PCSK2

proprotein convertase subtilisin/kexin type 2, the group of Proprotein convertase subtilisin/kexin family

Basic information

Region (hg38): 20:17226106-17484578

Previous symbols: [ "NEC2" ]

Links

ENSG00000125851 ∙ NCBI:5126 ∙ OMIM:162151 ∙ HGNC:8744 ∙ Uniprot:P16519 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PCSK2 gene.

• Inborn genetic diseases (10 variants)
• not provided (2 variants)

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	1
missense			9	1		10
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	9	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: gnomAD

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: dbNSFP

• 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