MPL Gene (Myeloproliferative Leukemia Virus Oncogene)
Thrombopoietin Receptor: Key Regulator of Megakaryopoiesis and Platelet Production
Gene Information Card
| Symbol | MPL |
|---|---|
| Full Name | MPL proto-oncogene, thrombopoietin receptor |
| Gene Type | protein-coding |
| Chromosomal Location | 1p34.2 |
| NCBI Gene ID | 4352 ncbi.nlm.nih.gov/gene/4352 |
| Ensembl ID | ENSG00000117400 |
| UniProt ID | P40238 |
| OMIM ID | 159530 |
| HGNC ID | 7217 |
| Aliases | TPOR, CD110, C-MPL, MPLV, THCYT2 |
Description
The MPL gene encodes the thrombopoietin receptor (TPOR), a type I cytokine receptor primarily expressed on hematopoietic stem cells, megakaryocytes, and platelets. Binding of its ligand, thrombopoietin (THPO), activates JAK2/STAT, MAPK, and PI3K signaling pathways, driving megakaryopoiesis and platelet production. Gain-of-function mutations in MPL are associated with myeloproliferative neoplasms (MPNs) such as essential thrombocythemia and primary myelofibrosis, while loss-of-function mutations cause congenital amegakaryocytic thrombocytopenia (CAMT).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Essential Thrombocythemia (ET) | Gain-of-function mutations (e.g., MPL W515L/K) constitutively activate the receptor, leading to uncontrolled megakaryocyte proliferation and thrombocytosis. | ClinVar, COSMIC |
| Primary Myelofibrosis (PMF) | MPL W515L/K mutations drive cytokine-independent signaling, contributing to bone marrow fibrosis and extramedullary hematopoiesis. | ClinVar, COSMIC |
| Congenital Amegakaryocytic Thrombocytopenia (CAMT) | Biallelic loss-of-function mutations (e.g., nonsense, frameshift) abolish thrombopoietin signaling, resulting in severe thrombocytopenia and progression to bone marrow failure. | ClinVar, OMIM |
| Myelodysplastic Syndrome (MDS) | Rare MPL mutations (e.g., S505N) may contribute to dysplastic megakaryopoiesis. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 12.5 | High |
| Spleen | 8.3 | Medium |
| Lung | 4.1 | Low |
| Liver | 2.8 | Low |
| Whole Blood | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Megakaryocytes | 25.0 | High expression; key for platelet production |
| CD34+ Hematopoietic Stem Cells | 18.2 | High expression; stem cell maintenance |
| Platelets | 15.0 | High expression; surface receptor |
| K562 (leukemia) | 3.5 | Moderate expression |
| HEK293 | 0.2 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| MPL W515L | Missense (G>A) | ~5% in ET, ~10% in PMF | Gain-of-function; constitutive activation of JAK2/STAT |
| MPL W515K | Missense (G>T) | ~1% in ET, ~3% in PMF | Gain-of-function; similar to W515L |
| MPL S505N | Missense (G>A) | Rare in MPNs, also in familial thrombocythemia | Gain-of-function; altered receptor dimerization |
| MPL R102P | Missense (G>C) | CAMT-associated | Loss-of-function; impaired ligand binding |
| MPL L265P | Missense (T>C) | CAMT-associated | Loss-of-function; defective trafficking |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (e.g., nonsense, frameshift, missense in extracellular domain) cause congenital amegakaryocytic thrombocytopenia (CAMT) by disrupting thrombopoietin binding or receptor trafficking, leading to absent megakaryopoiesis.
Gain of Function (GOF)
Missense mutations in the juxtamembrane domain (e.g., W515L, W515K, S505N) constitutively activate the receptor without ligand, driving myeloproliferative neoplasms (ET, PMF) via JAK2/STAT hyperactivation.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported for MPL; most pathogenic variants are either loss- or gain-of-function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• JAK-STAT signaling pathway (KEGG hsa04630)
• Thrombopoietin signaling (Reactome R-HSA-9009391)
• Hematopoietic cell lineage (KEGG hsa04640)
• PI3K-Akt signaling pathway (KEGG hsa04151)
Protein Summary
The MPL protein (thrombopoietin receptor, TPOR) is a 635-amino acid type I transmembrane glycoprotein. It consists of an extracellular ligand-binding domain with two cytokine receptor modules, a single transmembrane domain, and an intracellular domain containing Box1/Box2 motifs essential for JAK2 binding. Upon thrombopoietin binding, the receptor homodimerizes, activating JAK2, which phosphorylates STAT3/STAT5, MAPK, and PI3K pathways. MPL is critical for hematopoietic stem cell quiescence, megakaryocyte maturation, and platelet shedding. Mutations in MPL are central to both inherited thrombocytopenias and acquired myeloproliferative disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MPL Knockout HEK293 Cell Line | EDJ-KQ511 | Human | 4352 | Details Get a Quote |
| MPLKIP Knockout HEK293 Cell Line | EDJ-KQ3073 | Human | 136647 | Details Get a Quote |
| MPLKIP Knockout A-549 Cell Line | EDJ-KQ24354 | Human | 136647 | Details Get a Quote |
| MPLKIP Knockout HCT 116 Cell Line | EDJ-KQ24355 | Human | 136647 | Details Get a Quote |
| MPLKIP Knockout HeLa Cell Line | EDJ-KQ24356 | Human | 136647 | Details Get a Quote |
| MPL Knockout HeLa Cell Line | EDJ-KQ53898 | Human | 4352 | Details Get a Quote |
| MPL Knockout A-549 Cell Line | EDJ-KQ62389 | Human | 4352 | Details Get a Quote |
| MPL Knockout HCT 116 Cell Line | EDJ-KQ70858 | Human | 4352 | Details Get a Quote |
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