MPL
Chr 1ARADSomaticMPL proto-oncogene, thrombopoietin receptor
Also known as: C-MPL, CD110, MPLV, THCYT2, THPOR, TPOR
CD110 is the receptor for thrombopoietin that regulates hematopoietic stem cell renewal, megakaryocyte differentiation, and platelet formation through JAK2 signaling pathways. Mutations cause congenital amegakaryocytic thrombocytopenia (autosomal recessive inheritance pattern) presenting in infancy with severe bleeding due to absent or markedly reduced platelets, as well as autosomal dominant thrombocythemia and somatic myelofibrosis. This gene is highly intolerant to loss-of-function variants, reflecting its critical role in platelet production and hematopoietic stem cell function.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
361 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 25 | 6 | 6 | 0 | 37 |
Likely Pathogenic | 32 | 11 | 2 | 0 | 45 |
VUS | 2 | 130 | 8 | 9 | 149 |
Likely Benign | 0 | 5 | 46 | 60 | 111 |
Benign | 0 | 0 | 1 | 1 | 2 |
Conflicting | — | 11 | |||
| Total | 59 | 152 | 63 | 70 | 355 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MPL · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions)
ACTIVE NOT RECRUITINGA Study of Osimertinib With or Without Chemotherapy as 1st Line Treatment in Patients With Mutated Epidermal Growth Factor Receptor Non-Small Cell Lung Cancer (FLAURA2)
ACTIVE NOT RECRUITINGRegistry of Patients With MPNs in Taiwan
ACTIVE NOT RECRUITINGA Study to Learn More About How Well Treatment With Sevabertinib (BAY 2927088) Tablets Works and How Safe it is in Participants Who Have a Solid Tumor With Mutations of the Human Epidermal Growth Factor Receptor 2 (HER2)
RECRUITINGAnalyse of Tumour and Constitutional DNA for the Study of the Determinism in Child Neoplasia
ACTIVE NOT RECRUITINGPrevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History
NOT YET RECRUITINGEfficacy and Safety Comparison of Niraparib to Placebo in Participants With Human Epidermal Growth Factor 2 Negative (HER2-) Breast Cancer Susceptibility Gene Mutation (BRCAmut) or Triple-Negative Breast Cancer (TNBC) With Molecular Disease
ACTIVE NOT RECRUITINGMolecular and Clinical Analysis of Bone Marrow Failure: A Secondary Research Study
ENROLLING BY INVITATIONA Study of BN104 in the Treatment of Acute Leukemia
ACTIVE NOT RECRUITINGA Study of Bleximenib, Venetoclax and Azacitidine For Treatment of Participants With Newly Diagnosed Acute Myeloid Leukemia (AML)
RECRUITINGStudy of Safety and Efficacy of Brigatinib Plus Chemotherapy or Brigatinib Only in Advanced ALK-Positive Lung Cancer (MASTERPROTOCOL ALK)
ACTIVE NOT RECRUITINGA Study of Encorafenib Plus Cetuximab Taken Together With Pembrolizumab Compared to Pembrolizumab Alone in People With Previously Untreated Metastatic Colorectal Cancer
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools