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This gene encodes a protein that binds to the hepatocyte growth factor receptor to regulate cell growth, cell motility and morphogenesis in numerous cell and tissue types. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate alpha and beta chains, which form the mature heterodimer. This protein is secreted by mesenchymal cells and acts as a multi-functional cytokine on cells of mainly epithelial origin. This protein also plays a role in angiogenesis, tumorogenesis, and tissue regeneration. Although the encoded protein is a member of the peptidase S1 family of serine proteases, it lacks peptidase activity. Mutations in this gene are associated with nonsyndromic hearing loss. [provided by RefSeq, Nov 2015]
HGF (Hepatocyte Growth Factor) is a Protein Coding gene. Diseases associated with HGF include Deafness, Autosomal Recessive 39 and Autosomal Recessive Non-Syndromic Sensorineural Deafness Type Dfnb. Among its related pathways are RET signaling and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include identical protein binding and serine-type endopeptidase activity. An important paralog of this gene is MST1.
The MET receptor, also known as hepatocyte growth factor receptor (HGFR), is a proto-oncogenic receptor tyrosine kinase. The endogenous ligand for MET is hepatocyte growth factor/scatter factor (HGF), a disulfide-linked heterodimeric molecule.
GeneHancer (GH) Identifier | GH Type | GH Score |
GH Sources | Gene Association Score | Total Score | TSS distance (kb) | Number of Genes Away | Size (kb) | Transcription Factor Binding Sites |
Gene Targets |
---|---|---|---|---|---|---|---|---|---|---|
GH07J081768 | Promoter/Enhancer | 1.7 | EPDnew Ensembl ENCODE CraniofacialAtlas | 600.7 | +0.8 | 779 | 3.3 | PRDM10 MNT CTCF ARID3A BMI1 ZNF335 SPI1 RCOR1 ZNF398 RAD21 | HGF ENSG00000233491 LOC100128317 SEMA3C | |
GH07J082204 | Enhancer | 0.6 | Ensembl ENCODE | 5.5 | -434.3 | -434344 | 0.8 | BACH1 NFE2 MAFK NFE2L2 BHLHE40 HLF | HGF piR-38351-436 L13714-417 CACNA2D1 | |
GH07J082212 | Enhancer | 0.2 | ENCODE | 5.6 | -442.3 | -442266 | 1.2 | HGF L13714-417 piR-38351-436 CACNA2D1 | ||
GH07J081748 | Enhancer | 0.2 | FANTOM5 | 3 | +22.3 | 22276 | 0.3 | HGF ENSG00000233491 LOC100128317 SEMA3C | ||
GH07J081724 | Enhancer | 0.8 | Ensembl ENCODE dbSUPER | 0.3 | +45.0 | 44970 | 2.3 | SP1 JUND CEBPB FOS MAFK POLR2A | lnc-CD36-9 LOC100128317 ENSG00000233491 HGF SEMA3C |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0004252 | NOT serine-type endopeptidase activity | IBA,NAS | 2531289 |
GO:0005515 | protein binding | IPI | 1846706 |
GO:0008083 | growth factor activity | NAS | 2531289 |
GO:0042056 | chemoattractant activity | IDA | 21245381 |
GO:0042802 | identical protein binding | IPI | 17804794 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005576 | extracellular region | TAS | -- |
GO:0005615 | extracellular space | IEA | -- |
GO:0016020 | membrane | HDA | 19946888 |
GO:0031093 | platelet alpha granule lumen | TAS | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | RET signaling |
.92
|
.92
|
2 | Apoptotic Pathways in Synovial Fibroblasts |
Cellular Apoptosis Pathway
.85
Mitochondrial Apoptosis
.85
Apoptotic Pathways in Synovial Fibroblasts
.84
p53 Mediated Apoptosis
.84
DHA Signaling
.74
Telomerase Components in Cell Signaling
.72
PPAR Pathway
.66
|
Rac1 Pathway
.65
Glioma Invasiveness
.64
Actin-Based Motility by Rho Family GTPases
.62
ERK5 Signaling
.61
eIF2 Pathway
.60
Rap1 Pathway
.57
Nuclear Receptor Activation by Vitamin-A
.57
|
3 | PEDF Induced Signaling |
MIF Mediated Glucocorticoid Regulation
.94
MIF Regulation of Innate Immune Cells
.94
PEDF Induced Signaling
.73
all-trans-Retinoic Acid Signaling in Brain
.71
|
RAR-Gamma-RXR-Alpha Degradation
.62
IL-6 Pathway
.61
STAT3 Pathway
.47
Endothelin-1 Signaling Pathway
.46
|
4 | GAB1 signalosome |
.89
|
|
5 | MET promotes cell motility |
.45
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000165 | MAPK cascade | TAS | -- |
GO:0000187 | activation of MAPK activity | IEA | -- |
GO:0000278 | mitotic cell cycle | NAS | 2531289 |
GO:0000902 | cell morphogenesis | IEA | -- |
GO:0001837 | epithelial to mesenchymal transition | TAS | 14679171 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Dexamethasone | Approved, Investigational, Vet_approved | Pharma | Agonist | Anti-inflammatory glucocorticoid | 2886 | |
Heparin | Approved, Investigational | Pharma | Antagonist, Target | 1058 | ||
Bortezomib | Approved, Investigational | Pharma | Proteosome and NF-kappaB inhibitor, Other, Proteasome inhibitors | 910 | ||
Dexamethasone acetate | Approved, Investigational, Vet_approved | Pharma | 2886 | |||
Osimertinib | Approved | Pharma | 144 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
Norleual |
|
334994-34-2 |
|
|
||
PF 04217903 mesylate |
|
956906-93-7 |
|
|
||
SGX 523 |
|
1022150-57-7 |
|
|
Compound | Action | Cas Number |
---|---|---|
Norleual | Highly potent HGF/c-MET inhibitor; also AT4 antagonist | 334994-34-2 |
PF 04217903 mesylate | Highly selective MET inhibitor | 956906-93-7 |
PHA 665752 | Potent and selective MET inhibitor | 477575-56-7 |
SGX 523 | Selective and potent c-MET kinase inhibitor | 1022150-57-7 |
SU 11274 | Selective inhibitor of MET kinase activity | 658084-23-2 |
ExUns: | 1 | ^ | 2 | ^ | 3 | ^ | 4 | ^ | 5 | ^ | 6a | · | 6b | · | 6c | ^ | 7 | ^ | 8 | ^ | 9 | ^ | 10 | ^ | 11 | ^ | 12 | ^ | 13 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | ||||||||||||||||||||||||||||
SP2: | - | ||||||||||||||||||||||||||||
SP3: | |||||||||||||||||||||||||||||
SP4: | |||||||||||||||||||||||||||||
SP5: |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | HGF 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | HGF 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | HGF 30 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | HGF 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Hgf 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Hgf 30 |
|
||
Platypus (Ornithorhynchus anatinus) |
Mammalia | HGF 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | HGF 30 |
|
||
HGF/SF 31 |
|
OneToOne | |||
Lizard (Anolis carolinensis) |
Reptilia | HGF 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | hgf 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | hgfa 30 31 |
|
OneToMany | |
HGF (2 of 2) 31 |
|
OneToMany | |||
Fruit Fly (Drosophila melanogaster) |
Insecta | Tequila 31 |
|
OneToMany | |
Worm (Caenorhabditis elegans) |
Secernentea | svh-1 31 |
|
OneToMany | |
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
ManyToMany | |
-- 31 |
|
ManyToMany |
SNP ID | Clinical significance and condition | Chr 07 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
667244 | Uncertain Significance: not specified | 81,705,458(-) | C/T | MISSENSE_VARIANT | |
667245 | Uncertain Significance: not specified | 81,702,759(-) | T/TA | INTRON_VARIANT | |
681499 | Likely Benign: not provided | 81,706,417(-) | C/A | MISSENSE_VARIANT | |
682779 | Benign: not provided | 81,707,219(-) | C/A | INTRON_VARIANT | |
745720 | Likely Benign: not provided | 81,752,151(-) | G/A | SYNONYMOUS_VARIANT |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
dgv1101e201 | CNV | deletion | 23290073 |
dgv3601n106 | CNV | deletion | 24896259 |
esv2384607 | CNV | deletion | 18987734 |
esv2618632 | CNV | deletion | 19546169 |
esv2734743 | CNV | deletion | 23290073 |
esv3541994 | CNV | deletion | 23714750 |
esv3576398 | CNV | gain | 25503493 |
esv3613890 | CNV | loss | 21293372 |
esv3613891 | CNV | loss | 21293372 |
esv3807 | CNV | loss | 18987735 |
esv8642 | CNV | loss | 19470904 |
nsv1019753 | CNV | gain | 25217958 |
nsv1074527 | CNV | deletion | 25765185 |
nsv1124235 | CNV | deletion | 24896259 |
nsv1150903 | CNV | deletion | 26484159 |
nsv366332 | CNV | deletion | 16902084 |
nsv464609 | CNV | loss | 19166990 |
nsv607689 | CNV | loss | 21841781 |
nsv951366 | CNV | duplication | 24416366 |
nsv955962 | CNV | deletion | 24416366 |
Disorder | Aliases | PubMed IDs |
---|---|---|
deafness, autosomal recessive 39 |
|
|
autosomal recessive non-syndromic sensorineural deafness type dfnb |
|
|
salivary gland carcinoma |
|
|
obstructive nephropathy |
|
|
acute kidney failure |
|