• Gene id: 2324

Gene Summary

• Gene Symbol: FLT4   Gene   UCSC   Ensembl
• Aliases: CHTD7, FLT-4, FLT41, LMPH1A, LMPHM1, PCL, VEGFR-3, VEGFR3
• Gene name: fms related receptor tyrosine kinase 4
• Alternate names: vascular endothelial growth factor receptor 3, Feline McDonough Sarcoma (FMS)-like tyrosine kinase 4, VEGF receptor-3, fms related tyrosine kinase 4, fms-like tyrosine kinase 4, primary congenital lymphedema, tyrosine-protein kinase receptor FLT4,
• Gene location: 5q35.3 (24992929: 24962924)     Exons: 9     NC_000020.11
• Gene summary(Entrez): This gene encodes a tyrosine kinase receptor for vascular endothelial growth factors C and D. The protein is thought to be involved in lymphangiogenesis and maintenance of the lymphatic endothelium. Mutations in this gene cause hereditary lymphedema type
• OMIM: 136352

SNPs

rs1545125

Strand:    Allele origin:   Allele change:   Mutation type: snv

NC_000007.14   g.51083534A>G
NC_000007.13   g.51151231A>G
NG_051816.1   g.238328T>C|SEQ=[A/G]|GENE=COBL

Protein Summary

• Protein general information: P35916  
  • Name: Vascular endothelial growth factor receptor 3 (VEGFR 3) (EC 2.7.10.1) (Fms like tyrosine kinase 4) (FLT 4) (Tyrosine protein kinase receptor FLT4)
  • Length: 1363  
  • Mass: 152757
  • Tissue specificity: Detected in endothelial cells (at protein level). Widely expressed. Detected in fetal spleen, lung and brain. Detected in adult liver, muscle, thymus, placenta, lung, testis, ovary, prostate, heart, and kidney. {ECO
• Sequence:

  MQRGAALCLRLWLCLGLLDGLVSGYSMTPPTLNITEESHVIDTGDSLSISCRGQHPLEWAWPGAQEAPATGDKDS
  EDTGVVRDCEGTDARPYCKVLLLHEVHANDTGSYVCYYKYIKARIEGTTAASSYVFVRDFEQPFINKPDTLLVNR
  KDAMWVPCLVSIPGLNVTLRSQSSVLWPDGQEVVWDDRRGMLVSTPLLHDALYLQCETTWGDQDFLSNPFLVHIT
  GNELYDIQLLPRKSLELLVGEKLVLNCTVWAEFNSGVTFDWDYPGKQAERGKWVPERRSQQTHTELSSILTIHNV
  SQHDLGSYVCKANNGIQRFRESTEVIVHENPFISVEWLKGPILEATAGDELVKLPVKLAAYPPPEFQWYKDGKAL
  SGRHSPHALVLKEVTEASTGTYTLALWNSAAGLRRNISLELVVNVPPQIHEKEASSPSIYSRHSRQALTCTAYGV
  PLPLSIQWHWRPWTPCKMFAQRSLRRRQQQDLMPQCRDWRAVTTQDAVNPIESLDTWTEFVEGKNKTVSKLVIQN
  ANVSAMYKCVVSNKVGQDERLIYFYVTTIPDGFTIESKPSEELLEGQPVLLSCQADSYKYEHLRWYRLNLSTLHD
  AHGNPLLLDCKNVHLFATPLAASLEEVAPGARHATLSLSIPRVAPEHEGHYVCEVQDRRSHDKHCHKKYLSVQAL
  EAPRLTQNLTDLLVNVSDSLEMQCLVAGAHAPSIVWYKDERLLEEKSGVDLADSNQKLSIQRVREEDAGRYLCSV
  CNAKGCVNSSASVAVEGSEDKGSMEIVILVGTGVIAVFFWVLLLLIFCNMRRPAHADIKTGYLSIIMDPGEVPLE
  EQCEYLSYDASQWEFPRERLHLGRVLGYGAFGKVVEASAFGIHKGSSCDTVAVKMLKEGATASEHRALMSELKIL
  IHIGNHLNVVNLLGACTKPQGPLMVIVEFCKYGNLSNFLRAKRDAFSPCAEKSPEQRGRFRAMVELARLDRRRPG
  SSDRVLFARFSKTEGGARRASPDQEAEDLWLSPLTMEDLVCYSFQVARGMEFLASRKCIHRDLAARNILLSESDV
  VKICDFGLARDIYKDPDYVRKGSARLPLKWMAPESIFDKVYTTQSDVWSFGVLLWEIFSLGASPYPGVQINEEFC
  QRLRDGTRMRAPELATPAIRRIMLNCWSGDPKARPAFSELVEILGDLLQGRGLQEEEEVCMAPRSSQSSEEGSFS
  QVSTMALHIAQADAEDSPPSLQRHSLAARYYNWVSFPGCLARGAETRGSSRMKTFEEFPMTPTTYKGSVDNQTDS
  GMVLASEEFEQIESRHRQESGFSCKGPGQNVAVTRAHPDSQGRRRRPERGARGGQVFYNSEYGELSEPSEEDHCS
  PSARVTFFTDNSY

• Structural information:
  • Protein Domains: (30..12-)
    1 (/note="Ig-like-C2-type)
    (151..21-)
    2 (/note="Ig-like-C2-type)
    (219..32-)
    3 (/note="Ig-like-C2-type)
    (331..41-)
    4 (/note="Ig-like-C2-type)
    (422..55-)
    5 (/note="Ig-like-C2-type)
    (555..67-)
    (/note="Ig-lik-)
  • Interpro: IPR007110  IPR036179  IPR013783  IPR013098  IPR003599   IPR003598  IPR011009  IPR000719  IPR017441  IPR001245  IPR008266  IPR020635  IPR001824  IPR041348  IPR009137  
  • Prosite: PS50835 PS00107 PS50011 PS00109 PS00240
  • PDB: 4BSJ 4BSK
  • PDBsum: 4BSJ 4BSK
  • DIP: 5739
  • STRING: ENSP00000261937
• Other Databases: GeneCards:  FLT4  Malacards:  FLT4

Gene ontology

GO accession	Term name	Evidence code	Go category
GO:0043235	receptor complex	IBA	cellular component
GO:0038085	vascular endothelial growth factor binding	IBA	molecular function
GO:0033674	positive regulation of kinase activity	IBA	biological process
GO:0004714	transmembrane receptor protein tyrosine kinase activity	IBA	molecular function
GO:0002040	sprouting angiogenesis	IBA	biological process
GO:0007275	multicellular organism development	IBA	biological process
GO:0007169	transmembrane receptor protein tyrosine kinase signaling pathway	IBA	biological process
GO:0005887	integral component of plasma membrane	IBA	cellular component
GO:0005021	vascular endothelial growth factor-activated receptor activity	IBA	molecular function
GO:0046777	protein autophosphorylation	IDA	biological process
GO:0046777	protein autophosphorylation	IDA	biological process
GO:0018108	peptidyl-tyrosine phosphorylation	IDA	biological process
GO:0035924	cellular response to vascular endothelial growth factor stimulus	IDA	biological process
GO:0005886	plasma membrane	IDA	cellular component
GO:0042803	protein homodimerization activity	IDA	molecular function
GO:0046777	protein autophosphorylation	IDA	biological process
GO:0038084	vascular endothelial growth factor signaling pathway	IDA	biological process
GO:0036328	VEGF-C-activated receptor activity	IDA	molecular function
GO:0090037	positive regulation of protein kinase C signaling	IMP	biological process
GO:0048514	blood vessel morphogenesis	ISS	biological process
GO:0048010	vascular endothelial growth factor receptor signaling pathway	IMP	biological process
GO:0048010	vascular endothelial growth factor receptor signaling pathway	IMP	biological process
GO:0043066	negative regulation of apoptotic process	IMP	biological process
GO:0010595	positive regulation of endothelial cell migration	IMP	biological process
GO:0008284	positive regulation of cell population proliferation	IMP	biological process
GO:0008284	positive regulation of cell population proliferation	IMP	biological process
GO:0004714	transmembrane receptor protein tyrosine kinase activity	IMP	molecular function
GO:0002040	sprouting angiogenesis	ISS	biological process
GO:0001946	lymphangiogenesis	IMP	biological process
GO:0001946	lymphangiogenesis	ISS	biological process
GO:0001944	vasculature development	ISS	biological process
GO:0070374	positive regulation of ERK1 and ERK2 cascade	IMP	biological process
GO:0060312	regulation of blood vessel remodeling	ISS	biological process
GO:0046330	positive regulation of JNK cascade	IMP	biological process
GO:0043410	positive regulation of MAPK cascade	IMP	biological process
GO:0035924	cellular response to vascular endothelial growth factor stimulus	IMP	biological process
GO:0019903	protein phosphatase binding	IPI	molecular function
GO:0019838	growth factor binding	IPI	molecular function
GO:0010575	positive regulation of vascular endothelial growth factor production	IMP	biological process
GO:0005021	vascular endothelial growth factor-activated receptor activity	IMP	molecular function
GO:0005021	vascular endothelial growth factor-activated receptor activity	IMP	molecular function
GO:0001938	positive regulation of endothelial cell proliferation	IMP	biological process
GO:0001934	positive regulation of protein phosphorylation	IMP	biological process
GO:0001934	positive regulation of protein phosphorylation	IMP	biological process
GO:0005515	protein binding	IPI	molecular function
GO:0004713	protein tyrosine kinase activity	IEA	molecular function
GO:0004714	transmembrane receptor protein tyrosine kinase activity	IEA	molecular function
GO:0048010	vascular endothelial growth factor receptor signaling pathway	IEA	biological process
GO:0004672	protein kinase activity	IEA	molecular function
GO:0005021	vascular endothelial growth factor-activated receptor activity	IEA	molecular function
GO:0005524	ATP binding	IEA	molecular function
GO:0005887	integral component of plasma membrane	IEA	cellular component
GO:0006468	protein phosphorylation	IEA	biological process
GO:0007169	transmembrane receptor protein tyrosine kinase signaling pathway	IEA	biological process
GO:0016301	kinase activity	IEA	molecular function
GO:0005576	extracellular region	IEA	cellular component
GO:0004713	protein tyrosine kinase activity	IEA	molecular function
GO:0001525	angiogenesis	IEA	biological process
GO:0016740	transferase activity	IEA	molecular function
GO:0000166	nucleotide binding	IEA	molecular function
GO:0005737	cytoplasm	IEA	cellular component
GO:0005634	nucleus	IEA	cellular component
GO:0016310	phosphorylation	IEA	biological process
GO:0005524	ATP binding	IEA	molecular function
GO:0005886	plasma membrane	IEA	cellular component
GO:0016021	integral component of membrane	IEA	cellular component
GO:0016020	membrane	IEA	cellular component
GO:0004714	transmembrane receptor protein tyrosine kinase activity	TAS	molecular function
GO:0005021	vascular endothelial growth factor-activated receptor activity	TAS	molecular function
GO:0005887	integral component of plasma membrane	TAS	cellular component
GO:0007169	transmembrane receptor protein tyrosine kinase signaling pathway	TAS	biological process
GO:0004714	transmembrane receptor protein tyrosine kinase activity	IEA	molecular function
GO:0048010	vascular endothelial growth factor receptor signaling pathway	IDA	biological process
GO:0043235	receptor complex	IDA	cellular component
GO:0005021	vascular endothelial growth factor-activated receptor activity	IDA	molecular function
GO:0048010	vascular endothelial growth factor receptor signaling pathway	IGI	biological process
GO:0008284	positive regulation of cell population proliferation	IGI	biological process
GO:0005886	plasma membrane	TAS	cellular component
GO:0005886	plasma membrane	TAS	cellular component
GO:0048010	vascular endothelial growth factor receptor signaling pathway	TAS	biological process
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0001944	vasculature development	IEA	biological process
GO:0001946	lymphangiogenesis	IEA	biological process
GO:0002040	sprouting angiogenesis	IEA	biological process
GO:0003016	respiratory system process	IEA	biological process
GO:0008284	positive regulation of cell population proliferation	IEA	biological process
GO:0048514	blood vessel morphogenesis	IEA	biological process
GO:0001945	lymph vessel development	IEA	biological process
GO:0005021	vascular endothelial growth factor-activated receptor activity	IEA	molecular function
GO:0007585	respiratory gaseous exchange by respiratory system	IEA	biological process
GO:0048286	lung alveolus development	IEA	biological process
GO:0060312	regulation of blood vessel remodeling	IEA	biological process
GO:0001945	lymph vessel development	ISS	biological process
GO:0005576	extracellular region	IEA	cellular component
GO:0005886	plasma membrane	IEA	cellular component
GO:0005634	nucleus	IEA	cellular component
GO:0005737	cytoplasm	IEA	cellular component
GO:0005886	plasma membrane	IDA	cellular component
GO:0005654	nucleoplasm	IDA	cellular component
GO:0005515	protein binding	IPI	molecular function

KEGG pathways

Pathway id	Pathway name
hsa05200	Pathways in cancer
hsa04151	PI3K-Akt signaling pathway
hsa04010	MAPK signaling pathway
hsa04014	Ras signaling pathway
hsa04015	Rap1 signaling pathway
hsa04510	Focal adhesion
hsa05224	Breast cancer

Diseases

Associated diseases	References
Hereditary lymphedema	KEGG:H00535
Lymphangioma	KEGG:H01471
Hereditary lymphedema	KEGG:H00535
Lymphangioma	KEGG:H01471
Lymphangioma	PMID:17584927
systemic scleroderma	PMID:21865112
Aberrant CpGs in Low Motility Sperm	MIK: 21674046
Cryptorchidism	MIK: 28606200
Teratozoospermia	MIK: 17327269

PubMed references

PMID	Condition	Mutation	Ethnicity	Population details	Infertility_type	Associated_genes
17327269	Teratozoospermia			13 (5 controls, 8 cases)	Male infertility	GSE6967 analyzed by GEO2R (cutoff 1.5 fold)
21674046	Aberrant CpGs in Low Motility Sperm			18	Male infertility	GSE26881
28606200	Cryptorchidism			Monozgotic twins (1 control, I cwith cryptorchidism)	Male infertility	MeDIP-Seq