HGFAC
protein-codingHGF activator
Gene summary
This gene encodes a member of the peptidase S1 protein family. The encoded protein is first synthesized as an inactive single-chain precursor before being activated to a heterodimeric form by endoproteolytic processing. It acts as serine protease that converts hepatocyte growth factor to the active form. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HGFAC variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001528.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 2 | 3 | |||
| missense | 170 | 10 | 180 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 172 | 13 | 0 | 185 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001519.1 | 14 | MANE Select | |
| Ensembl | ENSP00000372224.4 | 14 | MANE Select | |
| RefSeq | NP_001284368.1 | 15 | Standard | |
| Ensembl | ENSP00000421801.1 | 15 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signal Transduction
- MET Receptor Activation
- Signaling by MET
- Signaling by Receptor Tyrosine Kinases
Biological Process
- proteolysis
Molecular Function
- serine-type endopeptidase activity
- serine-type peptidase activity
Cellular Component
- extracellular region
- extracellular space
- rough endoplasmic reticulum
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000382774
- Coding exons
- 14
- Length
- 7598
- Individuals with no LoFs
- 124697
- Homozygous LoFs
- 5
- Heterozygous LoFs
- 934
- Defined
- 125636
- p
- 0.00374
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.580 | 458 | 424 | 1.08 | 0.0000297 | 4129 |
| Missense (PolyPhen) | 199 | 178.61 | 1.1142 | 1723 | ||
| Synonymous | -1.98 | 230 | 195 | 1.18 | 0.0000154 | 1350 |
| Loss of Function | 2.09 | 17 | 29.2 | 0.583 | 0.00000133 | 330 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00052 | 0.00049 | rare |
| Latino/Admixed American | 0.0046 | 0.0044 | notable |
| Ashkenazi Jewish | 0.0071 | 0.0062 | notable |
| East Asian | 0.0034 | 0.0033 | notable |
| Finnish | 0.0046 | 0.0045 | notable |
| European (Non-Finnish) | 0.0031 | 0.0029 | notable |
| South Asian | 0.0063 | 0.0058 | notable |
| Other | 0.0098 | 0.0090 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Activates hepatocyte growth factor (HGF) by converting it from a single chain to a heterodimeric form.;
Recessive Scores
- pRec
- 0.105
Intolerance Scores
- LoFtool
- 0.144
- RVIS EVS
- 0.5
- RVIS percentile EVS
- 79.67
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.250
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |