PCSK2
proprotein convertase subtilisin/kexin type 2, the group of Proprotein convertase subtilisin/kexin family
Basic information
Region (hg38): 20:17226107-17484578
Previous symbols: [ "NEC2" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PCSK2 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | |||||
| missense | 15 | 16 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 1 | |||||
| Total | 0 | 0 | 15 | 1 | 2 |
Variants in PCSK2
This is a list of pathogenic ClinVar variants found in the PCSK2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 20-17227351-C-T | not specified | Uncertain significance (Feb 12, 2024) | ||
| 20-17227437-C-A | not specified | Likely benign (Apr 07, 2023) | ||
| 20-17227459-G-A | not specified | Uncertain significance (Aug 22, 2023) | ||
| 20-17227472-G-A | not specified | Uncertain significance (Jan 18, 2023) | ||
| 20-17260250-C-T | not specified | Uncertain significance (Jan 30, 2024) | ||
| 20-17260300-A-G | not specified | Uncertain significance (Feb 03, 2022) | ||
| 20-17260304-G-A | not specified | Uncertain significance (Jan 26, 2022) | ||
| 20-17260312-C-T | not specified | Uncertain significance (Oct 05, 2022) | ||
| 20-17260314-C-A | not specified | Uncertain significance (Mar 29, 2022) | ||
| 20-17360532-A-T | not specified | Uncertain significance (Feb 23, 2023) | ||
| 20-17409305-C-G | not specified | Uncertain significance (Sep 14, 2022) | ||
| 20-17429508-A-C | not specified | Uncertain significance (Nov 03, 2023) | ||
| 20-17436861-C-T | not specified | Uncertain significance (Jan 17, 2024) | ||
| 20-17465507-G-A | not specified | Uncertain significance (Jun 28, 2022) | ||
| 20-17465549-C-T | not specified | Uncertain significance (Jan 10, 2023) | ||
| 20-17465559-TG-T | Benign (Jun 14, 2018) | |||
| 20-17481830-G-A | Benign (Apr 04, 2018) | |||
| 20-17481991-T-C | not specified | Uncertain significance (Mar 28, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PCSK2 | protein_coding | protein_coding | ENST00000262545 | 12 | 258472 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.999 | 0.00147 | 125742 | 0 | 4 | 125746 | 0.0000159 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.55 | 199 | 398 | 0.500 | 0.0000235 | 4215 |
| Missense in Polyphen | 56 | 199.31 | 0.28097 | 2043 | ||
| Synonymous | -0.301 | 167 | 162 | 1.03 | 0.0000112 | 1240 |
| Loss of Function | 4.77 | 3 | 32.2 | 0.0931 | 0.00000172 | 333 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000289 | 0.0000289 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000264 | 0.0000264 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. Responsible for the release of glucagon from proglucagon in pancreatic A cells. {ECO:0000269|PubMed:28719828, ECO:0000269|PubMed:9287128}.;
- Pathway
- Levomethadyl Acetate Action Action Pathway;Fluoxetine Action Pathway;Citalopram Action Pathway;Escitalopram Action Pathway;Imipramine Action Pathway;Desipramine Action Pathway;Levallorphan Action Pathway;Dimethylthiambutene Action Pathway;Ethylmorphine Action Pathway;Pentazocine Action Pathway;Naltrexone Action Pathway;Buprenorphine Action Pathway;Alvimopan Action Pathway;Naloxone Action Pathway;Dihydromorphine Action Pathway;Nicotine Action Pathway;Nalbuphine Action Pathway;Ketobemidone Action Pathway;Lidocaine (Local Anaesthetic) Action Pathway;Mepivacaine Action Pathway;Chloroprocaine Action Pathway;Cocaine Action Pathway;Dibucaine Action Pathway;Levobupivacaine Action Pathway;Benzocaine Action Pathway;Bupivacaine Action Pathway;Levorphanol Action Pathway;Propoxyphene Action Pathway;Tramadol Action Action Pathway;Diphenoxylate Action Pathway;Anileridine Action Pathway;Methadone Action Pathway;Oxycodone Action Pathway;Oxybuprocaine Action Pathway;Prilocaine Action Pathway;Procaine Action Pathway;Proparacaine Action Pathway;Ropivacaine Action Pathway;Codeine Action Pathway;Morphine Action Pathway;Heroin Action Pathway;Alfentanil Action Pathway;Oxymorphone Action Pathway;Hydrocodone Action Pathway;Hydromorphone Action Pathway;Sufentanil Action Pathway;Remifentanil Action Pathway;Fentanyl Action Pathway;Carfentanil Action Pathway;3-Methylthiofentanyl Action Pathway;Methadyl Acetate Action Pathway;Dezocine Action Pathway;Peptide hormone metabolism;Metabolism of proteins;Insulin processing
(Consensus)
Recessive Scores
- pRec
- 0.268
Intolerance Scores
- loftool
- 0.158
- rvis_EVS
- -1.11
- rvis_percentile_EVS
- 6.72
Haploinsufficiency Scores
- pHI
- 0.658
- hipred
- Y
- hipred_score
- 0.768
- ghis
- 0.542
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.534
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Pcsk2
- Phenotype
- homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); neoplasm;
Gene ontology
- Biological process
- proteolysis;nervous system development;protein processing;peptide hormone processing;protein autoprocessing;insulin processing;enkephalin processing;islet amyloid polypeptide processing
- Cellular component
- extracellular space;nucleus;membrane;transport vesicle;secretory granule;dendrite;neuron projection;perikaryon;intracellular membrane-bounded organelle
- Molecular function
- serine-type endopeptidase activity;protein binding;protein-containing complex binding