Pathway Human Homo sapiens

Transcriptional regulation of brown and beige adipocyte differentiation

R-HSA-9843743 in Reactome release 97: under Adipogenesis, with 31 genes placed in it by the mapping files and 1 child pathway 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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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-9843743.1
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2024-03-27
Events inside: 1, counted from the record

Brown and beige adipocytes convert chemical energy produced by the oxidation of fatty acids and glucose into heat, which is important for thermoregulation and control of body weight. Brown and beige adipocytes largely share the transcription program involved in adaptive non-shivering thermogenesis but develop from different lineages (reviewed in Wang and Seale 2016, Ghaben and Scherer 2019). Brown adipocytes share their precursor cells with skeletal muscle cells and develop in discrete, homogeneous brown adipose tissue depots. Beige adipocytes share their precursor cells with white adipocytes and develop in white adipose tissue in response to environmental stimuli, mainly exposure to cold, with an ability to revert to a white adipocyte-like phenotype. Development of beige adipocytes in white adipose tissue is known as white adipose tissue browning (reviewed in Wang and Seale 2016).

Brown and beige adipocytes have been characterized in most detail in rodents. In humans, brown adipose tissue was thought to regress after infancy, but was shown by multiple studies published after 2007 to persist in substantial deposits into adulthood adulthood (reviewed in Bartlet and Heeren 2014, Wang and Seale 2016, Ghaben and Scherer 2019, and Cannon et al. 2020). Molecular profiles that correspond to both brown and beige rodent adipocytes have been identified in human brown-designated adipose tissue, and therefore both brown and beige adipocytes are now thought to be conserved in humans (Nedergaard et al. 2007; Virtanen et al. 2009; Cypess et al. 2009; Sharp et al. 2012; Wu et al. 2012; Nedergaard and Cannon 2013; de Jong et al. 2019; reviewed in Bartlet and Heereb 2014, Wang and Seale 2016, and Cannon et al. 2020).

The major protein marker of brown and beige adipocytes is Uncoupling protein 1 (UCP1). UCP1 resides at the inner mitochondrial membrane where it translocates protons (H+) from the intermembrane space into the mitochondrial matrix. UCP1 thus dissipates the proton-motive force to be used by ATP synthase, converting the energy released by the respiratory chain into heat (reviewed in Bartlet and Heereb 2014, Wang and Seale 2016). Brown adipose tissue is innervated by the sympathetic nervous system. Noradrenaline is secreted by sympathetic neurons when the central nervous system senses cold. Brown adipocytes possess adrenergic receptors on their surface that are activated by noradrenaline. Activated adrenergic receptors trigger a signaling cascade that induces lipolysis and activates UCP1 (reviewed in Wang and Seale 2016).

Multiple transcription factors that regulate the thermogenic molecular signature are shared between brown and beige adipocytes, such as EBF2, PRDM16, ZNF516, and PPARGC1A. Master regulators of adipogenesis, such as PPARG and CEBPB, are shared between white, brown, and beige adipocytes (reviewed in Wang and Seale 2016).

Besides its role in thermoregulation, white adipose tissue browning is implicated in cancer-associated cachexia, a complex tissue-wasting syndrome characterized by inflammation, hypermetabolism, increased energy expenditure, and anorexia (reviewed in Weber et al. 2022).

For review, please refer to Bartelt and Heeren 2014, Wang and Seale 2016, Ghaben and Scherer 2019, Cannon et al. 2020, Weber et al. 2022.

Literature Reactome attaches

Control of brown and beige fat developmentNat Rev Mol Cell Biol, 2016, vol. 17, p. 691-702PubMed 27552974
Metabolic Reprogramming in Adipose Tissue During Cancer CachexiaFront Oncol, 2022, vol. 12, p. 848394PubMed 35646636
Adipose tissue browning and metabolic healthNat Rev Endocrinol, 2014, vol. 10, p. 24-36PubMed 24146030
Human brown adipose tissue: Classical brown rather than brite/beige?Exp Physiol, 2020, vol. 105, p. 1191-1200PubMed 32378255
Adipogenesis and metabolic healthNat Rev Mol Cell Biol, 2019, vol. 20, p. 242-258PubMed 30610207
Functional brown adipose tissue in healthy adultsN Engl J Med, 2009, vol. 360, p. 1518-25PubMed 19357407
Unexpected evidence for active brown adipose tissue in adult humansAm J Physiol Endocrinol Metab, 2007, vol. 293, p. E444-52PubMed 17473055

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-02 ET · Reactome pathway browser"Transcriptional regulation of brown and beige adipocyte differentiation". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-9843743 with StableID: R-HSA-9843743.1 (accessed 2026-10-02 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 31 genes in this human pathway; showing 1 to 31, in pages of 100, sorted by symbol for reading. The order carries no ranking. 1 of the rows shown carries an id the identity file does not name, kept as the source wrote it.

Genes Reactome places in this human pathway, page 1 of 1
Gene	Authority id	Mapping file id	Evidence codes
GeneBMP7	AuthorityHGNC:1074	Mapping file id655 NCBI file	EvidenceIEA
GeneCHD3	AuthorityHGNC:1918	Mapping file id1107 NCBI file	EvidenceIEA
GeneCHD4	AuthorityHGNC:1919	Mapping file id1108 NCBI file	EvidenceIEA
GeneCIDEA	AuthorityHGNC:1976	Mapping file id1149 NCBI file	EvidenceIEA
GeneCOX7A1	AuthorityHGNC:2287	Mapping file id1346 NCBI file	EvidenceIEA
GeneDIO2	AuthorityHGNC:2884	Mapping file idENSG00000211448 Ensembl file	EvidenceIEA
GeneEBF2	AuthorityHGNC:19090	Mapping file id64641 NCBI file	EvidenceIEA
GeneELOVL3	AuthorityHGNC:18047	Mapping file id83401 NCBI file	EvidenceIEA
GeneGATAD2A	AuthorityHGNC:29989	Mapping file id54815 NCBI file	EvidenceIEA
GeneGATAD2B	AuthorityHGNC:30778	Mapping file id57459 NCBI file	EvidenceIEA
GeneHDAC1	AuthorityHGNC:4852	Mapping file id3065 NCBI file	EvidenceIEA
GeneHDAC2	AuthorityHGNC:4853	Mapping file id3066 NCBI file	EvidenceIEA
GeneHNRNPU	AuthorityHGNC:5048	Mapping file id3192 NCBI file	EvidenceIEA
GeneMBD3	AuthorityHGNC:6918	Mapping file id53615 NCBI file	EvidenceIEA
GeneMTA1	AuthorityHGNC:7410	Mapping file id9112 NCBI file	EvidenceIEA
GeneMTA2	AuthorityHGNC:7411	Mapping file id9219 NCBI file	EvidenceIEA
GeneMTA3	AuthorityHGNC:23784	Mapping file id57504 NCBI file	EvidenceIEA
GeneNCOA1	AuthorityHGNC:7668	Mapping file id8648 NCBI file	EvidenceIEA
GenePPARA	AuthorityHGNC:9232	Mapping file id5465 NCBI file	EvidenceIEA
GenePPARG	AuthorityHGNC:9236	Mapping file id5468 NCBI file	EvidenceIEA
GenePPARGC1A	AuthorityHGNC:9237	Mapping file id10891 NCBI file	EvidenceIEA
GenePPARGC1B	AuthorityHGNC:30022	Mapping file id133522 NCBI file	EvidenceIEA
GenePRDM16	AuthorityHGNC:14000	Mapping file id63976 NCBI file	EvidenceIEA
GeneRBBP4	AuthorityHGNC:9887	Mapping file id5928 NCBI file	EvidenceIEA
GeneRBBP7	AuthorityHGNC:9890	Mapping file id5931 NCBI file	EvidenceIEA
GeneRXRA	AuthorityHGNC:10477	Mapping file id6256 NCBI file	EvidenceIEA
GeneSMAD1	AuthorityHGNC:6767	Mapping file id4086 NCBI file	EvidenceIEA
GeneSMAD4	AuthorityHGNC:6770	Mapping file id4089 NCBI file	EvidenceIEA
GeneUCP1	AuthorityHGNC:12517	Mapping file id7350 NCBI file	EvidenceIEA
GeneZNF423	AuthorityHGNC:16762	Mapping file id23090 NCBI file	EvidenceIEA
Geneno symbol in the identity file	Authoritynone	Mapping file idMG736819 as written	EvidenceIEA

Evidence codes on this page: IEA, 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

AdipogenesisR-HSA-9843745110 genes

Children

Transcriptional regulation of brown and beige adipocyte differentiation by EBF2R-HSA-984459431 genes

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.