Pathway Human Homo sapiens

ATF4 activates genes in response to endoplasmic reticulum stress

R-HSA-380994 in Reactome release 97: under PERK regulates gene expression, with 27 genes placed in it by the mapping files and 0 child pathways in the hierarchy.

The same number in the other species

Reactome writes the mouse and rat events it infers from a human pathway under the human number with the species token. A door opens only where that species' own list in this release holds the id; neither of the other two lists holds it. Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

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This page reads the pathway's record from its source while you read the rest; with scripts off the card stays at its loading line. Reload with scripts on to see it, or open the source's own page from the link in the card.

01The record

Reactome's own record of this pathway

What this tells you

The pathway list, the hierarchy and the genes on this page are read from the files Reactome publishes for Reactome release 97, built into this site on 2026-09-09: the pathway list, the hierarchy relationship file and the two gene mapping files. The record card is the one live read, Reactome's own record of this pathway.

Reactome's download page describes the mapping files: Mapping files link the source database identifier to the lowest level pathway diagram or subset of the pathway, all levels of the pathway hierarchy or database identifier to all reactions. [R13] The gene list here is the all-levels mapping of NCBI Gene ids, filled from the all-levels mapping of Ensembl ids where the NCBI file has no row for a gene; each row names which file it came from by the shape of its source id. Each row carries the evidence codes the file writes for it, as written and unranked, and both where the file writes both; no page of Reactome's documentation the survey read defines the codes, so this page does not expand them. A gene id the identity files do not name is kept as the source's own id with no door rather than turned into a symbol.

On citing what a search finds, Reactome says: It should be remembered that while we strive to contain the most current and accurate data, Reactome should not be used in citations where other primary sources of information are available. [R12] The record card prints the literature Reactome attaches to a curated pathway for that reason. The data are public domain: All data in the Reactome database and files derived from that data are licensed under the Creative Commons Public Domain Dedication (CC0). User may copy, modify, and distribute these data, even for commercial purposes, without asking for permission. Attribution is encouraged but not required. [R10] The pathway illustrations are licensed apart, under CC BY 4.0, and none is shown here.

A gene on this list is one Reactome places in this pathway in this release, and that is all the row says: it does not say the gene is expressed in a tissue or associated with a disease, which are the other two explorers' questions, read from other sources. Reactome's papers of record are [R01] [R02].

[R01] Ragueneau E, Gong C, Sinquin P, Sevilla C, Beavers D, Grentner A, et al. (2026). The Reactome Knowledgebase 2026. Nucleic Acids Research 54:D673-D681. PMID 41251150, doi 10.1093/nar/gkaf1223.
[R02] Milacic M, Beavers D, Conley P, Gong C, Gillespie M, Griss J, et al. (2024). The Reactome Pathway Knowledgebase 2024. Nucleic Acids Research 52:D672-D678. PMID 37941124, doi 10.1093/nar/gkad1025.
[R10] Reactome, reactome.org. License Agreement. https://reactome.org/license, read 2026-09-09.
[R12] Reactome, reactome.org. Citing us. https://reactome.org/cite, read 2026-09-09.
[R13] Reactome, reactome.org. Download. https://reactome.org/download-data, read 2026-09-09.

Stable id: R-HSA-380994.5
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2009-06-24
Last updated: 2021-09-15
Events inside: 7, counted from the record

ATF4 is a transcription factor and activates expression of IL-8, MCP1, IGFBP-1, CHOP, HERP1 and ATF3.

Literature Reactome attaches

Endoplasmic reticulum (ER) chaperone regulation and survival of cells compensating for deficiency in the ER stress response kinase, PERKJ Biol Chem, 2008, vol. 283, p. 17020-9PubMed 18426796
Induction of CHOP expression by amino acid limitation requires both ATF4 expression and ATF2 phosphorylationJ Biol Chem, 2004, vol. 279, p. 5288-97PubMed 14630918
Regulation of Endoplasmic Reticulum Stress-induced Cell Death by ATF4 in Neuroectodermal Tumor CellsJ Biol Chem, 2010, vol. 285, p. 6091-100PubMed 20022965
Identification of inflammatory gene modules based on variations of human endothelial cell responses to oxidized lipidsProc Natl Acad Sci U S A, 2006, vol. 103, p. 12741-6PubMed 16912112
The unfolded protein response is an important regulator of inflammatory genes in endothelial cellsArterioscler Thromb Vasc Biol, 2006, vol. 26, p. 2490-6PubMed 16931790
Endoplasmic reticulum stress induction of insulin-like growth factor-binding protein-1 involves ATF4J Biol Chem, 2006, vol. 281, p. 19124-33PubMed 16687408
Herp is dually regulated by both the endoplasmic reticulum stress-specific branch of the unfolded protein response and a branch that is shared with other cellular stress pathwaysJ Biol Chem, 2004, vol. 279, p. 13792-9PubMed 14742429
Transcriptional induction of the human asparagine synthetase gene during the unfolded protein response does not require the ATF6 and IRE1/XBP1 arms of the pathwayBiochem J, 2009, vol. 417, p. 695-703PubMed 18840095

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-01 ET · Reactome pathway browser"ATF4 activates genes in response to endoplasmic reticulum stress". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-380994 with StableID: R-HSA-380994.5 (accessed 2026-10-01 ET). Reactome version 97 (CC0).

Reading this pathway's record from Reactome (the pathway record).Still reading. A first read of a pathway can take a while; this page waits up to 35 seconds for it, and its scripts then bring in the panel, or a line saying what did not arrive.

02The genes

Genes Reactome places in this human pathway

The mapping files place 27 genes in this human pathway; showing 1 to 27, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 1 of 1
Gene	Authority id	Mapping file id	Evidence codes
GeneASNS	AuthorityHGNC:753	Mapping file id440 NCBI file	EvidenceIEA
GeneATF3	AuthorityHGNC:785	Mapping file id467 NCBI file	EvidenceIEA
GeneATF4	AuthorityHGNC:786	Mapping file id468 NCBI file	EvidenceIEA, TAS
GeneATF6	AuthorityHGNC:791	Mapping file id22926 NCBI file	EvidenceIEA
GeneCCL2	AuthorityHGNC:10618	Mapping file id6347 NCBI file	EvidenceTAS
GeneCEBPB	AuthorityHGNC:1834	Mapping file id1051 NCBI file	EvidenceIEA
GeneCEBPG	AuthorityHGNC:1837	Mapping file id1054 NCBI file	EvidenceIEA
GeneCXCL8	AuthorityHGNC:6025	Mapping file id3576 NCBI file	EvidenceTAS
GeneDCP2	AuthorityHGNC:24452	Mapping file id167227 NCBI file	EvidenceTAS
GeneDDIT3	AuthorityHGNC:2726	Mapping file id1649 NCBI file	EvidenceIEA
GeneDIS3	AuthorityHGNC:20604	Mapping file id22894 NCBI file	EvidenceTAS
GeneEXOSC1	AuthorityHGNC:17286	Mapping file id51013 NCBI file	EvidenceTAS
GeneEXOSC2	AuthorityHGNC:17097	Mapping file id23404 NCBI file	EvidenceTAS
GeneEXOSC3	AuthorityHGNC:17944	Mapping file id51010 NCBI file	EvidenceTAS
GeneEXOSC4	AuthorityHGNC:18189	Mapping file id54512 NCBI file	EvidenceTAS
GeneEXOSC5	AuthorityHGNC:24662	Mapping file id56915 NCBI file	EvidenceTAS
GeneEXOSC6	AuthorityHGNC:19055	Mapping file id118460 NCBI file	EvidenceTAS
GeneEXOSC7	AuthorityHGNC:28112	Mapping file id23016 NCBI file	EvidenceTAS
GeneEXOSC8	AuthorityHGNC:17035	Mapping file id11340 NCBI file	EvidenceTAS
GeneEXOSC9	AuthorityHGNC:9137	Mapping file id5393 NCBI file	EvidenceTAS
GeneHERPUD1	AuthorityHGNC:13744	Mapping file id9709 NCBI file	EvidenceTAS
GeneIGFBP1	AuthorityHGNC:5469	Mapping file id3484 NCBI file	EvidenceTAS
GeneKHSRP	AuthorityHGNC:6316	Mapping file id8570 NCBI file	EvidenceTAS
GeneNFYA	AuthorityHGNC:7804	Mapping file id4800 NCBI file	EvidenceIEA
GeneNFYB	AuthorityHGNC:7805	Mapping file id4801 NCBI file	EvidenceIEA
GeneNFYC	AuthorityHGNC:7806	Mapping file id4802 NCBI file	EvidenceIEA
GenePARN	AuthorityHGNC:8609	Mapping file id5073 NCBI file	EvidenceTAS

Evidence codes on this page: IEA, TAS, as the mapping file writes them; a row carrying two was written twice by the file, once under each. The mapping file id says which file placed the gene: an NCBI Gene id from NCBI2Reactome_All_Levels.txt, an Ensembl gene id from Ensembl2Reactome_All_Levels.txt. The two files can disagree about a code, so a row's codes are the one file's view. Measured by this site's build over this release on 2026-09-09: of the 138,908 human pathway-gene pairs both files place, 207 (0.149 per cent, over 47 genes) carry TAS in the Ensembl file where the NCBI rows carry IEA alone.

Reactome mapping files, the human rows for this pathway · Reactome release 97 · read 2026-09-09 · Reactome downloads"NCBI2Reactome_All_Levels.txt" and "Ensembl2Reactome_All_Levels.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.

03The hierarchy

Parents and children in this release's hierarchy

Parents

PERK regulates gene expressionR-HSA-38104232 genes

Children

None: no pathway of this release's list names this one as a parent.

Reactome's hierarchy is a graph rather than a tree: a pathway can sit under more than one parent, and the gene counts are each pathway's own placements at every level under it, so a parent's count is not the sum of its children's.

Reactome, the human pathway list and hierarchy relationship file · Reactome release 97 · read 2026-09-09 · Reactome downloads"ReactomePathways.txt" and "ReactomePathwaysRelation.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.