QPCT
protein-codingglutaminyl-peptide cyclotransferase, the group of M28 metallopeptidases
Gene summary
This gene encodes human pituitary glutaminyl cyclase, which is responsible for the presence of pyroglutamyl residues in many neuroendocrine peptides. The amino acid sequence of this enzyme is 86% identical to that of bovine glutaminyl cyclase. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~30.5 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 QPCT variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012413.4. 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 | ||||
| missense | 72 | 2 | 1 | 75 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 74 | 2 | 1 | 77 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036545.1 | 7 | MANE Select | |
| Ensembl | ENSP00000344829.3 | 7 | MANE Select | |
| Ensembl | ENSP00000385391.1 | 6 | Standard | |
| Ensembl | ENSP00000389227.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neutrophil degranulation
- Innate Immune System
- Immune System
Biological Process
- cellular protein modification process
- peptidyl-pyroglutamic acid biosynthetic process, using glutaminyl-peptide cyclotransferase
- neutrophil degranulation
Molecular Function
- zinc ion binding
- glutaminyl-peptide cyclotransferase activity
Cellular Component
- extracellular region
- specific granule lumen
- extracellular exosome
- tertiary granule lumen
- ficolin-1-rich granule lumen
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000338415
- Coding exons
- 7
- Length
- 28749
- Individuals with no LoFs
- 125520
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 228
- Defined
- 125748
- p
- 0.000907
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.940 | 234 | 197 | 1.19 | 0.0000101 | 2330 |
| Missense (PolyPhen) | 93 | 81.998 | 1.1342 | 993 | ||
| Synonymous | -0.345 | 83 | 79.1 | 1.05 | 0.00000423 | 717 |
| Loss of Function | -0.319 | 22 | 20.4 | 1.08 | 0.00000120 | 217 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00068 | 0.00068 | rare |
| Latino/Admixed American | 0.0011 | 0.0011 | notable |
| Ashkenazi Jewish | 0.0011 | 0.0011 | notable |
| East Asian | 0.00027 | 0.00027 | rare |
| Finnish | 0.00018 | 0.00018 | rare |
| European (Non-Finnish) | 0.0012 | 0.0012 | notable |
| South Asian | 0.00052 | 0.00052 | rare |
| Other | 0.00065 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Responsible for the biosynthesis of pyroglutamyl peptides. Has a bias against acidic and tryptophan residues adjacent to the N-terminal glutaminyl residue and a lack of importance of chain length after the second residue. Also catalyzes N-terminal pyroglutamate formation. In vitro, catalyzes pyroglutamate formation of N-terminally truncated form of APP amyloid-beta peptides [Glu-3]-amyloid-beta. May be involved in the N-terminal pyroglutamate formation of several amyloid-related plaque-forming peptides. {ECO:0000269|PubMed:15063747, ECO:0000269|PubMed:18486145, ECO:0000269|PubMed:21288892}.;
Recessive Scores
- pRec
- 0.267
Intolerance Scores
- LoFtool
- 0.876
- RVIS EVS
- 0.31
- RVIS percentile EVS
- 72.6
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.222
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |