MPL MPL proto-oncogene, thrombopoietin receptor [Homo sapiens (human)] - Gene

Summary

Official Symbol: MPLprovided by HGNC
Official Full Name: MPL proto-oncogene, thrombopoietin receptorprovided by HGNC
Primary source: HGNC:HGNC:7217
See related: Ensembl:ENSG00000117400 MIM:159530; AllianceGenome:HGNC:7217
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: MPLV; TPOR; C-MPL; CD110; THPOR; THCYT2
Summary: 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]
Expression: Low expression observed in reference dataset See more
Orthologs: mouse all
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Genomic context

Location:: 1p34.2

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (43337818..43354466)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (43208365..43225013)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (43803489..43820137)

Chromosome 1 - NC_000001.11 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
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?

Germline MPL mutations may be a rare cause of "triple-negative" thrombocytosis.
Title: Germline MPL mutations may be a rare cause of "triple-negative" thrombocytosis.
PF4 activates the c-Mpl-Jak2 pathway in platelets.
Title: PF4 activates the c-Mpl-Jak2 pathway in platelets.
JAK2, CALR, and MPL Mutation Profiles in Colombian patients with BCR-ABL Negative Myeloproliferative Neoplasms.
Title: JAK2, CALR, and MPL Mutation Profiles in Colombian patients with BCR-ABL Negative Myeloproliferative Neoplasms.
A novel mutation in MECOM affects MPL regulation in vitro and results in thrombocytopenia and bone marrow failure.
Title: A novel mutation in MECOM affects MPL regulation in vitro and results in thrombocytopenia and bone marrow failure.
Assessment of intestinal status in MPL[W515L] mutant myeloproliferative neoplasms mice model.
Title: Assessment of intestinal status in MPL(W515L) mutant myeloproliferative neoplasms mice model.
Genomic and computational analysis of four novel variants of MPL gene in Congenital Amegakaryocytic Thrombocytopenia.
Title: Genomic and computational analysis of four novel variants of MPL gene in Congenital Amegakaryocytic Thrombocytopenia.
MPL gene mutation is a possible risk factor for thrombosis in patients with essential thrombocythemia in Japan.
Title: MPL gene mutation is a possible risk factor for thrombosis in patients with essential thrombocythemia in Japan.
Clonal evolution in hereditary thrombocytosis with MPL T487A mutation.
Title: Clonal evolution in hereditary thrombocytosis with MPL T487A mutation.
The Impact of JAK2 V617F, CALR, and MPL Mutations as Molecular Diagnostic Markers of Myeloproliferative Neoplasms in Kurdish Patients. A Single-center Experience.
Title: The Impact of JAK2 V617F, CALR, and MPL Mutations as Molecular Diagnostic Markers of Myeloproliferative Neoplasms in Kurdish Patients. A Single-center Experience.
Frequency of JAK2V617F, MPL and CALR driver mutations and associated clinical characteristics in a Norwegian patient cohort with myeloproliferative neoplasms.
Title: Frequency of JAK2V617F, MPL and CALR driver mutations and associated clinical characteristics in a Norwegian patient cohort with myeloproliferative neoplasms.

Submit: New GeneRIF Correction See all GeneRIFs (219)

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
Congenital amegakaryocytic thrombocytopenia 1 MedGen: C5882667 OMIM: 604498 GeneReviews: Not available	not available
Primary myelofibrosis MedGen: C0001815 OMIM: 254450 GeneReviews: Not available	not available
Thrombocythemia 2 MedGen: C3275998 OMIM: 601977 GeneReviews: Not available	not available

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

MARC_4067-4068:996679330:1 (e-PCR)
- UniSTS:269316

RH80231 (e-PCR)
- UniSTS:87088

PMC15907P1 (e-PCR)
- UniSTS:271440

PMC15907P2 (e-PCR)
- UniSTS:271441

PMC15907P3 (e-PCR)
- UniSTS:271442

PMC15907P4 (e-PCR)
- UniSTS:271443

PMC15907P5 (e-PCR)
- UniSTS:271444

D13S1553 (e-PCR)
- UniSTS:473482

SHGC-74727 (e-PCR)
- UniSTS:50836

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables thrombopoietin receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables thrombopoietin receptor activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in basophil homeostasis	IEA Inferred from Electronic Annotation more info
involved_in cellular response to hypoxia	IEA Inferred from Electronic Annotation more info
involved_in eosinophil homeostasis	IEA Inferred from Electronic Annotation more info
involved_in monocyte homeostasis	IEA Inferred from Electronic Annotation more info
involved_in neutrophil homeostasis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of lymphocyte proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of platelet formation	IEA Inferred from Electronic Annotation 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

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
is_active_in external side of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in neuronal cell body	IEA Inferred from Electronic Annotation more info
located_in nuclear membrane	IDA Inferred from Direct Assay more info
is_active_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: thrombopoietin receptor

Names: TPO-R; myeloproliferative leukemia protein; myeloproliferative leukemia virus oncogene; proto-oncogene c-Mpl

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_007525.1 RefSeqGene

Range

5001..21661

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_510

mRNA and Protein(s)

NM_005373.3 → NP_005364.1 thrombopoietin receptor precursor

See identical proteins and their annotated locations for NP_005364.1

Status: REVIEWED

Source sequence(s)

AL139289, M90102

Consensus CDS

CCDS483.1

UniProtKB/Swiss-Prot

P40238, Q5JUZ0

UniProtKB/TrEMBL

Q5JUY5

Related

ENSP00000361548.3, ENST00000372470.9

Conserved Domains (2) summary

cd00063
Location:395 → 485

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

pfam09067
Location:25 → 128

EpoR_lig-bind; Erythropoietin receptor, ligand binding