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Atlas / Gene / FLT4

FLT4

gene
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Also known as VEGFR3PCLVEGFR-3

Summary

FLT4 (fms related receptor tyrosine kinase 4, HGNC:3767) is a protein-coding gene on chromosome 5q35.3, encoding Vascular endothelial growth factor receptor 3 (P35916). Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development.

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 IA.

Source: NCBI Gene 2324 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): congenital heart defects, multiple types, 7 (Definitive, ClinGen) — +4 more curated relationships
  • GWAS associations: 3
  • Clinical variants (ClinVar): 657 total — 36 pathogenic, 35 likely-pathogenic (top 5% of genes corpus-wide)
  • Regional missense constraint (gnomAD): 1 of 5 regions constrained (≈4% of expected missense variation)
  • GTEx eGene: eQTL in 17 tissues, sQTL in 16 (q < 0.05)
  • Phenotypes (HPO): 50
  • Drug target: yes — 6 curated mechanism-of-action drugs, 39 via a complex or family; 72 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
  • Approved drugs (ChEMBL mechanism of action): 1 — Sunitinib
  • Approved drugs acting on a complex or family including it: 9 — Axitinib, Fruquintinib, Lenvatinib Mesylate, +6 more (Vascular endothelial growth factor receptor)
  • Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 10 cancer types (inferred from mutation patterns)
  • Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.27 (highly constrained)
  • MANE Select transcript: NM_182925
  • Interaction hub: 1,814 STRING partners (top 9% of genes corpus-wide)

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:3767
Approved symbolFLT4
Namefms related receptor tyrosine kinase 4
Location5q35.3
Locus typegene with protein product
StatusApproved
AliasesVEGFR3, PCL, VEGFR-3
Ensembl geneENSG00000037280
Ensembl biotypeprotein_coding
OMIM136352
Entrez2324

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 11 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined

MANE Select: ENST00000261937

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 6, TSL 2: 2, TSL 3: 1, TSL 4: 2, TSL 5: 1

ENST00000261937, ENST00000393347, ENST00000424276, ENST00000502293, ENST00000502603, ENST00000502649, ENST00000507059, ENST00000510000, ENST00000512795, ENST00000513527, ENST00000514810, ENST00000619105, ENST00000861588, ENST00000937381, ENST00000955857, ENST00000955858, ENST00001001647, ENST00001133294

RefSeq mRNA: 3 — MANE Select: NM_182925 NM_001354989, NM_002020, NM_182925

CCDS: CCDS43412, CCDS4457, CCDS87360

Canonical transcript exons

ENST00000261937 — 30 exons

ExonStartEnd
ENSE00001186304180601506180603390
ENSE00002219238180649488180649600
ENSE00002235949180613011180613110
ENSE00002240553180619253180619366
ENSE00002257775180619665180619769
ENSE00002499595180614068180614179
ENSE00003493921180630225180630337
ENSE00003501996180629696180629835
ENSE00003509123180620609180620715
ENSE00003530114180625869180626031
ENSE00003538597180621542180621904
ENSE00003553426180621106180621252
ENSE00003562906180626111180626265
ENSE00003566384180622731180622839
ENSE00003568067180629943180630105
ENSE00003571346180619021180619109
ENSE00003582753180612506180612611
ENSE00003594373180630555180630799
ENSE00003615754180611331180611479
ENSE00003638556180609905180610025
ENSE00003645334180608968180609053
ENSE00003652996180631682180631778
ENSE00003654534180623935180624061
ENSE00003668430180629259180629427
ENSE00003675036180616367180616489
ENSE00003678483180620173180620308
ENSE00003681687180616900180616994
ENSE00003685911180618770180618920
ENSE00003688545180620876180621007
ENSE00003692028180628882180628999

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 91.43.

FANTOM5 (CAGE): breadth broad, TPM avg 2.3307 / max 154.7193, expressed in 418 samples.

Highest expression (Bgee): lobe of thyroid gland, thyroid gland, apex of heart, lung, upper lobe of left lung.

Genetic regulation across tissues (GTEx eQTL / sQTL)

FLT4 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 17 tissues and its splicing (sQTL) in 16 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 33 significant tissue × QTL associations:

TissueQTLq-valueSlopeLead variant
Thyroidsqtl1.0e-44-0.985:180610773:G:A
Brain Caudate basal gangliaeqtl1.4e-37-0.945:180616388:G:A
Adipose Subcutaneoussqtl2.4e-35-0.925:180610773:G:A
Brain Putamen basal gangliaeqtl1.0e-27+0.845:180618700:G:GGGTTACCCTA
Breast Mammary Tissuesqtl3.4e-26-1.005:180610773:G:A
Lungsqtl6.9e-26-0.865:180610773:G:A
Whole Bloodeqtl1.5e-24-0.495:180566813:T:C
Adipose Visceral Omentumsqtl1.5e-10-0.585:180606031:G:A
Testiseqtl1.3e-08+0.245:180619426:C:CTGGCCGCTTAGCTAAGGCACAG
Nerve Tibialeqtl2.8e-07+0.245:180619426:C:CTGGCCGCTTAGCTAAGGCACAG
Muscle Skeletalsqtl1.4e-05+0.425:180606031:G:A
Brain Nucleus accumbens basal gangliaeqtl2.6e-05-0.355:180610988:C:T
Muscle Skeletaleqtl1.2e-04+0.185:180619492:CAG:C
Adipose Subcutaneouseqtl1.3e-04+0.185:180619426:C:CTGGCCGCTTAGCTAAGGCACAG
Testissqtl2.3e-04-0.465:180613918:G:A
Skin Sun Exposed Lower legsqtl5.5e-04-0.535:180612606:C:T
Skin Not Sun Exposed Suprapubicsqtl3.0e-03-0.525:180612606:C:T
Esophagus Mucosasqtl3.4e-03-0.275:180613918:G:A
Lungeqtl4.5e-03+0.135:180619492:CAG:C
Small Intestine Terminal Ileumsqtl4.7e-03-0.695:180610773:G:A

FANTOM5 promoters

3 alternative TSS:

Promoter IDTPM avgSamples expressed
653161.7147317
653170.4996244
653140.116427

Top tissues by expression

showing 100 of 287 tissues by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
right lobe of thyroid glandUBERON:000111991.43gold quality
left lobe of thyroid glandUBERON:000112090.94gold quality
thyroid glandUBERON:000204689.67gold quality
apex of heartUBERON:000209887.85gold quality
right lungUBERON:000216787.47gold quality
upper lobe of left lungUBERON:000895287.43gold quality
sural nerveUBERON:001548887.37gold quality
omental fat padUBERON:001041487.27gold quality
peritoneumUBERON:000235887.21gold quality
upper lobe of lungUBERON:000894886.59gold quality
adipose tissue of abdominal regionUBERON:000780886.00gold quality
spleenUBERON:000210685.21gold quality
metanephros cortexUBERON:001053384.57gold quality
buccal mucosa cellCL:000233683.44gold quality
right uterine tubeUBERON:000130283.39gold quality
left uterine tubeUBERON:000130382.85gold quality
body of uterusUBERON:000985382.82gold quality
left adrenal gland cortexUBERON:003582582.73gold quality
left adrenal glandUBERON:000123482.29gold quality
right adrenal glandUBERON:000123382.23gold quality
subcutaneous adipose tissueUBERON:000219081.34gold quality
adrenal cortexUBERON:000123581.27gold quality
adrenal glandUBERON:000236981.16gold quality
right adrenal gland cortexUBERON:003582781.10gold quality
endocervixUBERON:000045880.80gold quality
ectocervixUBERON:001224980.69gold quality
adenohypophysisUBERON:000219680.35gold quality
mucosa of stomachUBERON:000119979.73gold quality
placentaUBERON:000198779.46gold quality
lower esophagus mucosaUBERON:003583479.22gold quality
lower esophagus muscularis layerUBERON:003583379.14gold quality
lower esophagusUBERON:001347379.13gold quality
pituitary glandUBERON:000000778.92gold quality
adipose tissueUBERON:000101378.91gold quality
heart left ventricleUBERON:000208478.66gold quality
small intestine Peyer’s patchUBERON:000345478.42gold quality
esophagogastric junction muscularis propriaUBERON:003584178.27gold quality
cardiac ventricleUBERON:000208278.11gold quality
connective tissueUBERON:000238477.95gold quality
right lobe of liverUBERON:000111477.84gold quality
lymph nodeUBERON:000002977.44gold quality
adult mammalian kidneyUBERON:000008277.44gold quality
lungUBERON:000204877.22gold quality
putamenUBERON:000187476.84gold quality
muscle layer of sigmoid colonUBERON:003580576.56gold quality
small intestineUBERON:000210876.54gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099176.33gold quality
esophagusUBERON:000104376.31gold quality
right ovaryUBERON:000211876.00gold quality
adrenal tissueUBERON:001830376.00gold quality
gall bladderUBERON:000211075.98gold quality
caudate nucleusUBERON:000187375.81gold quality
heartUBERON:000094875.54gold quality
myometriumUBERON:000129675.52gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047375.35gold quality
hindlimb stylopod muscleUBERON:000425275.09gold quality
right atrium auricular regionUBERON:000663174.58gold quality
gastrocnemiusUBERON:000138874.50gold quality
esophagus mucosaUBERON:000246974.40gold quality
vaginaUBERON:000099674.39gold quality
lower lobe of lungUBERON:000894974.16gold quality
left coronary arteryUBERON:000162674.14gold quality
muscle of legUBERON:000138374.12gold quality
left ovaryUBERON:000211973.93gold quality
skin of legUBERON:000151173.57gold quality
skeletal muscle tissue of biceps brachiiUBERON:000450273.44gold quality
fundus of stomachUBERON:000116073.35gold quality
sigmoid colonUBERON:000115973.29gold quality
tibial nerveUBERON:000132373.18gold quality
coronary arteryUBERON:000162173.08gold quality
body of stomachUBERON:000116172.97gold quality
smooth muscle tissueUBERON:000113572.88gold quality
cardiac atriumUBERON:000208172.82gold quality
vermiform appendixUBERON:000115472.73gold quality
skin of abdomenUBERON:000141672.65gold quality
stomachUBERON:000094572.35gold quality
colonic epitheliumUBERON:000039772.19gold quality
transverse colonUBERON:000115772.03gold quality
intestineUBERON:000016072.01gold quality
tendon of biceps brachiiUBERON:000818871.95silver quality
liverUBERON:000210771.76gold quality
caecumUBERON:000115371.51gold quality
colonUBERON:000115571.21gold quality
prostate glandUBERON:000236771.04gold quality
female reproductive systemUBERON:000047471.03gold quality
zone of skinUBERON:000001470.99gold quality
large intestineUBERON:000005970.83gold quality
ganglionic eminenceUBERON:000402370.82gold quality
anatomical systemUBERON:000046770.77gold quality
skeletal muscle organUBERON:001489270.68gold quality
muscle organUBERON:000163070.66gold quality
multicellular organismUBERON:000046870.64gold quality
material anatomical entityUBERON:000046570.63gold quality
ovaryUBERON:000099270.54gold quality
kidneyUBERON:000211370.41gold quality
ascending aortaUBERON:000149669.66gold quality
granulocyteCL:000009469.52gold quality
cortical plateUBERON:000534369.40gold quality
cortex of kidneyUBERON:000122569.35gold quality
thoracic aortaUBERON:000151569.32gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

ExperimentMarker?Max mean expression
E-MTAB-9801yes605.03
E-ANND-3yes7.94
E-MTAB-9067yes7.71
E-MTAB-8271no125.34

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cellAxisnTPMProtein (IHC)
Spleentissue12.8low
Adipose tissuetissue10.1low
Lungtissue9.3medium
Thyroid glandtissue7.7low
Pituitary glandtissue7.6
Fallopian tubetissue7.4medium
Placentatissue6.2low
Hippocampustissue5.5low
Lymph nodetissue5.4not detected
Vaginatissue5.3low
Heart muscletissue5.0high
Appendixtissue4.6high
Skeletal muscletissue4.5high
Choroid plexustissue4.5
Endometrium 1tissue4.2not detected
Nucleus accumbenstissue4.1
Kidneytissue4.1high
Ovarytissue4.0low
Smooth muscletissue3.9low
Tonguetissue3.9
Adrenal glandtissue3.9high
Livertissue3.7not detected
Gallbladdertissue3.7medium
Locus coeruleustissue3.7
Cervixtissue3.6medium
Breasttissue3.5medium
Postcentral gyrustissue3.4
Epididymistissue3.3medium
Small intestinetissue3.0high
Testistissue2.9medium
Duodenumtissue2.8medium
Esophagustissue2.7medium
Seminal vesicletissue2.4medium
Urinary bladdertissue2.4medium
Skin 1tissue2.3medium
Parathyroid glandtissue2.3
Salivary glandtissue1.9medium
Superior colliculitissue1.8
Colontissue1.7medium
Pancreastissue1.6low
Prostatetissue1.6medium
Tonsiltissue1.5medium
Stomach 1tissue1.4low
Bone marrowtissue1.4not detected
Caudate putamentissue1.4
Rectumtissue1.3high
Frontal cortextissue1.2
Thymustissue1.1
Retinatissue0.8
Ponstissue0.6
Cerebellumtissue0.6high
Spinal cordtissue0.6
Medulla oblongatatissue0.5
Hypothalamustissue0.5
Substantia nigratissue0.5
Hippocampal formationtissue0.5
Olfactory bulbtissue0.5
Cerebral cortextissue0.4medium
Motor cortextissue0.4
Basal gangliatissue0.4low

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Hippocampus, CA2 (9.7), Posterior thalamic nucleus (7.7), Caudate nucleus (7.5), Nucleus basalis of Meynert (7.2), Dentate gyrus (6.8).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F7, ETS1, ETS2, GLI3, HR, NFATC1, NFKB1, NFKB, NR2F2, PROX1, RBPJ, RELA, TBX1

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.265, missense Z 3.03 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000261937 splits into 5 regions with different missense tolerance; 1 is missense-constrained (≈4% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)Missense obs / expo/eConstrained
5:180,603,195–180,613,038295 / 311.00.95no
5:180,613,039–180,614,17317 / 76.20.22yes (p 1.2e-11)
5:180,614,174–180,628,964878 / 1016.70.86no
5:180,628,965–180,630,572163 / 281.10.58no
5:180,630,573–180,649,545157 / 178.70.88no

Literature-anchored findings (GeneRIF, showing 40)

  • A potential mechanism involved in hemangioma formation is the alteration of the FLT4 signaling pathway in endothelial and/or pericytic cells. (PMID:11807987)
  • VEGF-C signaling through FLT-4 (VEGFR-3) mediates leukemic cell proliferation, survival, and resistance to chemotherapy. (PMID:11877295)
  • Suppression of tumor lymphangiogenesis and lymph node metastasis by blocking vascular endothelial growth factor receptor 3 signaling. (PMID:12048269)
  • Vascular endothelial growth factor receptor-3 (VEGFR-3) and its ligand VEGF-C are expressed in human colorectal adenocarcinoma. (PMID:12168824)
  • generation of endothelial cells from CD34+ cells is associated with expression of VEGFR3 on the cell surface (PMID:12393704)
  • Data demonstrate the expression of vascular endothelial growth factor receptor-3 and vascular endothelial growth factor-C on corneal dendritic cells, which implicate a potential relationship between lymphangiogenesis and leukocyte trafficking in the eye. (PMID:12819011)
  • the carboxyl-terminal tail of VEGFR-3 provides important regulatory tyrosine phosphorylation sites with potential signal transduction capacity and these sites are differentially used in ligand-induced homo- and heterodimeric receptor complexes (PMID:12881528)
  • VEGF-C/flt-4 system can promote vasculogenesis in stroma of breast cancer. The number of Flt-4 positive vessels is closely related to lymph node metastasis. (PMID:14558949)
  • Specific VEGFR3 expression, examined in 27 B-CLL samples, was positive in 26 of them. The VEGF transduction pathway may be very active in CLL cells. Both its paracrine & autocrine pathways may contribute to their enhanced survival. (PMID:14687619)
  • VEGF-C and its receptor FLT-4 play a role in the development of gastric cancer, and the tumors with expression of VEGF-C and FLT-4 are more likely to have lymph node metastasis. (PMID:14760756)
  • VEGFR-3 may protect against oxidative damage in endothelial cells, and that patients with hereditary lymphoedema may be susceptible to ROS-induced cell damage. (PMID:15102829)
  • expression levels were significantly elevated in primary prostatic tumors with sentinel lymph node involvement compared to those lacking lymph node involvement (PMID:15107801)
  • vascular endothelial growth factor receptor-3 may have a role in lymph node metastasis in prostate cancer (PMID:15297417)
  • integrin alpha5beta1 participates in the activation of both VEGFR-3 and its downstream PI3 kinase/Akt signaling pathway, which is essential for fibronectin-mediated lymphatic endothelial cell survival and proliferation. (PMID:15389531)
  • VEGFR-3 needs to be associated to VEGFR-2 to induce ligand-dependent cellular responses (PMID:15474514)
  • Patients with primary lymphedema have serum level of VEGF-D significantly higher than controls.The increased levels of VEGF-D suggest that primary lymphedema may be based on defective stimulation of VEGFR-3. (PMID:15693535)
  • Ang1 has a role in lymphatic vessel endothelial proliferation, Tie2 expression, and VEGFR-3 upregulation (PMID:15746084)
  • KSHV gB can activate VEGFR-3 on the microvascular endothelium and modulate endothelial cell migration and proliferation via an interaction between the alpha3beta1 integrin and the VEGFR-3 receptor (PMID:15878864)
  • increased expression of VEGF-C and VEGFR-3 play a role in prostate cancer progression and in metastasis to regional lymph nodes (PMID:15880525)
  • There was a close correlation between the expressions of VEGFR-3, CD31 and prostate tumor metastases. (PMID:16044920)
  • Overexpression of vascular endothelial growth factor receptor 3 is associated with lung adenocarcinoma (PMID:16116610)
  • VEGF-C and its receptor FLT-4 play an important role in the lymphatic metastasis of laryngeal and hypopharyngeal squamous cell carcinoma. (PMID:16375119)
  • VEGFR-3/flt4 was expressed in cancer stromal cells. (PMID:16525637)
  • VEGF-D/VEGFR-3 signaling plays a critical role in osteoblast maturation (PMID:16624815)
  • The VEGF-3/VEGFR-c ratio was positively associated with lymph node metastasis in non-small cell lung cancer . (PMID:16755294)
  • multiple myeloma cells (but not B-cell chronic lymphocytic leukemia cells) induced a dramatic increase in expression of VEGFR-1 and VEGFR-3 on human bone marrow endothelial cells (PMID:16959214)
  • These results suggest that the expression of VEGFRs and NRPs on keratinocytes may constitute important regulators for its activity and may possibly be responsible for the autocrine signaling in the epidermis. (PMID:17088944)
  • This is the first report of an exon 22 mutation of VEGFR3 in Milroy disease. (PMID:17458866)
  • VEGFR-3 may play a role in the abnormal endometrial angiogenesis of idiopathic menorrhagia. (PMID:17487423)
  • expression of VEGFR-3(S) is up-regulated in >75% of hepatitis B x antigen positive hepatocellular carcinoma (HCC) nodules; HBxAg may short circuit VEGFR-3(S) signaling in liver cancer (PMID:17539024)
  • Both VEGF-A and angiopoietin-2 upregulated the expression of VEGFR-3 in cultured lymphatic endothelial cells (PMID:17597103)
  • In non-small-cell lung cancer cells, VEGF-C/VEGFR-3 coexpression suggests an autocrine/paracrine loop responsible for a high proliferation rate in tumour cells. (PMID:17686546)
  • interaction of CEACAM1 with Prox1 and VEGFR-3 plays a crucial role in tumor lymphangiogenesis and reprogramming of vascular endothelial cells to lymphatic endothelial cells (PMID:17761831)
  • Expression of VEGF-C, VEGF-D and their receptor VEGFR-3 in diffuse large B-cell lymphomas. (PMID:17926187)
  • data suggest that VEGF-C alters lymphatic endothelial function through a mechanism involving VEGFR-3 (PMID:17935478)
  • the spectrum of the VEGFR-3 gene mutations causing HL-I (PMID:17945164)
  • Data demonstrate that Notch1 and VEGFR-3 interact genetically, that Notch directly induces VEGFR-3 in blood endothelial cells to regulate vascular development, and that Notch and VEGF signaling may function in tumor lymphangiogenesis. (PMID:17948123)
  • Increased expression of VEGFR-3 is associated with acute myeloid leukaemia (PMID:18006056)
  • VEGFR-3 was expressed in malignant cells from different subtypes of MM (PMID:18008346)
  • VEGFR3 single nucleotide polymorphisms andthe haplotype GC in the VEGFA gene are associated with psoriasis in Koreans (PMID:18094729)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
danio_rerioflt4ENSDARG00000104453
mus_musculusFlt4ENSMUSG00000020357
rattus_norvegicusFlt4ENSRNOG00000002511

Paralogs (53): INSRR (ENSG00000027644), MUSK (ENSG00000030304), EPHA3 (ENSG00000044524), ROS1 (ENSG00000047936), LTK (ENSG00000062524), ERBB3 (ENSG00000065361), TIE1 (ENSG00000066056), FGFR2 (ENSG00000066468), FGFR3 (ENSG00000068078), EPHA8 (ENSG00000070886), FGFR1 (ENSG00000077782), EPHA6 (ENSG00000080224), TYRO3 (ENSG00000092445), FLT1 (ENSG00000102755), MET (ENSG00000105976), EPHB6 (ENSG00000106123), PDGFRB (ENSG00000113721), EPHA4 (ENSG00000116106), TEK (ENSG00000120156), FLT3 (ENSG00000122025), KDR (ENSG00000128052), EPHB2 (ENSG00000133216), PDGFRA (ENSG00000134853), EPHA7 (ENSG00000135333), IGF1R (ENSG00000140443), NTRK3 (ENSG00000140538), ERBB2 (ENSG00000141736), EPHA2 (ENSG00000142627), EPHA5 (ENSG00000145242), EGFR (ENSG00000146648), EPHA1 (ENSG00000146904), NTRK2 (ENSG00000148053), MERTK (ENSG00000153208), EPHB1 (ENSG00000154928), KIT (ENSG00000157404), FGFR4 (ENSG00000160867), DDR2 (ENSG00000162733), RYK (ENSG00000163785), MST1R (ENSG00000164078), LMTK2 (ENSG00000164715), RET (ENSG00000165731), AXL (ENSG00000167601), ROR2 (ENSG00000169071), ALK (ENSG00000171094), INSR (ENSG00000171105), ERBB4 (ENSG00000178568), CSF1R (ENSG00000182578), EPHB3 (ENSG00000182580), EPHA10 (ENSG00000183317), ROR1 (ENSG00000185483), EPHB4 (ENSG00000196411), NTRK1 (ENSG00000198400), DDR1 (ENSG00000204580)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:95561) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 27 distinct phenotype terms.

Mouse phenotype (MP)Records
chylous ascites4
abnormal lymphatic vessel morphology2
abnormal lymph circulation2
embryonic growth retardation2
absent lymphatic vessels2
embryonic lethality during organogenesis, complete penetrance2
abnormal adipose tissue distribution1
abnormal vascular development1
abnormal intestine morphology1
abnormal liver morphology1
thick dermal layer1
abnormal blood vessel morphology1
pale yolk sac1
edema1
pericardial edema1
postnatal lethality1
hydrops fetalis1
extremity edema1
lymphedema1
abnormal vitelline vascular remodeling1
abnormal anterior cardinal vein morphology1
abnormal dorsal aorta morphology1
hemopericardium1
abnormal lymphangiogenesis1
neonatal lethality, complete penetrance1

+2 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

OrganismUniProtIdentityMethod
Pongo abeliiQ5R5V499.6%Diamond
Bos taurusP4348199.4%Diamond
Capra hircusQ2831799.4%Diamond
Cavia porcellusP5704499.3%Diamond
Felis catusQ2888999.2%Diamond
Canis lupus familiarisO9779998.4%Diamond
Sus scrofaQ2HWD698.1%Diamond
Callithrix jacchusQ76II094.6%Diamond
Gallus gallusP1846192.7%Diamond
Notophthalmus viridescensQ9114787.9%Diamond
Pleurodeles waltlQ9128587.8%Diamond
Coturnix coturnixQ9033081.0%Diamond
Xenopus laevisP2218280.6%Diamond
Takifugu rubripesQ8AXC773.2%Diamond
Coturnix japonicaP5258373.1%Diamond
Ciona intestinalisQ4H3K660.1%Diamond
Halocynthia roretziQ95YM959.9%Diamond
Feline sarcoma virus (STRAIN HARDY-ZUCKERMAN 4)P0404899.2%Diamond
Feline sarcoma virus (STRAIN MCDONOUGH)P0054599.1%Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

SymbolTypeEntrez
LINC02222ncRNA105377765
CNOT6protein-coding57472
SCGB3A1protein-coding92304

Protein

Protein identifiers

Vascular endothelial growth factor receptor 3 — P35916 (reviewed: P35916)

Alternative names: Fms-like tyrosine kinase 4, Tyrosine-protein kinase receptor FLT4

All UniProt accessions (4): B5A927, D6RFF2, E9PD35, P35916

UniProt curated annotations — full annotation on UniProt →

Function. Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced production of VEGFC, and to a lesser degree VEGFA, thereby creating a positive feedback loop that enhances FLT4 signaling. Modulates KDR signaling by forming heterodimers. The secreted isoform 3 may function as a decoy receptor for VEGFC and/or VEGFD and play an important role as a negative regulator of VEGFC-mediated lymphangiogenesis and angiogenesis. Binding of vascular growth factors to isoform 1 or isoform 2 leads to the activation of several signaling cascades; isoform 2 seems to be less efficient in signal transduction, because it has a truncated C-terminus and therefore lacks several phosphorylation sites. Mediates activation of the MAPK1/ERK2, MAPK3/ERK1 signaling pathway, of MAPK8 and the JUN signaling pathway, and of the AKT1 signaling pathway. Phosphorylates SHC1. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Promotes phosphorylation of MAPK8 at ‘Thr-183’ and ‘Tyr-185’, and of AKT1 at ‘Ser-473’.

Subunit / interactions. Interacts with VEGFC and VEGFD. Monomer in the absence of bound VEGFC or VEGFD. Homodimer in the presence of bound VEGFC or VEGFD. Can also form a heterodimer with KDR. Interacts with PTPN14; the interaction is enhanced by stimulation with VEGFC. Interacts with CRK, GRB2, PTK2/FAK1, SHC1, PIK3R1 and PTPN11/SHP-2. Identified in a complex with SRC and ITGB1.

Subcellular location. Cell membrane. Cytoplasm. Nucleus Cell membrane Cell membrane Secreted.

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.

Post-translational modifications. Autophosphorylated on tyrosine residues upon ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Phosphorylation in response to H(2)O(2) is mediated by a process that requires SRC and PRKCD activity. Phosphorylation at Tyr-1068 is required for autophosphorylation at additional tyrosine residues. Phosphorylation at Tyr-1063 and Tyr-1337 is important for interaction with CRK and subsequent activation of MAPK8. Phosphorylation at Tyr-1230, Tyr-1231 and Tyr-1337 is important for interaction with GRB2 and subsequent activation of the AKT1 and MAPK1/ERK2 and/or MAPK3/ERK1 signaling pathways. In response to endothelial cell adhesion onto collagen, can also be phosphorylated in the absence of FLT4 kinase activity by SRC at Tyr-830, Tyr-833, Tyr-853, Tyr-1063, Tyr-1333, and Tyr-1337.

Disease relevance. Lymphatic malformation 1 (LMPHM1) [MIM:153100] A form of primary lymphedema, a disease characterized by swelling of body parts due to developmental anomalies and functional defects of the lymphatic system. Patients with lymphedema may suffer from recurrent local infections. LMPHM1 is an autosomal dominant form with variable expression and severity. Onset is usually at birth or in early childhood but can occur later. Affected individuals manifest lymphedema, predominantly in the lower limbs, and hypoplasia of lymphatic vessels. Additional features are hemangioma and nail dysplasia or papillomatosis. The disease is caused by variants affecting the gene represented in this entry. Hemangioma, capillary infantile (HCI) [MIM:602089] A condition characterized by dull red, firm, dome-shaped hemangiomas, sharply demarcated from surrounding skin, usually presenting at birth or occurring within the first two or three months of life. They result from highly proliferative, localized growth of capillary endothelium and generally undergo regression and involution without scarring. Disease susceptibility is associated with variants affecting the gene represented in this entry. Plays an important role in tumor lymphangiogenesis, in cancer cell survival, migration, and formation of metastases. Congenital heart defects, multiple types, 7 (CHTD7) [MIM:618780] An autosomal dominant disorder with incomplete penetrance characterized by congenital developmental abnormalities involving structures of the heart. Common defects include tetralogy of Fallot, pulmonary stenosis or atresia, absent pulmonary valve, right aortic arch, double aortic arch, and major aortopulmonary collateral arteries. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Present in an inactive conformation in the absence of bound ligand. Binding of VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by MAZ51.

Domain organisation. The first and second Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFC binding. The fourth and fifth Ig-like C2-type domains are sufficient for homodimerization. The fifth and seventh Ig-like C2-type domains are required for autophosphorylation and further activation.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.

Isoforms (3)

UniProt IDNamesCanonical?
P35916-21, Longyes
P35916-12, Short
P35916-33, sVegfr3

RefSeq proteins (3): NP_001341918, NP_002011, NP_891555* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000719Prot_kinase_domDomain
IPR001245Ser-Thr/Tyr_kinase_cat_domDomain
IPR001824Tyr_kinase_rcpt_3_CSConserved_site
IPR003598Ig_sub2Domain
IPR003599Ig_subDomain
IPR007110Ig-like_domDomain
IPR008266Tyr_kinase_ASActive_site
IPR011009Kinase-like_dom_sfHomologous_superfamily
IPR013098Ig_I-setDomain
IPR013783Ig-like_foldHomologous_superfamily
IPR017441Protein_kinase_ATP_BSBinding_site
IPR020635Tyr_kinase_cat_domDomain
IPR036179Ig-like_dom_sfHomologous_superfamily
IPR041348VEGFR-2_TMDDomain
IPR050122RTKFamily
IPR055229VEGFR1-3_5thDomain
IPR055238VEGFR1-3_N_Ig-likeDomain

Pfam: PF07679, PF07714, PF13927, PF17988, PF21339, PF22854, PF22971

Enzyme classification (BRENDA)

  • EC 2.7.10.1 — receptor protein-tyrosine kinase (BRENDA: 44 organisms, 214 substrates, 574 inhibitors, 11 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
ATP0.0011–0.1294
AC-DYFE-6-CHLORO-W-NHME0.00511
AC-DYFGW-NHME0.071
YFEW0.2321

Catalyzed reactions (Rhea)

  • L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (119 total): sequence variant 35, strand 13, glycosylation site 12, mutagenesis site 12, modified residue 11, domain 8, disulfide bond 7, sequence conflict 6, splice variant 3, helix 2, binding site 2, topological domain 2, signal peptide 1, chain 1, turn 1, region of interest 1, active site 1, transmembrane region 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDBTitleMethodResolution (Å)
4BSJCrystal structure of VEGFR-3 extracellular domains D4-5X-RAY DIFFRACTION2.5
4BSKCrystal structure of VEGF-C in complex with VEGFR-3 domains D1-2X-RAY DIFFRACTION4.2

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P35916-F172.820.28

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Tyr protein kinases, Transporters, Accessory Factors Involved in Transport, Predicted membrane proteins, Predicted secreted proteins, Predicted intracellular proteins, Plasma proteins, RAS pathway related proteins, Cancer-related genes, Candidate cancer biomarkers, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes, Congenital malformations, Congenital malformations of the circulatory system, Congenital malformations of skin

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; centrosome; plasma membrane

Antibody reliability (HPA): IH approved · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1)

PositionRole
1037proton acceptor

Ligand- & substrate-binding residues (2)

PositionRole
851–859ATP
879ATP

Post-translational modifications (11)

TypePositions
Phosphotyrosine830, 833, 853, 1063, 1068, 1230, 1231, 1265, 1333, 1337, 1363

Disulfide bonds (7)

TypePositions
Disulfide bond51–111, 158–206, 252–310, 445–534, 466–486, 578–653, 699–751

Glycosylation sites (12)

TypePositions
N-linked (glcnac…) asparagine33, 104, 166, 251, 299, 411, 515, 527, 594, 683, 690, 758

Mutagenesis-validated functional residues (12)

PositionPhenotype
446decreases autophosphorylation on tyrosine residues upon ligand binding; when associated with a-516. abolishes autophosphorylation on …
516decreases autophosphorylation on tyrosine residues upon ligand binding; when associated with e-446. abolishes autophosphorylation on …
737decreases autophosphorylation on tyrosine residues upon ligand binding. abolishes autophosphorylation on tyrosine residues upon ligand …
879abolishes enzyme activity.
1063loss of phosphorylation site. no effect on stimulation of cell proliferation and cell migration.
1068global loss of autophosphorylation. abolishes stimulation of cell proliferation and cell migration.
1230loss of phosphorylation site. strongly reduces stimulation of cell proliferation and cell migration.
1231loss of phosphorylation site. strongly reduces stimulation of cell proliferation and cell migration.
1265loss of phosphorylation site. no effect on stimulation of cell proliferation and cell migration.
1333loss of phosphorylation site. reduced autophosphorylation.
1337reduced autophosphorylation. strongly reduces stimulation of cell proliferation and cell migration.
1363loss of phosphorylation site. slightly reduced autophosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 12; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

12 pathways:

IDPathwayEvidence
R-HSA-195399VEGF binds to VEGFR leading to receptor dimerizationcurated
R-HSA-9855142Cellular responses to mechanical stimuli—
R-HSA-8953897Cellular responses to stimuli—
R-HSA-9856530High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cellselectronic
R-HSA-9013695NOTCH4 Intracellular Domain Regulates Transcriptionelectronic
R-HSA-9860931Response of endothelial cells to shear stress—
R-HSA-162582Signal Transduction—
R-HSA-157118Signaling by NOTCH—
R-HSA-9013694Signaling by NOTCH4—
R-HSA-9006934Signaling by Receptor Tyrosine Kinases—
R-HSA-194138Signaling by VEGF—
R-HSA-194313VEGF ligand-receptor interactions—

MSigDB gene sets: 353 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, REACTOME_SIGNALING_BY_NOTCH, GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_SIGNALING_PATHWAY, TGCGCANK_UNKNOWN, GOBP_REGULATION_OF_PHOSPHORYLATION, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_RESPIRATORY_SYSTEM_PROCESS, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_POSITIVE_REGULATION_OF_ENDOTHELIAL_CELL_MIGRATION, VART_KSHV_INFECTION_ANGIOGENIC_MARKERS_UP, GOBP_SPROUTING_ANGIOGENESIS, GOBP_REGULATION_OF_ENDOTHELIAL_CELL_MIGRATION

GO Biological Process (25): positive regulation of protein phosphorylation (GO:0001934), positive regulation of endothelial cell proliferation (GO:0001938), vasculature development (GO:0001944), lymph vessel development (GO:0001945), lymphangiogenesis (GO:0001946), sprouting angiogenesis (GO:0002040), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), positive regulation of cell population proliferation (GO:0008284), positive regulation of vascular endothelial growth factor production (GO:0010575), positive regulation of endothelial cell migration (GO:0010595), cell migration (GO:0016477), peptidyl-tyrosine phosphorylation (GO:0018108), positive regulation of cell migration (GO:0030335), cellular response to vascular endothelial growth factor stimulus (GO:0035924), vascular endothelial growth factor signaling pathway (GO:0038084), negative regulation of apoptotic process (GO:0043066), positive regulation of MAPK cascade (GO:0043410), positive regulation of JNK cascade (GO:0046330), protein autophosphorylation (GO:0046777), vascular endothelial growth factor receptor signaling pathway (GO:0048010), blood vessel morphogenesis (GO:0048514), regulation of blood vessel remodeling (GO:0060312), positive regulation of ERK1 and ERK2 cascade (GO:0070374), angiogenesis (GO:0001525), protein phosphorylation (GO:0006468)

GO Molecular Function (13): transmembrane receptor protein tyrosine kinase activity (GO:0004714), vascular endothelial growth factor receptor activity (GO:0005021), ATP binding (GO:0005524), growth factor binding (GO:0019838), protein phosphatase binding (GO:0019903), protein homodimerization activity (GO:0042803), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein tyrosine kinase activity (GO:0004713), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (7): extracellular region (GO:0005576), nucleus (GO:0005634), cytosol (GO:0005829), plasma membrane (GO:0005886), signaling receptor complex (GO:0043235), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

9 top-level categories:

CategoryPathways
Signal Transduction2
VEGF ligand-receptor interactions1
Signaling by NOTCH41
Response of endothelial cells to shear stress1
Signaling by Receptor Tyrosine Kinases1
Signaling by VEGF1
Signaling by NOTCH1
Cellular responses to stimuli1
Cellular responses to mechanical stimuli1

GO top-level categories

showing 60 of 70 GO namespaces:

CategoryTerms
cellular anatomical structure4
protein phosphorylation3
animal gross anatomical part developmental process2
cell surface receptor protein tyrosine kinase signaling pathway2
regulation of protein phosphorylation1
positive regulation of protein modification process1
positive regulation of phosphorylation1
endothelial cell proliferation1
regulation of endothelial cell proliferation1
positive regulation of epithelial cell proliferation1
system development1
circulatory system development1
vasculature development1
anatomical structure morphogenesis1
lymph vessel morphogenesis1
anatomical structure formation involved in morphogenesis1
angiogenesis1
enzyme-linked receptor protein signaling pathway1
cell population proliferation1
regulation of cell population proliferation1
positive regulation of cellular process1
positive regulation of cytokine production1
vascular endothelial growth factor production1
regulation of vascular endothelial growth factor production1
regulation of endothelial cell migration1
positive regulation of cell migration1
endothelial cell migration1
cell motility1
cell migration1
regulation of cell migration1
positive regulation of cell motility1
cellular response to growth factor stimulus1
cellular response to vascular endothelial growth factor stimulus1
apoptotic process1
regulation of apoptotic process1
negative regulation of programmed cell death1
MAPK cascade1
regulation of MAPK cascade1
positive regulation of intracellular signal transduction1
JNK cascade1
positive regulation of MAPK cascade1
regulation of JNK cascade1
protein tyrosine kinase activity1
transmembrane receptor protein kinase activity1
transmembrane receptor protein tyrosine kinase activity1
vascular endothelial growth factor signaling pathway1
vascular endothelial growth factor binding1
adenyl ribonucleotide binding1
purine ribonucleoside triphosphate binding1
anion binding1
protein binding1
phosphatase binding1
identical protein binding1
protein dimerization activity1
nucleoside phosphate binding1
heterocyclic compound binding1
kinase activity1
phosphotransferase activity, alcohol group as acceptor1
catalytic activity, acting on a protein1
protein kinase activity1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 23 of 45 annotations. The rest are phylogenetic / computational / electronic (IEA).

23 experimentally-supported GO terms:

GO termNSEvidence
cellular response to vascular endothelial growth factor stimulusBPdirect assay
lymphangiogenesisBPmutant phenotype
negative regulation of apoptotic processBPmutant phenotype
peptidyl-tyrosine phosphorylationBPdirect assay
positive regulation of ERK1 and ERK2 cascadeBPmutant phenotype
positive regulation of JNK cascadeBPmutant phenotype
positive regulation of MAPK cascadeBPmutant phenotype
positive regulation of cell population proliferationBPmutant phenotype
positive regulation of endothelial cell migrationBPmutant phenotype
positive regulation of endothelial cell proliferationBPmutant phenotype
positive regulation of protein phosphorylationBPmutant phenotype
positive regulation of vascular endothelial growth factor productionBPmutant phenotype
protein autophosphorylationBPdirect assay
vascular endothelial growth factor receptor signaling pathwayBPdirect assay
vascular endothelial growth factor signaling pathwayBPdirect assay
cytosolCCdirect assay
plasma membraneCCdirect assay
signaling receptor complexCCdirect assay
growth factor bindingMFphysical interaction
protein homodimerization activityMFdirect assay
protein phosphatase bindingMFphysical interaction
transmembrane receptor protein tyrosine kinase activityMFmutant phenotype
vascular endothelial growth factor receptor activityMFdirect assay

Protein interactions and networks

STRING

showing 15 of 1,814 interactions by confidence (×1000):

Protein AProtein BPartner UniProtScore
FLT4VEGFCP49767967
FLT4VEGFDO43915951
FLT4LYVE1Q9Y5Y7933
FLT4VEGFBP49765876
FLT4PGFP49763846
FLT4FOXC2Q99958817
FLT4DLL4Q9NR61798
FLT4CDH5P33151782
FLT4SOX18P35713780
FLT4NRP2O60462772
FLT4PROX1Q92786759
FLT4PDPNQ86YL7756
FLT4EFNB2P52799751
FLT4PECAM1P16284704
FLT4FGF2P09038696

IntAct

Human interaction partners of FLT4 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

11 partners by confidence:

PartnerInteraction typeMIscoreRecords
KDRphysical association0.7005
HSP90AB1physical association0.6402
LRRK1direct interaction0.4401
PKMphosphorylation reaction0.4401
ILVBLassociation0.4201
CEACAM4physical association0.4002
VEGFCphysical association0.4002
ATF7IPphysical association0.3701
DUSP19physical association0.3701
ESYT2proximity0.2701
IKBKGdirect interaction0.0001

BioGRID (299 interactions; top human partners by supporting records): SHC1 (Reconstituted Complex; 5 records), LGALS8 (Affinity Capture-MS; 3 records), PTGER3 (Affinity Capture-MS; 3 records), TMEM52B (Affinity Capture-MS; 3 records), ARCN1 (Affinity Capture-MS; 2 records), CALR (Affinity Capture-MS; 2 records), CANX (Affinity Capture-MS; 2 records), CDC37 (Affinity Capture-MS; 2 records), DNAJB11 (Affinity Capture-MS; 2 records), FIGF (Reconstituted Complex; 2 records), GLUD1 (Affinity Capture-MS; 2 records), GRB2 (Reconstituted Complex; 2 records), HAX1 (Affinity Capture-MS; 2 records), HSD17B12 (Affinity Capture-MS; 2 records), HSP90AA1 (Affinity Capture-MS; 2 records)

SIGNOR signaling

showing 26 of 40 signaling interactions:

AEffectBMechanism
FLT4“up-regulates activity”FLT4phosphorylation
sunitinibdown-regulatesFLT4“chemical inhibition”
SRCup-regulatesFLT4phosphorylation
axitinibdown-regulatesFLT4“chemical inhibition”
nintedanibdown-regulatesFLT4“chemical inhibition”
“Brivanib alaninate”down-regulatesFLT4“chemical inhibition”
lenvatinibdown-regulatesFLT4“chemical inhibition”
KRN-633down-regulatesFLT4“chemical inhibition”
N-[[3-fluoro-4-[[2-(1-methyl-4-imidazolyl)-7-thieno[3,2-b]pyridinyl]oxy]anilino]-sulfanylidenemethyl]-2-phenylacetamidedown-regulatesFLT4“chemical inhibition”
motesanibdown-regulatesFLT4“chemical inhibition”
“pazopanib hydrochloride”down-regulatesFLT4“chemical inhibition”
Telatinibdown-regulatesFLT4“chemical inhibition”
1-[2-chloro-4-[(6,7-dimethoxy-4-quinolinyl)oxy]phenyl]-3-(5-methyl-3-isoxazolyl)ureadown-regulatesFLT4“chemical inhibition”
TBX1“up-regulates quantity by expression”FLT4“transcriptional regulation”
pazopanib“down-regulates activity”FLT4“chemical inhibition”
sunitinib“down-regulates activity”FLT4“chemical inhibition”
regorafenib“down-regulates activity”FLT4“chemical inhibition”
VEGFDup-regulatesFLT4binding
VEGFCup-regulatesFLT4binding
FLT4unknownSHC1phosphorylation
FLT4down-regulatesRPS6KA3phosphorylation
nintedanib“down-regulates activity”FLT4“chemical inhibition”
motesanib“down-regulates activity”FLT4“chemical inhibition”
“sorafenib tosylate”“down-regulates activity”FLT4“chemical inhibition”
linifanib“down-regulates activity”FLT4“chemical inhibition”
FLT4“up-regulates activity”GLO1phosphorylation

Protein complexes (CORUM) (11)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

11 complexes by size:

ComplexSubunitsMembers
★ FLT4-NRP2-VEGFD complex3FLT4, NRP2, VEGFD
★ FLT4-ITGB1-SRC complex3FLT4, ITGB1, SRC
★ FLT4-NRP2-VEGFC complex3NRP2, VEGFC, FLT4
★ FLT4-ITGA5-ITGB1 complex3FLT4, ITGA5, ITGB1
★ CDH5-FLT4-KDR complex3CDH5, FLT4, KDR
★ FLT4-VEGFC complex2FLT4, VEGFC
★ FLT4-VEGFD complex2FLT4, VEGFD
★ FLT4-KDR receptor complex2FLT4, KDR
★ FLT4-IL1B complex2FLT4, IL1B
★ CAV1-FLT4 complex2CAV1, FLT4
★ FLT4-NRP2 receptor complex2FLT4, NRP2

Ligand–receptor pairs (CellPhoneDB) (2)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

2 ligand–receptor pairs:

PartnerThis gene’s roleSignaling class
VEGFCreceptorSignaling by Vascular endothelial growth factor
VEGFDreceptorSignaling by Vascular endothelial growth factor

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 10 cancer types — ANGS, BCC, BLCA, CCRCC, CHRCC, HCC, LUAD, LUSC, NBL, UCEC.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for FLT4: 657 ClinVar records (71 pathogenic / likely pathogenic); 2 PharmGKB clinical annotations; 3 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

657 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic36
Likely pathogenic35
Uncertain significance300
Likely benign122
Benign111

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 71 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant IDHGVSClassificationReviewSubmitters
16259NM_182925.5(FLT4):c.2569G>A (p.Gly857Arg)Pathogeniccriteria provided, multiple submitters, no conflicts4
932061NM_182925.5(FLT4):c.3410C>T (p.Pro1137Leu)Likely pathogeniccriteria provided, multiple submitters, no conflicts5
16260NM_182925.5(FLT4):c.3122G>C (p.Arg1041Pro)Pathogeniccriteria provided, single submitter3
812612NM_182925.5(FLT4):c.89del (p.Pro30fs)Pathogeniccriteria provided, single submitter2
1806294NM_182925.5(FLT4):c.1755C>G (p.Tyr585Ter)Pathogeniccriteria provided, single submitter1
2445224NM_182925.5(FLT4):c.3332G>A (p.Gly1111Glu)Pathogeniccriteria provided, single submitter1
2630521NM_182925.5(FLT4):c.2815del (p.Leu939fs)Pathogeniccriteria provided, single submitter1
2636940NM_182925.5(FLT4):c.3019dup (p.Ser1007fs)Pathogeniccriteria provided, single submitter1
3279269NM_182925.5(FLT4):c.488_489dup (p.Gly164fs)Pathogeniccriteria provided, single submitter1
3387754NM_182925.5(FLT4):c.1657+6T>CPathogeniccriteria provided, single submitter1
3390372NM_182925.5(FLT4):c.985+1G>APathogeniccriteria provided, single submitter1
3766055NM_182925.5(FLT4):c.2554G>T (p.Gly852Cys)Pathogeniccriteria provided, single submitter1
3778773NM_182925.5(FLT4):c.1706dup (p.Glu570fs)Pathogeniccriteria provided, single submitter1
4056442NM_182925.5(FLT4):c.1548+1G>APathogeniccriteria provided, single submitter1
4082986NM_182925.5(FLT4):c.541C>T (p.Gln181Ter)Pathogeniccriteria provided, single submitter1

Per-variant reference — Sugi Variant

Explore FLT4’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 3,446):

Position(s)EffectΔscoreSites
5:180614066–180614067donor_loss1.00003
5:180616371donor_gain1.0000
5:180616490–180616491acceptor_loss1.00006
5:180616495acceptor_gain1.0000
5:180618769donor_loss1.0000
5:180620309–180620310acceptor_loss1.00005
5:180620611donor_gain1.0000
5:180620716–180620717acceptor_loss1.00003
5:180620874–180620875donor_loss1.00005
5:180620878donor_gain1.0000

AlphaMissense

2,599 missense substitutions predicted likely pathogenic (of 8,932 scored), across 643 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

ResidueLikely-pathogenic substitutionsMean am_pathogenicityMax am_pathogenicity
M108190.9610.998
M102590.9500.994
M113490.9190.994
M88090.9030.983
N104280.9991.000
D105580.9991.000
D103780.9971.000
D109680.9960.999
H103580.9950.999
F105680.9940.999
F85680.9781.000
D106180.9760.993
D30480.9660.990
F116280.9660.995
F110880.9590.993
F112480.9560.997
D74280.9480.981
F26480.9460.994
F108780.9400.993
N91180.9360.996

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Kidney Renal Clear Cell Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

CancerPrognosticp-value
Kidney Renal Clear Cell Carcinoma (TCGA)favorable5.61e-06
Kidney Renal Clear Cell Carcinoma (validation)favorable8.45e-05
Liver Hepatocellular Carcinoma (validation)favorable0.000255
Lung Squamous Cell Carcinoma (TCGA)unfavorable0.000996

Disease associations

OMIM: gene MIM:136352 | disease phenotypes: MIM:153100, MIM:618780, MIM:236750, MIM:602089

GenCC curated gene-disease

5 curated gene-disease records:

DiseaseClassificationInheritanceRecords
lymphatic malformation 1DefinitiveAutosomal dominant4
capillary infantile hemangiomaStrongAutosomal dominant
congenital heart defects, multiple types, 7StrongAutosomal dominant3
tetralogy of fallotSupportiveAutosomal dominant
lymphatic malformationSupportiveAutosomal dominant

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

2 validity classifications:

DiseaseClassificationInheritance
congenital heart defects, multiple types, 7DefinitiveAD
lymphatic malformation 1DefinitiveAD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (7 panels, 6 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

7 panels:

PanelRating
DDG2Pgreen
Fetal anomaliesgreen
Fetal hydropsgreen
Paediatric disordersgreen
Primary lymphoedemagreen
Vascular skin disordersgreen
Rare genetic inflammatory skin disordersamber

Mondo (6): lymphatic malformation 1 (MONDO:0007919), congenital heart defects, multiple types, 7 (MONDO:0032913), non-immune hydrops fetalis (MONDO:0009369), capillary infantile hemangioma (MONDO:0011191), tetralogy of fallot (MONDO:0008542), lymphatic malformation (MONDO:0019313)

Orphanet (4): Milroy disease (Orphanet:79452), Non-immune hydrops fetalis (Orphanet:363999), NON RARE IN EUROPE: Infantile capillary hemangioma (Orphanet:464293), OBSOLETE: Familial capillary hemangioma (Orphanet:91415)

HPO phenotypes

50 phenotypes (HPO-id order):

HPOTerm
HP:0000006Autosomal dominant inheritance
HP:0000028Cryptorchidism
HP:0000034Hydrocele testis
HP:0000233Thin vermilion border
HP:0000268Dolichocephaly
HP:0000286Epicanthus
HP:0000337Broad forehead
HP:0000520Proptosis
HP:0000708Atypical behavior
HP:0000716Depression
HP:0000739Anxiety
HP:0000962Hyperkeratosis
HP:0001004Lymphedema
HP:0001015Prominent superficial veins
HP:0001028Hemangioma
HP:0001055Erysipelas
HP:0001156Brachydactyly
HP:0001328Specific learning disability
HP:0001511Intrauterine growth retardation
HP:0001636Tetralogy of Fallot
HP:0001642Pulmonic stenosis
HP:0001785Ankle swelling
HP:0001790Nonimmune hydrops fetalis
HP:0001999Abnormal facial shape
HP:0002619Varicose veins
HP:0002624Abnormal venous morphology
HP:0003550Predominantly lower limb lymphedema
HP:0003577Congenital onset
HP:0003593Infantile onset
HP:0003759Hypoplasia of lymphatic vessels
HP:0004209Clinodactyly of the 5th finger
HP:0004467Preauricular pit
HP:0004935Pulmonary artery atresia
HP:0005105Abnormal nasal morphology
HP:0005134Absence of the pulmonary valve
HP:0005306Capillary hemangioma
HP:0007448Hyperkeratosis over edematous areas
HP:0008069Neoplasm of the skin
HP:0009891Underdeveloped supraorbital ridges
HP:0010741Pedal edema
HP:0011590Double aortic arch
HP:0012020Right aortic arch
HP:0012227Urethral stricture
HP:0012740Papilloma
HP:0031834Aortopulmonary collateral arteries
HP:0032344Upslanting toenail
HP:0100658Cellulitis
HP:0100725Lichenification
HP:0100797Toenail dysplasia
HP:0200058Angiosarcoma

GWAS associations

3 associations:

StudyTraitp-value
GCST006585_2187Blood protein levels6e-13
GCST90002401_62Platelet distribution width4e-10
GCST006137_9Serum folate levels7e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO IDTrait name
EFO:0007984platelet component distribution width

MeSH disease descriptors

2 disease descriptors:

DescriptorNameTree numbers
D013771Tetralogy of FallotC14.240.400.849; C14.280.400.849; C16.131.240.400.849
C535860Hemangioma, capillary infantile *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL1955 (SINGLE PROTEIN), CHEMBL2095227 (PROTEIN FAMILY), CHEMBL2111409 (SELECTIVITY GROUP), CHEMBL3301389 (PROTEIN-PROTEIN INTERACTION)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the FLT4 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

6 curated-mechanism drugs:

DrugModalityMax phase
SUNITINIBSmall molecule4
CATEQUENTINIBSmall molecule3
FAMITINIBSmall molecule3
TELATINIBSmall molecule2
IMC-3C5Unknown1
JNJ-26483327Small molecule1

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes FLT4 — the drug acts on the assembly or class, not necessarily on this subunit alone.

39 drugs via a complex or family:

DrugTarget (ChEMBL)MembersMax phase
AXITINIBVascular endothelial growth factor receptor34
FRUQUINTINIBVascular endothelial growth factor receptor34
LENVATINIB MESYLATEVascular endothelial growth factor receptor34
NINTEDANIB ESYLATEVascular endothelial growth factor receptor34
PAZOPANIB HYDROCHLORIDEVascular endothelial growth factor receptor34
REGORAFENIBVascular endothelial growth factor receptor34
SORAFENIB TOSYLATEVascular endothelial growth factor receptor34
TIVOZANIBVascular endothelial growth factor receptor34
VANDETANIBVascular endothelial growth factor receptor34
BRIVANIBVascular endothelial growth factor receptor33
BRIVANIB ALANINATEVascular endothelial growth factor receptor33
CEDIRANIBVascular endothelial growth factor receptor33
DOVITINIBVascular endothelial growth factor receptor33
IBCASERTIBVascular endothelial growth factor receptor33
LINIFANIBVascular endothelial growth factor receptor33
MOTESANIBVascular endothelial growth factor receptor33
SEMAXANIBVascular endothelial growth factor receptor33
SURUFATINIBVascular endothelial growth factor receptor33
VATALANIBVascular endothelial growth factor receptor33
AG-13958Vascular endothelial growth factor receptor32
BMS-690514Vascular endothelial growth factor receptor32
CEP-11981Vascular endothelial growth factor receptor32
FORETINIBVascular endothelial growth factor receptor32
GLESATINIBVascular endothelial growth factor receptor32
ILORASERTIBVascular endothelial growth factor receptor32
LUCITANIBVascular endothelial growth factor receptor32
SU-014813Vascular endothelial growth factor receptor32
X-82Vascular endothelial growth factor receptor32
XL-820Vascular endothelial growth factor receptor32
XL-999Vascular endothelial growth factor receptor32
4SC-203Vascular endothelial growth factor receptor31
CEP-5214Vascular endothelial growth factor receptor31
CEP-7055Vascular endothelial growth factor receptor31
CP-459632Vascular endothelial growth factor receptor31
KRN-633Vascular endothelial growth factor receptor31
L-21649Vascular endothelial growth factor receptor31
OSI-930Vascular endothelial growth factor receptor31
RG-1530Vascular endothelial growth factor receptor31
TAK-593Vascular endothelial growth factor receptor31

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 506,059 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 72 molecules by phase:

MoleculeNamePhasePatents
CHEMBL535SUNITINIB480,232
CHEMBL1289926AXITINIB416,510
CHEMBL3545311BRIGATINIB45,988
CHEMBL2105717CABOZANTINIB411,799
CHEMBL1983268ENTRECTINIB43,737
CHEMBL553ERLOTINIB4109,860
CHEMBL1287853FEDRATINIB43,770
CHEMBL3301607FILGOTINIB43,101
CHEMBL4303214FRUQUINTINIB4793
CHEMBL939GEFITINIB4119,425
CHEMBL1852688INFIGRATINIB42,298
CHEMBL1834657INFIGRATINIB PHOSPHATE4330
CHEMBL1289601LENVATINIB49,224
CHEMBL608533MIDOSTAURIN47,641
CHEMBL502835NINTEDANIB48,978
CHEMBL3039504NINTEDANIB ESYLATE4691
CHEMBL477772PAZOPANIB416,241
CHEMBL576982QUIZARTINIB44,647
CHEMBL1946170REGORAFENIB413,318
CHEMBL1336SORAFENIB487,476
CHEMBL1289494TIVOZANIB4
CHEMBL24828VANDETANIB4
CHEMBL377300BRIVANIB3
CHEMBL491473CEDIRANIB3
CHEMBL290352CEP-13473
CHEMBL522892DOVITINIB3
CHEMBL300138ENZASTAURIN3
CHEMBL603469LESTAURTINIB3
CHEMBL223360LINIFANIB3
CHEMBL572881MOTESANIB3
CHEMBL276711SEMAXANIB3
CHEMBL4297190SURUFATINIB3
CHEMBL101253VATALANIB3
CHEMBL2079588TELATINIB2
CHEMBL495727AT-92832
CHEMBL3989870BERZOSERTIB2
CHEMBL4080062BFH-7722
CHEMBL1967878CENISERTIB2
CHEMBL4116008CERDULATINIB2
CHEMBL402548DANUSERTIB2
CHEMBL215152DEFOSBARASERTIB2
CHEMBL103667DORAMAPIMOD2
CHEMBL6246ELLAGIC ACID2
CHEMBL1230609FORETINIB2
CHEMBL1980297ILORASERTIB2
CHEMBL2220486LUCITANIB2
CHEMBL564829MILCICLIB2
CHEMBL1822792MK-24612
CHEMBL3689071NARMAFOTINIB2
CHEMBL3586404ONATASERTIB2
CHEMBL253969OSI-6322
CHEMBL475251R-4062
CHEMBL558752RAF-2652
CHEMBL1738757REBASTINIB2
CHEMBL565612SOTRASTAURIN2
CHEMBL1721885SU-0148132
CHEMBL363648TAK-7152
CHEMBL124660TANDUTINIB2
CHEMBL572878TOZASERTIB2
CHEMBL3109738JNJ-264833271

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

2 annotations by evidence level (1 strongest → 4):

VariantAssociationLevelDrugsPhenotypes
rs307821Efficacy3sunitinibRenal Cell Carcinoma
rs307826Efficacy3sunitinibRenal Cell Carcinoma

PharmGKB variants

2 variants:

VariantGenesLevelScore#Clin annotsDrugs
rs307821FLT4, SCGB3A132.251sunitinib
rs307826FLT432.751sunitinib

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

7 published findings:

VariantDrug(s)CategoryFindingPMID
rs307821sunitinibEfficacyGenotypes AA + AC is associated with decreased progression-free survival when treated with sunitinib in people with Carcinoma, Renal Cell as compared to genotype CC.PMID:23462807
rs307826sunitinibEfficacyGenotypes CC + CT is associated with decreased overall survival when treated with sunitinib in people with Carcinoma, Renal Cell as compared to genotype TT.PMID:23462807
rs6877011sunitinibEfficacyAllele C is associated with increased overall survival and progression-free survival when treated with sunitinib in people with Carcinoma, Renal Cell as compared to allele G.PMID:23511629
rs6877011sunitinibEfficacyGenotype GG is associated with decreased likelihood of Disease Progression when treated with sunitinib in people with Gastrointestinal Stromal Tumors as compared to genotype CG.PMID:27896475
rs307826sunitinibToxicityGenotype CT is associated with increased severity of Diarrhea when treated with sunitinib in people with Gastrointestinal Stromal Tumors or Renal Cell Carcinoma as compared to genotype TT.PMID:41485482
rs307826sunitinibEfficacyGenotype CT is associated with reduced progression-free survival when treated with sunitinib in people with Carcinoma, Renal Cell as compared to genotype TT.PMID:22015057
rs307821sunitinibEfficacyGenotype AC is associated with decreased progression-free survival when treated with sunitinib in people with Carcinoma, Renal Cell as compared to genotype CC.PMID:22015057

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Type IV RTKs: VEGF (vascular endothelial growth factor) receptor family

Most potent curated ligand interactions (29 total), top 25:

LigandActionAffinityParameter
tivozanibInhibition9.62pIC50
fruquintinibInhibition9.3pIC50
catequentinibInhibition9.0pIC50
sitravatinibInhibition8.7pIC50
foretinibInhibition8.55pIC50
cediranibInhibition8.52pIC50
dovitinibInhibition8.52pIC50
compound 8i [PMID: 22765894]Inhibition8.52pIC50
compound 8h [PMID: 22765894]Inhibition8.49pIC50
lenvatinibInhibition8.28pIC50
motesanibInhibition8.22pIC50
tesevatinibInhibition8.06pIC50
ibcasertibInhibition8.05pIC50
sunitinibInhibition8.05pIC50
tafetinibInhibition7.92pIC50
nintedanibInhibition7.89pIC50
RIPK1 inhibitor 22bInhibition7.7pIC50
sorafenibInhibition7.7pIC50
pexmetinibInhibition7.38pIC50
ilorasertibInhibition7.37pIC50
pazopanibInhibition7.33pIC50
MK-2461Inhibition7.11pIC50
compound 38k [PMID: 34351741]Inhibition6.96pIC50
CHMFL-KIT-64Inhibition6.92pIC50
VEGF receptor tyrosine kinase inhibitor IIIInhibition6.9pIC50

Binding affinities (BindingDB)

538 measured of 745 human assays (760 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
CHEMBL3939307IC500.1 nM
CHEMBL6150730IC500.18 nM
CHEMBL4163870IC500.19 nM
3-[3-[4-[dideuterio(methylamino)methyl]phenyl]isoxazol-5-yl]-5-(4-isopropylsulfonylphenyl)pyrazin-2-amineIC500.2 nM
CHEMBL6162898IC500.22 nM
BDBM50375663IC500.23 nM
CHEMBL6114929IC500.28 nM
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]ureaKD0.37 nM
AP-26113IC500.37 nM
CHEMBL5407330IC500.73 nM
CHEMBL5410108IC500.76 nM
CHEMBL5412144IC500.86 nM
CHEMBL5403470IC500.88 nM
CHEMBL5394759IC500.98 nM
CHEMBL5421802IC500.99 nM
Jak Inhibitor 1EC501 nM
CHEMBL3764474IC501 nM
BAY-579352IC501 nM
CHEMBL5393865IC501 nM
CHEMBL5438830IC501.1 nM
(Z)-1-(3,4-Dimethoxyphenyl)-3-[2-oxo-3-(1H-pyrrol-2-ylmethylene)-2,3-dihydro-1H-indol-6-yl]ureaIC501.2 nM
CHEMBL5411585IC501.4 nM
(Z)-1-(4-Methoxyphenyl)-3-[2-oxo-3-(1H-pyrrol-2-ylmethylene)-2,3-dihydro-1H-indol-6-yl]ureaIC501.5 nM
(Z)-1-Naphthalen-2-yl-3-[2-oxo-3-(1H-pyrrol-2-ylmethylene)-2,3-dihydro-1H-indol-6-yl]ureaIC501.5 nM
REGORAFENIBIC501.5 nM
CHEMBL6146585IC501.6 nM
StaurosporineKD1.7 nM
CHEMBL3765306IC501.9 nM
CHEMBL2064666IC501.9 nM
tert-butyl N-[1-[4-[[4-[2-[2-(1-carbamoylcyclopropyl)phenyl]ethyl]-5-chloropyrimidin-2-yl]amino]phenyl]ethyl]carbamateIC502 nMUS-9238644: VEGFR3 inhibitors
(3S,5Z,8S,9R,11E)-8,9,16-trihydroxy-14-methoxy-3-methyl-3,4,9,10-tetrahydro-1H-benzo[c][1]oxacyclotetradecine-1,7(8H)-dioneIC502 nM
CHEMBL4791998IC502 nM
CHEMBL6103505IC502 nM
2-amino-1-ethyl-7-(3-hydroxy-3-thiophen-3-ylbut-1-ynyl)-N-methyl-4-oxo-1,8-naphthyridine-3-carboxamideIC502 nMUS-8470847: Derivatives of 7-alkynyl-1,8-naphthyridones, preparation method thereof and use of same in therapeutics
CHEMBL4160854IC502.1 nM
(Z)-5-{6-[3-(4-Methoxyphenyl)-ureido]-2-oxo-1,2-dihydroindol-3-ylidene-methyl}-4-methyl-1H-pyrrole-3-carboxylic acidIC502.1 nM
CHEMBL5421149IC502.1 nM
5-((5-(4-((4-(2-hydroxyethyl)piperazin-1-yl)methyl)-3-(trifluoromethyl)phenylcarbamoyl)-2-methylphenyl)ethynyl)-N,1-dimethyl-1H-imidazole-2-carboxamideIC502.2 nM
CHEMBL5410264IC502.2 nM
CHEMBL6173446IC502.3 nM
CHEMBL5408069IC502.5 nM
FIIN-1KD2.8 nM
CHEMBL5436823IC502.9 nM
CHEMBL5403747IC502.9 nM
1-[2-[2-[2-[(1-methylpyrazol-4-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamideIC503 nMUS-9238644: VEGFR3 inhibitors
1-[2-[2-[5-chloro-2-[[1-(2-methoxyethyl)pyrazol-4-yl]amino]pyrimidin-4-yl]ethyl]phenyl]cyclopropane-1-carboxamideIC503 nMUS-9238644: VEGFR3 inhibitors
CHEMBL3335371IC503 nM
rac-9-isobutyl-5-methyl-12-(tetrahydro-2H-pyran-2-yl)-5,7,8,9-tetrahydro-1H-indazolo[5,4-a]pyrrolo[3,4-c]carbazol-3(2H)-oneIC503 nM
CHEMBL5400860IC503.1 nM
CHEMBL5409075IC503.1 nM

ChEMBL bioactivities

1194 potent at pChembl≥5 of 1226 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
10.00IC500.1nMCHEMBL3939307
10.00IC500.1nMAXITINIB
9.96IC500.11nMVANDETANIB
9.90Ki0.1259nMCHEMBL273187
9.74IC500.18nMCHEMBL5403470
9.74IC500.18nMCHEMBL5421802
9.70IC500.2nMCHEMBL1940109
9.70Ki0.1995nMCHEMBL404366
9.62IC500.24nMTIVOZANIB
9.50Ki0.3162nMCHEMBL271441
9.50Ki0.3162nMCHEMBL1986979
9.50Ki0.3162nMCHEMBL272938
9.46IC500.35nMCHEMBL5407330
9.42IC500.38nMCHEMBL5412144
9.41IC500.39nMCHEMBL5410264
9.40IC500.4nMCHEMBL1940108
9.40Ki0.3981nMCHEMBL1993996
9.40Ki0.3981nMCHEMBL374044
9.38IC500.42nMCHEMBL5394759
9.37IC500.43nMCHEMBL5421149
9.30IC500.5nMCHEMBL1668411
9.27IC500.54nMCHEMBL5436823
9.25IC500.56nMCHEMBL6146585
9.24IC500.58nMCHEMBL5393865
9.24IC500.58nMCHEMBL5410108
9.17IC500.68nMCHEMBL6146128
9.17IC500.67nMCHEMBL6103505
9.15IC500.7nMSTAUROSPORINE
9.14IC500.73nMCHEMBL2012519
9.10IC500.8nMCHEMBL5403747
9.10IC500.8nMCHEMBL1173411
9.10Ki0.7943nMCHEMBL373798
9.10Ki0.7943nMCHEMBL402846
9.10Ki0.7943nMCHEMBL1994638
9.06IC500.87nMCHEMBL5411025
9.05IC500.9nMSTAUROSPORINE
9.00IC501nMCHEMBL3891581
9.00IC501nMAT-9283
9.00IC501nMCHEMBL5176837
9.00IC501nMSURUFATINIB
9.00Ki1nMCHEMBL1996255
9.00Ki1nMCHEMBL403402
8.99IC501.03nMCHEMBL5408069
8.96IC501.1nMTAK-593
8.96IC501.1nMCHEMBL193306
8.96IC501.1nMCHEMBL4453304
8.96IC501.1nMCHEMBL6142589
8.95IC501.13nMCHEMBL2012519
8.94IC501.14nMCHEMBL5433332
8.92IC501.2nMCHEMBL4303275

PubChem BioAssay actives

731 with measured affinity, of 2717 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
Vandetanib1895650: Inhibition of VEGFR3 (unknown origin)ic500.0001uM
N-methyl-2-[[3-(2-pyridin-2-ylethyl)-2H-indazol-6-yl]sulfanyl]benzamide1331764: Inhibition of VEGFR3 (unknown origin)ic500.0001uM
Axitinib1424500: Inhibition of VEGFR3 (unknown origin)ic500.0001uM
1-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]-3-(1-cyclopentylpyrazol-4-yl)urea1975504: Inhibition of VEGFR3 (unknown origin)ic500.0002uM
1-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]-3-(3-fluoro-4-methylphenyl)urea1975504: Inhibition of VEGFR3 (unknown origin)ic500.0002uM
2-[4-[6-methoxy-7-(2-methoxyethoxy)quinazolin-4-yl]oxypyrazol-1-yl]-N-(3-methoxyphenyl)acetamide639906: Inhibition of VEGFR3 phosphorylation by cell based assayic500.0002uM
Tivozanib2159214: Inhibition of VEGFR-3 phosphorylation in serum starved human HUVEC cells incubated for 1 hr by immunoblotting analysisic500.0002uM
1-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]-3-[4-(trifluoromethoxy)phenyl]urea1975504: Inhibition of VEGFR3 (unknown origin)ic500.0003uM
N-[5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrol-3-yl]-3-(4-methylpiperazin-1-yl)propanamide1155231: Binding affinity to VEGFR3 (unknown origin)ki0.0003uM
1-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]-3-(4-methylphenyl)urea1975504: Inhibition of VEGFR3 (unknown origin)ic500.0004uM
1-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]-3-(1-propan-2-ylpyrazol-4-yl)urea1975504: Inhibition of VEGFR3 (unknown origin)ic500.0004uM
1-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]-3-[3-(trifluoromethyl)phenyl]urea1975504: Inhibition of VEGFR3 (unknown origin)ic500.0004uM
1-[2-fluoro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]-3-(1-propan-2-ylpyrazol-4-yl)urea1975504: Inhibition of VEGFR3 (unknown origin)ic500.0004uM
2-[4-(6,7-dimethoxyquinazolin-4-yl)oxypyrazol-1-yl]-N-(3-methoxyphenyl)acetamide639906: Inhibition of VEGFR3 phosphorylation by cell based assayic500.0004uM
(4S,6Z,9S,10R,12E)-9,10,18-trihydroxy-16-methoxy-4-methyl-3-oxabicyclo[12.4.0]octadeca-1(14),6,12,15,17-pentaene-2,8-dione568311: Inhibition of human recombinant VEGFR3 in cell free system after 90 minsic500.0005uM
1-butyl-3-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]urea1975504: Inhibition of VEGFR3 (unknown origin)ic500.0005uM
1-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]-3-(1-methylindol-5-yl)urea1975504: Inhibition of VEGFR3 (unknown origin)ic500.0006uM
2-[4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]-N-(3-propan-2-yl-1,2-oxazol-5-yl)acetamide2214731: Inhibition of FLT4 (unknown origin)ic500.0006uM
1-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]-3-(2-fluoro-5-methylphenyl)urea1975504: Inhibition of VEGFR3 (unknown origin)ic500.0006uM
(4S,6Z,9S,10S)-9,10,18-trihydroxy-16-methoxy-4-methyl-3-oxabicyclo[12.4.0]octadeca-1(14),6,15,17-tetraene-2,8-dione1540765: Inhibition of human VEGFR3 using poly[Glu:Tyr] (4:1) substrate and [gamma-33P]-ATP by radiometric biochemical kinase assayic500.0007uM
2-[4-[1-[4-[2-[(3-tert-butyl-1,2-oxazol-5-yl)amino]-2-oxoethyl]phenyl]benzimidazol-5-yl]pyrazol-1-yl]acetic acid2214731: Inhibition of FLT4 (unknown origin)ic500.0007uM
2-[4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]-N-(3-propyl-1,2-oxazol-5-yl)acetamide2214731: Inhibition of FLT4 (unknown origin)ic500.0007uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one1715340: Inhibition of human FLT4 using poly[Glu:Tyr] (4:1) as substrate by [gamma-33P]-ATP assayic500.0007uM
1-(1-benzofuran-5-yl)-3-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]urea1975504: Inhibition of VEGFR3 (unknown origin)ic500.0008uM
5-[(Z)-[6-[(4-methoxyphenyl)carbamoylamino]-2-oxo-1H-indol-3-ylidene]methyl]-4-methyl-1H-pyrrole-3-carboxylic acid491749: Inhibition of VEGFR3ic500.0008uM
1-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]-3-(2,4-dimethoxyphenyl)urea1975504: Inhibition of VEGFR3 (unknown origin)ic500.0009uM
6-[7-methoxy-6-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-N-pyrrolidin-3-ylpyridin-2-amine1894589: Inhibition of FLT4 (unknown origin)ic500.0010uM
1-cyclopropyl-3-[5-[6-(morpholin-4-ylmethyl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl]urea412576: Inhibition of VEGFR3ic500.0010uM
1-benzyl-3-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]urea1975504: Inhibition of VEGFR3 (unknown origin)ic500.0010uM
N-[2-(dimethylamino)ethyl]-1-[3-[[4-[(2-methyl-1H-indol-5-yl)oxy]pyrimidin-2-yl]amino]phenyl]methanesulfonamide2131262: Inhibition of VEGFR3 (unknown origin)ic500.0010uM
4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline2136108: Inhibition of VEGFR-3 (unknown origin) in presence of ATPic500.0010uM
2,4-difluoro-N-methoxy-5-[[6-(5-methyl-1,3-oxazol-2-yl)-5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl]amino]benzamide248164: Inhibition of VEGF-stimulated human umbilical vein endothelial cell proliferationic500.0011uM
(10S,12Z,15S,16R)-6,15,16-trihydroxy-4-methoxy-10-methyl-9-oxatricyclo[15.3.1.02,7]henicosa-1(21),2(7),3,5,12,17,19-heptaene-8,14-dione1540765: Inhibition of human VEGFR3 using poly[Glu:Tyr] (4:1) substrate and [gamma-33P]-ATP by radiometric biochemical kinase assayic500.0011uM
ethyl 2-[4-[1-[4-[2-[(3-tert-butyl-1,2-oxazol-5-yl)amino]-2-oxoethyl]phenyl]benzimidazol-5-yl]pyrazol-1-yl]acetate2214731: Inhibition of FLT4 (unknown origin)ic500.0011uM
1-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]-3-[(4-fluorophenyl)methyl]urea1975504: Inhibition of VEGFR3 (unknown origin)ic500.0011uM
N-[5-[2-(cyclopropanecarbonylamino)imidazo[1,2-b]pyridazin-6-yl]oxy-2-methylphenyl]-2,5-dimethylpyrazole-3-carboxamide710631: Inhibition of VEGFR3ic500.0011uM
N-(3-tert-butyl-1,2-oxazol-5-yl)-2-[4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]acetamide2214731: Inhibition of FLT4 (unknown origin)ic500.0012uM
1-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]-3-(4-phenylphenyl)urea1975504: Inhibition of VEGFR3 (unknown origin)ic500.0012uM
1-[2-chloro-4-[6-methoxy-7-(2-pyrrolidin-1-ylethoxy)quinazolin-4-yl]oxyphenyl]-3-(1-propan-2-ylpyrazol-4-yl)urea1975504: Inhibition of VEGFR3 (unknown origin)ic500.0012uM
2-amino-1-ethyl-7-[(3R)-3-hydroxy-4-methoxy-3-methylbut-1-ynyl]-N-methyl-4-oxo-1,8-naphthyridine-3-carboxamide1540765: Inhibition of human VEGFR3 using poly[Glu:Tyr] (4:1) substrate and [gamma-33P]-ATP by radiometric biochemical kinase assayic500.0012uM
(7Z)-N-[2-(diethylamino)ethyl]-7-(5-fluoro-2-oxo-1H-indol-3-ylidene)-2-methyl-1,4,5,6-tetrahydroindole-3-carboxamide773007: Inhibition of VEGFR3 (unknown origin)ic500.0013uM
N-(3-tert-butyl-1,2-oxazol-5-yl)-2-[4-[5-(1H-pyrazol-4-yl)benzimidazol-1-yl]phenyl]acetamide2214731: Inhibition of FLT4 (unknown origin)ic500.0014uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide624854: Binding constant for FLT4 kinase domainkd0.0015uM
5-[[6-(5-ethyl-1,3,4-oxadiazol-2-yl)-5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl]amino]-2,4-difluoro-N-methoxybenzamide248164: Inhibition of VEGF-stimulated human umbilical vein endothelial cell proliferationic500.0018uM
2-hydroxy-3-(2-hydroxyanilino)-6-imino-5-oxocyclohexa-1,3-diene-1-carboxamide735318: Inhibition of Flt4 (unknown origin) after 20 mins by scintillation countingic500.0018uM
1-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]-3-(3-fluorophenyl)urea1975504: Inhibition of VEGFR3 (unknown origin)ic500.0020uM
N-(4-chlorophenyl)-6-(6,7-dimethoxyquinolin-4-yl)oxynaphthalene-1-carboxamide326912: Inhibition of VEGFR3ic500.0020uM
N-[4-[2-(3-tert-butylanilino)-1-methylbenzimidazol-5-yl]oxy-2-pyridinyl]acetamide1255117: Inhibition of VEGFR (unknown origin)ic500.0020uM
Lenvatinib2231225: Inhibition of VEGFR3 (unknown origin)ic500.0020uM
2,4-difluoro-N-methoxy-5-[[6-[5-(methylsulfonylmethyl)-1,3,4-oxadiazol-2-yl]-5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl]amino]benzamide248164: Inhibition of VEGF-stimulated human umbilical vein endothelial cell proliferationic500.0021uM

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
bisphenol Adecreases expression, decreases methylation2
3-(4-dimethylamino-naphthalen-1-ylmethylene)-1,3-dihydro-indol-2-oneaffects reaction, increases expression, decreases expression, decreases phosphorylation2
ponatinibdecreases activity2
Arsenic Trioxidedecreases expression2
Benzo(a)pyreneaffects methylation, decreases methylation, increases methylation2
fluorene-9-bisphenoldecreases expression1
2,5,2’,5’-tetrachlorobiphenylincreases expression1
sodium arseniteincreases expression1
butyraldehydeincreases expression1
aflatoxin B2affects methylation, decreases methylation1
lysophosphatidic acidaffects reaction, increases expression1
caffeic acidincreases reaction, decreases expression1
pentanalincreases expression1
perfluorooctane sulfonic aciddecreases activity1
4-methoxycinnamate methyl esterdecreases expression, increases reaction1
3-nitrobenzanthronedecreases expression1
scriptaidaffects expression1
kaempferol-3-O-rutinosideincreases phosphorylation, increases reaction1
abrinedecreases expression1
bisphenol Sincreases methylation1
5H-benzo(4,5)cyclohepta(1,2-b)pyridin-5-onedecreases activity1
SAR131675increases phosphorylation, decreases reaction1
Sunitinibdecreases expression1
Ciclopiroxdecreases phosphorylation, decreases reaction1
Air Pollutantsincreases abundance, increases expression1
Antifungal Agentsdecreases phosphorylation, decreases reaction1
Cisplatinincreases expression1
Diethylhexyl Phthalatedecreases expression1
Drugs, Chinese Herbaldecreases expression, increases reaction1
Malathionincreases expression1

ChEMBL screening assays

717 unique, capped per target: 683 binding, 32 functional, 2 admet

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1000445BindingInhibition of human VEGFR3 expressed in baculovirus insect cell systemMixed-lineage kinase 1 and mixed-lineage kinase 3 subtype-selective dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-ones: optimization, mixed-lineage kinase 1 crystallography, and oral in vivo activity in 1-methyl-4-phenyltetrahydropyridine models. — *J Med Chem*
CHEMBL1963812FunctionalPUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: FLT4PubChem BioAssay data set
CHEMBL4013842ADMETInhibition of human FLT4 preincubated for 15 mins followed by peptide substrate addition measured after 3 hrs by caliper capillary electrophoresis methodDiscovery of the Irreversible Covalent FGFR Inhibitor 8-(3-(4-Acryloylpiperazin-1-yl)propyl)-6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(methylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (PRN1371) for the Treatment of Solid Tumors. — *J Med Chem*

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_B8G4Abcam HCT 116 FLT4 KOCancer cell lineMale
CVCL_B8VYAbcam MCF-7 FLT4 KOCancer cell lineFemale
CVCL_B9IDAbcam A-549 FLT4 KOCancer cell lineMale
CVCL_D7Q1Ubigene A-549 FLT4 KOCancer cell lineMale
CVCL_D9F0Ubigene HEK293 FLT4 KOTransformed cell lineFemale
CVCL_SN76HAP1 FLT4 (-)Cancer cell lineMale

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 405 trials:

NCTPhaseStatusTitle
NCT01971593Phase 4TERMINATEDThe Effects of Eplerenone on Markers of Myocardial Fibrosis in Adult Congenital Heart Disease
NCT07728825Phase 4COMPLETEDIntralesional Bleomycin Sclerotherapy for Low-Flow Vascular Malformations of the Head and Neck
NCT00852930Phase 4COMPLETEDLow Level Laser Treatment and Breast Cancer Related Lymphedema
NCT01068431Phase 4COMPLETEDShort Term Effectiveness Study of Juxta-Fit Versus Trico Bandages in the Treatment of Leg Lymphedema
NCT02257970Phase 4COMPLETEDLymphedema Study for Arm or Leg Lymphedema
NCT02375945Phase 4COMPLETEDComparison Between a Non-elastic Falcro Device and Current Method After Total Knee Arthroplasty
NCT03584633Phase 4COMPLETEDEffect of Exercise on Indocyanine Green (ICG) Lymphography Imaging
NCT00564993Phase 3TERMINATEDCardiac Function Under Stress for Early Detection of the Right Ventricular Insufficiency After Repair of Tetralogy of Fallot
NCT07285005Phase 3RECRUITINGA Study to Investigate Efficacy and Safety of KP-001 Compared With Placebo in Patients Aged ≥2 Years With Common VM, Common LM, or KTS/CLOVES Syndrome
NCT00028951Phase 3COMPLETEDFibrin Sealant in Decreasing Lymphedema Following Surgery to Remove Lymph Nodes in Patients With Cancer of the Vulva
NCT00201890Phase 3COMPLETEDTrial of Decongestive Lymphatic Therapy for Lymphedema in Women With Breast Cancer DELTA STUDY
NCT00577317Phase 3TERMINATEDFlexitouch® Home Maintenance Therapy or Standard Home Maintenance Therapy in Treating Patients With Lower-Extremity Lymphedema Caused by Treatment for Cervical Cancer, Vulvar Cancer, or Endometrial Cancer
NCT02927496Phase 3COMPLETEDA 24 Month Study, to Compare the Efficacy of Doxycycline vs. Placebo for Improving Filarial Lymphedema in Mali
NCT02929121Phase 3COMPLETEDA 24 Month Study to Compare Efficacy of Doxycycline vs Placebo for Improving Filarial Lymphedema in India
NCT02929134Phase 3COMPLETEDA 24 Month Study to Compare Efficacy of Doxycycline vs Placebo for Improving Filarial Lymphedema in Sri Lanka
NCT04228991Phase 3ACTIVE_NOT_RECRUITINGHypofractionated LocoRegional Radiotherapy in Breast Cancer
NCT06144164Phase 3RECRUITINGA Study of a Comprehensive Prevention Program to Reduce Lymphedema After Axillary Lymph Node Dissection in People With Breast Cancer
NCT00848393Phase 2COMPLETEDMeasures to Lower the Stress Response in Pediatric Cardiac Surgery
NCT02010905Phase 2UNKNOWNRight Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-angiotensin-aldosterone System
NCT02335242Phase 2COMPLETEDSildenafil for the Treatment of Lymphatic Malformations
NCT03243019Phase 2RECRUITINGEfficacy of Rapamycin in the Treatment of Cervico-facial Lymphatic Malformations
NCT03427619Phase 2COMPLETEDOK432 (Picibanil) in the Treatment of Lymphatic Malformations
NCT03972592Phase 2COMPLETEDTopical Sirolimus in Cutaneous Lymphatic Malformations
NCT04861064Phase 2RECRUITINGWeekly Sirolimus Therapy
NCT05871970Phase 2RECRUITINGSafety and Efficacy Study of Intracystic TARA-002 for the Treatment of Lymphatic Malformations in Participants 6 Months to Less Than 18 Years of Age
NCT05983159Phase 2RECRUITINGA Trial of Targeted Therapies for Patients With Slow-Flow or Fast-Flow Vascular Malformations
NCT06437158Phase 2RECRUITINGUse of Bleomycin in the Sclerotherapy of Lymphatic Malformations for Pediatric Patients
NCT06789913Phase 2RECRUITINGA Phase 2 Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, in Adults and Children With PIK3CA Related Overgrowth Spectrum and Malformations Driven by PIK3CA Mutation (The ReInspire Study)
NCT00022204Phase 2COMPLETEDVitamin E and Pentoxifylline in Treating Women With Lymphedema After Radiation Therapy for Breast Cancer
NCT00058851Phase 2COMPLETEDMassage Therapy for Breast Cancer Treatment-Related Swelling of the Arms
NCT00064857Phase 2COMPLETEDPycnogenol for the Treatment of Lymphedema of the Arm in Breast Cancer Survivors
NCT00077090Phase 2UNKNOWNHyperbaric Oxygen Therapy Compared With Standard Therapy in Treating Chronic Arm Lymphedema in Patients Who Have Undergone Radiation Therapy for Cancer
NCT00155220Phase 2UNKNOWNTreatment of Lymphedema: Application of the Kinesio Taping
NCT00188604Phase 2COMPLETEDThe Use of Selenium to Treat Secondary Lymphedema - Breast Cancer
NCT00214032Phase 2COMPLETEDPycnogenol for the Treatment of Lymphedema
NCT00589121Phase 2COMPLETEDImage-Guided Radiation Therapy in Treating Patients With Primary Soft Tissue Sarcoma of the Shoulder, Arm, Hip, or Leg
NCT00827372Phase 2COMPLETEDA Study of Vascular Endothelial Growth Factor (VEGF) Inhibition in Patients With Unilateral Upper Extremity Lymphedema Following Treatment for Cancer
NCT01003951Phase 2COMPLETEDAcupuncture for the Treatment of Chronic Lymphedema
NCT01276054Phase 2TERMINATEDSentinel and/or Axillary Lymph Node Biopsy With or Without Axillary Reverse Mapping in Reducing Incidence and Severity of Arm Lymphedema in Stage 0-2 Patients.
NCT01318785Phase 2UNKNOWNTherapeutical Assessment of Compression Armsleeves for Lymphatic Indications
NCT01406769Phase 2COMPLETEDBioimpedance Spectroscopy in Detecting Lower-Extremity Lymphedema in Patients With Stage I, Stage II, Stage III, or Stage IV Vulvar Cancer Undergoing Surgery and Lymphadenectomy
NCT02700529Phase 2COMPLETEDUbenimex in Adult Patients With Lymphedema of The Lower Limb (ULTRA)
NCT02895724Phase 2UNKNOWNHyperbaric Oxygen Therapy to Reduce Lymphedema After Breast Cancer -an Explorative Clinical Trial
NCT03658967Phase 2COMPLETEDClinical Study With Lymfactin® in the Treatment of Patients With Secondary Lymphedema (AdeLE)
NCT03776721Phase 2COMPLETEDTreatment of Breast Cancer-related Lymphedema With Stem Cells and Fat Grafting
NCT06494111Phase 2RECRUITINGSystemic Therapy of Open-label Prophylactic Pravastatin or Pentoxifylline/Tocopherol Prevention of Lymphedema Advancing to Eventual Fibrosis: an Interventional Registry-embedded Bayesian Randomized Trial for Radiation Sequelae (STOP4-LATE-FIBROSE)
NCT06912763Phase 2RECRUITINGReversing External-beam Radiotherapy-associated Fibrosis Syndrome: an Interventional Bayesian Adaptive Randomized-controlled Orphan Drug Platform Trial for Orodental Sequelae (Reverse-fibrose)
NCT06989099Phase 2RECRUITINGLymphedema Prevention Through Immediate Lymphatic Reconstruction (LILY) Trial.
NCT00573066Phase 1COMPLETEDUnderstanding Dexmedetomidine In Infants Post-Operative From Cardiac Surgery
NCT01915277Phase 1COMPLETEDA Phase I Study of Dexmedetomidine Bolus and Infusion in Corrective Infant Cardiac Surgery: Safety and Pharmacokinetics
NCT04713657Phase 1RECRUITINGBeta-blocker Administration for Cardiomyocyte Division
NCT01212965Phase 1TERMINATEDSelenium in the Treatment of Complicated Lymphatic Malformations
NCT04994002Phase 1WITHDRAWNA Pharmacokinetic, Pharmacodynamic, Safety and Tolerability Study of CERC-006 in Adults With Complex Lymphatic Malformations
NCT00318513Phase 1UNKNOWNSafety Study of Bevacizumab to Treat Women With a History of Breast Cancer and Suffering From Upper Extremity Lymphedema
NCT00393497Phase 1COMPLETEDA Pilot Study of VEGF Inhibition in Patients With Lymphedema Following Breast Cancer Treatment
NCT01470378Phase 1UNKNOWNManual Lymphatic Drainage in Women Undergone to Thigh Lifting
NCT02496013Phase 1UNKNOWNClinical Translation of a Novel Albumin-Binding PET Radiotracer 68Ga-NEB
NCT02949726Phase 1COMPLETEDLymphatic and Systemic Immunity Changes in Post-radiation Lymphedema Development
NCT02994771Phase 1TERMINATEDA Phase I Study With Lymfactin® in the Treatment of Patients With Secondary Lymphedema
NCT04393168Phase 1COMPLETEDProof-of-concept Study of LymphMonitor 1.0 to Assess the Lymphatic Vessel Function

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for FLT4 across ~30M SureChEMBL compounds — explore on Sugi Predict.

About this page

Built deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source. Provided for research and reference, not medical advice or a diagnosis. Data may be incomplete, especially for rare conditions. Consult a qualified clinician.

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This page pulls from 99 datasets indexed by BioBTree:

alliance_phenotypealphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruscellphonedbchembl_activitychembl_assaychembl_documentchembl_mechanismchembl_moleculechembl_targetciviccivic_assertioncivic_evidencecivic_variantclingen_dosageclingen_gene_validityclingen_variantclinical_trialsclinvarcollectricorumctd_gene_interactiondepmapdepmap_dependencydiamond_similarityefoensemblentrezexonfantom5_genefantom5_promotergenccgenerifgnomad_constraintgnomad_rmcgogoparentgtex_egenegtopdbgtopdb_interactiongwasgwas_studyhgnchpahpa_expressionhpa_pathologyhpointactinterprointogenjasparmeshmgimimmirdbmondomsigdbneighborentrezorphanetorthologorthologentrezpanelapp_geneparalogpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_var_annotationpharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontaxonomytranscriptufeatureuniprot