Pathway Human Homo sapiens

Nuclear Receptor transcription pathway

R-HSA-383280 in Reactome release 97: under Generic Transcription Pathway, with 53 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-383280 (mouse), R-RNO-383280 (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-383280.3
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2009-12-15
Last updated: 2019-03-25
Events inside: 2, counted from the record

A classic example of bifunctional transcription factors is the family of Nuclear Receptor (NR) proteins. These are DNA-binding transcription factors that bind certain hormones, vitamins, and other small, diffusible signaling molecules. The non-liganded NRs recruit specific corepressor complexes of the NCOR/SMRT type, to mediate transcriptional repression of the target genes to which they are bound. During signaling, ligand binding to a specific domain the NR proteins induces a conformational change that results in the exchange of the associated CoR complex, and its replacement by a specific coactivator complex of the TRAP / DRIP / Mediator type. These coactivator complexes typically nucleate around a MED1 coactivator protein that is directly bound to the NR transcription factor.

A general feature of the 49 human NR proteins is that in the unliganded state, they each bind directly to an NCOR corepressor protein, either NCOR1 or NCOR2 (NCOR2 was previously named "SMRT"). This NCOR protein nucleates the assembly of additional, specific corepressor proteins, depending on the cell and DNA context. The NR-NCOR interaction is mediated by a specific protein interaction domain (PID) present in the NRs that binds to specific cognate PID(s) present in the NCOR proteins. Thus, the human NRs each take part in an NR-NCOR binding reaction in the absence of binding by their ligand.

A second general feature of the NR proteins is that they each contain an additional, but different PID that mediates specific binding interactions with MED1 proteins. In the ligand-bound state, NRs each take part in an NR-MED1 binding reaction to form an NR-MED1 complex. The bound MED1 then functions to nucleate the assembly of additional specific coactivator proteins, depending on the cell and DNA context, such as what specific target gene promoter they are bound to, and in what cell type.

The formation of specific MED1-containing coactivator complexes on specific NR proteins has been well-characterized for a number of the human NR proteins (see Table 1 in (Bourbon, 2004)). For example, binding of thyroid hormone (TH) to the human TH Receptor (THRA or THRB) was found to result in the recruitment of a specific complex of Thyroid Receptor Associated Proteins - the TRAP coactivator complex - of which the TRAP220 subunit was later identified to be the Mediator 1 (MED1) homologue.

Similarly, binding of Vitamin D to the human Vitamin D3 Receptor was found to result in the recruitment of a specific complex of D Receptor Interacting Proteins - the DRIP coactivator complex, of which the DRIP205 subunit was later identified to be human MED1.

Literature Reactome attaches

Reactome's record attaches no literature to this pathway.

Reactome's record lists 11 orthologous events, R-RNO-383280 (Rattus norvegicus), R-MMU-383280 (Mus musculus) among the species this site serves, and 9 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-09-30 ET · Reactome pathway browser"Nuclear Receptor transcription pathway". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-383280 with StableID: R-HSA-383280.3 (accessed 2026-09-30 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 53 genes in this human pathway; showing 1 to 53, 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
GeneAR	AuthorityHGNC:644	Mapping file id367 NCBI file	EvidenceTAS
GeneESR1	AuthorityHGNC:3467	Mapping file id2099 NCBI file	EvidenceTAS
GeneESR2	AuthorityHGNC:3468	Mapping file id2100 NCBI file	EvidenceTAS
GeneESRRA	AuthorityHGNC:3471	Mapping file id2101 NCBI file	EvidenceTAS
GeneESRRB	AuthorityHGNC:3473	Mapping file id2103 NCBI file	EvidenceTAS
GeneESRRG	AuthorityHGNC:3474	Mapping file id2104 NCBI file	EvidenceTAS
GeneHNF4A	AuthorityHGNC:5024	Mapping file id3172 NCBI file	EvidenceTAS
GeneHNF4G	AuthorityHGNC:5026	Mapping file id3174 NCBI file	EvidenceTAS
GeneMED1	AuthorityHGNC:9234	Mapping file id5469 NCBI file	EvidenceTAS
GeneNCOR1	AuthorityHGNC:7672	Mapping file id9611 NCBI file	EvidenceTAS
GeneNCOR2	AuthorityHGNC:7673	Mapping file id9612 NCBI file	EvidenceTAS
GeneNR0B1	AuthorityHGNC:7960	Mapping file id190 NCBI file	EvidenceTAS
GeneNR0B2	AuthorityHGNC:7961	Mapping file id8431 NCBI file	EvidenceTAS
GeneNR1D1	AuthorityHGNC:7962	Mapping file id9572 NCBI file	EvidenceTAS
GeneNR1D2	AuthorityHGNC:7963	Mapping file id9975 NCBI file	EvidenceTAS
GeneNR1H2	AuthorityHGNC:7965	Mapping file id7376 NCBI file	EvidenceTAS
GeneNR1H3	AuthorityHGNC:7966	Mapping file id10062 NCBI file	EvidenceTAS
GeneNR1H4	AuthorityHGNC:7967	Mapping file id9971 NCBI file	EvidenceTAS
GeneNR1I2	AuthorityHGNC:7968	Mapping file id8856 NCBI file	EvidenceTAS
GeneNR1I3	AuthorityHGNC:7969	Mapping file id9970 NCBI file	EvidenceTAS
GeneNR2C1	AuthorityHGNC:7971	Mapping file id7181 NCBI file	EvidenceTAS
GeneNR2C2	AuthorityHGNC:7972	Mapping file id7182 NCBI file	EvidenceTAS
GeneNR2C2AP	AuthorityHGNC:30763	Mapping file id126382 NCBI file	EvidenceTAS
GeneNR2E1	AuthorityHGNC:7973	Mapping file id7101 NCBI file	EvidenceTAS
GeneNR2E3	AuthorityHGNC:7974	Mapping file id10002 NCBI file	EvidenceTAS
GeneNR2F1	AuthorityHGNC:7975	Mapping file id7025 NCBI file	EvidenceTAS
GeneNR2F6	AuthorityHGNC:7977	Mapping file id2063 NCBI file	EvidenceTAS
GeneNR3C1	AuthorityHGNC:7978	Mapping file id2908 NCBI file	EvidenceTAS
GeneNR3C2	AuthorityHGNC:7979	Mapping file id4306 NCBI file	EvidenceTAS
GeneNR4A1	AuthorityHGNC:7980	Mapping file id3164 NCBI file	EvidenceTAS
GeneNR4A2	AuthorityHGNC:7981	Mapping file id4929 NCBI file	EvidenceTAS
GeneNR4A3	AuthorityHGNC:7982	Mapping file id8013 NCBI file	EvidenceTAS
GeneNR5A1	AuthorityHGNC:7983	Mapping file id2516 NCBI file	EvidenceTAS
GeneNR5A2	AuthorityHGNC:7984	Mapping file id2494 NCBI file	EvidenceTAS
GeneNR6A1	AuthorityHGNC:7985	Mapping file id2649 NCBI file	EvidenceTAS
GeneNRBF2	AuthorityHGNC:19692	Mapping file id29982 NCBI file	EvidenceTAS
GeneNRBP1	AuthorityHGNC:7993	Mapping file id29959 NCBI file	EvidenceTAS
GenePGR	AuthorityHGNC:8910	Mapping file id5241 NCBI file	EvidenceTAS
GenePPARA	AuthorityHGNC:9232	Mapping file id5465 NCBI file	EvidenceTAS
GenePPARD	AuthorityHGNC:9235	Mapping file id5467 NCBI file	EvidenceTAS
GenePPARG	AuthorityHGNC:9236	Mapping file id5468 NCBI file	EvidenceTAS
GeneRARA	AuthorityHGNC:9864	Mapping file id5914 NCBI file	EvidenceTAS
GeneRARB	AuthorityHGNC:9865	Mapping file id5915 NCBI file	EvidenceTAS
GeneRARG	AuthorityHGNC:9866	Mapping file id5916 NCBI file	EvidenceTAS
GeneRORA	AuthorityHGNC:10258	Mapping file id6095 NCBI file	EvidenceTAS
GeneRORB	AuthorityHGNC:10259	Mapping file id6096 NCBI file	EvidenceTAS
GeneRORC	AuthorityHGNC:10260	Mapping file id6097 NCBI file	EvidenceTAS
GeneRXRA	AuthorityHGNC:10477	Mapping file id6256 NCBI file	EvidenceTAS
GeneRXRB	AuthorityHGNC:10478	Mapping file id6257 NCBI file	EvidenceTAS
GeneRXRG	AuthorityHGNC:10479	Mapping file id6258 NCBI file	EvidenceTAS
GeneTHRA	AuthorityHGNC:11796	Mapping file id7067 NCBI file	EvidenceTAS
GeneTHRB	AuthorityHGNC:11799	Mapping file id7068 NCBI file	EvidenceTAS
GeneVDR	AuthorityHGNC:12679	Mapping file id7421 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

Generic Transcription PathwayR-HSA-2124361,251 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.