FURIN
protein-codingfurin, paired basic amino acid cleaving enzyme, the group of Proprotein convertase subtilisin/kexin family
Gene summary
This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. It encodes a type 1 membrane bound protease that is expressed in many tissues, including neuroendocrine, liver, gut, and brain. The encoded protein undergoes an initial autocatalytic processing event in the ER and then sorts to the trans-Golgi network through endosomes where a second autocatalytic event takes place and the catalytic activity is acquired. Like other members of this convertase family, the product of this gene specifically cleaves substrates at single or paired basic residues. Some of its substrates include proparathyroid hormone, transforming growth factor beta 1 precursor, proalbumin, pro-beta-secretase, membrane type-1 matrix metalloproteinase, beta subunit of pro-nerve growth factor and von Willebrand factor. It is thought to be one of the proteases responsible for the activation of HIV envelope glycoproteins gp160 and gp140, and may play a role in tumor progression. Unlike SARS-CoV and other coronaviruses, the spike protein of SARS-CoV-2 is thought to be uniquely cleaved by this protease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2020]
- PCSK3
- FUR
- PACE
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.0 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 FURIN variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002569.4. 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 | 3 | 4 | |||
| missense | 105 | 2 | 107 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 8 | 8 | ||||
| Total | 0 | 0 | 116 | 5 | 0 | 121 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002560.1 | 15 | MANE Select | |
| Ensembl | ENSP00000268171.2 | 15 | MANE Select | |
| RefSeq | NP_001276752.1 | 15 | Standard | |
| RefSeq | NP_001276753.1 | 15 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| furinb | Danio rerio | Structure: interhyal-epihyal joint Quality: absent abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Influenza A - Homo sapiens (human)
- Keratinization
- Developmental Biology
- Disease
- Signal Transduction
Biological Process
- signal peptide processing
- transforming growth factor beta receptor signaling pathway
- cell population proliferation
- regulation of signal transduction
- negative regulation of endopeptidase activity
Molecular Function
- protease binding
- endopeptidase activity
- serine-type endopeptidase activity
- serine-type endopeptidase inhibitor activity
- protein binding
Cellular Component
- Golgi membrane
- extracellular region
- extracellular space
- endoplasmic reticulum
- Golgi lumen
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000268171
- Coding exons
- 15
- Length
- 14867
- Individuals with no LoFs
- 125730
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125735
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.50 | 366 | 528 | 0.693 | 0.0000351 | 5115 |
| Missense (PolyPhen) | 69 | 184.55 | 0.37389 | 1831 | ||
| Synonymous | -0.662 | 249 | 236 | 1.05 | 0.0000176 | 1639 |
| Loss of Function | 5.47 | 3 | 40.7 | 0.0738 | 0.00000217 | 403 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Ubiquitous endoprotease within constitutive secretory pathways capable of cleavage at the RX(K/R)R consensus motif (PubMed:11799113, PubMed:1629222, PubMed:1713771, PubMed:2251280, PubMed:24666235, PubMed:25974265, PubMed:7592877, PubMed:7690548, PubMed:9130696). Mediates processing of TGFB1, an essential step in TGF-beta-1 activation (PubMed:7737999). {ECO:0000269|PubMed:11799113, ECO:0000269|PubMed:1629222, ECO:0000269|PubMed:1713771, ECO:0000269|PubMed:2251280, ECO:0000269|PubMed:24666235, ECO:0000269|PubMed:25974265, ECO:0000269|PubMed:7592877, ECO:0000269|PubMed:7690548, ECO:0000269|PubMed:7737999, ECO:0000269|PubMed:9130696}.; FUNCTION: (Microbial infection) Required for H7N1 and H5N1 influenza virus infection probably by cleaving hemagglutinin. {ECO:0000269|PubMed:25974265}.;
Recessive Scores
- pRec
- 0.770
Intolerance Scores
- LoFtool
- 0.0230
- RVIS EVS
- -0.79
- RVIS percentile EVS
- 12.57
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.786
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |