FLT4 fms related receptor tyrosine kinase 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: FLT4provided by HGNC
Official Full Name: fms related receptor tyrosine kinase 4provided by HGNC
Primary source: HGNC:HGNC:3767
See related: Ensembl:ENSG00000037280 MIM:136352; AllianceGenome:HGNC:3767
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PCL; CHTD7; FLT-4; FLT41; LMPH1A; LMPHM1; VEGFR3; VEGFR-3
Summary: 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. [provided by RefSeq, Jul 2008]
Expression: Broad expression in spleen (RPKM 7.7), lung (RPKM 6.7) and 21 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 5q35.3

Exon count:: 34

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (180601506..180650298, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (181157398..181206988, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (180028506..180076600, complement)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

FLT4 gene polymorphisms influence isolated ventricular septal defect predisposition in a Southwest China population.
Title: FLT4 gene polymorphisms influence isolated ventricular septal defect predisposition in a Southwest China population.
A family with Milroy disease caused by the FLT4/VEGFR3 gene variant c.2774 T > A.
Title: A family with Milroy disease caused by the FLT4/VEGFR3 gene variant c.2774 T > A.
The Alzheimer's disease-linked protease BACE2 cleaves VEGFR3 and modulates its signaling.
Title: The Alzheimer's disease-linked protease BACE2 cleaves VEGFR3 and modulates its signaling.
miR-455-3p regulates lymphangiogenesis in silicosis by regulating VEGF-C/VEGFR3.
Title: miR-455-3p regulates lymphangiogenesis in silicosis by regulating VEGF-C/VEGFR3.
Association study of FLT4 and HYDIN single nucleotide polymorphisms with atrial septal defect susceptibility in the Han Chinese population of Southwest China.
Title: Association study of FLT4 and HYDIN single nucleotide polymorphisms with atrial septal defect susceptibility in the Han Chinese population of Southwest China.
Profibrotic VEGFR3-Dependent Lymphatic Vessel Growth in Autoimmune Valvular Carditis.
Title: Profibrotic VEGFR3-Dependent Lymphatic Vessel Growth in Autoimmune Valvular Carditis.
The pathological roles and potential mechanisms of vascular endothelial growth factor receptor-3 in gastric cancer.
Title: The pathological roles and potential mechanisms of vascular endothelial growth factor receptor-3 in gastric cancer.
FLT4 as a marker for predicting prognostic risk of refractory acute myeloid leukemia.
Title: FLT4 as a marker for predicting prognostic risk of refractory acute myeloid leukemia.
VEGFR3 is required for button junction formation in lymphatic vessels.
Title: VEGFR3 is required for button junction formation in lymphatic vessels.
VEGFR3 suppression through miR-1236 inhibits proliferation and induces apoptosis in ovarian cancer via ERK1/2 and AKT signaling pathways.
Title: VEGFR3 suppression through miR-1236 inhibits proliferation and induces apoptosis in ovarian cancer via ERK1/2 and AKT signaling pathways.

Submit: New GeneRIF Correction See all GeneRIFs (221)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Capillary infantile hemangioma MedGen: C1865871 OMIM: 602089 GeneReviews: Not available	Compare labs
Congenital heart defects, multiple types, 7 MedGen: C5394062 OMIM: 618780 GeneReviews: Not available	Compare labs
Hereditary lymphedema type I MedGen: C1704423 OMIM: 153100 GeneReviews: Milroy Disease	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH94055 (e-PCR)
- UniSTS:90113

SHGC-148175 (e-PCR)
- UniSTS:176242

RH80182 (e-PCR)
- UniSTS:87282

D5S2778 (e-PCR)
- UniSTS:473846

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables GPI-linked ephrin receptor activity	IEA Inferred from Electronic Annotation more info
enables boss receptor activity	IEA Inferred from Electronic Annotation more info
enables brain-derived neurotrophic factor receptor activity	IEA Inferred from Electronic Annotation more info
enables epidermal growth factor receptor activity	IEA Inferred from Electronic Annotation more info
enables fibroblast growth factor receptor activity	IEA Inferred from Electronic Annotation more info
enables growth factor binding	IBA Inferred from Biological aspect of Ancestor more info
enables growth factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables hepatocyte growth factor receptor activity	IEA Inferred from Electronic Annotation more info
enables histone H2AXY142 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3Y41 kinase activity	IEA Inferred from Electronic Annotation more info
enables insulin receptor activity	IEA Inferred from Electronic Annotation more info
enables insulin-like growth factor receptor activity	IEA Inferred from Electronic Annotation more info
enables macrophage colony-stimulating factor receptor activity	IEA Inferred from Electronic Annotation more info
enables placental growth factor receptor activity	IEA Inferred from Electronic Annotation more info
enables platelet-derived growth factor alpha-receptor activity	IEA Inferred from Electronic Annotation more info
enables platelet-derived growth factor beta-receptor activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
enables protein phosphatase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein tyrosine kinase collagen receptor activity	IEA Inferred from Electronic Annotation more info
enables stem cell factor receptor activity	IEA Inferred from Electronic Annotation more info
enables transmembrane receptor protein tyrosine kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables transmembrane-ephrin receptor activity	IEA Inferred from Electronic Annotation more info
enables vascular endothelial growth factor receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables vascular endothelial growth factor receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables vascular endothelial growth factor receptor activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in Kit signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in blood vessel morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in brain-derived neurotrophic factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in cell surface receptor protein tyrosine kinase signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in cellular response to vascular endothelial growth factor stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to vascular endothelial growth factor stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in collagen-activated tyrosine kinase receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in ephrin receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in epidermal growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in fibroblast growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in hepatocyte growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in insulin receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in insulin-like growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in lung alveolus development	IEA Inferred from Electronic Annotation more info
involved_in lymph vessel development	ISS Inferred from Sequence or Structural Similarity more info
involved_in lymphangiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in lymphangiogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in macrophage colony-stimulating factor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in multicellular organism development	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in peptidyl-tyrosine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in platelet-derived growth factor receptor-alpha signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in platelet-derived growth factor receptor-beta signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of ERK1 and ERK2 cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of JNK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of MAPK cascade	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of MAPK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell migration	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of endothelial cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of endothelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of vascular endothelial growth factor production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of blood vessel remodeling	ISS Inferred from Sequence or Structural Similarity more info
involved_in respiratory system process	IEA Inferred from Electronic Annotation more info
involved_in sprouting angiogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in sprouting angiogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in vascular endothelial growth factor receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within vascular endothelial growth factor receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in vascular endothelial growth factor receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in vascular endothelial growth factor receptor-1 signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in vascular endothelial growth factor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in vasculature development	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in cytosol	IDA Inferred from Direct Assay more info
located_in extracellular region	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
part_of receptor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of receptor complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: vascular endothelial growth factor receptor 3

Names: 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

NP_001341918.1

EC 2.7.10.1

NP_002011.2

EC 2.7.10.1

NP_891555.2

EC 2.7.10.1

XP_011532780.1

EC 2.7.10.1

XP_011532786.1

EC 2.7.10.1

XP_016864752.1

EC 2.7.10.1

XP_016864755.1

EC 2.7.10.1

XP_016864757.1

EC 2.7.10.1

XP_047272958.1

EC 2.7.10.1

XP_047272959.1

EC 2.7.10.1

XP_054208150.1

EC 2.7.10.1

XP_054208151.1

EC 2.7.10.1

XP_054208152.1

EC 2.7.10.1

XP_054208153.1

EC 2.7.10.1

XP_054208154.1

EC 2.7.10.1

XP_054208155.1

EC 2.7.10.1

XP_054208156.1

EC 2.7.10.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011536.1 RefSeqGene

Range

5025..53119

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001354989.2 → NP_001341918.1 vascular endothelial growth factor receptor 3 isoform 3 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains an alternate 3' terminal exon compared to variant 1. This results in an isoform (3) with a shorter C-terminus compared to isoform 1.

Source sequence(s)

AC122714

Consensus CDS

CCDS87360.1

UniProtKB/TrEMBL

E9PD35

Related

ENSP00000426057.1, ENST00000502649.5

Conserved Domains (6) summary

cd05862
Location:245 → 329

Ig_VEGFR; Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R)

cd05863
Location:352 → 418

Ig_VEGFR-3; Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 3 (VEGFR-3)

smart00408
Location:693 → 755

IGc2; Immunoglobulin C-2 Type

smart00410
Location:564 → 657

IG_like; Immunoglobulin like

cd05102
Location:837 → 1176

PTKc_VEGFR3; Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3

pfam13895
Location:137 → 224

Ig_2; Immunoglobulin domain
NM_002020.5 → NP_002011.2 vascular endothelial growth factor receptor 3 isoform 2 precursor

See identical proteins and their annotated locations for NP_002011.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate 3' terminal exon compared to variant 1. This results in an isoform (2) with a shorter C-terminus compared to isoform 1.

Source sequence(s)

AC122714, AY233382, DB455035, X68203

Consensus CDS

CCDS43412.1

UniProtKB/Swiss-Prot

P35916

Related

ENSP00000377016.3, ENST00000393347.7

Conserved Domains (10) summary

cd05862
Location:245 → 329

Ig1_VEGFR; First immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R)

cd05863
Location:352 → 418

Ig2_VEGFR-3; Second immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 3 (VEGFR-3)

smart00408
Location:693 → 755

IGc2; Immunoglobulin C-2 Type

smart00409
Location:564 → 657

IG; Immunoglobulin

smart00410
Location:238 → 327

IG_like; Immunoglobulin like

pfam07679
Location:678 → 765

I-set; Immunoglobulin I-set domain

cd05102
Location:837 → 1176

PTKc_VEGFR3; Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3

pfam07714
Location:845 → 1169

Pkinase_Tyr; Protein tyrosine kinase

pfam13895
Location:138 → 224

Ig_2; Immunoglobulin domain

cl11960
Location:570 → 658

Ig; Immunoglobulin domain
NM_182925.5 → NP_891555.2 vascular endothelial growth factor receptor 3 isoform 1 precursor

See identical proteins and their annotated locations for NP_891555.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AC122714, AY233383, DB455035, X68203

Consensus CDS

CCDS4457.1

UniProtKB/Swiss-Prot

A8K6L4, B5A926, P35916, Q16067, Q86W07, Q86W08

Related

ENSP00000261937.6, ENST00000261937.11

Conserved Domains (10) summary

cd05862
Location:245 → 329

Ig1_VEGFR; First immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R)

cd05863
Location:352 → 418

Ig2_VEGFR-3; Second immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 3 (VEGFR-3)

smart00408
Location:693 → 755

IGc2; Immunoglobulin C-2 Type

smart00409
Location:564 → 657

IG; Immunoglobulin

smart00410
Location:238 → 327

IG_like; Immunoglobulin like

pfam07679
Location:678 → 765

I-set; Immunoglobulin I-set domain

cd05102
Location:837 → 1176

PTKc_VEGFR3; Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3

pfam07714
Location:845 → 1169

Pkinase_Tyr; Protein tyrosine kinase

pfam13895
Location:138 → 224

Ig_2; Immunoglobulin domain

cl11960
Location:570 → 658

Ig; Immunoglobulin domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000005.10 Reference GRCh38.p14 Primary Assembly

Range

180601506..180650298 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017009268.2 → XP_016864757.1 vascular endothelial growth factor receptor 3 isoform X4
XM_017009263.2 → XP_016864752.1 vascular endothelial growth factor receptor 3 isoform X2
XM_011534478.4 → XP_011532780.1 vascular endothelial growth factor receptor 3 isoform X1

Conserved Domains (10) summary

cd05862
Location:322 → 406

Ig1_VEGFR; First immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R)

cd05863
Location:429 → 495

Ig2_VEGFR-3; Second immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 3 (VEGFR-3)

smart00408
Location:770 → 832

IGc2; Immunoglobulin C-2 Type

smart00409
Location:641 → 734

IG; Immunoglobulin

smart00410
Location:315 → 404

IG_like; Immunoglobulin like

pfam07679
Location:755 → 842

I-set; Immunoglobulin I-set domain

cd05102
Location:914 → 1253

PTKc_VEGFR3; Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3

pfam07714
Location:922 → 1246

Pkinase_Tyr; Protein tyrosine kinase

pfam13895
Location:215 → 301

Ig_2; Immunoglobulin domain

cl11960
Location:647 → 735

Ig; Immunoglobulin domain
XM_011534484.3 → XP_011532786.1 vascular endothelial growth factor receptor 3 isoform X7

Conserved Domains (10) summary

cd05862
Location:92 → 176

Ig1_VEGFR; First immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R)

cd05863
Location:199 → 265

Ig2_VEGFR-3; Second immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 3 (VEGFR-3)

smart00408
Location:540 → 602

IGc2; Immunoglobulin C-2 Type

smart00409
Location:411 → 504

IG; Immunoglobulin

smart00410
Location:85 → 174

IG_like; Immunoglobulin like

pfam07679
Location:525 → 612

I-set; Immunoglobulin I-set domain

cd05102
Location:684 → 1023

PTKc_VEGFR3; Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3

pfam07714
Location:692 → 1016

Pkinase_Tyr; Protein tyrosine kinase

pfam13895
Location:1 → 71

Ig_2; Immunoglobulin domain

cl11960
Location:417 → 505

Ig; Immunoglobulin domain
XM_047417002.1 → XP_047272958.1 vascular endothelial growth factor receptor 3 isoform X5
XM_017009266.2 → XP_016864755.1 vascular endothelial growth factor receptor 3 isoform X3
XM_047417003.1 → XP_047272959.1 vascular endothelial growth factor receptor 3 isoform X6

Alternate T2T-CHM13v2.0

Genomic

NC_060929.1 Alternate T2T-CHM13v2.0

Range

181157398..181206988 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054352178.1 → XP_054208153.1 vascular endothelial growth factor receptor 3 isoform X4
XM_054352176.1 → XP_054208151.1 vascular endothelial growth factor receptor 3 isoform X2
XM_054352175.1 → XP_054208150.1 vascular endothelial growth factor receptor 3 isoform X1
XM_054352181.1 → XP_054208156.1 vascular endothelial growth factor receptor 3 isoform X7
XM_054352179.1 → XP_054208154.1 vascular endothelial growth factor receptor 3 isoform X5
XM_054352177.1 → XP_054208152.1 vascular endothelial growth factor receptor 3 isoform X3
XM_054352180.1 → XP_054208155.1 vascular endothelial growth factor receptor 3 isoform X6