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THPO thrombopoietin [ Homo sapiens (human) ]

Gene ID: 7066, updated on 13-Apr-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
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Genomic context

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Location:
3q27.1
Exon count:
7
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (184371935..184379688, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (187181188..187188943, complement)
105.20220307 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. Novel THPO variant in hereditary thrombocytopenia: A potential candidate variant for predisposition to myeloid neoplasm. Kwon SR, et al. PLoS One, 2022. PMID 36534659, Free PMC Article
  2. Clinical applications of thrombopoietin silencing: A possible therapeutic role in COVID-19? Alentado VJ, et al. Cytokine, 2021 Oct. PMID 34247039, Free PMC Article
  3. A novel thrombopoietin (THPO) mutation altering mRNA splicing in a case of familial thrombocytosis. Prouzet-Mauléon V, et al. Br J Haematol, 2020 Jul. PMID 32430933
  4. Endogenous thrombopoietin promotes non-small-cell lung carcinoma cell proliferation and migration by regulating EGFR signalling. Zou Z, et al. J Cell Mol Med, 2020 Jun. PMID 32337844, Free PMC Article
  5. Monoallelic loss-of-function THPO variants cause heritable thrombocytopenia. Cornish N, et al. Blood Adv, 2020 Mar 10. PMID 32150607, Free PMC Article

See all (146) 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: CN372721 OMIM: 620481 GeneReviews: Not available
not available
Thrombocythemia 1
MedGen: C3277671 OMIM: 187950 GeneReviews: Not available
Compare labs
Thrombocytopenia 9
MedGen: CN372715 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)

Genotypes

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 IEA
Inferred from Electronic Annotation
more info
  
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
  
located_in extracellular space IEA
Inferred from Electronic Annotation
more info
  

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_2023_10

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

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