HGF

hepatocyte growth factor

Basic information

Region (hg38): 7:81699010-81770438

Previous symbols: [ "DFNB39" ]

Links

ENSG00000019991 ∙ NCBI:3082 ∙ OMIM:142409 ∙ HGNC:4893 ∙ Uniprot:P14210 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive nonsyndromic hearing loss 39 (Strong), mode of inheritance: Unknown
• autosomal recessive nonsyndromic hearing loss 39 (Limited), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Moderate), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 39 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 39	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	14512973; 19576567

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HGF gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HGF gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	24	2	29
missense			64	1		65
nonsense		1	3			4
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			5	9		14
non coding			6	65	30	101
Total	0	1	77	90	32

Variants in HGF

This is a list of pathogenic ClinVar variants found in the HGF region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-81702114-T-C		Nonsyndromic Hearing Loss, Mixed	Likely benign (Jun 14, 2016)
7-81702185-T-A		Nonsyndromic Hearing Loss, Mixed	Uncertain significance (Jun 14, 2016)
7-81702480-T-C		Nonsyndromic Hearing Loss, Mixed	Uncertain significance (Jun 14, 2016)
7-81702585-G-T		Hearing impairment	Uncertain significance (Apr 12, 2021)
7-81702589-G-A		not specified	Conflicting classifications of pathogenicity (Mar 17, 2022)
7-81702622-T-G			Uncertain significance (Jan 13, 2022)
7-81702627-T-C			Uncertain significance (May 01, 2023)
7-81702645-C-T			Uncertain significance (Aug 16, 2022)
7-81702663-C-T			Uncertain significance (Jun 13, 2022)
7-81702673-T-C			Uncertain significance (Feb 09, 2021)
7-81702684-C-T			Uncertain significance (Mar 21, 2022)
7-81702749-A-G			Conflicting classifications of pathogenicity (Sep 11, 2023)
7-81702752-A-G			Likely benign (May 31, 2018)
7-81702757-C-G			Uncertain significance (Mar 18, 2022)
7-81702759-T-TA		not specified	Uncertain significance (May 29, 2018)
7-81702789-A-C			Likely benign (Nov 24, 2020)
7-81702807-G-T			Likely benign (Jun 12, 2020)
7-81702835-G-T			Benign (Jun 29, 2018)
7-81702897-T-C			Likely benign (Dec 21, 2018)
7-81702917-T-C			Likely benign (Feb 16, 2019)
7-81705384-T-C			Likely benign (Dec 22, 2022)
7-81705419-C-T			Uncertain significance (May 01, 2023)
7-81705446-G-GACTCATTC			Uncertain significance (Dec 16, 2021)
7-81705449-T-A			Uncertain significance (Dec 16, 2021)
7-81705458-C-T		not specified	Uncertain significance (Feb 26, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HGF	protein_coding	protein_coding	ENST00000222390	18	71433

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000531	125732	0	14	125746	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.85	305	410	0.744	0.0000220	4777
Missense in Polyphen		111	183.68	0.6043		2135
Synonymous	-0.673	145	135	1.07	0.00000703	1314
Loss of Function	5.82	7	52.6	0.133	0.00000339	537

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.0000997	0.0000992
East Asian	0.000163	0.000163
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.0000441	0.0000440
Middle Eastern	0.000163	0.000163
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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. Activating ligand for the receptor tyrosine kinase MET by binding to it and promoting its dimerization. {ECO:0000269|PubMed:15167892, ECO:0000269|PubMed:20624990}.
• Disease: DISEASE: Deafness, autosomal recessive, 39 (DFNB39) [MIM:608265]: A form of profound prelingual sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:19576567}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Gastric cancer - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Renal cell carcinoma - Homo sapiens (human);Melanoma - Homo sapiens (human);Malaria - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);Androgen Receptor Network in Prostate Cancer;Differentiation Pathway;Extracellular vesicle-mediated signaling in recipient cells;Nuclear Receptors Meta-Pathway;NRF2 pathway;Focal Adhesion;Signaling of Hepatocyte Growth Factor Receptor;Lung fibrosis;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Interleukin-4 and 13 signaling;PI3K-Akt Signaling Pathway;MET in type 1 papillary renal cell carcinoma;Interleukin-7 signaling;Disease;Signal Transduction;Signaling by Interleukins;MET interacts with TNS proteins;Cytokine Signaling in Immune system;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;HGF;Immune System;MET activates RAP1 and RAC1;GPCR signaling-G alpha s Epac and ERK;Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;GPCR signaling-G alpha s PKA and ERK;MET activates STAT3;Hemostasis;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;Signaling events mediated by TCPTP;PIP3 activates AKT signaling;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;Direct p53 effectors;Constitutive Signaling by Aberrant PI3K in Cancer;PI3K/AKT Signaling in Cancer;GPCR signaling-G alpha i;MET Receptor Activation;MET activates RAS signaling;MET activates PI3K/AKT signaling;MET activates PTK2 signaling;MET promotes cell motility;Negative regulation of MET activity;Signaling by MET;Signaling by Receptor Tyrosine Kinases;MET activates PTPN11;Intracellular signaling by second messengers;Stabilization and expansion of the E-cadherin adherens junction;Diseases of signal transduction;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Syndecan-1-mediated signaling events;Arf6 signaling events;Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling;FGF signaling pathway (Consensus)

Recessive Scores

• pRec: 0.759

Intolerance Scores

• loftool: 0.131
• rvis_EVS: -0.42
• rvis_percentile_EVS: 25.64

Haploinsufficiency Scores

• pHI: 0.398
• hipred: Y
• hipred_score: 0.694
• ghis: 0.512

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.523

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Hgf
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); embryo phenotype; liver/biliary system phenotype; cellular phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: MAPK cascade;activation of MAPK activity;mitotic cell cycle;cell morphogenesis;epithelial to mesenchymal transition;liver development;positive regulation of protein phosphorylation;platelet degranulation;proteolysis;regulation of signaling receptor activity;negative regulation of autophagy;positive regulation of phosphatidylinositol 3-kinase signaling;peptidyl-tyrosine phosphorylation;cytokine-mediated signaling pathway;hyaluronan metabolic process;positive regulation of cell migration;animal organ regeneration;positive regulation of myelination;negative regulation of interleukin-6 production;positive regulation of interleukin-10 production;negative regulation of peptidyl-serine phosphorylation;cellular response to hepatocyte growth factor stimulus;negative regulation of apoptotic process;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;positive regulation of osteoblast differentiation;positive regulation of angiogenesis;positive regulation of transcription by RNA polymerase II;phosphatidylinositol phosphorylation;hepatocyte growth factor receptor signaling pathway;negative regulation of inflammatory response;positive regulation of peptidyl-tyrosine phosphorylation;positive chemotaxis;myoblast proliferation;positive regulation of protein kinase B signaling;cell chemotaxis;regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling;positive regulation of neuron projection regeneration;negative regulation of release of cytochrome c from mitochondria;regulation of p38MAPK cascade;negative regulation of hydrogen peroxide-mediated programmed cell death;negative regulation of extrinsic apoptotic signaling pathway via death domain receptors;regulation of tau-protein kinase activity;positive regulation of DNA biosynthetic process
• Cellular component: extracellular region;extracellular space;membrane;platelet alpha granule lumen
• Molecular function: serine-type endopeptidase activity;protein tyrosine kinase activity;Ras guanyl-nucleotide exchange factor activity;protein binding;growth factor activity;chemoattractant activity;identical protein binding;phosphatidylinositol-4,5-bisphosphate 3-kinase activity;protein heterodimerization activity