Mpl gene mpl proto-oncogene, thrombopoietin receptor Normal Function

---

Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/)
1
MPL gene
MPL proto-oncogene, thrombopoietin receptor
Normal Function
 
The MPL gene provides instructions for making the thrombopoietin receptor protein, 
which promotes the growth and division (proliferation) of cells. This receptor is 
especially important for the proliferation of certain blood cells called megakaryocytes, 
which produce platelets, the cells involved in blood clotting. Research suggests that the 
thrombopoietin receptor may also play a role in the maintenance of hematopoietic stem 
cells, which are stem cells located within the bone marrow that have the potential to 
develop into red blood cells, white blood cells, and platelets.
The thrombopoietin receptor is turned on (activated) when a protein called 
thrombopoietin attaches (binds) to it. The activated thrombopoietin receptor stimulates a 
signaling pathway called the JAK/STAT pathway, which transmits chemical signals from 
outside the cell to the cell's nucleus and is important for controlling the production of 
blood cells.
Health Conditions Related to Genetic Changes
Essential thrombocythemia
Several mutations in the MPL gene have been associated with a small number of cases 
of essential thrombocythemia, a condition characterized by an increased number of 
platelets in the blood. Platelets are the blood cells involved in blood clotting, and 
abnormal clotting (thrombosis) is common in people with essential thrombocythemia.
MPL gene mutations associated with essential thrombocythemia change a single 
protein building block (amino acid) in the thrombopoietin receptor protein. An inherited 
form of the condition, called familial essential thrombocythemia, is caused by an MPL 
gene mutation that results in the replacement of the amino acid serine with the amino 
acid asparagine at position 505 in the protein (written as Ser505Asn or S505N). 
Essential thrombocythemia that does not run in families (sporadic essential 
thrombocythemia) has been associated with MPL gene mutations that result in the 
replacement of the amino acid tryptophan at position 515 with another amino acid, most 
commonly leucine. These mutations are generally referred to as W515 mutations.
Amino acid changes at position 505 or 515 result in a thrombopoietin receptor protein 

---

Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/)
2
that is constantly turned on (constitutively activated), which, in essential thrombocythemia, 
leads to the overproduction of abnormal megakaryocytes and an increased number of 
platelets. Excess platelets can cause thrombosis, which leads to many signs and 
symptoms of essential thrombocythemia. 
Primary myelofibrosis
Several mutations in the MPL gene have been identified in some people with primary 
myelofibrosis. This condition is characterized by scar tissue (fibrosis) in the bone 
marrow, the tissue that produces blood cells.
Like essential thrombocythemia, primary myelofibrosis is associated with the MPL gene 
mutations referred to as W515 mutations. These mutations lead to a constitutively 
activated thrombopoietin receptor protein, which results in the overproduction of 
abnormal megakaryocytes. These megakaryocytes stimulate other cells to release 
collagen, a protein that normally provides structural support for the cells in the bone 
marrow but causes scar tissue formation in primary myelofibrosis. Because of the 
fibrosis, the bone marrow cannot produce enough normal blood cells, leading to the 
signs and symptoms of the condition.
It is unknown how the same gene mutations can be associated with different conditions. 
Other disorders
Mutations in the MPL gene cause a rare condition called congenital amegakaryocytic 
thrombocytopenia (CAMT). This condition begins in infancy and is characterized by low 
numbers of megakaryocytes (megakaryocytopenia) and platelets (thrombocytopenia). 
CAMT can lead to an impairment of bone marrow function known as bone marrow 
failure.
The MPL gene mutations involved in CAMT lead to a reduced functioning or 
nonfunctioning thrombopoietin receptor protein. People with no thrombopoietin receptor 
function have a severe form of the condition called CAMT I. People with some 
remaining thrombopoietin receptor function have a milder form of the condition called 
CAMT II.