PCSK5

proprotein convertase subtilisin/kexin type 5, the group of Proprotein convertase subtilisin/kexin family

Basic information

Region (hg38): 9:75890644-76362975

Links

ENSG00000099139 ∙ NCBI:5125 ∙ OMIM:600488 ∙ HGNC:8747 ∙ Uniprot:Q92824 ∙ 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 PCSK5 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PCSK5 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			2	8	8	18
missense			41	7	6	54
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding						0
Total	0	0	44	15	14

Variants in PCSK5

This is a list of pathogenic ClinVar variants found in the PCSK5 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-75891197-C-T		not specified	Uncertain significance (Jan 26, 2022)
9-75891215-C-T		not specified	Uncertain significance (Jun 17, 2024)
9-75891265-C-A			Benign (Jun 19, 2018)
9-75891271-T-C			Benign (Feb 13, 2020)
9-75891273-G-A		not specified	Uncertain significance (Jun 02, 2024)
9-75891316-G-A			Benign (May 24, 2018)
9-75891339-T-A		not specified	Uncertain significance (May 23, 2024)
9-75891363-A-G		not specified	Uncertain significance (Mar 17, 2023)
9-75891367-A-T		PCSK5-related disorder	Uncertain significance (Jan 12, 2024)
9-75932383-G-A		not specified	Uncertain significance (Jun 16, 2024)
9-75932394-G-A		not specified	Uncertain significance (Jul 14, 2022)
9-75932424-A-G		not specified	Uncertain significance (Mar 12, 2024)
9-75986163-A-G		not specified	Uncertain significance (May 04, 2023)
9-75986177-G-A		not specified	Uncertain significance (Apr 29, 2024)
9-75986182-T-C			Likely benign (May 01, 2023)
9-75986198-C-G		not specified	Uncertain significance (Jan 04, 2024)
9-76023751-A-G		not specified	Uncertain significance (Aug 12, 2021)
9-76023765-C-G		not specified	Uncertain significance (Sep 12, 2023)
9-76023772-A-G		not specified	Uncertain significance (Jun 17, 2024)
9-76023773-C-T			Benign (May 08, 2018)
9-76023814-A-G		not specified	Uncertain significance (Jul 25, 2023)
9-76023881-C-T		not specified	Uncertain significance (Mar 06, 2015)
9-76026996-C-T		PCSK5-related disorder	Likely benign (Nov 16, 2023)
9-76068039-C-T			Benign (May 24, 2018)
9-76071897-T-C		not specified	Uncertain significance (Dec 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PCSK5	protein_coding	protein_coding	ENST00000545128	37	471696

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.54e-12	1.00	125613	0	135	125748	0.000537

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.57	840	1.08e+3	0.780	0.0000610	12320
Missense in Polyphen		206	423.92	0.48594		4761
Synonymous	0.623	398	414	0.961	0.0000264	3274
Loss of Function	5.79	39	102	0.382	0.00000514	1249

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000853	0.000783
Ashkenazi Jewish	0.00131	0.00129
East Asian	0.00180	0.00174
Finnish	0.0000926	0.0000924
European (Non-Finnish)	0.000593	0.000554
Middle Eastern	0.00180	0.00174
South Asian	0.000233	0.000196
Other	0.000168	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine endoprotease that processes various proproteins by cleavage at paired basic amino acids, recognizing the RXXX[KR]R consensus motif. Likely functions in the constitutive and regulated secretory pathways. Plays an essential role in pregnancy establishment by proteolytic activation of a number of important factors such as BMP2, CALD1 and alpha-integrins. {ECO:0000269|PubMed:19764806, ECO:0000269|PubMed:20555025, ECO:0000269|PubMed:22740495}.
• Pathway: Signal Transduction;Transport of small molecules;NGF processing;Expression and Processing of Neurotrophins;Signaling by NTRKs;Assembly of active LPL and LIPC lipase complexes;Plasma lipoprotein assembly, remodeling, and clearance;Plasma lipoprotein remodeling;Signaling by Receptor Tyrosine Kinases (Consensus)

Recessive Scores

• pRec: 0.242

Intolerance Scores

• loftool: 0.825
• rvis_EVS: 2.84
• rvis_percentile_EVS: 99.1

Haploinsufficiency Scores

• pHI: 0.122
• hipred: Y
• hipred_score: 0.639

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.774

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Pcsk5
• Phenotype: 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); hematopoietic system 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); respiratory system phenotype; embryo phenotype; skeleton phenotype; renal/urinary system phenotype; immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; digestive/alimentary phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; cellular phenotype; craniofacial phenotype

Zebrafish Information Network

• Gene name: pcsk5a
• Affected structure: lateral line
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: kidney development;renin secretion into blood stream;cardiac septum development;signal peptide processing;cell-cell signaling;determination of left/right symmetry;heart development;embryo implantation;anterior/posterior pattern specification;protein processing;peptide hormone processing;viral life cycle;respiratory tube development;limb morphogenesis;cytokine biosynthetic process;peptide biosynthetic process;embryonic digestive tract development;embryonic skeletal system development;regulation of lipoprotein lipase activity;coronary vasculature development
• Cellular component: extracellular region;extracellular space;Golgi apparatus;Golgi lumen;trans-Golgi network;membrane;integral component of membrane;secretory granule;integral component of Golgi membrane
• Molecular function: endopeptidase activity;serine-type endopeptidase activity;protein binding;peptidase activity;peptide binding