PCSK6

proprotein convertase subtilisin/kexin type 6, the group of Proprotein convertase subtilisin/kexin family

Basic information

Region (hg38): 15:101289784-101525202

Previous symbols: [ "PACE4" ]

Links

ENSG00000140479 ∙ NCBI:5046 ∙ OMIM:167405 ∙ HGNC:8569 ∙ Uniprot:P29122 ∙ 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 PCSK6 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PCSK6 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				7	1	8
missense			1	2	2	5
nonsense						0
start loss						0
frameshift					1	1
inframe indel				1		1
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding			3			3
Total	0	0	4	10	4

Variants in PCSK6

This is a list of pathogenic ClinVar variants found in the PCSK6 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-101291970-C-T		not specified	Uncertain significance (Aug 15, 2023)
15-101292003-G-C		not specified	Uncertain significance (Jul 13, 2022)
15-101293054-T-A		not specified	Uncertain significance (Dec 14, 2023)
15-101293096-C-G		not specified	Uncertain significance (Apr 22, 2024)
15-101305277-G-A			Likely benign (Sep 20, 2018)
15-101313475-G-A			Likely benign (Dec 31, 2019)
15-101318331-C-T			Benign (Dec 31, 2019)
15-101322570-T-C			Likely benign (Dec 31, 2019)
15-101370469-C-T			Likely benign (Oct 01, 2022)
15-101370481-G-A		not specified	Likely benign (Jul 04, 2017)
15-101370529-G-C			Benign (Dec 31, 2019)
15-101382116-A-G		not specified	Benign (Mar 28, 2016)
15-101384371-C-T			Benign (Dec 31, 2019)
15-101393350-G-A			Likely benign (Nov 01, 2022)
15-101398473-G-A			Likely benign (May 25, 2018)
15-101432020-G-A			Likely benign (Nov 01, 2022)
15-101489480-G-GGC			Benign (Jan 17, 2024)
15-101489563-G-GGCGCCCCCC			Likely benign (Jan 01, 2023)
15-101489572-C-A			Likely benign (Jun 01, 2022)
15-101489663-G-A		not specified	Uncertain significance (Feb 27, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PCSK6	protein_coding	protein_coding	ENST00000348070	23	224588

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.31e-13	0.999	125508	0	59	125567	0.000235

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.41	438	530	0.827	0.0000328	6206
Missense in Polyphen		128	216.64	0.59085		2300
Synonymous	0.588	209	220	0.950	0.0000159	1831
Loss of Function	3.14	29	53.9	0.538	0.00000299	608

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000764	0.000752
Ashkenazi Jewish	0.00	0.00
East Asian	0.000166	0.000163
Finnish	0.0000490	0.0000462
European (Non-Finnish)	0.000250	0.000246
Middle Eastern	0.000166	0.000163
South Asian	0.000229	0.000229
Other	0.000165	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 secretory pathway, with unique restricted distribution in both neuroendocrine and non-neuroendocrine tissues.
• Pathway: Keratinization;Developmental Biology;Signal Transduction;Transport of small molecules;NGF processing;Expression and Processing of Neurotrophins;Signaling by NODAL;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;Formation of the cornified envelope (Consensus)

Recessive Scores

• pRec: 0.241

Haploinsufficiency Scores

• pHI: 0.269
• hipred: N
• hipred_score: 0.492
• ghis: 0.532

Essentials

• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.501

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pcsk6
• Phenotype: skeleton 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); digestive/alimentary phenotype; vision/eye phenotype; reproductive system 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); 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); neoplasm; embryo phenotype; respiratory system phenotype; craniofacial phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: zygotic determination of anterior/posterior axis, embryo;determination of left/right symmetry;glycoprotein metabolic process;protein processing;peptide hormone processing;regulation of BMP signaling pathway;nerve growth factor production;secretion by cell;regulation of lipoprotein lipase activity;cornification
• Cellular component: extracellular region;extracellular space;endoplasmic reticulum;Golgi lumen;plasma membrane;cell surface;membrane;collagen-containing extracellular matrix
• Molecular function: endopeptidase activity;serine-type endopeptidase activity;protein binding;heparin binding;nerve growth factor binding