THPO thrombopoietin [Homo sapiens (human)] - Gene

Summary

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Official Symbol: THPOprovided by HGNC
Official Full Name: thrombopoietinprovided by HGNC
Primary source: HGNC:11795
See related: Ensembl:ENSG00000090534; HPRD:02500; MIM:600044; Vega:OTTHUMG00000156745
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; MKCSF; MPLLG; THCYT1
Summary: Megakaryocytopoiesis is the cellular development process that leads to platelet production. The 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. Alternate splicing results in multiple transcript variants of this gene.[provided by RefSeq, Jun 2012]

Genomic context

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Location :: 3q27

Sequence :: Chromosome: 3; NC_000003.11 (184089773..184095932, complement)

See THPO in Epigenomics, MapViewer

Chromosome 3 - NC_000003.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Platelet count and serum thrombopoietin level as predictors for morbidity and/or mortality in thrombocytopenic neonates.
Title: Platelet count and serum thrombopoietin level as predictors for morbidity and/or mortality in thrombocytopenic neonates.
Data indicate increased levels of serum thrombopoietin (TPO) were found in necrotizing pancreatitis.
Title: Involvement of thrombopoietin in acinar cell necrosis in L-arginine-induced acute pancreatitis in mice.
Mutation in the THPO gene is not associated with aplastic anaemia in Japanese children.
Title: Mutation in the THPO gene is not associated with aplastic anaemia in Japanese children.
Thrombopoietin is a biomarker and mediator of cardiovascular damage in critical diseases [review]
Title: Thrombopoietin as biomarker and mediator of cardiovascular damage in critical diseases.
Findings establish that Clock regulates Thpo and Mpl expression in vivo, and demonstrate an important link between the body's circadian timing mechanisms and megakaryopoiesis.
Title: Diurnal expression of the thrombopoietin gene is regulated by CLOCK.
Overstimulation of the THPO pathway might therefore predispose to clonal hematopoietic disease and to congenital abnormalities.
Title: Hereditary thrombocythemia caused by a thrombopoietin (THPO) gain-of-function mutation associated with multiple myeloma and congenital limb defects.
Data show that serum thrombopoietin levels in the affected family members were significantly higher than in the non-affected family members or healthy controls.
Title: A novel splice donor mutation in the thrombopoietin gene leads to exon 2 skipping in a Filipino family with hereditary thrombocythemia.
pattern of megakaryocytopoiesis is associated with up-regulated thrombopoietin (TPO) signaling through mammalian target of rapamycin (mTOR) and elevated levels of full-length GATA-1 and its targets
Title: Developmental differences in megakaryocytopoiesis are associated with up-regulated TPO signaling through mTOR and elevated GATA-1 levels in neonatal megakaryocytes.
Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo.
Title: Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo.
Findings thus suggest that decreased thrombopoietin production accompanying liver dysfunction may be related to thrombocytopenia besides myelosuppression in anorexia nervosa with malnutrition.
Title: Thrombopoietin and thrombocytopenia in anorexia nervosa with severe liver dysfunction.

Submit: New GeneRIF Correction See all (72)

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

NHGRI GWAS Catalog

New gene functions in megakaryopoiesis and platelet formation.

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
P40225	P40238	MPL	HPRD	PubMed
BioGRID:112922	BioGRID:119296	APH1A	BioGRID	PubMed	Two-hybrid
BioGRID:112922	BioGRID:108347	EP300	BioGRID	PubMed	Two-hybrid
BioGRID:112922	BioGRID:114677	NUMBL	BioGRID	PubMed	Two-hybrid

Pathways from BioSystems

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Hematopoietic cell lineage, organism-specific biosystem (from KEGG)
Hematopoietic cell lineage, organism-specific biosystemBlood-cell development progresses from a hematopoietic stem cell (HSC), which can undergo either self-renewal or differentiation into a multilineage committed progenitor cell: a common lymphoid proge...
Hematopoietic cell lineage, conserved biosystem (from KEGG)
Hematopoietic cell lineage, conserved biosystemBlood-cell development progresses from a hematopoietic stem cell (HSC), which can undergo either self-renewal or differentiation into a multilineage committed progenitor cell: a common lymphoid proge...
Hemostasis, organism-specific biosystem (from REACTOME)
Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
Platelet Aggregation (Plug Formation), organism-specific biosystem (from REACTOME)
Platelet Aggregation (Plug Formation), organism-specific biosystemThe tethering of platelets to the site of vascular injury is the first step in the formation of a platelet thrombus. Firm adhesion of these tethered platelets, as well as the additional recruitment o...
Platelet activation, signaling and aggregation, organism-specific biosystem (from REACTOME)
Platelet activation, signaling and aggregation, organism-specific biosystemPlatelet activation begins with the initial binding of adhesive ligands and of the excitatory platelet agonists (released or generated at the sites of vascular trauma) to cognate receptors on the pla...

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

Homology

Homologs of the THPO gene: The THPO gene is conserved in chimpanzee, dog, cow, mouse, and rat.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
cytokine activity	IEA Inferred from Electronic Annotation more info
growth factor activity	TAS Traceable Author Statement more info	PubMed
hormone activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
blood coagulation	TAS Traceable Author Statement more info
cell proliferation	IEA Inferred from Electronic Annotation more info
multicellular organismal development	TAS Traceable Author Statement more info	PubMed
myeloid cell differentiation	IEA Inferred from Electronic Annotation more info
platelet activation	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
extracellular space	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: thrombopoietin

Names: thrombopoietin; MPL ligand; c-mpl ligand; thrombopoietin nirs variant 1; megakaryocyte stimulating factor; megakaryocyte colony-stimulating factor; megakaryocyte growth and development factor; myeloproliferative leukemia virus oncogene ligand

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

5001..11160

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000460.2 → NP_000451.1 thrombopoietin isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

D32047, L33410

Consensus CDS

CCDS3265.1

UniProtKB/Swiss-Prot

P40225

Related

ENSP00000204615, OTTHUMP00000210502, ENST00000204615, OTTHUMT00000345554

Conserved Domains (1) summary

pfam00758
Location:24 – 188
Blast Score: 405

EPO_TPO; Erythropoietin/thrombopoietin
NM_001177597.1 → NP_001171068.1 thrombopoietin isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1.

Source sequence(s)

AC078797, BC143982, BX108191, L33410

Consensus CDS

CCDS54693.1

UniProtKB/Swiss-Prot

P40225

Related

ENSP00000410763, OTTHUMP00000210503, ENST00000445696, OTTHUMT00000345555

Conserved Domains (1) summary

pfam00758
Location:24 – 184
Blast Score: 386

EPO_TPO; Erythropoietin/thrombopoietin
NM_001177598.1 → NP_001171069.1 thrombopoietin isoform 3 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate splice site in the 3' coding region, which results in a frameshift, compared to variant 1. It encodes isoform 3, which has a shorter and distinct C-terminus, compared to isoform 1.

Source sequence(s)

AB102890, AC078797, BX108191, L33410

UniProtKB/Swiss-Prot

P40225

UniProtKB/TrEMBL

Q5FBX8

Conserved Domains (1) summary

pfam00758
Location:24 – 106
Blast Score: 296

EPO_TPO; Erythropoietin/thrombopoietin

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

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

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000003.11 Reference GRCh37.p10 Primary Assembly

Range

184089773..184095932, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000135.1 Alternate HuRef

Range

181496308..181502467, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018914.1 Alternate CHM1_1.0

Range

183956007..183962167, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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.

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01058445.1 (1660..7819)	None
genomic	AC078797.20 (113349..119508)	None
genomic	AMYH01013718.1 (56947..63107)	None
genomic	CH471052.2	EAW78243.1
		EAW78244.1
		EAW78245.1
genomic	D32046.1	BAA06807.1
genomic	L36051.1	AAC37568.1
genomic	S76771.1	AAB33390.1
genomic	U17071.1	AAA74083.1
mRNA	AB014681.1	BAA34930.1
mRNA	AB014682.1	BAA34931.1
mRNA	AB014683.1	BAA34932.1
mRNA	AB102890.1	BAD89419.1
mRNA	AB102892.1	BAD89421.1
mRNA	AB102894.1	BAD89423.1
mRNA	AK311002.1	None
mRNA	BC130322.1	AAI30323.1
mRNA	BC136338.1	AAI36339.1
mRNA	BC143982.1	AAI43983.1
mRNA	BX108191.1	None
mRNA	D32047.1	BAA21930.1
mRNA	L33410.1	AAA59857.1
mRNA	L36052.1	AAC37566.1
mRNA	U11025.1	AAA50553.1
mRNA	U42977.1	None
mRNA	U59493.1	AAB03392.1
mRNA	U59494.1	AAB03393.1
mRNA	U59495.1	AAB03394.1