PCSK7 Gene

Name	proprotein convertase subtilisin/kexin type 7
Description	This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. It encodes a type 1 membrane bound protease that is expressed in many tissues, including neuroendocrine, liver, gut, and brain. The encoded protein undergoes an initial autocatalytic processing event in the ER and then sorts to the trans-Golgi network through endosomes where a second autocatalytic event takes place and the catalytic activity is acquired. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. It can process proalbumin and is thought to be responsible for the activation of HIV envelope glycoproteins gp160 and gp140. This gene has been implicated in the transcriptional regulation of housekeeping genes and plays a role in the regulation of iron metabolism. A t(11;14)(q23;q32) chromosome translocation associated with B-cell lymphoma occurs between this gene and its inverted counterpart. [provided by RefSeq, Feb 2014]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nProprotein convertase subtilisin/kexin type 7 (PCSK7) is a member of the proprotein convertase family that processes a range of precursor proteins. Biochemical studies have demonstrated that PCSK7 exhibits substrate‐specific cleavage activity—for instance, it selectively removes the C‐terminal propeptide of VEGF‐D, thereby enhancing its receptor binding and angiogenic potential (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "]). In addition, PCSK7 contributes indirectly to the processing of the membrane‐bound epidermal growth factor precursor (pro‐EGF), leading to the generation of an active form that more potently activates the epidermal growth factor receptor (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "]). Moreover, its activity is implicated in immune surveillance by participating in a quality‐control checkpoint that rescues unstable major histocompatibility complex (MHC) class I molecules and by uniquely mediating the shedding of human transferrin receptor 1 (hTfR1) to facilitate iron homeostasis (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "]).\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe proper function of PCSK7 relies not only on its substrate specificity but also on its unique intracellular trafficking and membrane dynamics. PCSK7 is synthesized as a membrane‐bound zymogen and traffics to the cell surface via both conventional Golgi‐dependent and alternative secretory routes—a process heavily influenced by determinants within its transmembrane domain (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "]). Once at the plasma membrane, PCSK7 undergoes clathrin‐mediated internalization; a short segment within its cytosolic tail, featuring a conserved EXEXXXL motif, is essential for interaction with adaptor proteins such as AP-2, which directs it into endosomal compartments where substrates like hTfR1 are efficiently processed (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "]).\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic and clinical studies have now linked PCSK7 to several metabolic and liver-related disorders. Genome-wide analyses have identified PCSK7 variants as major determinants of soluble transferrin receptor levels and iron homeostasis (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "]). In addition, multiple independent studies have associated specific PCSK7 single-nucleotide polymorphisms with dyslipidemia—including alterations in triglycerides and high-density lipoprotein cholesterol—as well as with insulin resistance, rendering it a candidate gene in cardiovascular disease risk, including acute coronary syndrome (["}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "15"}]}, {"type": "t", "text": "]). Furthermore, PCSK7 genetic variation has been implicated as a risk factor for liver fibrosis and cirrhosis in hereditary hemochromatosis and for hepatic steatosis in liver transplant recipients (["}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "19"}]}, {"type": "t", "text": "]). Together, these findings suggest that beyond its classical proteolytic roles, PCSK7 is a multifunctional enzyme whose activity and intracellular localization are tightly regulated and whose genetic variations have significant implications for iron metabolism, lipid homeostasis, and liver pathology.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Martin Fugère, Polizois C Limperis, Véronique Beaulieu-Audy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibitory potency and specificity of subtilase-like pro-protein convertase (SPC) prodomains."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M107467200"}], "href": "https://doi.org/10.1074/jbc.M107467200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11723118"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11723118"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Bradley K McColl, Karri Paavonen, Tara Karnezis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proprotein convertases promote processing of VEGF-D, a critical step for binding the angiogenic receptor VEGFR-2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.06-7060com"}], "href": "https://doi.org/10.1096/fj.06-7060com"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17242158"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17242158"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Estelle Rousselet, Suzanne Benjannet, Edwidge Marcinkiewicz, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Post-endoplasmic reticulum rescue of unstable MHC class I requires proprotein convertase PC7."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.0900308"}], "href": "https://doi.org/10.4049/jimmunol.0900308"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20164418"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20164418"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Johann Guillemot, Maryssa Canuel, Rachid Essalmani, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Novel association to the proprotein convertase PCSK7 gene locus revealed by analysing soluble transferrin receptor (sTfR) levels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddq538"}], "href": "https://doi.org/10.1093/hmg/ddq538"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21149283"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21149283"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Shin Kato, Ruiguang Zhang, Jesse D Roberts "}, {"type": "b", "children": [{"type": "t", "text": "Proprotein convertases play an important role in regulating PKGI endoproteolytic cleavage and nuclear transport."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Lung Cell Mol Physiol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajplung.00391.2012"}], "href": "https://doi.org/10.1152/ajplung.00391.2012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23686857"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23686857"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Jian Fu, Jirong Zhang, Yulan Gong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of HIF-1 alpha by the proprotein convertases furin and PC7 in human squamous carcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Carcinog (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mc.22131"}], "href": "https://doi.org/10.1002/mc.22131"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24436242"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24436242"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Felix Stickel, Stephan Buch, Heinz Zoller, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evaluation of genome-wide loci of iron metabolism in hereditary hemochromatosis identifies PCSK7 as a host risk factor of liver cirrhosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddu076"}], "href": "https://doi.org/10.1093/hmg/ddu076"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24556216"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24556216"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Tao Huang, Jinyan Huang, Qibin Qi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PCSK7 genotype modifies effect of a weight-loss diet on 2-year changes of insulin resistance: the POUNDS LOST trial."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes Care (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/dc14-0473"}], "href": "https://doi.org/10.2337/dc14-0473"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25504030"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25504030"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Makoto Kurano, Kazuhisa Tsukamoto, Shigeo Kamitsuji, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association study of serum lipids confirms previously reported associations as well as new associations of common SNPs within PCSK7 gene with triglyceride."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jhg.2015.170"}], "href": "https://doi.org/10.1038/jhg.2015.170"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26763881"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26763881"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Paola Dongiovanni, Marica Meroni, Guido Baselli, et al. "}, {"type": "b", "children": [{"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "PCSK7"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " gene variation bridges atherogenic dyslipidemia with hepatic inflammation in NAFLD patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Lipid Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1194/jlr.P090449"}], "href": "https://doi.org/10.1194/jlr.P090449"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30918065"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30918065"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Giuditta Benincasa, Paola de Candia, Dario Costa, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Variations in TM6SF2, PCSK9 and PCSK7 genes and risk of hepatic steatosis after liver transplantation: a cross-sectional study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Gastroenterol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12876-021-02041-8"}], "href": "https://doi.org/10.1186/s12876-021-02041-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34876018"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34876018"}]}]}]}
Synonyms	LPC, PC8, PC7, SPC7
Proteins	PCSK7_HUMAN
NCBI Gene ID	9159
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PCSK7 has 8,172 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 115 datasets.

Click the + buttons to view associations for PCSK7 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PCSK7 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PCSK7 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of PCSK7 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of PCSK7 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of PCSK7 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of PCSK7 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PCSK7 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of PCSK7 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PCSK7 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PCSK7 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of PCSK7 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PCSK7 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of PCSK7 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with PCSK7 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PCSK7 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PCSK7 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PCSK7 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of PCSK7 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with PCSK7 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PCSK7 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PCSK7 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PCSK7 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing PCSK7 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing PCSK7 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with PCSK7 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with PCSK7 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of PCSK7 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PCSK7 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with PCSK7 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with PCSK7 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by PCSK7 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with PCSK7 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with PCSK7 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with PCSK7 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with PCSK7 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with PCSK7 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PCSK7 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at PCSK7 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PCSK7 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PCSK7 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing PCSK7 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.