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Vascular endothelial growth factor (VEGF) is a major growth factor for endothelial cells. This gene encodes one of the two receptors of the VEGF. This receptor, known as kinase insert domain receptor, is a type III receptor tyrosine kinase. It functions as the main mediator of VEGF-induced endothelial proliferation, survival, migration, tubular morphogenesis and sprouting. The signalling and trafficking of this receptor are regulated by multiple factors, including Rab GTPase, P2Y purine nucleotide receptor, integrin alphaVbeta3, T-cell protein tyrosine phosphatase, etc.. Mutations of this gene are implicated in infantile capillary hemangiomas. [provided by RefSeq, May 2009]
KDR (Kinase Insert Domain Receptor) is a Protein Coding gene. Diseases associated with KDR include Hemangioma, Capillary Infantile and Hemangioma. Among its related pathways are Cell adhesion_Plasmin signaling and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is FLT4.
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 |
---|---|---|---|---|---|---|---|---|---|---|
GH04J055123 | Promoter/Enhancer | 1.7 | EPDnew Ensembl ENCODE CraniofacialAtlas | 600.7 | +1.7 | 1695 | 5.4 | FOXA1 POLR2A KLF9 ZBTB20 FOXA2 ZBTB26 ZNF335 SPI1 ETS1 SIN3A | KDR SRD5A3 lnc-KDR-3-001 lnc-KDR-3-002 piR-57460-521 KIT | |
GH04J055180 | Enhancer | 1 | Ensembl ENCODE dbSUPER | 61.1 | -59.0 | -59006 | 7.6 | CTCF JUND REST ZNF24 HMBOX1 CEBPB FOS SMC3 YY1 FOSL1 | KDR lnc-SRD5A3-6 lnc-KDR-5 SRD5A3 | |
GH04J055169 | Enhancer | 0.7 | Ensembl ENCODE | 55.6 | -44.1 | -44112 | 1 | CTCF PKNOX1 NFE2 MAFG FOXA1 MNT EMSY | piR-55361-412 KDR piR-43105-492 SRD5A3 | |
GH04J055175 | Enhancer | 0.7 | ENCODE dbSUPER | 50.9 | -50.4 | -50430 | 1.9 | JUN GABPA JUND FOSL1 SPI1 ETV1 FOS GABPB1 | lnc-SRD5A3-6 piR-43105-492 KDR lnc-KDR-5 SRD5A3 | |
GH04J055172 | Enhancer | 0.8 | FANTOM5 ENCODE dbSUPER | 40.4 | -47.4 | -47365 | 0.3 | ESR1 NR2F2 JUND JUN | piR-43105-492 KDR piR-55361-412 SRD5A3 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0004672 | protein kinase activity | IEA | -- |
GO:0004713 | protein tyrosine kinase activity | EXP,IDA | 10037737 |
GO:0004714 | transmembrane receptor protein tyrosine kinase activity | TAS | 1417831 |
GO:0005021 | vascular endothelial growth factor-activated receptor activity | IBA,IDA | 1417831 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005576 | extracellular region | IEA | -- |
GO:0005634 | nucleus | IEA | -- |
GO:0005737 | cytoplasm | IEA | -- |
GO:0005768 | endosome | IEA,IDA | 23262137 |
GO:0005769 | early endosome | ISS | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | 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
Nuclear Receptor Activation by Vitamin-A
.57
|
2 | 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
|
3 | ERK Signaling |
ERK Signaling
.61
Rho Family GTPases
.61
MAPK Signaling
.58
|
Molecular Mechanisms of Cancer
.51
ILK Signaling
.49
|
4 | Nanog in Mammalian ESC Pluripotency |
GSK3 Signaling
.62
Nanog in Mammalian ESC Pluripotency
.62
|
14-3-3 Induced Intracellular Signaling
.59
eNOS Signaling
.48
|
5 | CREB Pathway |
CREB Pathway
.68
IP3 Pathway
.68
|
Activation of PKC through GPCR
.63
Intracellular Calcium Signaling
.50
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0001525 | angiogenesis | TAS | 10022831 |
GO:0001569 | branching involved in blood vessel morphogenesis | IMP | 23688497 |
GO:0001570 | vasculogenesis | ISS | -- |
GO:0001934 | positive regulation of protein phosphorylation | IDA | 19033661 |
GO:0001938 | positive regulation of endothelial cell proliferation | IMP | 10022831 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Sorafenib | Approved, Investigational | Pharma | Target, antagonist, inhibitors, inhibitor | Raf kinases and tyrosine kinases inhibitor, RAF, VEGFR2, and PDGFR-beta inhibitors, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors | 779 | |
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 | |
Pazopanib | Approved | Pharma | Target, inhibitor | VEFGR, c-Kit, and PDGFR inhibitor, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) 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 | |
Axitinib | Approved, Investigational | Pharma | Target, inhibitor, Inhibition | Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors | 144 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist | 58-64-0 |
|
Compound | Action | Cas Number |
---|---|---|
(E)-FeCP-oxindole | 884338-18-5 | |
(Z)-FeCP-oxindole | 1137967-28-2 | |
AEE788 (NVP-AEE788) | EGFR/HER-2/VEGFR inhibitor | 497839-62-0 |
Apatinib | VEGFR2 inhibitor, orally bioavailable, selective | 811803-05-1 |
Axitinib (AG 013736) | VEGFR1/ c-Kit inhibitor | 319460-85-0 |
AZD2932 | inhibitor of VEGFR-2, PDGFRβ, Flt-3, and c-Kit | 883986-34-3 |
BMS-794833 | Met/VEGFR-2 inhibitor,potent and ATP-competitive | 1174046-72-0 |
Brivanib (BMS-540215) | VEGFR-2 inhibitor,ATP-competitive | 649735-46-6 |
Brivanib Alaninate (BMS-582664) | VEGFR2 inhibitor,ATP-competitive | 649735-63-7 |
Cabozantinib (XL184, BMS-907351) | VEGFR2/Met/Ret/Kit/FLT//AXL inhibitor | 849217-68-1 |
Cabozantinib malate (XL184) | MET andVEGF receptor2 inhibitor | 1140909-48-3 |
Cediranib (AZD217) | VEGFR inhibitor receptor,highly potent | 288383-20-0 |
DMH4 | 515880-75-8 | |
Dovitinib (TKI258) Lactate | Oral tyrosine kinase inhibitor (TKI) against FGFR1–3, VEGFR1–3, and platelet-derived growth factor receptor (PDGFR) | 915769-50-5 |
Dovitinib Dilactic acid | 852433-84-2 | |
Foretinib (GSK1363089) | VEGF and HGF receptor inhibitor | 849217-64-7 |
Fruquintinib(HMPL-013) | Potent and selective inhibitor of VEGFR 1, 2, 3 | 1194506-26-7 |
Golvatinib (E7050) | C-Met/VEGFR-2 inhibitor | 928037-13-2 |
Ki8751 | VEGFR-2 inhibitor,potent and selective | 228559-41-9 |
KRN 633 | VEGFR inhibitor,ATP-competitive | 286370-15-8 |
Lenvatinib (E7080) | VEGFR inhibitor | 417716-92-8 |
Linifanib (ABT-869) | VEGFR/PDGFR inhibitor | 796967-16-3 |
MGCD-265 | Met/Flt/Flk/Ron/Tie-2 inhibitor | 875337-44-3 |
Motesanib Diphosphate (AMG-706) | VEGFR/ PDGFR/c-Kit/Ret inhibitor | 857876-30-3 |
Nintedanib (BIBF 1120) | VEGFR/PDGFR/FGFR inhibitor | 928326-83-4 |
OSI-930 | Inhibitor of Kit, KDR, Flt, CSF-1R, c-Raf and Lck | 728033-96-3 |
Pazopanib (GW-786034) | VEGFR/PDGFR/FGFR inhibitor | 635702-64-6 |
Pazopanib Hydrochloride | VEGFR/PDGFR/FGFR/c-Kit/ c-Fms inhibitor | 635702-64-6 |
PD 173074 | FGFR inhibitor | 219580-11-7 |
PF-477736 | Chk1 inhibitor | 952021-60-2 |
PP121 | Dual inhibitor of tyrosine and phosphoinositide kinases | 1092788-83-4 |
RAF265 | Multiple intracellular kinases inhibitor | 927880-90-8 |
Regorafenib | Inhibitor of VEGFR/PDGFR/FGFR/mutant kit/RET/Raf-1 | 755037-03-7 |
Regorafenib monohydrate | Tyrosine kinase inhibitor | 1019206-88-2 |
Semaxanib (SU5416) | VEGFR(Flk-1/KDR) inhibitor | 194413-58-6 |
SKLB1002 | VEGFR2 inhibitor,potent and ATP-competitve | 1225451-84-2 |
SKLB610 | Potent VEGFR inhibitor | 1125780-41-7 |
Sorafenib | Raf kinases and tyrosine kinases inhibitor | 284461-73-0 |
Sorafenib Tosylate | Raf kinases and tyrosine kinases inhibitor | 475207-59-1 |
SU 4312 | 5812-07-7 | |
SU 5402 | VEGFR2/FGFR/PDGFR/EGFR inhibitor | 215543-92-3 |
SU14813 | Tyrosine kinase inhibitor | 627908-92-3 |
SU14813 maleate | VEGFR/PDGFR/Kit/FLT-3 inhibitor | 849643-15-8 |
SU5416 | VEGF receptor inhibitor and AHR agonist | 204005-46-9 |
Sunitinib | RTK inhibitor | 557795-19-4 |
Sunitinib malate | VEGFR/PDGFRβ/ KIT/ FLT3/RET/CSF-1R inhibitor | 341031-54-7 |
TAK-593 | VEGFR2 inhibitor | 1005780-62-0 |
Telatinib (BAY 57-9352) | VEGFR-2/-3,PDGFR-β and c-Kit inhibitor | 332012-40-5 |
TG 100801 | Multi-kinase inhibitor | 867331-82-6 |
Tivozanib (AV-951) | VEGFR inhibitor,potent and selective | 475108-18-0 |
TSU-68 (SU6668,Orantinib) | PDGFR/Flk-1/FGFR1 inhibitor,potent and competitive | 252916-29-3 |
Vandetanib (ZD6474) | VEGFR2/EGFR antagonist | 443913-73-3 |
Vandetanib hydrochloride | VEGFR/EGFR inhibitor | 524722-52-9 |
Vatalanib | VEGFR-1/-2 inhibitor,cell-permeable | 212141-54-3 |
Vatalanib (PTK787) 2HCl | Tyrosine kinase receptor inhibitor | 212141-51-0 |
ZM 306416 | VEGFR (Flt and KDR) inhibitor | 690206-97-4 |
ZM323881 | VEGFR-2/KDR inhibitor,potent and selective | 193001-14-8 |
ExUns: | 1 | ^ | 2 | ^ | 3 | ^ | 4 | ^ | 5 | ^ | 6 | ^ | 7 | ^ | 8 | ^ | 9 | ^ | 10 | ^ | 11 | ^ | 12 | ^ | 13 | ^ | 14 | ^ | 15 | ^ | 16 | ^ | 17 | ^ | 18 | ^ | 19a | · | 19b | ^ | 20 | ^ | 21a | · | 21b | ^ | 22 | ^ | 23 | ^ | 24 | ^ |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP2: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP3: |
ExUns: | 25 | ^ | 26 | ^ | 27 | ^ | 28 | ^ | 29 | ^ | 30 | ^ | 31a | · | 31b |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | |||||||||||||||
SP2: | |||||||||||||||
SP3: |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | KDR 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | KDR 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | KDR 30 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Kdr 30 |
|
||
Mouse (Mus musculus) |
Mammalia | Kdr 30 17 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | KDR 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | KDR 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | KDR 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | KDR 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | kdr 30 |
|
||
African clawed frog (Xenopus laevis) |
Amphibia | kdr-A-prov 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | kdr 30 31 |
|
OneToOne | |
Fruit Fly (Drosophila melanogaster) |
Insecta | tor 32 |
|
|
|
Cad96Ca 31 |
|
ManyToMany | |||
Pvr 31 |
|
ManyToMany | |||
Worm (Caenorhabditis elegans) |
Secernentea | R09D1.12 32 |
|
|
|
ver-3 32 |
|
|
|||
ver-2 32 |
|
|
|||
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
OneToMany |
SNP ID | Clinical significance and condition | Chr 04 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
695374 | Benign: not provided | 55,107,903(-) | G/A | INTRON_VARIANT | |
695502 | Benign: not provided | 55,090,058(-) | C/T | SYNONYMOUS_VARIANT | |
695564 | Likely Benign: not provided | 55,095,651(-) | T/C | MISSENSE_VARIANT | |
695607 | Benign: not provided | 55,104,796(-) | A/G | SYNONYMOUS_VARIANT | |
695646 | Benign: not provided | 55,105,881(-) | C/T | SYNONYMOUS_VARIANT |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
esv3569428 | CNV | loss | 25503493 |
esv3569429 | CNV | loss | 25503493 |
nsv526344 | CNV | gain | 19592680 |
nsv829939 | CNV | gain | 17160897 |
Disorder | Aliases | PubMed IDs |
---|---|---|
hemangioma, capillary infantile |
|
|
hemangioma |
|
|
cervical adenosquamous carcinoma |
|
|
vascular cancer |
|
|
corneal neovascularization |
|