition to myeloid neoplasm.
    4. Increased B4GALT1 expression is associated with platelet surface galactosylation and thrombopoietin plasma levels in MPNs.
      Title: Increased B4GALT1 expression is associated with platelet surface galactosylation and thrombopoietin plasma levels in MPNs.
    5. Clinical applications of thrombopoietin silencing: A possible therapeutic role in COVID-19?
      Title: Clinical applications of thrombopoietin silencing: A possible therapeutic role in COVID-19?
    6. Monoallelic loss-of-function THPO variants cause heritable thrombocytopenia.
      Title: Monoallelic loss-of-function THPO variants cause heritable thrombocytopenia.
    7. Endogenous thrombopoietin promotes non-small-cell lung carcinoma cell proliferation and migration by regulating EGFR signalling.
      Title: Endogenous thrombopoietin promotes non-small-cell lung carcinoma cell proliferation and migration by regulating EGFR signalling.
    8. Cooperative Role of Thrombopoietin and Vascular Endothelial Growth Factor-A in the Progression of Liver Cirrhosis to Hepatocellular Carcinoma.
      Title: Cooperative Role of Thrombopoietin and Vascular Endothelial Growth Factor-A in the Progression of Liver Cirrhosis to Hepatocellular Carcinoma.
    9. A novel thrombopoietin (THPO) mutation altering mRNA splicing in a case of familial thrombocytosis.
      Title: A novel thrombopoietin (THPO) mutation altering mRNA splicing in a case of familial thrombocytosis.
    10. c-Mpl and TPO expression in the human central nervous system neurons inhibits neuronal apoptosis.
      Title: c-Mpl and TPO expression in the human central nervous system neurons inhibits neuronal apoptosis.
    Submit: New GeneRIF Correction See all GeneRIFs (110)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Amegakaryocytic thrombocytopenia, congenital, 2
    MedGen: C5882679 OMIM: 620481 GeneReviews: Not available
    		not available
    Thrombocythemia 1
    MedGen: C3277671 OMIM: 187950 GeneReviews: Not available
    		Compare labs
    Thrombocytopenia 9
    MedGen: C5882678 OMIM: 620478 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    Genome-wide association study of hematological and biochemical traits in a Japanese population.
    EBI GWAS Catalog
    New gene functions in megakaryopoiesis and platelet formation.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC163194

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables cytokine activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables growth factor activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables hormone activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables signaling receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in cell population proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cell surface receptor signaling pathway via STAT IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in megakaryocyte development IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in megakaryocyte differentiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in megakaryocyte differentiation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of ERK1 and ERK2 cascade IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of ERK1 and ERK2 cascade ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of MAPK cascade IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of cell population proliferation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of hematopoietic stem cell proliferation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    acts_upstream_of_or_within positive regulation of hematopoietic stem cell proliferation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of megakaryocyte differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of protein phosphorylation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in thrombopoietin-mediated signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in thrombopoietin-mediated signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in thrombopoietin-mediated signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    is_active_in extracellular region IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    thrombopoietin
    Names
    MPL ligand
    c-mpl ligand
    megakaryocyte colony-stimulating factor
    megakaryocyte growth and development factor
    megakaryocyte stimulating factor
    myeloproliferative leukemia virus oncogene ligand
    prepro-thrombopoietin
    thrombopoietin nirs

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_012136.1 RefSeqGene

      Range
      4938..11210
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_580

    mRNA and Protein(s)

    1. NM_000460.4 → NP_000451.1  thrombopoietin isoform 1 precursor

      See identical proteins and their annotated locations for NP_000451.1

      Status: REVIEWED

      Source sequence(s)
      AA479058, AC078797, BC136338, BC143982, L33410
      Consensus CDS
      CCDS3265.1
      UniProtKB/Swiss-Prot
      A1L3Y0, B7ZLR8, B9EGA8, P40225, Q13020, Q15790, Q15791, Q15792
      Related
      ENSP00000494504.1, ENST00000647395.1
      Conserved Domains (1) summary
      pfam00758
      Location:25 → 176
      EPO_TPO; Erythropoietin/thrombopoietin

    2. NM_001177597.2 → NP_001171068.1  thrombopoietin isoform 2 precursor

      See identical proteins and their annotated locations for NP_001171068.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) represents use of the downstream promoter and comprises six exons. It uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. The resulting isoform (2) lacks an internal segment, compared to isoform 1.
      Source sequence(s)
      AA479058, AC078797, BC143982, L33410
      Consensus CDS
      CCDS54693.1
      UniProtKB/Swiss-Prot
      P40225
      Related
      ENSP00000410763.2, ENST00000445696.6
      Conserved Domains (1) summary
      pfam00758
      Location:25 → 172
      EPO_TPO; Erythropoietin/thrombopoietin

    3. NM_001177598.2 → NP_001171069.1  thrombopoietin isoform 3 precursor

      See identical proteins and their annotated locations for NP_001171069.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) represents use of the downstream promoter and comprises six exons. It uses an alternate splice site in the 3' coding region, which results in a frameshift, compared to variant 1. The resulting isoform (3) has a shorter and distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AA479058, AA480029, AB102890, AC078797, BC143982
      Consensus CDS
      CCDS93431.1
      UniProtKB/TrEMBL
      Q5FBX8
      Related
      ENSP00000497233.1, ENST00000650229.1
      Conserved Domains (1) summary
      pfam00758
      Location:25 → 153
      EPO_TPO; Erythropoietin/thrombopoietin

    4. NM_001289997.1 → NP_001276926.1  thrombopoietin isoform 4 precursor

      See identical proteins and their annotated locations for NP_001276926.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) represents use of the downstream promoter and comprises six exons. It lacks an internal segment in the 3' exon, which results in a frameshift, compared to variant 1. The resulting isoform (4) has a shorter and distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AA479058, AC078797, AK311002, BC143982, L33410, U11025
      Consensus CDS
      CCDS77867.1
      UniProtKB/TrEMBL
      F8W6L1
      Related
      ENSP00000411704.2, ENST00000421442.2
      Conserved Domains (1) summary
      pfam00758
      Location:25 → 159
      EPO_TPO; Erythropoietin/thrombopoietin

    5. NM_001289998.1 → NP_001276927.1  thrombopoietin isoform 1 precursor

      See identical proteins and their annotated locations for NP_001276927.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) represents use of the upstream promoter and comprises seven exons. It is longer at the 5' end, compared to variant 1. This variant can initiate translation from two in-frame AUG sites. The isoform (1) represented in this Refseq is derived from the downstream AUG start codon and is identical to the isoform encoded by variant 1.
      Source sequence(s)
      AA479058, AC078797, BC136338, BC143982, L33410
      Consensus CDS
      CCDS3265.1
      UniProtKB/Swiss-Prot
      A1L3Y0, B7ZLR8, B9EGA8, P40225, Q13020, Q15790, Q15791, Q15792
      Conserved Domains (1) summary
      pfam00758
      Location:25 → 176
      EPO_TPO; Erythropoietin/thrombopoietin

    6. NM_001290003.1 → NP_001276932.1  thrombopoietin isoform 5

      See identical proteins and their annotated locations for NP_001276932.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) represents use of the upstream promoter and comprises seven exons. It is longer at the 5' end, compared to variant 1. This variant can initiate translation from two in-frame AUG sites. The isoform (5) represented in this Refseq is derived from the upstream AUG start codon and is longer at the N-terminus, compared to isoform 1. This isoform was described as a uAUG4 product in PMID: 9834204 and had no thrombopoietin bioactivity.
      Source sequence(s)
      AA479058, AC078797, BC136338, BC143982, L33410
      Consensus CDS
      CCDS93432.1
      UniProtKB/TrEMBL
      A0A3B3ITS0
      Related
      ENSP00000497904.1, ENST00000649095.1
      Conserved Domains (1) summary
      pfam00758
      Location:165 → 316
      EPO_TPO; Erythropoietin/thrombopoietin

    7. NM_001290022.1 → NP_001276951.1  thrombopoietin isoform 2 precursor

      See identical proteins and their annotated locations for NP_001276951.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) represents use of the upstream promoter and comprises seven exons. This variant is longer at the 5' end and has an alternate in-frame splice site in the 3' coding region, compared to variant 1. This variant includes two main in-frame AUG sites, but translation initiated from the upstream AUG codon for this variant is not reported in literature. The isoform (2) represented in this RefSeq is derived from the downstream AUG start codon; it is identical to the isoform encoded by variant 2 and lacks an internal segment, as compared to isoform 1. This variant was reported in PMID: 7822271.
      Source sequence(s)
      AA479058, AC078797, BC143982, L33410
      Consensus CDS
      CCDS54693.1
      UniProtKB/Swiss-Prot
      P40225
      Conserved Domains (1) summary
      pfam00758
      Location:25 → 172
      EPO_TPO; Erythropoietin/thrombopoietin

    8. NM_001290026.1 → NP_001276955.1  thrombopoietin isoform 3 precursor

      See identical proteins and their annotated locations for NP_001276955.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) represents use of the upstream promoter and comprises seven exons. This variant is longer at the 5' end and has an alternate splice site in the 3' coding region, which results in a frameshift, compared to variant 1. This variant includes two main in-frame AUG sites, but translation initiated from the upstream AUG codon for this variant is not reported in literature. The isoform (3) represented in this RefSeq is derived from the downstream AUG start codon; it is identical to the isoform encoded by variant 3 and lacks an internal segment, as compared to isoform 1. This variant was reported in PMID: 7822271.
      Source sequence(s)
      AA479058, AA480029, AB102890, AC078797, BC143982
      Consensus CDS
      CCDS93431.1
      UniProtKB/TrEMBL
      Q5FBX8
      Conserved Domains (1) summary
      pfam00758
      Location:25 → 153
      EPO_TPO; Erythropoietin/thrombopoietin

    9. NM_001290027.1 → NP_001276956.1  thrombopoietin isoform 4 precursor

      See identical proteins and their annotated locations for NP_001276956.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (8) represents use of the upstream promoter and comprises seven exons. It includes two main in-frame AUG sites, but translation initiated from the upstream AUG codon for this variant is not reported in literature. The isoform (4) represented in this RefSeq is derived from the downstream AUG start codon; it is identical to the isoform encoded by variant 4 and lacks an internal segment, as compared to isoform 1. This variant was reported in PMID: 7822271.
      Source sequence(s)
      AA479058, AC078797, AK311002, BC143982, L33410, U11025
      Consensus CDS
      CCDS77867.1
      UniProtKB/TrEMBL
      F8W6L1
      Conserved Domains (1) summary
      pfam00758
      Location:25 → 159
      EPO_TPO; Erythropoietin/thrombopoietin

    10. NM_001290028.1 → NP_001276957.1  thrombopoietin isoform 1 precursor

      See identical proteins and their annotated locations for NP_001276957.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (9) represents use of the upstream promoter, but lacks an internal exon, compared to other transcripts with the same upstream promoter usage. This variant has an alternate 5' UTR exon and encodes the same isoform (1), compared to variant 1. This variant was reported in PMID: 9834204.
      Source sequence(s)
      AA479058, AC078797, BC136338, BC143982, L33410
      Consensus CDS
      CCDS3265.1
      UniProtKB/Swiss-Prot
      A1L3Y0, B7ZLR8, B9EGA8, P40225, Q13020, Q15790, Q15791, Q15792
      Conserved Domains (1) summary
      pfam00758
      Location:25 → 176
      EPO_TPO; Erythropoietin/thrombopoietin

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      184371935..184379688 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047448788.1 → XP_047304744.1  thrombopoietin isoform X1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      187181188..187188943 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054347667.1 → XP_054203642.1  thrombopoietin isoform X1

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_199228.1: Suppressed sequence

      Description
      NM_199228.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.

    2. NM_199356.1: Suppressed sequence

      Description
      NM_199356.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P40225.1 GenPept UniProtKB/Swiss-Prot:P40225

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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