PGC
protein-codingprogastricsin, the group of Pepsinogens
Gene summary
This gene encodes an aspartic proteinase that belongs to the peptidase family A1. The encoded protein is a digestive enzyme that is produced in the stomach and constitutes a major component of the gastric mucosa. This protein is also secreted into the serum. This protein is synthesized as an inactive zymogen that includes a highly basic prosegment. This enzyme is converted into its active mature form at low pH by sequential cleavage of the prosegment that is carried out by the enzyme itself. Polymorphisms in this gene are associated with susceptibility to gastric cancers. Serum levels of this enzyme are used as a biomarker for certain gastric diseases including Helicobacter pylori related gastritis. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 1. [provided by RefSeq, Oct 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~17.4 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 PGC variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002630.4. 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 | 1 | 2 | |||
| missense | 64 | 4 | 68 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 66 | 5 | 0 | 71 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002621.1 | 9 | MANE Select | |
| Ensembl | ENSP00000362116.3 | 9 | MANE Select | |
| RefSeq | NP_001159896.1 | 7 | Standard | |
| Ensembl | ENSP00000349094.4 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- miR-targeted genes in epithelium - TarBase
Biological Process
- positive regulation of antibacterial peptide production
- proteolysis
- digestion
- protein catabolic process
Molecular Function
- aspartic-type endopeptidase activity
Cellular Component
- extracellular space
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000373025
- Coding exons
- 9
- Length
- 17399
- Individuals with no LoFs
- 125648
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 100
- Defined
- 125748
- p
- 0.000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0484 | 228 | 230 | 0.991 | 0.0000128 | 2544 |
| Missense (PolyPhen) | 77 | 76.771 | 1.003 | 897 | ||
| Synonymous | 0.588 | 95 | 103 | 0.926 | 0.00000680 | 760 |
| Loss of Function | 0.490 | 17 | 19.3 | 0.880 | 8.23e-7 | 219 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0011 | 0.0010 | notable |
| Latino/Admixed American | 0.00041 | 0.00040 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.00047 | 0.00046 | rare |
| European (Non-Finnish) | 0.00041 | 0.00040 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0.00066 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Hydrolyzes a variety of proteins.;
Intolerance Scores
- LoFtool
- 0.901
- RVIS EVS
- 0.26
- RVIS percentile EVS
- 70.52
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.722
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |