SERPINA6 Gene

HGNC Family	Serpin peptidase inhibitors (SERPIN)
Name	serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 6
Description	This gene encodes an alpha-globulin protein with corticosteroid-binding properties. This is the major transport protein for glucorticoids and progestins in the blood of most vertebrates. The gene localizes to a chromosomal region containing several closely related serine protease inhibitors which may have evolved by duplication events. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSERPINA6 encodes corticosteroid‐binding globulin (CBG), the primary plasma transport protein for cortisol and other corticosteroids. CBG regulates the systemic bioavailability and tissue delivery of cortisol by reversibly binding it in circulation. Although predominantly synthesized in the liver, CBG is also expressed at lower levels in other tissues—including brain and adipose tissue—thereby contributing to both systemic and local glucocorticoid action. The protein’s concentration, binding affinity, and circulating levels are modulated by genetic factors, hormonal influences (e.g., insulin, IL-6), and inflammatory mediators."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructural and biochemical studies have revealed that CBG functions via conformational transitions that modulate steroid binding. High‐resolution crystal structures demonstrate that proteolytic cleavage of CBG’s reactive center loop triggers an allosteric, “stressed-to‐relaxed” transition that reorganizes its hormone–binding site, leading to reduced corticosteroid affinity. In addition, complex N‐glycosylation patterns on CBG further fine-tune its steroid-binding properties, affecting hormone delivery and release. Such post‐translational modifications provide a mechanism by which CBG can respond dynamically to changes in the physiological environment."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic variation and rare mutations in SERPINA6 have been linked to alterations in plasma CBG levels and cortisol‐binding activity, with significant physiological consequences. Variants that modify CBG’s concentration or binding affinity influence total and free cortisol levels, thereby affecting stress response, inflammatory regulation, metabolic homeostasis, and cardiovascular risk. Indeed, changes in CBG function have been associated with conditions ranging from chronic fatigue and insulin resistance to variations in adipose tissue deposition and predisposition to cardiovascular disease, as illustrated by genome‐wide association studies and functional analyses of CBG regulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "15"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "José-Manuel Fernandez-Real, Michel Pugeat, Mar Grasa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serum corticosteroid-binding globulin concentration and insulin resistance syndrome: a population study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2001-011843"}], "href": "https://doi.org/10.1210/jc.2001-011843"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12364459"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12364459"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "J M Joyner, L J Hutley, A W Bachmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Greater replication and differentiation of preadipocytes in inherited corticosteroid-binding globulin deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Endocrinol Metab (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpendo.00262.2002"}], "href": "https://doi.org/10.1152/ajpendo.00262.2002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12554596"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12554596"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "David J Torpy, A W Bachmann, M Gartside, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association between chronic fatigue syndrome and the corticosteroid-binding globulin gene ALA SER224 polymorphism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocr Res (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1081/erc-200035599"}], "href": "https://doi.org/10.1081/erc-200035599"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15554358"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15554358"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "José-Manuel Fernandez-Real, Michel Pugeat, Abel López-Bermejo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Corticosteroid-binding globulin affects the relationship between circulating adiponectin and cortisol in men and women."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Metabolism (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.metabol.2004.11.015"}], "href": "https://doi.org/10.1016/j.metabol.2004.11.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15877287"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15877287"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Pascal Barat, Martine Duclos, Blandine Gatta, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Corticosteroid binding globulin gene polymorphism influences cortisol driven fat distribution in obese women."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Obes Res (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/oby.2005.179"}], "href": "https://doi.org/10.1038/oby.2005.179"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16222046"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16222046"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Derek D Cyr, Joseph E Lucas, J Will Thompson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of serum proteins associated with IL28B genotype among patients with chronic hepatitis C."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0021854"}], "href": "https://doi.org/10.1371/journal.pone.0021854"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21750736"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21750736"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Giovanni Cizza, Livia Bernardi, Nicoletta Smirne, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical manifestations of highly prevalent corticosteroid-binding globulin mutations in a village in southern Italy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2011-1321"}], "href": "https://doi.org/10.1210/jc.2011-1321"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21795453"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21795453"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Hai-Yan Lin, Caroline Underhill, Jing-Hui Lei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High frequency of SERPINA6 polymorphisms that reduce plasma corticosteroid-binding globulin activity in Chinese subjects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2011-3141"}], "href": "https://doi.org/10.1210/jc.2011-3141"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22337907"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22337907"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Bernd R Gardill, Michael R Vogl, Hai-Yan Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Corticosteroid-binding globulin: structure-function implications from species differences."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0052759"}], "href": "https://doi.org/10.1371/journal.pone.0052759"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23300763"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23300763"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Elena V Sivukhina, Gustav F Jirikowski "}, {"type": "b", "children": [{"type": "t", "text": "Adrenal steroids in the brain: role of the intrinsic expression of corticosteroid-binding globulin (CBG) in the stress response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Steroids (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.steroids.2013.11.001"}], "href": "https://doi.org/10.1016/j.steroids.2013.11.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24246737"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24246737"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Jennifer L Bolton, Caroline Hayward, Nese Direk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome wide association identifies common variants at the SERPINA6/SERPINA1 locus influencing plasma cortisol and corticosteroid binding globulin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1004474"}], "href": "https://doi.org/10.1371/journal.pgen.1004474"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25010111"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25010111"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Marc Simard, Lesley A Hill, John G Lewis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Naturally occurring mutations of human corticosteroid-binding globulin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2014-3130"}], "href": "https://doi.org/10.1210/jc.2014-3130"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25322275"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25322275"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Nicolette Verhoog, Fatima Allie-Reid, Wim Vanden Berghe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of corticosteroid-binding globulin gene expression by glucocorticoids involves C/EBPβ."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0110702"}], "href": "https://doi.org/10.1371/journal.pone.0110702"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25335188"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25335188"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Zeynep Sumer-Bayraktar, Oliver C Grant, Vignesh Venkatakrishnan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Asn347 Glycosylation of Corticosteroid-binding Globulin Fine-tunes the Host Immune Response by Modulating Proteolysis by Pseudomonas aeruginosa and Neutrophil Elastase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M116.735258"}], "href": "https://doi.org/10.1074/jbc.M116.735258"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27339896"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27339896"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Andrew A Crawford, Sean Bankier, Elisabeth Altmaier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Variation in the SERPINA6/SERPINA1 locus alters morning plasma cortisol, hepatic corticosteroid binding globulin expression, gene expression in peripheral tissues, and risk of cardiovascular disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s10038-020-00895-6"}], "href": "https://doi.org/10.1038/s10038-020-00895-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33469137"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33469137"}]}]}]}
Synonyms	CBG
Proteins	CBG_HUMAN
NCBI Gene ID	866
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SERPINA6 has 5,125 functional associations with biological entities spanning 8 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) extracted from 109 datasets.

Click the + buttons to view associations for SERPINA6 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SERPINA6 Gene

Functional Associations

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

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by SERPINA6 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SERPINA6 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 SERPINA6 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 SERPINA6 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 SERPINA6 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SERPINA6 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 SERPINA6 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 SERPINA6 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 SERPINA6 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 SERPINA6 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SERPINA6 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 SERPINA6 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SERPINA6 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SERPINA6 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 SERPINA6 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with SERPINA6 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with SERPINA6 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of SERPINA6 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of SERPINA6 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SERPINA6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SERPINA6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with SERPINA6 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 SERPINA6 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 SERPINA6 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SERPINA6 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SERPINA6 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SERPINA6 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by SERPINA6 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for SERPINA6 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving SERPINA6 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with SERPINA6 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 SERPINA6 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 SERPINA6 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 SERPINA6 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 SERPINA6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SERPINA6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for SERPINA6 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at SERPINA6 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 SERPINA6 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SERPINA6 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.