PCSK1N
protein-codingproprotein convertase subtilisin/kexin type 1 inhibitor, the group of Granins
Gene summary
The protein encoded by this gene functions as an inhibitor of prohormone convertase 1, which regulates the proteolytic cleavage of neuroendocrine peptide precursors. The proprotein is further processed into multiple short peptides. A polymorphism within this gene may be associated with obesity. [provided by RefSeq, Aug 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.5 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 PCSK1N variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_013271.5. 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 | 0 | |||||
| missense | 48 | 1 | 49 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 48 | 1 | 0 | 49 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_037403.1 | 3 | MANE Select | |
| Ensembl | ENSP00000218230.5 | 3 | MANE Select | |
| Ensembl | ENSP00000554151.1 | 3 | Standard | |
| Ensembl | ENSP00000554151.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- response to dietary excess
- neuropeptide signaling pathway
- response to cold
- negative regulation of endopeptidase activity
- peptide hormone processing
Molecular Function
- endopeptidase inhibitor activity
- serine-type endopeptidase inhibitor activity
- signaling receptor binding
Cellular Component
- extracellular space
- trans-Golgi network
- secretory granule
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000218230
- Coding exons
- 3
- Length
- 4532
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.813 | 42 | 59.7 | 0.704 | 0.00000459 | 1513 |
| Missense (PolyPhen) | 17 | 31.839 | 0.53394 | 799 | ||
| Synonymous | 1.31 | 20 | 29.0 | 0.689 | 0.00000230 | 646 |
| Loss of Function | 1.38 | 0 | 2.23 | 0.00 | 1.45e-7 | 65 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May function in the control of the neuroendocrine secretory pathway. Proposed be a specific endogenous inhibitor of PCSK1. ProSAAS and Big PEN-LEN, both containing the C-terminal inhibitory domain, but not the further processed peptides reduce PCSK1 activity in the endoplasmic reticulum and Golgi. It reduces the activity of the 84 kDa form but not the autocatalytically derived 66 kDa form of PCSK1. Subsequent processing of proSAAS may eliminate the inhibition. Slows down convertase-mediated processing of proopiomelanocortin and proenkephalin. May control the intracellular timing of PCSK1 rather than its total level of activity. The function of the processed secreted peptides is not known (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.112
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Low | Low | Low |