ATF6 Gene

HGNC Family	Basic leucine zipper proteins
Name	activating transcription factor 6
Description	This gene encodes a transcription factor that activates target genes for the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. Although it is a transcription factor, this protein is unusual in that it is synthesized as a transmembrane protein that is embedded in the ER. It functions as an ER stress sensor/transducer, and following ER stress-induced proteolysis, it functions as a nuclear transcription factor via a cis-acting ER stress response element (ERSE) that is present in the promoters of genes encoding ER chaperones. This protein has been identified as a survival factor for quiescent but not proliferative squamous carcinoma cells. There have been conflicting reports about the association of polymorphisms in this gene with diabetes in different populations, but another polymorphism has been associated with increased plasma cholesterol levels. This gene is also thought to be a potential therapeutic target for cystic fibrosis. [provided by RefSeq, Aug 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Activating transcription factor 6 (ATF6) is a key transmembrane sensor and effector of the mammalian unfolded protein response (UPR) that is dedicated to restoring endoplasmic reticulum (ER) homeostasis under stress conditions. Under basal conditions, ATF6 is retained in the ER through binding with BiP; however, when unfolded proteins accumulate, BiP dissociates, permitting ATF6 to exit the ER and traffic to the Golgi apparatus. There, site‐specific proteolysis releases its cytosolic N‐terminal domain, which translocates to the nucleus to activate transcription of ER chaperones (such as BiP) and other quality control proteins that enhance the cell’s protein folding capacity (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its role in inducing chaperones for refolding, ATF6 also contributes to broader UPR signaling by promoting the expression of components such as XBP1 mRNA. This transcript is then processed by IRE1 to form an active transcription factor that cooperates with ATF6 in upregulating UPR target genes, highlighting a functional interplay and partial redundancy between these UPR branches (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Temporal regulation within the UPR has also been described, with ATF6 acting predominantly during an early “refolding” phase, which is followed later by the IRE1–XBP1 branch, responsible for both refolding and degradation of misfolded proteins. This delineation of function ensures that cells initially attempt recovery before committing to degradation pathways if stress persists (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, analyses of the luminal domain of ATF6 have revealed distinct regions that are vital for its stress sensing and subsequent proteolytic activation, further underscoring its specificity in detecting ER perturbations. In parallel, related factors in the same CREB/ATF family, such as the astrocyte‐selective ER stress transducer OASIS, share mechanistic similarities with ATF6 in activating ER stress‐responsive genes to confer cytoprotection (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these studies underscore ATF6’s central role as an adaptive regulator during ER stress, coordinating transcriptional responses that promote protein folding and ER integrity while interfacing with other UPR branches to determine cell fate.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jingshi Shen, Xi Chen, Linda Hendershot, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of Golgi localization signals."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1534-5807(02)00203-4"}], "href": "https://doi.org/10.1016/s1534-5807(02"}, {"type": "t", "text": "00203-4) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12110171"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12110171"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xi Chen, Jingshi Shen, Ron Prywes "}, {"type": "b", "children": [{"type": "t", "text": "The luminal domain of ATF6 senses endoplasmic reticulum (ER) stress and causes translocation of ATF6 from the ER to the Golgi."}]}, {"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.M110636200"}], "href": "https://doi.org/10.1074/jbc.M110636200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11821395"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11821395"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "H Yoshida, T Matsui, A Yamamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0092-8674(01)00611-0"}], "href": "https://doi.org/10.1016/s0092-8674(01"}, {"type": "t", "text": "00611-0) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11779464"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11779464"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ann-Hwee Lee, Neal N Iwakoshi, Laurie H Glimcher "}, {"type": "b", "children": [{"type": "t", "text": "XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.23.21.7448-7459.2003"}], "href": "https://doi.org/10.1128/MCB.23.21.7448-7459.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14559994"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14559994"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Kyungho Lee, Witoon Tirasophon, Xiaohua Shen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.964702"}], "href": "https://doi.org/10.1101/gad.964702"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11850408"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11850408"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Hiderou Yoshida, Toshie Matsui, Nobuko Hosokawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A time-dependent phase shift in the mammalian unfolded protein response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1534-5807(03)00022-4"}], "href": "https://doi.org/10.1016/s1534-5807(03"}, {"type": "t", "text": "00022-4) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12586069"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12586069"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Shinichi Kondo, Tomohiko Murakami, Kouko Tatsumi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "OASIS, a CREB/ATF-family member, modulates UPR signalling in astrocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb1213"}], "href": "https://doi.org/10.1038/ncb1213"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15665855"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15665855"}]}]}]}
Synonyms	ACHM7, ATF6A
Proteins	ATF6A_HUMAN
NCBI Gene ID	22926
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ATF6 has 11,430 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 128 datasets.

Click the + buttons to view associations for ATF6 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ATF6 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 ATF6 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 ATF6 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 ATF6 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 ATF6 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 ATF6 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 ATF6 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 ATF6 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 ATF6 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 ATF6 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 ATF6 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 ATF6 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ATF6 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 ATF6 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ATF6 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of ATF6 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ATF6 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 ATF6 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 ATF6 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 ATF6 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ATF6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ATF6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with ATF6 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 ATF6 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 ATF6 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ATF6 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ATF6 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ATF6 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with ATF6 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of ATF6 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by ATF6 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with ATF6 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 ATF6 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 ATF6 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 ATF6 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 ATF6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ATF6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for ATF6 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at ATF6 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 ATF6 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ATF6 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.