THPO thrombopoietin [Homo sapiens (human)] - Gene

Summary

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

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_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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?
Monoallelic loss-of-function THPO variants cause heritable thrombocytopenia.
Title: Monoallelic loss-of-function THPO variants cause heritable thrombocytopenia.
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.
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.
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.
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	not available
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 EBI GWAS CatalogPubMed
New gene functions in megakaryopoiesis and platelet formation. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

THPO_1099 (e-PCR)
- UniSTS:277813

NoName (e-PCR)
- UniSTS:481911

D3S4165 (e-PCR)
- UniSTS:11641

G60274 (e-PCR)
- UniSTS:137379

NoName (e-PCR)
- UniSTS:490439

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

NG_012136.1 RefSeqGene

Range

4938..11210

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_580

mRNA and Protein(s)

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
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
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
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
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
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
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
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
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
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

NC_000003.12 Reference GRCh38.p14 Primary Assembly

Range

184371935..184379688 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047448788.1 → XP_047304744.1 thrombopoietin isoform X1

Alternate T2T-CHM13v2.0

Genomic

NC_060927.1 Alternate T2T-CHM13v2.0

Range

187181188..187188943 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054347667.1 → XP_054203642.1 thrombopoietin isoform X1

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

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.
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.