Pathway Human Homo sapiens

Estrogen-dependent gene expression

R-HSA-9018519 in Reactome release 97: under ESR-mediated signaling, with 149 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: R-MMU-9018519 (mouse), R-RNO-9018519 (rat). 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-9018519.3
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2018-03-21
Last updated: 2022-04-07
Events inside: 66, counted from the record

Estrogens mediate their transcriptional effects through interaction with the estrogen receptors, ESR1 (also known as ER alpha) and ESR2 (ER beta). ESR1 and ESR2 share overlapping but distinct functions, with ESR1 playing the primary role in transcriptional activation in most cell types (Hah and Krauss, 2014; Haldosén et al, 2014. The receptors function as ligand-dependent dimers and can activate target genes either through direct binding to an estrogen responsive element (ERE) in the target gene promoter, or indirectly through interaction with another DNA-binding protein such as RUNX1, SP1, AP1 or NF-kappa beta (reviewed in Bai and Gust, 2009; Hah and Krause, 2014). Binding of estrogen receptors to the DNA promotes the assembly of higher order transcriptional complexes containing methyltransferases, histone acetyltransferases and other transcriptional activators, which promote transcription by establishing active chromatin marks and by recruiting general transcription factors and RNA polymerase II. ESR1- and estrogen-dependent recruitment of up to hundreds of coregulators has been demonstrated by varied co-immunoprecipitation and proteomic approaches (Kittler et al, 2013; Mohammed et al, 2013; Foulds et al, 2013; Mohammed et al, 2015; Liu et al, 2014; reviewed in Magnani and Lupien, 2014; Arnal, 2017). In some circumstances, ligand-bound receptors can also promote the assembly of a repression complex at a target gene, and in some cases, heterodimers of ESR1 and ESR2 serve as repressors of ESR1-mediated target gene activation (reviewed in Hah and Kraus, 2014; Arnal et al, 2017). Phosphorylation of the estrogen receptor also modulates its activity, and provides cross-talk between nuclear estrogen-dependent signaling and non-genomic estrogen signaling from the plasma membrane (reviewed in Anbalagan and Rowan, 2015; Halodsèn et al, 2014; Schwartz et al, 2016)

A number of recent genome wide studies highlight the breadth of the transcriptional response to estrogen. The number of predicted estrogen-dependent target genes ranges from a couple of hundred (based on microarray studies) to upwards of 10000, based on ChIP-chip or ChIP-seq (Cheung and Kraus, 2010; Kinnis and Kraus, 2008; Lin et al, 2004; Welboren et al, 2009; Ikeda et al, 2015; Lin et al, 2007; Carroll et al, 2006). Many of these predicted sites may not represent transcriptionally productive binding events, however. A study examining ESR1 binding by ChIP-seq in 20 primary breast cancers identified a core of 484 ESR-binding events that were conserved in at least 75% of ER+ tumors, which may represent a more realistic estimate (Ross-Innes et al, 2012). These studies also highlight the long-range effect of estrogen receptor-binding, with distal enhancer or promoter elements regulating the expression of many target genes, often through looping or other higher order chromatin structures (Kittler et al, 2013; reviewed in Dietz and Carroll, 2008; Liu and Cheung, 2014; Magnani and Lupien, 2014). Transcription from a number of estrogen-responsive target genes also appears to be primed by the binding of pioneering transcription factors such as FOXA1, GATA3, PBX1 among others. These factors bind to heterochromatin by virtue of their winged helix domains and promote chromatin opening, allowing subsequent recruitment of other transcription factors (reviewed in Zaret and Carroll, 2011; Fiorito et al, 2013; Arnal et al, 2017; Magnani et al, 2011)

Literature Reactome attaches

Hormone-regulated transcriptomes: lessons learned from estrogen signaling pathways in breast cancer cellsMol. Cell. Endocrinol., 2014, vol. 382, p. 652-64PubMed 23810978
Estrogen receptor beta in breast cancerMol. Cell. Endocrinol., 2014, vol. 382, p. 665-72PubMed 23954741
Breast cancer, estrogen receptor and ligandsArch. Pharm. (Weinheim), 2009, vol. 342, p. 133-49PubMed 19274700
Membrane and Nuclear Estrogen Receptor Alpha Actions: From Tissue Specificity to Medical ImplicationsPhysiol. Rev., 2017, vol. 97, p. 1045-1087PubMed 28539435
Estrogen receptor alpha phosphorylation and its functional impact in human breast cancerMol. Cell. Endocrinol., 2015, vol. 418, p. 264-72PubMed 25597633
Rapid steroid hormone actions via membrane receptorsBiochim. Biophys. Acta, 2016, vol. 1863, p. 2289-98PubMed 27288742
Genomic analyses of hormone signaling and gene regulationAnnu. Rev. Physiol., 2010, vol. 72, p. 191-218

Reactome's record lists 13 orthologous events, R-RNO-9018519 (Rattus norvegicus), R-MMU-9018519 (Mus musculus) among the species this site serves, and 11 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-01 ET · Reactome pathway browser"Estrogen-dependent gene expression". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-9018519 with StableID: R-HSA-9018519.3 (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 149 genes in this human pathway; showing 1 to 100, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 1 of 2
Gene	Authority id	Mapping file id	Evidence codes
GeneAGO1	AuthorityHGNC:3262	Mapping file id26523 NCBI file	EvidenceTAS
GeneAGO2	AuthorityHGNC:3263	Mapping file id27161 NCBI file	EvidenceTAS
GeneAGO3	AuthorityHGNC:18421	Mapping file id192669 NCBI file	EvidenceTAS
GeneAGO4	AuthorityHGNC:18424	Mapping file id192670 NCBI file	EvidenceTAS
GeneATF2	AuthorityHGNC:784	Mapping file id1386 NCBI file	EvidenceTAS
GeneAXIN1	AuthorityHGNC:903	Mapping file id8312 NCBI file	EvidenceTAS
GeneBCL2	AuthorityHGNC:990	Mapping file id596 NCBI file	EvidenceTAS
GeneCARM1	AuthorityHGNC:23393	Mapping file id10498 NCBI file	EvidenceTAS
GeneCBFB	AuthorityHGNC:1539	Mapping file id865 NCBI file	EvidenceTAS
GeneCCND1	AuthorityHGNC:1582	Mapping file id595 NCBI file	EvidenceTAS
GeneCCNT1	AuthorityHGNC:1599	Mapping file id904 NCBI file	EvidenceTAS
GeneCDK9	AuthorityHGNC:1780	Mapping file id1025 NCBI file	EvidenceTAS
GeneCHD1	AuthorityHGNC:1915	Mapping file id1105 NCBI file	EvidenceTAS
GeneCITED1	AuthorityHGNC:1986	Mapping file id4435 NCBI file	EvidenceTAS
GeneCREBBP	AuthorityHGNC:2348	Mapping file id1387 NCBI file	EvidenceTAS
GeneCTSD	AuthorityHGNC:2529	Mapping file id1509 NCBI file	EvidenceTAS
GeneCXCL12	AuthorityHGNC:10672	Mapping file id6387 NCBI file	EvidenceTAS
GeneCXXC5	AuthorityHGNC:26943	Mapping file id51523 NCBI file	EvidenceTAS
GeneDDX5	AuthorityHGNC:2746	Mapping file id1655 NCBI file	EvidenceTAS
GeneEBAG9	AuthorityHGNC:3123	Mapping file id9166 NCBI file	EvidenceTAS
GeneEP300	AuthorityHGNC:3373	Mapping file id2033 NCBI file	EvidenceTAS
GeneERBB4	AuthorityHGNC:3432	Mapping file id2066 NCBI file	EvidenceTAS
GeneESR1	AuthorityHGNC:3467	Mapping file id2099 NCBI file	EvidenceTAS
GeneFKBP4	AuthorityHGNC:3720	Mapping file id2288 NCBI file	EvidenceTAS
GeneFOS	AuthorityHGNC:3796	Mapping file id2353 NCBI file	EvidenceTAS
GeneFOSB	AuthorityHGNC:3797	Mapping file id2354 NCBI file	EvidenceTAS
GeneFOXA1	AuthorityHGNC:5021	Mapping file id3169 NCBI file	EvidenceTAS
GeneGATA3	AuthorityHGNC:4172	Mapping file id2625 NCBI file	EvidenceTAS
GeneGPAM	AuthorityHGNC:24865	Mapping file id57678 NCBI file	EvidenceTAS
GeneGREB1	AuthorityHGNC:24885	Mapping file id9687 NCBI file	EvidenceTAS
GeneGTF2A1	AuthorityHGNC:4646	Mapping file id2957 NCBI file	EvidenceTAS
GeneGTF2A2	AuthorityHGNC:4647	Mapping file id2958 NCBI file	EvidenceTAS
GeneGTF2F1	AuthorityHGNC:4652	Mapping file id2962 NCBI file	EvidenceTAS
GeneGTF2F2	AuthorityHGNC:4653	Mapping file id2963 NCBI file	EvidenceTAS
GeneH2AB1	AuthorityHGNC:22516	Mapping file id474382 NCBI file	EvidenceTAS
GeneH2AC14	AuthorityHGNC:4727	Mapping file id8331 NCBI file	EvidenceTAS
GeneH2AC18	AuthorityHGNC:4736	Mapping file id8337 NCBI file	EvidenceTAS
GeneH2AC19	AuthorityHGNC:29668	Mapping file id723790 NCBI file	EvidenceTAS
GeneH2AC20	AuthorityHGNC:4738	Mapping file id8338 NCBI file	EvidenceTAS
GeneH2AC4	AuthorityHGNC:4734	Mapping file id8335 NCBI file	EvidenceTAS
GeneH2AC6	AuthorityHGNC:4733	Mapping file id8334 NCBI file	EvidenceTAS
GeneH2AC7	AuthorityHGNC:4729	Mapping file id3013 NCBI file	EvidenceTAS
GeneH2AC8	AuthorityHGNC:4724	Mapping file id3012 NCBI file	EvidenceTAS
GeneH2AJ	AuthorityHGNC:14456	Mapping file id55766 NCBI file	EvidenceTAS
GeneH2AX	AuthorityHGNC:4739	Mapping file id3014 NCBI file	EvidenceTAS
GeneH2AZ2	AuthorityHGNC:20664	Mapping file id94239 NCBI file	EvidenceTAS
GeneH2BC1	AuthorityHGNC:18730	Mapping file id255626 NCBI file	EvidenceTAS
GeneH2BC10	AuthorityHGNC:4756	Mapping file id8346 NCBI file	EvidenceTAS
GeneH2BC11	AuthorityHGNC:4761	Mapping file id8970 NCBI file	EvidenceTAS
GeneH2BC12	AuthorityHGNC:13954	Mapping file id85236 NCBI file	EvidenceTAS
GeneH2BC12L	AuthorityHGNC:4762	Mapping file id54145 NCBI file	EvidenceTAS
GeneH2BC13	AuthorityHGNC:4748	Mapping file id8340 NCBI file	EvidenceTAS
GeneH2BC14	AuthorityHGNC:4750	Mapping file id8342 NCBI file	EvidenceTAS
GeneH2BC15	AuthorityHGNC:4749	Mapping file id8341 NCBI file	EvidenceTAS
GeneH2BC17	AuthorityHGNC:4758	Mapping file id8348 NCBI file	EvidenceTAS
GeneH2BC21	AuthorityHGNC:4760	Mapping file id8349 NCBI file	EvidenceTAS
GeneH2BC26	AuthorityHGNC:20514	Mapping file id128312 NCBI file	EvidenceTAS
GeneH2BC3	AuthorityHGNC:4751	Mapping file id3018 NCBI file	EvidenceTAS
GeneH2BC4	AuthorityHGNC:4757	Mapping file id8347 NCBI file	EvidenceTAS
GeneH2BC5	AuthorityHGNC:4747	Mapping file id3017 NCBI file	EvidenceTAS
GeneH2BC6	AuthorityHGNC:4753	Mapping file id8344 NCBI file	EvidenceTAS
GeneH2BC7	AuthorityHGNC:4752	Mapping file id8343 NCBI file	EvidenceTAS
GeneH2BC8	AuthorityHGNC:4746	Mapping file id8339 NCBI file	EvidenceTAS
GeneH2BC9	AuthorityHGNC:4755	Mapping file id8345 NCBI file	EvidenceTAS
GeneH3-3A	AuthorityHGNC:4764	Mapping file id3020 NCBI file	EvidenceTAS
GeneH3-3B	AuthorityHGNC:4765	Mapping file id3021 NCBI file	EvidenceTAS
GeneH3C1	AuthorityHGNC:4766	Mapping file id8350 NCBI file	EvidenceTAS
GeneH3C10	AuthorityHGNC:4775	Mapping file id8357 NCBI file	EvidenceTAS
GeneH3C11	AuthorityHGNC:4771	Mapping file id8354 NCBI file	EvidenceTAS
GeneH3C12	AuthorityHGNC:4774	Mapping file id8356 NCBI file	EvidenceTAS
GeneH3C13	AuthorityHGNC:25311	Mapping file id653604 NCBI file	EvidenceTAS
GeneH3C14	AuthorityHGNC:20503	Mapping file id126961 NCBI file	EvidenceTAS
GeneH3C15	AuthorityHGNC:20505	Mapping file id333932 NCBI file	EvidenceTAS
GeneH3C2	AuthorityHGNC:4776	Mapping file id8358 NCBI file	EvidenceTAS
GeneH3C3	AuthorityHGNC:4768	Mapping file id8352 NCBI file	EvidenceTAS
GeneH3C4	AuthorityHGNC:4767	Mapping file id8351 NCBI file	EvidenceTAS
GeneH3C6	AuthorityHGNC:4769	Mapping file id8353 NCBI file	EvidenceTAS
GeneH3C7	AuthorityHGNC:4773	Mapping file id8968 NCBI file	EvidenceTAS
GeneH3C8	AuthorityHGNC:4772	Mapping file id8355 NCBI file	EvidenceTAS
GeneH4C1	AuthorityHGNC:4781	Mapping file id8359 NCBI file	EvidenceTAS
GeneH4C11	AuthorityHGNC:4785	Mapping file id8363 NCBI file	EvidenceTAS
GeneH4C12	AuthorityHGNC:4784	Mapping file id8362 NCBI file	EvidenceTAS
GeneH4C13	AuthorityHGNC:4791	Mapping file id8368 NCBI file	EvidenceTAS
GeneH4C14	AuthorityHGNC:4794	Mapping file id8370 NCBI file	EvidenceTAS
GeneH4C15	AuthorityHGNC:29607	Mapping file id554313 NCBI file	EvidenceTAS
GeneH4C16	AuthorityHGNC:20510	Mapping file id121504 NCBI file	EvidenceTAS
GeneH4C2	AuthorityHGNC:4789	Mapping file id8366 NCBI file	EvidenceTAS
GeneH4C3	AuthorityHGNC:4787	Mapping file id8364 NCBI file	EvidenceTAS
GeneH4C4	AuthorityHGNC:4782	Mapping file id8360 NCBI file	EvidenceTAS
GeneH4C5	AuthorityHGNC:4790	Mapping file id8367 NCBI file	EvidenceTAS
GeneH4C6	AuthorityHGNC:4783	Mapping file id8361 NCBI file	EvidenceTAS
GeneH4C8	AuthorityHGNC:4788	Mapping file id8365 NCBI file	EvidenceTAS
GeneH4C9	AuthorityHGNC:4793	Mapping file id8294 NCBI file	EvidenceTAS
GeneHDAC1	AuthorityHGNC:4852	Mapping file id3065 NCBI file	EvidenceTAS
GeneHSP90AA1	AuthorityHGNC:5253	Mapping file id3320 NCBI file	EvidenceTAS
GeneHSP90AB1	AuthorityHGNC:5258	Mapping file id3326 NCBI file	EvidenceTAS
GeneJUN	AuthorityHGNC:6204	Mapping file id3725 NCBI file	EvidenceTAS
GeneJUND	AuthorityHGNC:6206	Mapping file id3727 NCBI file	EvidenceTAS
GeneKANK1	AuthorityHGNC:19309	Mapping file id23189 NCBI file	EvidenceTAS
GeneKAT2B	AuthorityHGNC:8638	Mapping file id8850 NCBI file	EvidenceTAS

Evidence codes on this page: 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

ESR-mediated signalingR-HSA-8939211222 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.