FURIN

protein-coding

furin, 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]

Previous symbols:
  • PCSK3
  • FUR
  • PACE

MANE transcript

NM_002569.4

Inheritance

—

ClinVar variants

U:116B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr15:90,868,588-90,883,564

External References & Databases

Transcript & Mutation Effects

hg38 • Region Span ~15.0 kb
Loading mutation effect viewer...

GenCC 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

2 Conditions Cataloged
not specifiedTotal: 101
not providedTotal: 6

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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
3
clinvar
4
missense
105
clinvar
2
clinvar
107
nonsense
1
clinvar
1
start loss
0
frameshift
1
clinvar
1
splice donor/acceptor (+/-2bp)
8
clinvar
8
Total0011650121
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 54 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_002569.4RefSeqNP_002560.115MANE Select
ENST00000268171.8EnsemblENSP00000268171.215MANE Select
NM_001289823.2RefSeqNP_001276752.115Standard
NM_001289824.2RefSeqNP_001276753.115Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
furinbDanio 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: gnomAD

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-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.503665280.6930.00003515115
Missense (PolyPhen)69184.550.373891831
Synonymous-0.6622492361.050.00001761639
Loss of Function5.47340.70.07380.00000217403

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000580.000058rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish0.0000460.000046rare
European (Non-Finnish)0.0000180.000018rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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