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The official name of this gene is “platelet-derived growth factor receptor, alpha polypeptide.”
PDGFRA is the gene's official symbol. The PDGFRA gene is also known by other names, listed below.
The PDGFRA gene provides instructions for making a protein called platelet-derived growth factor receptor alpha (PDGFRA), which is part of a family of proteins called receptor tyrosine kinases (RTKs). Receptor tyrosine kinases transmit signals from the cell surface into the cell through a process called signal transduction. The PDGFRA protein is found in the cell membrane of certain cell types where a specific protein, called platelet-derived growth factor, attaches (binds) to it. This binding turns on (activates) the PDGFRA protein, which then activates other proteins inside the cell by adding a cluster of oxygen and phosphorus atoms (a phosphate group) at specific positions (a process called phosphorylation). This process leads to the activation of a series of proteins in multiple signaling pathways.
The signaling pathways stimulated by the PDGFRA protein control many important cellular processes such as cell growth and division (proliferation) and cell survival. PDGFRA protein signaling is important for the development of many types of cells throughout the body.
The PDGFRA gene belongs to a family of genes called CD (CD molecules). It also belongs to a family of genes called immunoglobulin superfamily, I-set domain containing (immunoglobulin superfamily, I-set domain containing).
A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.
Genetic abnormalities that involve the PDGFRA gene cause a type of blood cell cancer called PDGFRA-associated chronic eosinophilic leukemia. This condition is characterized by an increased number of eosinophils, a type of white blood cell involved in allergic reactions. These genetic abnormalities are somatic mutations, which are mutations acquired during a person's lifetime that are present only in certain cells. The most common of these genetic abnormalities is a deletion of genetic material from chromosome 4 that brings together parts of two genes, FIP1L1 and PDGFRA, creating the FIP1L1-PDGFRA fusion gene. Occasionally, genes other than FIP1L1 are fused with the PDGFRA gene. Mutations that change single DNA building blocks in the PDGFRA gene (point mutations) can also cause this condition, although these mutations are seen very rarely.
The protein produced from the FIP1L1-PDGFRA fusion gene (as well as other PDGFRA fusion genes) has the function of the PDGFRA protein. However, unlike the normal PDGFRA protein, the fusion protein does not require binding of the platelet-derived growth factor protein to be activated. Similarly, point mutations in the PDGFRA gene can result in a PDGFRA protein that is activated without ligand binding. As a result, the signaling pathways are constantly turned on (constitutively activated), which increases the proliferation and survival of cells. When the FIP1L1-PDGFRA fusion gene mutation or point mutations in the PDGFRA gene occur in early blood cells, the growth of eosinophils (and occasionally other blood cells) is poorly controlled, leading to PDGFRA-associated chronic eosinophilic leukemia. It is unclear why eosinophils are preferentially affected by this genetic change.
Mutations in the PDGFRA gene are associated with gastrointestinal stromal tumors (GISTs). GISTs are a type of tumor that occurs in the gastrointestinal tract, most commonly in the stomach or small intestine. The majority of GISTs associated with a mutation in the PDGFRA gene occur in the stomach. In most cases, the genetic changes are acquired during a person's lifetime and are called somatic mutations. Somatic mutations, which lead to sporadic GISTs, are present only in the tumor cells and are not inherited. Less commonly, PDGFRA gene mutations that increase the risk of developing GISTs are inherited from a parent, which can lead to familial GISTs.
PDGFRA gene mutations associated with GISTs create a protein that no longer requires binding of the platelet-derived growth factor protein to be activated. As a result, the PDGFRA protein and the signaling pathways are constitutively activated, which increases cell proliferation and survival, leading to tumor formation.
PDGFRA gene mutations that lead to a constitutively active PDGFRA protein are also associated with inflammatory fibroid polyps, which are small, noncancerous (benign) tumors that form in the gastrointestinal tract. These tumors are made up of fibrous tissue and usually contain cells known to cause inflammation (inflammatory cells). As in GISTs, the constitutively active PDGFRA protein leads to the overgrowth of cells and formation of tumors.
Cytogenetic Location: 4q12
Molecular Location on chromosome 4: base pairs 54,229,096 to 54,298,244
The PDGFRA gene is located on the long (q) arm of chromosome 4 at position 12.
More precisely, the PDGFRA gene is located from base pair 54,229,096 to base pair 54,298,244 on chromosome 4.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
You and your healthcare professional may find the following resources about PDGFRA helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
benign ; biomarker ; cancer ; cell ; cell membrane ; cell proliferation ; chromosome ; chronic ; deletion ; DNA ; eosinophils ; familial ; fusion gene ; gastrointestinal ; gene ; growth factor ; inflammation ; inherited ; intestine ; leukemia ; ligand ; mutation ; oxygen ; pharmacogenetics ; phosphate ; phosphorus ; phosphorylation ; proliferation ; protein ; receptor ; signal transduction ; sporadic ; stomach ; tissue ; transduction ; tumor ; tyrosine
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.