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This gene encodes a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family. These growth factors are mitogens for cells of mesenchymal origin. The identity of the growth factor bound to a receptor monomer determines whether the functional receptor is a homodimer or a heterodimer, composed of both platelet-derived growth factor receptor alpha and beta polypeptides. Studies suggest that this gene plays a role in organ development, wound healing, and tumor progression. Mutations in this gene have been associated with idiopathic hypereosinophilic syndrome, somatic and familial gastrointestinal stromal tumors, and a variety of other cancers. [provided by RefSeq, Mar 2012]
Commonly mutated in GI tract tumors, PDGFR family genes (mutually exclusive to KIT mutations) are a hallmark of gastrointestinal stromal tumors. Gene fusions involving the PDGFRA kinase domain are highly correlated with eosinophilia, and the WHO classifies myeloid and lymphoid neoplasms with these characteristics as a distinct disorder. Mutations in the 842 region of PDGFRA have been often found to confer resistance to the tyrosine kinase inhibitor, imatinib.
PDGFRA (Platelet Derived Growth Factor Receptor Alpha) is a Protein Coding gene. Diseases associated with PDGFRA include Gist-Plus Syndrome and Hypereosinophilic Syndrome, Idiopathic. Among its related pathways are RET signaling and Phospholipase D signaling pathway. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and protein kinase activity. An important paralog of this gene is ENSG00000282278.
Platelet-derived growth factor receptors (PDGFRs) are catalytic receptors that have intracellular tyrosine kinase activity. They have roles in the regulation of many biological processes including embryonic development, angiogenesis, cell proliferation and differentiation.
GeneHancer (GH) Identifier | GH Type | GH Score |
GH Sources | Gene Association Score | Total Score | TSS distance (kb) | Number of Genes Away | Size (kb) | Transcription Factor Binding Sites |
Gene Targets |
---|---|---|---|---|---|---|---|---|---|---|
GH04J054224 | Promoter/Enhancer | 2.5 | EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER | 606.6 | +0.8 | 791 | 10.6 | CEBPG CTCF ZBTB33 TEAD4 PRDM10 ZNF143 ZIC2 PATZ1 REST RAD21 | PDGFRA GSX2 piR-59769-458 KIT ENSG00000282278 | |
GH04J054264 | Promoter | 0.3 | EPDnew | 611 | +35.8 | 35830 | 0.1 | PDGFRA piR-48759-228 piR-59769-458 KIT ENSG00000282278 | ||
GH04J054258 | Promoter | 0.3 | EPDnew | 600.3 | +29.7 | 29687 | 0.1 | PDGFRA piR-48759-228 piR-59769-458 KIT ENSG00000282278 | ||
GH04J054261 | Promoter | 0.3 | EPDnew | 600.3 | +32.0 | 31951 | 0.1 | PDGFRA piR-48759-228 piR-59769-458 KIT ENSG00000282278 | ||
GH04J054267 | Promoter | 0.3 | EPDnew | 600.3 | +38.5 | 38490 | 0.1 | piR-48759-228 PDGFRA lnc-CHIC2-5 KIT ENSG00000282278 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0004672 | protein kinase activity | IDA | 24190966 |
GO:0004713 | protein tyrosine kinase activity | IEA | -- |
GO:0004714 | transmembrane receptor protein tyrosine kinase activity | IBA,IDA | 1646396 |
GO:0005018 | platelet-derived growth factor alpha-receptor activity | IMP | 2554309 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005623 | cell | IEA | -- |
GO:0005634 | nucleus | ISS | -- |
GO:0005654 | nucleoplasm | IDA | -- |
GO:0005737 | cytoplasm | ISS | -- |
GO:0005794 | Golgi apparatus | ISS | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | RET signaling |
.92
|
.92
|
2 | Apoptotic Pathways in Synovial Fibroblasts |
Cellular Apoptosis Pathway
.85
Mitochondrial Apoptosis
.85
Apoptotic Pathways in Synovial Fibroblasts
.84
p53 Mediated Apoptosis
.84
DHA Signaling
.74
Telomerase Components in Cell Signaling
.72
PPAR Pathway
.66
|
Rac1 Pathway
.65
Actin-Based Motility by Rho Family GTPases
.62
ERK5 Signaling
.61
eIF2 Pathway
.60
Rap1 Pathway
.57
Nuclear Receptor Activation by Vitamin-A
.57
|
3 | GPCR Pathway |
Paxillin Interactions
.73
Ras Pathway
.73
GPCR Pathway
.62
Pancreatic Adenocarcinoma
.59
|
Breast Cancer Regulation by Stathmin1
.58
NFAT in Immune Response
.58
Estrogen Pathway
.55
P2Y Receptor Signaling
.38
|
4 | GAB1 signalosome |
.89
|
|
5 | ERK Signaling |
ERK Signaling
.61
Rho Family GTPases
.61
MAPK Signaling
.58
|
Molecular Mechanisms of Cancer
.51
ILK Signaling
.49
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000165 | MAPK cascade | TAS | -- |
GO:0001553 | luteinization | ISS | -- |
GO:0001701 | in utero embryonic development | IEA | -- |
GO:0001775 | cell activation | TAS | 10508235 |
GO:0002244 | hematopoietic progenitor cell differentiation | IBA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Sunitinib | Approved, Investigational | Pharma | Target, inhibitor | VEGFR/PDGFRβ/ KIT/ FLT3/RET/CSF-1R inhibitor, RTK inhibitor, Potent VEGFR, PDGFRbeta and KIT inhibitor, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors | 552 | |
imatinib | Approved | Pharma | Target, antagonist, inhibitor | Kinase Inhibitors, SRC/BCR-ABL tyrosine kinase inhibitors | 0 | |
regorafenib | Approved | Pharma | Target, inhibitor | Inhibitor of VEGFR/PDGFR/FGFR/mutant kit/RET/Raf-1, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors | 0 | |
Becaplermin | Approved, Investigational | Pharma | Target, inhibitor | 24 | ||
Lenvatinib | Approved, Investigational | Pharma | Target, inhibitor | Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors | 155 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist | 58-64-0 |
|
||
N-desmethylimatinib |
|
|||||
SU 6668 |
|
252916-29-3 |
|
|
Compound | Action | Cas Number |
---|---|---|
DMPQ dihydrochloride | Potent, selective inhibitor of PDGFRbeta | 1123491-15-5 |
SU 6668 | PDGFR, VEGFR and FGFR inhibitor | 252916-29-3 |
Toceranib | Potent PDGFR and VEGFR inhibitor | 356068-94-5 |
Compound | Action | Cas Number |
---|---|---|
AG-18 | EGFR/PDGFR inhibitor | 118409-57-7 |
Amuvatinib (MP-470, HPK 56) | Tyrosine kinase inhibitor | 850879-09-3 |
Apatinib | VEGFR2 inhibitor, orally bioavailable, selective | 811803-05-1 |
CP-673451 | PDGFRα/β inhibitor,potent and selective | 343787-29-1 |
Crenolanib (CP-868596) | PDGFR-β inhibitor,potent and selective | 670220-88-9 |
DMPQ dihydrochloride | 1123491-15-5 | |
Dovitinib (TKI258) Lactate | Oral tyrosine kinase inhibitor (TKI) against FGFR1–3, VEGFR1–3, and platelet-derived growth factor receptor (PDGFR) | 915769-50-5 |
Flumatinib mesylate | 895519-91-2 | |
Imatinib (STI571) | Protein-tyrosine kinase inhibitor | 152459-95-5 |
Imatinib hydrochloride | V-Abl/c-Kit/PDGFR inhibitor | 862366-25-4 |
Imatinib Mesylate (STI571) | Abl/c-kit/PDGFR inhibitor | 220127-57-1 |
Linifanib (ABT-869) | VEGFR/PDGFR inhibitor | 796967-16-3 |
Masitinib (AB1010) | Tyrosine kinase inhibitor, potent and selective | 790299-79-5 |
MK-2461 | C-Met (WT/mutants) inhibitor | 917879-39-1 |
Motesanib Diphosphate (AMG-706) | VEGFR/ PDGFR/c-Kit/Ret inhibitor | 857876-30-3 |
Nintedanib (BIBF 1120) | VEGFR/PDGFR/FGFR inhibitor | 928326-83-4 |
Pazopanib (GW-786034) | VEGFR/PDGFR/FGFR inhibitor | 635702-64-6 |
Pazopanib Hydrochloride | VEGFR/PDGFR/FGFR/c-Kit/ c-Fms inhibitor | 635702-64-6 |
PP121 | Dual inhibitor of tyrosine and phosphoinositide kinases | 1092788-83-4 |
Regorafenib | Inhibitor of VEGFR/PDGFR/FGFR/mutant kit/RET/Raf-1 | 755037-03-7 |
Sennoside B | 128-57-4 | |
SU 16f | 251356-45-3 | |
SU 4312 | 5812-07-7 | |
SU 5402 | VEGFR2/FGFR/PDGFR/EGFR inhibitor | 215543-92-3 |
Sunitinib | RTK inhibitor | 557795-19-4 |
Toceranib | c-Kit/VEGFR/PDGFR inhibtor | 356068-94-5 |
TSU-68 (SU6668,Orantinib) | PDGFR/Flk-1/FGFR1 inhibitor,potent and competitive | 252916-29-3 |
Tyrphostin 9 | Selective EGFR/PDGFR inhibitor | 10537-47-0 |
Tyrphostin AG 1296 | PDGFR inhibitor,selective and ATP-competitive | 146535-11-7 |
ExUns: | 1a | · | 1b | · | 1c | ^ | 2 | ^ | 3 | ^ | 4 | ^ | 5 | ^ | 6 | ^ | 7 | ^ | 8a | · | 8b | · | 8c | · | 8d | ^ | 9 | ^ | 10 | ^ | 11 | ^ | 12 | ^ | 13 | ^ | 14 | ^ | 15 | ^ | 16 | ^ | 17a | · | 17b | ^ | 18a | · | 18b | ^ | 19 | ^ |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | - | - | - | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||
SP2: | - | - | - | - | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||
SP3: | - | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP4: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP5: | - | - | - | - | ||||||||||||||||||||||||||||||||||||||||||||||||
SP6: | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||||||
SP7: | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||||||
SP8: | - | - | ||||||||||||||||||||||||||||||||||||||||||||||||||
SP9: |
ExUns: | 20 | ^ | 21 | ^ | 22a | · | 22b | ^ | 23 | ^ | 24 | ^ | 25 | ^ | 26 | ^ | 27 | ^ | 28 | ^ | 29 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | - | - | ||||||||||||||||||
SP2: | |||||||||||||||||||||
SP3: | - | ||||||||||||||||||||
SP4: | |||||||||||||||||||||
SP5: | |||||||||||||||||||||
SP6: | |||||||||||||||||||||
SP7: | |||||||||||||||||||||
SP8: | |||||||||||||||||||||
SP9: |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | PDGFRA 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | PDGFRA 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | PDGFRA 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Pdgfra 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Pdgfra 30 |
|
||
Oppossum (Monodelphis domestica) |
Mammalia | PDGFRA 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | -- 31 |
|
OneToMany | |
-- 31 |
|
OneToMany | |||
-- 31 |
|
OneToMany | |||
-- 31 |
|
OneToMany | |||
Chicken (Gallus gallus) |
Aves | PDGFRA 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | PDGFRA 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | LOC100124862 30 |
|
||
Str.9869 30 |
|
||||
African clawed frog (Xenopus laevis) |
Amphibia | pdgfra-prov 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | pdgfra 30 30 |
|
||
Fruit Fly (Drosophila melanogaster) |
Insecta | CG3277 32 |
|
|
|
Worm (Caenorhabditis elegans) |
Secernentea | C24G6.2 30 |
|
||
R09D1.12 32 |
|
|
|||
ver-2 32 |
|
|
SNP ID | Clinical significance and condition | Chr 04 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
240354 | Uncertain Significance: Gastrointestinal stromal tumor | 54,263,911(+) | TG/CA | MISSENSE_VARIANT | |
459018 | Uncertain Significance: Gastrointestinal stromal tumor; not specified | 54,274,887(+) | CA/TG | MISSENSE_VARIANT | |
638914 | Uncertain Significance: Gastrointestinal stromal tumor | 54,285,391(+) | C/G | MISSENSE_VARIANT | |
639043 | Uncertain Significance: Gastrointestinal stromal tumor | 54,270,651(+) | G/T | MISSENSE_VARIANT | |
639349 | Uncertain Significance: Gastrointestinal stromal tumor | 54,290,373(+) | C/T | MISSENSE_VARIANT |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
dgv5209n100 | CNV | gain | 25217958 |
esv2763361 | CNV | loss | 21179565 |
esv3569425 | CNV | loss | 25503493 |
esv3569426 | CNV | loss | 25503493 |
nsv1002905 | CNV | loss | 25217958 |
nsv1008497 | CNV | gain | 25217958 |
nsv1123794 | CNV | deletion | 24896259 |
Disorder | Aliases | PubMed IDs |
---|---|---|
gist-plus syndrome |
|
|
hypereosinophilic syndrome, idiopathic |
|
|
gastrointestinal stromal tumor |
|
|
myeloid and lymphoid neoplasms associated with pdgfra rearrangement |
|
|
chronic eosinophilic leukemia |
|
|