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 101 to 149, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 2 of 2
Gene	Authority id	Mapping file id	Evidence codes
GeneKAT5	AuthorityHGNC:5275	Mapping file id10524 NCBI file	EvidenceTAS
GeneKCTD6	AuthorityHGNC:22235	Mapping file id200845 NCBI file	EvidenceTAS
GeneKDM1A	AuthorityHGNC:29079	Mapping file id23028 NCBI file	EvidenceTAS
GeneKDM4B	AuthorityHGNC:29136	Mapping file id23030 NCBI file	EvidenceTAS
GeneKPNA2	AuthorityHGNC:6395	Mapping file id3838 NCBI file	EvidenceTAS
GeneMED1	AuthorityHGNC:9234	Mapping file id5469 NCBI file	EvidenceTAS
GeneMOV10	AuthorityHGNC:7200	Mapping file id4343 NCBI file	EvidenceTAS
GeneMYB	AuthorityHGNC:7545	Mapping file id4602 NCBI file	EvidenceTAS
GeneMYC	AuthorityHGNC:7553	Mapping file id4609 NCBI file	EvidenceTAS
GeneNCOA1	AuthorityHGNC:7668	Mapping file id8648 NCBI file	EvidenceTAS
GeneNCOA2	AuthorityHGNC:7669	Mapping file id10499 NCBI file	EvidenceTAS
GeneNCOA3	AuthorityHGNC:7670	Mapping file id8202 NCBI file	EvidenceTAS
GeneNR5A2	AuthorityHGNC:7984	Mapping file id2494 NCBI file	EvidenceTAS
GeneNRIP1	AuthorityHGNC:8001	Mapping file id8204 NCBI file	EvidenceTAS
GenePGR	AuthorityHGNC:8910	Mapping file id5241 NCBI file	EvidenceTAS
GenePOLR2A	AuthorityHGNC:9187	Mapping file id5430 NCBI file	EvidenceTAS
GenePOLR2B	AuthorityHGNC:9188	Mapping file id5431 NCBI file	EvidenceTAS
GenePOLR2C	AuthorityHGNC:9189	Mapping file id5432 NCBI file	EvidenceTAS
GenePOLR2D	AuthorityHGNC:9191	Mapping file id5433 NCBI file	EvidenceTAS
GenePOLR2E	AuthorityHGNC:9192	Mapping file id5434 NCBI file	EvidenceTAS
GenePOLR2F	AuthorityHGNC:9193	Mapping file id5435 NCBI file	EvidenceTAS
GenePOLR2G	AuthorityHGNC:9194	Mapping file id5436 NCBI file	EvidenceTAS
GenePOLR2H	AuthorityHGNC:9195	Mapping file id5437 NCBI file	EvidenceTAS
GenePOLR2I	AuthorityHGNC:9196	Mapping file id5438 NCBI file	EvidenceTAS
GenePOLR2J	AuthorityHGNC:9197	Mapping file id5439 NCBI file	EvidenceTAS
GenePOLR2K	AuthorityHGNC:9198	Mapping file id5440 NCBI file	EvidenceTAS
GenePOLR2L	AuthorityHGNC:9199	Mapping file id5441 NCBI file	EvidenceTAS
GenePOU2F1	AuthorityHGNC:9212	Mapping file id5451 NCBI file	EvidenceTAS
GenePRMT1	AuthorityHGNC:5187	Mapping file id3276 NCBI file	EvidenceTAS
GenePTGES3	AuthorityHGNC:16049	Mapping file id10728 NCBI file	EvidenceTAS
GeneRAD21	AuthorityHGNC:9811	Mapping file id5885 NCBI file	EvidenceTAS
GeneRUNX1	AuthorityHGNC:10471	Mapping file id861 NCBI file	EvidenceTAS
GeneSMC1A	AuthorityHGNC:11111	Mapping file id8243 NCBI file	EvidenceTAS
GeneSMC3	AuthorityHGNC:2468	Mapping file id9126 NCBI file	EvidenceTAS
GeneSP1	AuthorityHGNC:11205	Mapping file id6667 NCBI file	EvidenceTAS
GeneSTAG1	AuthorityHGNC:11354	Mapping file id10274 NCBI file	EvidenceTAS
GeneSTAG2	AuthorityHGNC:11355	Mapping file id10735 NCBI file	EvidenceTAS
GeneTBP	AuthorityHGNC:11588	Mapping file id6908 NCBI file	EvidenceTAS
GeneTFF1	AuthorityHGNC:11755	Mapping file id7031 NCBI file	EvidenceTAS
GeneTFF3	AuthorityHGNC:11757	Mapping file id7033 NCBI file	EvidenceTAS
GeneTGFA	AuthorityHGNC:11765	Mapping file id7039 NCBI file	EvidenceTAS
GeneTLE3	AuthorityHGNC:11839	Mapping file id7090 NCBI file	EvidenceTAS
GeneTNRC6A	AuthorityHGNC:11969	Mapping file id27327 NCBI file	EvidenceTAS
GeneTNRC6B	AuthorityHGNC:29190	Mapping file id23112 NCBI file	EvidenceTAS
GeneTNRC6C	AuthorityHGNC:29318	Mapping file id57690 NCBI file	EvidenceTAS
GeneUSF1	AuthorityHGNC:12593	Mapping file id7391 NCBI file	EvidenceTAS
GeneUSF2	AuthorityHGNC:12594	Mapping file id7392 NCBI file	EvidenceTAS
GeneYY1	AuthorityHGNC:12856	Mapping file id7528 NCBI file	EvidenceTAS
GeneZNF217	AuthorityHGNC:13009	Mapping file id7764 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.