HGF

Chr 7AR

hepatocyte growth factor

Also known as: DFNB39, F-TCF, HGFB, HPTA, SF

NCBI Gene: 3082ENSG00000019991UniProt: P14210

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]

Primary Disease Associations & Inheritance

Deafness, autosomal recessive 39MIM #608265
AR
336
ClinVar variants
27
Pathogenic / LP
1.00
pLI score· haploinsufficient
12
Active trials
Clinical Summary— HGF
🧬
Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
27 Pathogenic / Likely Pathogenic· 147 VUS of 336 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.25LOEUF
pLI 0.999
Z-score 5.82
OE 0.13 (0.07–0.25)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.85Z-score
OE missense 0.74 (0.68–0.82)
305 obs / 410.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.13 (0.07–0.25)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.68–0.82)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.07
0≤1.21.6
LoF obs/exp: 7 / 52.6Missense obs/exp: 305 / 410.2Syn Z: -0.67

ClinVar Variant Classifications

336 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic6
VUS147
Likely Benign120
Benign34
Conflicting8
21
Pathogenic
6
Likely Pathogenic
147
VUS
120
Likely Benign
34
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
20
1
21
Likely Pathogenic
1
0
5
0
6
VUS
0
129
15
3
147
Likely Benign
0
2
84
34
120
Benign
0
1
31
2
34
Conflicting
—8
Total113215540336

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

HGF · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

HGF-related deafness

limited
ARLoss Of FunctionAbsent Gene Product
Ear
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Deafness, autosomal recessive 39

MIM #608265

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — HGF
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
An HGF-dependent positive feedback loop between bladder cancer cells and fibroblasts mediates lymphangiogenesis and lymphatic metastasis.
Li Y et al.·Cancer Commun (Lond)
2023
Targeting the vascular and perivascular niches as a regenerative therapy for lung and liver fibrosis.
Cao Z et al.·Sci Transl Med
2017
Gene of the month: HGF.
Fajardo-Puerta AB et al.·J Clin Pathol
2016Review
Hereditary gingival fibromatosis--a review.
DeAngelo S et al.·Compend Contin Educ Dent
2007Review
Targeting MET for glioma therapy.
Awad AJ et al.·Neurosurg Focus
2014Review
Hepatocyte Growth Factor Gene Therapy for Ischemic Diseases.
Wang LS et al.·Hum Gene Ther
2018Review
Biomarker development in MET-targeted therapy.
Zhang Y et al.·Oncotarget
2016Review
Gene therapy in peripheral artery disease.
Sanada F et al.·Expert Opin Biol Ther
2015Review
Hepatocyte growth factor (HGF) and hemodialysis: physiopathology and clinical implications.
Libetta C et al.·Clin Exp Nephrol
2016Review
Hepatocyte growth factor and Met in drug discovery.
Sakai K et al.·J Biochem
2015Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Chronic Obstructive Pulmonary Disease

Predicting Risk Factors for Exacerbation of Chronic Obstructive Pulmonary Disease

RECRUITING
NCT03450603Xinhua Hospital, Shanghai Jiao Tong University School of MedicineStarted 2017-12-10
RacismStressInflammation

The Impact of a Race-Based Stress Reduction Intervention

RECRUITING
NCT05902741Phase NALoyola UniversityStarted 2023-10-18
RiSEHEP
Autosomal Dominant Polycystic KidneyOverweight and Obesity

Daily Caloric Restriction in ADPKD

ACTIVE NOT RECRUITING
NCT04907799Phase NAUniversity of Colorado, DenverStarted 2021-11-03
Daily caloric restrictionStandard advice control
Prostate Cancer

GU-01: Glycyrrhizin in Prostate Cancer

RECRUITING
NCT06378346Phase PHASE2University of Illinois at ChicagoStarted 2024-07-25
ObservationGlycyrrhizin - 75 mgGlycyrrhizin - 150 mg
Migraine DisordersPainAutoimmune Diseases

The Role of Cytokines and Regulatory T Lymphocytes in Migraine Pathophysiology.

RECRUITING
NCT06426316Phase NAUniversity Hospital, Clermont-FerrandStarted 2025-06-02
Blood test
Sickle Cell Disease

Cannabinoids for the Reduction of Inflammation and Sickle Cell Related Pain

RECRUITING
NCT05519111Phase PHASE2Icahn School of Medicine at Mount SinaiStarted 2025-04-03
DronabinolPlacebo
Inflammatory Breast Cancer (IBC)

Study Of Ruxolitinib (INCB018424) With Preoperative Chemotherapy For Triple Negative Inflammatory Breast Cancer

ACTIVE NOT RECRUITING
NCT02876302Phase PHASE2Dana-Farber Cancer InstituteStarted 2018-01-24
RuxolitinibPaclitaxelDoxorubicin
Atherosclerosis Cardiovascular DiseaseObesityMetabolic Syndrome

Deciphering the Effect of Moderate Wine Consumption on Healthy Aging Through Postprandial Extracellular Vesicles.

RECRUITING
NCT07361887Phase NAUniversity of SevilleStarted 2025-11-01
White WineRed WineWater
Solid Tumor, AdultColorectal CancerNSCLC

A Study to Evaluate the Safety and Efficacy of Mesothelin-Targeting Logic-gated CAR T, in Participants With Solid Tumors That Express MSLN and Have Lost HLA-A*02 Expression

RECRUITING
NCT06051695Phase PHASE1, PHASE2A2 Biotherapeutics Inc.Started 2024-04-03
A2B694A2B543xT CDx with HLA-LOH Assay
Healthy Adults

Safety and Efficacy of Klotho and Follistatin Gene Therapy

RECRUITING
NCT07285629Phase EARLY_PHASE1MinicircleStarted 2025-12-16
Follistatin and klotho gene therapy
Radiation-induced Oral Mucositis

Spirulina-Derived Product Alleviates Oral Mucositis in Patients Undergoing Radiotherapy for Malignant Head and Neck Tumors

RECRUITING
NCT07040969Phase PHASE2West China HospitalStarted 2025-06-27
Spray of spirulina derivativesSpray of placeboRadiotherapy
Menopause

Getting Under the Skin of the Menopausal Hot Flush

RECRUITING
NCT06222073Liverpool John Moores UniversityStarted 2023-01-01

External Resources

Links to major genomics databases and tools