HGF (hepatocyte growth factor)

Gene

• Entrez ID: 3082
• Gene name: Hepatocyte growth factor
• Gene symbol: HGF
• Synonyms (NCBI Gene): DFNB39, F-TCF, HGFB, HPTA, SF
• Chromosome: 7
• Chromosome location: 7q21.11
• Summary: 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

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs137853235	C>T	Pathogenic	Synonymous variant, intron variant, coding sequence variant
rs145494248	C>G,T	Benign, conflicting-interpretations-of-pathogenicity	Genic downstream transcript variant, coding sequence variant, missense variant
rs145598174	A>G	Likely-benign, conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs148714837	C>T	Benign-likely-benign, likely-benign, conflicting-interpretations-of-pathogenicity	Synonymous variant, genic downstream transcript variant, coding sequence variant
rs367800414	A>G	Conflicting-interpretations-of-pathogenicity	Synonymous variant, genic downstream transcript variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT054477	hsa-miR-199a-3p	Luciferase reporter assay, QRTPCR, Western blot	23657814
MIRT054645	hsa-miR-26a-5p	ELISA, Immunohistochemistry, Luciferase reporter assay, qRT-PCR, Western blot	28393839
MIRT054645	hsa-miR-26a-5p	ELISA, Immunohistochemistry, Luciferase reporter assay, qRT-PCR, Western blot	28393839
MIRT054645	hsa-miR-26a-5p	ELISA, Luciferase reporter assay, qRT-PCR	28386375
MIRT732936	hsa-miR-144-3p	RNA-seq	33804111
MIRT734648	hsa-miR-28-3p	Western blotting, Immunoprecipitaion (IP), Immunofluorescence, qRT-PCR, Flow cytometry, ELISA	34094709
MIRT734649	hsa-miR-193a-5p	Western blotting, Immunoprecipitaion (IP), Immunofluorescence, qRT-PCR, Flow cytometry, ELISA	34094709
MIRT1044894	hsa-miR-4446-5p	CLIP-seq
MIRT1044895	hsa-miR-3168	CLIP-seq
MIRT1044896	hsa-miR-4277	CLIP-seq
MIRT1044897	hsa-miR-4424	CLIP-seq
MIRT1044898	hsa-miR-4645-3p	CLIP-seq
MIRT1044899	hsa-miR-4795-3p	CLIP-seq
MIRT1044900	hsa-miR-570	CLIP-seq
MIRT1044901	hsa-miR-582-5p	CLIP-seq
MIRT2451140	hsa-miR-4495	CLIP-seq
MIRT2545797	hsa-miR-1244	CLIP-seq
MIRT2545798	hsa-miR-1305	CLIP-seq
MIRT2545799	hsa-miR-199b-3p	CLIP-seq
MIRT2545800	hsa-miR-3065-5p	CLIP-seq
MIRT2545801	hsa-miR-3129-5p	CLIP-seq
MIRT2545802	hsa-miR-3159	CLIP-seq
MIRT2545803	hsa-miR-3613-5p	CLIP-seq
MIRT2545804	hsa-miR-3692	CLIP-seq
MIRT2545805	hsa-miR-3925-3p	CLIP-seq
MIRT2545806	hsa-miR-421	CLIP-seq
MIRT2545807	hsa-miR-4445	CLIP-seq
MIRT2545808	hsa-miR-4522	CLIP-seq
MIRT2545809	hsa-miR-4703-3p	CLIP-seq
MIRT2545810	hsa-miR-4712-5p	CLIP-seq
MIRT2545811	hsa-miR-495	CLIP-seq
MIRT2545812	hsa-miR-511	CLIP-seq
MIRT1044900	hsa-miR-570	CLIP-seq
MIRT2545813	hsa-miR-580	CLIP-seq
MIRT2545814	hsa-miR-651	CLIP-seq
MIRT2545815	hsa-miR-766	CLIP-seq
MIRT2545816	hsa-miR-770-5p	CLIP-seq
MIRT2545797	hsa-miR-1244	CLIP-seq
MIRT2545798	hsa-miR-1305	CLIP-seq
MIRT2545799	hsa-miR-199b-3p	CLIP-seq
MIRT2545800	hsa-miR-3065-5p	CLIP-seq
MIRT2545801	hsa-miR-3129-5p	CLIP-seq
MIRT2545802	hsa-miR-3159	CLIP-seq
MIRT2545803	hsa-miR-3613-5p	CLIP-seq
MIRT2545804	hsa-miR-3692	CLIP-seq
MIRT2545805	hsa-miR-3925-3p	CLIP-seq
MIRT2545806	hsa-miR-421	CLIP-seq
MIRT2545807	hsa-miR-4445	CLIP-seq
MIRT2545808	hsa-miR-4522	CLIP-seq
MIRT2545809	hsa-miR-4703-3p	CLIP-seq
MIRT2545810	hsa-miR-4712-5p	CLIP-seq
MIRT2545811	hsa-miR-495	CLIP-seq
MIRT2545812	hsa-miR-511	CLIP-seq
MIRT1044900	hsa-miR-570	CLIP-seq
MIRT2545813	hsa-miR-580	CLIP-seq
MIRT2545814	hsa-miR-651	CLIP-seq
MIRT2545815	hsa-miR-766	CLIP-seq
MIRT2545816	hsa-miR-770-5p	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
NFIC	Unknown	10860846
SP1	Activation	9223667
SP3	Activation	9223667
STAT3	Activation	12168776
STAT3	Unknown	23954444
TFAP2A	Repression	10860846

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000278	Process	Mitotic cell cycle	NAS	2531289
GO:0000902	Process	Cell morphogenesis	IEA
GO:0001837	Process	Epithelial to mesenchymal transition	TAS	14679171
GO:0001889	Process	Liver development	IEA
GO:0004175	Function	Endopeptidase activity	IBA
GO:0004252	Function	Serine-type endopeptidase activity	NAS	2531289
GO:0005102	Function	Signaling receptor binding	IBA
GO:0005515	Function	Protein binding	IPI	1846706, 12694198, 15167892, 16537482, 17804794, 17981115, 18585357, 20624990, 22897854, 25416956
GO:0005576	Component	Extracellular region	IEA
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA
GO:0006508	Process	Proteolysis	NAS	2531289
GO:0007165	Process	Signal transduction	IEA
GO:0008083	Function	Growth factor activity	IEA
GO:0008083	Function	Growth factor activity	NAS	2531289
GO:0010507	Process	Negative regulation of autophagy	NAS	24743740
GO:0014856	Process	Skeletal muscle cell proliferation	IEA
GO:0016020	Component	Membrane	HDA	19946888
GO:0022603	Process	Regulation of anatomical structure morphogenesis	IEA
GO:0030335	Process	Positive regulation of cell migration	IDA	21245381
GO:0031093	Component	Platelet alpha granule lumen	TAS
GO:0032715	Process	Negative regulation of interleukin-6 production	IEA
GO:0032733	Process	Positive regulation of interleukin-10 production	IEA
GO:0035729	Process	Cellular response to hepatocyte growth factor stimulus	IDA	21245381
GO:0042056	Function	Chemoattractant activity	IDA	21245381
GO:0042802	Function	Identical protein binding	IPI	17804794, 20624990, 22897854
GO:0043066	Process	Negative regulation of apoptotic process	IBA
GO:0043066	Process	Negative regulation of apoptotic process	IEA
GO:0043410	Process	Positive regulation of MAPK cascade	IDA	20655899
GO:0043410	Process	Positive regulation of MAPK cascade	IEA
GO:0045669	Process	Positive regulation of osteoblast differentiation	NAS	22521434
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	NAS	22521434
GO:0048012	Process	Hepatocyte growth factor receptor signaling pathway	IBA
GO:0048012	Process	Hepatocyte growth factor receptor signaling pathway	IDA	21245381
GO:0048012	Process	Hepatocyte growth factor receptor signaling pathway	IEA
GO:0048513	Process	Animal organ development	IEA
GO:0050673	Process	Epithelial cell proliferation	IEA
GO:0050728	Process	Negative regulation of inflammatory response	IEA
GO:0050918	Process	Positive chemotaxis	IEA
GO:0051239	Process	Regulation of multicellular organismal process	IEA
GO:0051450	Process	Myoblast proliferation	IEA
GO:0051897	Process	Positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IDA	20655899
GO:0060326	Process	Cell chemotaxis	IDA	21245381
GO:0060665	Process	Regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling	IDA	14517989
GO:0060665	Process	Regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling	IEA
GO:0090201	Process	Negative regulation of release of cytochrome c from mitochondria	IDA	20655899
GO:1900744	Process	Regulation of p38MAPK cascade	IEA
GO:1901299	Process	Negative regulation of hydrogen peroxide-mediated programmed cell death	IDA	20655899
GO:1902042	Process	Negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	IEA
GO:2000573	Process	Positive regulation of DNA biosynthetic process	IDA	2531289

Other IDs

• MIM: 142409
• HGNC: 4893
• e!Ensembl: ENSG00000019991

Protein

• UniProt ID: P14210
• Protein name: Hepatocyte growth factor (Hepatopoietin-A) (Scatter factor) (SF) [Cleaved into: Hepatocyte growth factor alpha chain; Hepatocyte growth factor beta chain]
• Protein function: Potent mitogen for mature parenchymal hepatocyte cells, seems to be a hepatotrophic factor, and acts as a growth factor for a broad spectrum of tissues and cell types (PubMed:20624990). Activating ligand for the receptor tyrosine kinase MET by b
• PDB: 1BHT, 1GMN, 1GMO, 1GP9, 1NK1, 1SHY, 1SI5, 2HGF, 2QJ2, 3HMS, 3HMT, 3HN4, 3MKP, 3SP8, 4D3C, 4K3J, 4O3T, 4O3U, 5COE, 5CP9, 5CS1, 5CS3, 5CS5, 5CS9, 5CSQ, 5CT1, 5CT2, 5CT3, 7MO7, 7MO8, 7MO9, 7MOA, 7MOB, 7OCL, 7OCM
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00024	PAN_1	40 → 124	PAN domain	Domain
  PF00051	Kringle	128 → 206	Kringle domain	Domain
  PF00051	Kringle	211 → 288	Kringle domain	Domain
  PF00051	Kringle	305 → 383	Kringle domain	Domain
  PF00051	Kringle	391 → 469	Kringle domain	Domain
  PF00089	Trypsin	495 → 716	Trypsin	Domain

• Sequence:

  MWVTKLLPALLLQHVLLHLLLLPIAIPYAEGQRKRRNTIHEFKKSAKTTLIKIDPALKIK
  TKKVNTADQCANRCTRNKGLPFTCKAFVFDKARKQCLWFPFNSMSSGVKKEFGHEFDLYE
  NKDYIRNCIIGKGRSYKGTVSITKSGIKCQPWSSMIPHEHSFLPSSYRGKDLQENYCRNP
  RGEEGGPWCFTSNPEVRYEVCDIPQCSEVECMTCNGESYRGLMDHTESGKICQRWDHQTP
  HRHKFLPERYPDKGFDDNYCRNPDGQPRPWCYTLDPHTRWEYCAIKTCADNTMNDTDVPL
  ETTECIQGQGEGYRGTVNTIWNGIPCQRWDSQYPHEHDMTPENFKCKDLRENYCRNPDGS
  ESPWCFTTDPNIRVGYCSQIPNCDMSHGQDCYRGNGKNYMGNLSQTRSGLTCSMWDKNME
  DLHRHIFWEPDASKLNENYCRNPDDDAHGPWCYTGNPLIPWDYCPISRCEGDTTPTIVNL
  DHPVISCAKTKQLRVVNGIPTRTNIGWMVSLRYRNKHICGGSLIKESWVLTARQCFPSRD
  LKDYEAWLGIHDVHGRGDEKCKQVLNVSQLVYGPEGSDLVLMKLARPAVLDDFVSTIDLP
  NYGCTIPEKTSCSVYGWGYTGLINYDGLLRVAHLYIMGNEKCSQHHRGKVTLNESEICAG
  AEKIGSGPCEGDYGGPLVCEQHKMRMVLGVIVPGRGCAIPNRPGIFVRVAYYAKWIHKII
  LTYKVPQS

• Sequence length: 728

Pathways

KEGG:

EGFR tyrosine kinase inhibitor resistance
MAPK signaling pathway
Ras signaling pathway
Rap1 signaling pathway
Calcium signaling pathway
PI3K-Akt signaling pathway
Focal adhesion
Malaria
Pathways in cancer
Proteoglycans in cancer
Chemical carcinogenesis - reactive oxygen species
Renal cell carcinoma
Melanoma
Non-small cell lung cancer
Hepatocellular carcinoma
Gastric cancer

Reactome:

Platelet degranulation
PIP3 activates AKT signaling
Constitutive Signaling by Aberrant PI3K in Cancer
RAF/MAP kinase cascade
Interleukin-4 and Interleukin-13 signaling
MET Receptor Activation
Negative regulation of MET activity
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
MET activates RAS signaling
MET activates PI3K/AKT signaling
MET activates PTPN11
MET activates PTK2 signaling
MET interacts with TNS proteins
MET activates RAP1 and RAC1
MET receptor recycling
MET activates STAT3

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Autosomal recessive nonsyndromic hearing loss 39	Pathogenic	rs137853235, rs1788701297, rs900334407	RCV000016089 RCV000016090 RCV000016091	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Sensorineural hearing loss disorder	Pathogenic	rs1788701297	RCV005420504	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ANGLE CLOSURE GLAUCOMA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ASTROCYTOMA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDER	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL RECESSIVE ISOLATED SENSORINEURAL DEAFNESS TYPE DFNB	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BARRETT ESOPHAGUS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARCINOMA, HEPATOCELLULAR	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARCINOMA, SQUAMOUS CELL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARDIOMYOPATHIES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COPPER-OVERLOAD CIRRHOSIS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEAFNESS, AUTOSOMAL RECESSIVE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEAFNESS, AUTOSOMAL RECESSIVE 39	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETIC NEUROPATHIES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GOUT	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GRAFT-VS-HOST DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hearing impairment	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
HEARING LOSS, AUTOSOMAL RECESSIVE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEPATITIS, CHRONIC	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HGF-related disorder	Uncertain significance; Conflicting classifications of pathogenicity; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERBILIRUBINEMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERBILIRUBINEMIA, HEREDITARY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTENSIVE DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KERATOCONUS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LEUKEMIA, MYELOID, ACUTE	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER CIRRHOSIS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER CIRRHOSIS, EXPERIMENTAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER FAILURE, ACUTE	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER NEOPLASMS, EXPERIMENTAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG DISEASES, INTERSTITIAL	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MESOTHELIOMA, MALIGNANT	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MULTIPLE MYELOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYOCARDIAL INFARCTION	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYOCARDIAL ISCHEMIA	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYOPIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEUROBLASTOMA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonsyndromic Hearing Loss, Mixed	Conflicting classifications of pathogenicity; Uncertain significance; Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OLIGODENDROGLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PANCREATITIS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PARKINSON DISEASE	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PRIMARY CARDIOMYOPATHY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATE CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATE CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PULMONARY FIBROSIS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SENSORINEURAL HEARING LOSS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SENSORINEURAL HEARING LOSS OF BILATERAL EARS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SYSTEMIC SCLERODERMA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
THROMBOSIS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VASCULAR DISEASES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VITILIGO	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations