Pathway Human Homo sapiens

Transcriptional regulation by RUNX1

R-HSA-8878171 in Reactome release 97: under Generic Transcription Pathway, with 225 genes placed in it by the mapping files and 12 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-8878171 (mouse), R-RNO-8878171 (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-8878171.5
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2017-06-12
Last updated: 2023-03-29
Events inside: 12, counted from the record

The RUNX1 (AML1) transcription factor is a master regulator of hematopoiesis (Ichikawa et al. 2004) that is frequently translocated in acute myeloid leukemia (AML), resulting in formation of fusion proteins with altered transactivation profiles (Lam and Zhang 2012, Ichikawa et al. 2013). In addition to RUNX1, its heterodimerization partner CBFB is also frequently mutated in AML (Shigesada et al. 2004, Mangan and Speck 2011).

The core domain of CBFB binds to the Runt domain of RUNX1, resulting in formation of the RUNX1:CBFB heterodimer. CBFB does not interact with DNA directly. The Runt domain of RUNX1 mediated both DNA binding and heterodimerization with CBFB (Tahirov et al. 2001), while RUNX1 regions that flank the Runt domain are involved in transactivation (reviewed in Zhang et al. 2003) and negative regulation (autoinhibition). CBFB facilitates RUNX1 binding to DNA by stabilizing Runt domain regions that interact with the major and minor grooves of the DNA (Tahirov et al. 2001, Backstrom et al. 2002, Bartfeld et al. 2002). The transactivation domain of RUNX1 is located C-terminally to the Runt domain and is followed by the negative regulatory domain. Autoinhibiton of RUNX1 is relieved by interaction with CBFB (Kanno et al. 1998).

Transcriptional targets of the RUNX1:CBFB complex involve genes that regulate self-renewal of hematopoietic stem cells (HSCs) (Zhao et al. 2014), as well as commitment and differentiation of many hematopoietic progenitors, including myeloid (Friedman 2009) and megakaryocytic progenitors (Goldfarb 2009), regulatory T lymphocytes (Wong et al. 2011) and B lymphocytes (Boller and Grosschedl 2014).

RUNX1 binds to promoters of many genes involved in ribosomal biogenesis (Ribi) and is thought to stimulate their transcription. RUNX1 loss-of-function decreases ribosome biogenesis and translation in hematopoietic stem and progenitor cells (HSPCs). RUNX1 loss-of-function is therefore associated with a slow growth, but at the same time it results in reduced apoptosis and increases resistance of cells to genotoxic and endoplasmic reticulum stress, conferring an overall selective advantage to RUNX1 deficient HSPCs (Cai et al. 2015).

RUNX1 is implicated as a tumor suppressor in breast cancer. RUNX1 forms a complex with the activated estrogen receptor alpha (ESR1) and regulates expression of estrogen-responsive genes (Chimge and Frenkel 2013).

RUNX1 is overexpressed in epithelial ovarian carcinoma where it may contribute to cell proliferation, migration and invasion (Keita et al. 2013).

RUNX1 may cooperate with TP53 in transcriptional activation of TP53 target genes upon DNA damage (Wu et al. 2013).

RUNX1 is needed for the maintenance of skeletal musculature (Wang et al. 2005).

During mouse embryonic development, Runx1 is expressed in most nociceptive sensory neurons, which are involved in the perception of pain. In adult mice, Runx1 is expressed only in nociceptive sensory neurons that express the Ret receptor and is involved in regulation of expression of genes encoding ion channels (sodium-gated, ATP-gated and hydrogen ion-gated) and receptors (thermal receptors, opioid receptor MOR and the Mrgpr class of G protein coupled receptors). Mice lacking Runx1 show defective perception of thermal and neuropathic pain (Chen CL et al. 2006). Runx1 is thought to activate the neuronal differentiation of nociceptive dorsal root ganglion cells during embryonal development possibly through repression of Hes1 expression (Kobayashi et al. 2012). In chick and mouse embryos, Runx1 expression is restricted to the dorso-medial domain of the dorsal root ganglion, to TrkA-positive cutaneous sensory neurons. Runx3 expression in chick and mouse embryos is restricted to ventro-lateral domain of the dorsal root ganglion, to TrkC-positive proprioceptive neurons (Chen AI et al. 2006, Kramer et al. 2006). RUNX1 mediated regulation of neuronally expressed genes will be annotated when mechanistic details become available.

Literature Reactome attaches

The RUNX1 transcription factor is expressed in serous epithelial ovarian carcinoma and contributes to cell proliferation, migration and invasionCell Cycle, 2013, vol. 12, p. 972-86PubMed 23442798
Runt-related transcription factor 1 (RUNX1) stimulates tumor suppressor p53 protein in response to DNA damage through complex formation and acetylationJ. Biol. Chem., 2013, vol. 288, p. 1353-64PubMed 23148227
Runx1 prevents wasting, myofibrillar disorganization, and autophagy of skeletal muscleGenes Dev., 2005, vol. 19, p. 1715-22PubMed 16024660
Runx1/AML-1 ranks as a master regulator of adult hematopoiesisCell Cycle, 2004, vol. 3, p. 722-4PubMed 15213471
A role for RUNX1 in hematopoiesis and myeloid leukemiaInt. J. Hematol., 2013, vol. 97, p. 726-34PubMed 23613270
RUNX1 and RUNX1-ETO: roles in hematopoiesis and leukemogenesisFront Biosci (Landmark Ed), 2012, vol. 17, p. 1120-39PubMed 22201794
RUNX1 mutations in clonal myeloid disorders: from conventional cytogenetics to next generation sequencing, a story 40 years in the making

Reactome's record lists 10 orthologous events, R-RNO-8878171 (Rattus norvegicus), R-MMU-8878171 (Mus musculus) among the species this site serves, and 8 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-05 ET · Reactome pathway browser"Transcriptional regulation by RUNX1". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-8878171 with StableID: R-HSA-8878171.5 (accessed 2026-10-05 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 225 genes in this human pathway; showing 101 to 200, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 2 of 3
Gene	Authority id	Mapping file id	Evidence codes
GeneH4C15	AuthorityHGNC:29607	Mapping file id554313 NCBI file	EvidenceIEA, TAS
GeneH4C16	AuthorityHGNC:20510	Mapping file id121504 NCBI file	EvidenceIEA, TAS
GeneH4C2	AuthorityHGNC:4789	Mapping file id8366 NCBI file	EvidenceIEA, TAS
GeneH4C3	AuthorityHGNC:4787	Mapping file id8364 NCBI file	EvidenceIEA, TAS
GeneH4C4	AuthorityHGNC:4782	Mapping file id8360 NCBI file	EvidenceIEA, TAS
GeneH4C5	AuthorityHGNC:4790	Mapping file id8367 NCBI file	EvidenceIEA, TAS
GeneH4C6	AuthorityHGNC:4783	Mapping file id8361 NCBI file	EvidenceIEA, TAS
GeneH4C8	AuthorityHGNC:4788	Mapping file id8365 NCBI file	EvidenceIEA, TAS
GeneH4C9	AuthorityHGNC:4793	Mapping file id8294 NCBI file	EvidenceIEA, TAS
GeneHDAC1	AuthorityHGNC:4852	Mapping file id3065 NCBI file	EvidenceTAS
GeneHIPK2	AuthorityHGNC:14402	Mapping file id28996 NCBI file	EvidenceTAS
GeneIFNG	AuthorityHGNC:5438	Mapping file id3458 NCBI file	EvidenceTAS
GeneIL2	AuthorityHGNC:6001	Mapping file id3558 NCBI file	EvidenceTAS
GeneIL2RA	AuthorityHGNC:6008	Mapping file id3559 NCBI file	EvidenceTAS
GeneIL3	AuthorityHGNC:6011	Mapping file id3562 NCBI file	EvidenceTAS
GeneITCH	AuthorityHGNC:13890	Mapping file id83737 NCBI file	EvidenceTAS
GeneITGA2B	AuthorityHGNC:6138	Mapping file id3674 NCBI file	EvidenceTAS
GeneKAT2B	AuthorityHGNC:8638	Mapping file id8850 NCBI file	EvidenceTAS
GeneKCTD6	AuthorityHGNC:22235	Mapping file id200845 NCBI file	EvidenceTAS
GeneKMT2A	AuthorityHGNC:7132	Mapping file id4297 NCBI file	EvidenceIEA, TAS
GeneKMT2B	AuthorityHGNC:15840	Mapping file id9757 NCBI file	EvidenceTAS
GeneKMT2C	AuthorityHGNC:13726	Mapping file id58508 NCBI file	EvidenceTAS
GeneKMT2D	AuthorityHGNC:7133	Mapping file id8085 NCBI file	EvidenceTAS
GeneLDB1	AuthorityHGNC:6532	Mapping file id8861 NCBI file	EvidenceTAS
GeneLGALS3	AuthorityHGNC:6563	Mapping file id3958 NCBI file	EvidenceTAS
GeneLIFR	AuthorityHGNC:6597	Mapping file id3977 NCBI file	EvidenceTAS
GeneLMO1	AuthorityHGNC:6641	Mapping file id4004 NCBI file	EvidenceTAS
GeneLMO2	AuthorityHGNC:6642	Mapping file id4005 NCBI file	EvidenceTAS
GeneMIR27A	AuthorityHGNC:31613	Mapping file idENSG00000207808 Ensembl file	EvidenceTAS
GeneMNAT1	AuthorityHGNC:7181	Mapping file id4331 NCBI file	EvidenceTAS
GeneMOV10	AuthorityHGNC:7200	Mapping file id4343 NCBI file	EvidenceTAS
GeneMYB	AuthorityHGNC:7545	Mapping file id4602 NCBI file	EvidenceTAS
GeneMYL9	AuthorityHGNC:15754	Mapping file id10398 NCBI file	EvidenceTAS
GeneNFATC2	AuthorityHGNC:7776	Mapping file id4773 NCBI file	EvidenceTAS
GeneNFE2	AuthorityHGNC:7780	Mapping file id4778 NCBI file	EvidenceTAS
GeneNR4A3	AuthorityHGNC:7982	Mapping file id8013 NCBI file	EvidenceTAS
GeneOCLN	AuthorityHGNC:8104	Mapping file id100506658 NCBI file	EvidenceTAS
GenePAX5	AuthorityHGNC:8619	Mapping file id5079 NCBI file	EvidenceTAS
GenePBRM1	AuthorityHGNC:30064	Mapping file id55193 NCBI file	EvidenceTAS
GenePCGF5	AuthorityHGNC:28264	Mapping file id84333 NCBI file	EvidenceTAS
GenePF4	AuthorityHGNC:8861	Mapping file id5196 NCBI file	EvidenceTAS
GenePHC1	AuthorityHGNC:3182	Mapping file id1911 NCBI file	EvidenceTAS
GenePHC2	AuthorityHGNC:3183	Mapping file id1912 NCBI file	EvidenceTAS
GenePHC3	AuthorityHGNC:15682	Mapping file id80012 NCBI file	EvidenceTAS
GenePML	AuthorityHGNC:9113	Mapping file id5371 NCBI file	EvidenceTAS
GenePRKCB	AuthorityHGNC:9395	Mapping file id5579 NCBI file	EvidenceTAS
GenePRKCQ	AuthorityHGNC:9410	Mapping file id5588 NCBI file	EvidenceTAS
GenePRMT1	AuthorityHGNC:5187	Mapping file id3276 NCBI file	EvidenceTAS
GenePRMT6	AuthorityHGNC:18241	Mapping file id55170 NCBI file	EvidenceTAS
GenePSMA1	AuthorityHGNC:9530	Mapping file id5682 NCBI file	EvidenceTAS
GenePSMA2	AuthorityHGNC:9531	Mapping file id5683 NCBI file	EvidenceTAS
GenePSMA3	AuthorityHGNC:9532	Mapping file id5684 NCBI file	EvidenceTAS
GenePSMA4	AuthorityHGNC:9533	Mapping file id5685 NCBI file	EvidenceTAS
GenePSMA5	AuthorityHGNC:9534	Mapping file id5686 NCBI file	EvidenceTAS
GenePSMA6	AuthorityHGNC:9535	Mapping file id5687 NCBI file	EvidenceTAS
GenePSMA7	AuthorityHGNC:9536	Mapping file id5688 NCBI file	EvidenceTAS
GenePSMB1	AuthorityHGNC:9537	Mapping file id5689 NCBI file	EvidenceTAS
GenePSMB2	AuthorityHGNC:9539	Mapping file id5690 NCBI file	EvidenceTAS
GenePSMB3	AuthorityHGNC:9540	Mapping file id5691 NCBI file	EvidenceTAS
GenePSMB4	AuthorityHGNC:9541	Mapping file id5692 NCBI file	EvidenceTAS
GenePSMB5	AuthorityHGNC:9542	Mapping file id5693 NCBI file	EvidenceTAS
GenePSMB6	AuthorityHGNC:9543	Mapping file id5694 NCBI file	EvidenceTAS
GenePSMB7	AuthorityHGNC:9544	Mapping file id5695 NCBI file	EvidenceTAS
GenePSMC1	AuthorityHGNC:9547	Mapping file id5700 NCBI file	EvidenceTAS
GenePSMC2	AuthorityHGNC:9548	Mapping file id5701 NCBI file	EvidenceTAS
GenePSMC3	AuthorityHGNC:9549	Mapping file id5702 NCBI file	EvidenceTAS
GenePSMC4	AuthorityHGNC:9551	Mapping file id5704 NCBI file	EvidenceTAS
GenePSMC5	AuthorityHGNC:9552	Mapping file id5705 NCBI file	EvidenceTAS
GenePSMC6	AuthorityHGNC:9553	Mapping file id5706 NCBI file	EvidenceTAS
GenePSMD1	AuthorityHGNC:9554	Mapping file id5707 NCBI file	EvidenceTAS
GenePSMD11	AuthorityHGNC:9556	Mapping file id5717 NCBI file	EvidenceTAS
GenePSMD12	AuthorityHGNC:9557	Mapping file id5718 NCBI file	EvidenceTAS
GenePSMD13	AuthorityHGNC:9558	Mapping file id5719 NCBI file	EvidenceTAS
GenePSMD14	AuthorityHGNC:16889	Mapping file id10213 NCBI file	EvidenceTAS
GenePSMD2	AuthorityHGNC:9559	Mapping file id5708 NCBI file	EvidenceTAS
GenePSMD3	AuthorityHGNC:9560	Mapping file id5709 NCBI file	EvidenceTAS
GenePSMD6	AuthorityHGNC:9564	Mapping file id9861 NCBI file	EvidenceTAS
GenePSMD7	AuthorityHGNC:9565	Mapping file id5713 NCBI file	EvidenceTAS
GenePSMD8	AuthorityHGNC:9566	Mapping file id5714 NCBI file	EvidenceTAS
GenePTPN11	AuthorityHGNC:9644	Mapping file id5781 NCBI file	EvidenceTAS
GeneRBBP5	AuthorityHGNC:9888	Mapping file id5929 NCBI file	EvidenceTAS
GeneRING1	AuthorityHGNC:10018	Mapping file id6015 NCBI file	EvidenceTAS
GeneRNF2	AuthorityHGNC:10061	Mapping file id6045 NCBI file	EvidenceTAS
GeneRPS27A	AuthorityHGNC:10417	Mapping file id6233 NCBI file	EvidenceTAS
GeneRSPO3	AuthorityHGNC:20866	Mapping file id84870 NCBI file	EvidenceTAS
GeneRUNX1	AuthorityHGNC:10471	Mapping file id861 NCBI file	EvidenceIEA, TAS
GeneRUNX2	AuthorityHGNC:10472	Mapping file id860 NCBI file	EvidenceTAS
GeneRYBP	AuthorityHGNC:10480	Mapping file id23429 NCBI file	EvidenceTAS
GeneSCMH1	AuthorityHGNC:19003	Mapping file id22955 NCBI file	EvidenceTAS
GeneSEM1	AuthorityHGNC:10845	Mapping file id7979 NCBI file	EvidenceTAS
GeneSERPINB13	AuthorityHGNC:8944	Mapping file id5275 NCBI file	EvidenceTAS
GeneSETD1A	AuthorityHGNC:29010	Mapping file id9739 NCBI file	EvidenceTAS
GeneSETD1B	AuthorityHGNC:29187	Mapping file id23067 NCBI file	EvidenceTAS
GeneSIN3A	AuthorityHGNC:19353	Mapping file id25942 NCBI file	EvidenceTAS
GeneSIN3B	AuthorityHGNC:19354	Mapping file id23309 NCBI file	EvidenceTAS
GeneSMARCA2	AuthorityHGNC:11098	Mapping file id6595 NCBI file	EvidenceTAS
GeneSMARCA4	AuthorityHGNC:11100	Mapping file id6597 NCBI file	EvidenceTAS
GeneSMARCB1	AuthorityHGNC:11103	Mapping file id6598 NCBI file	EvidenceTAS
GeneSMARCC1	AuthorityHGNC:11104	Mapping file id6599 NCBI file	EvidenceTAS
GeneSMARCC2	AuthorityHGNC:11105	Mapping file id6601 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

Generic Transcription PathwayR-HSA-2124361,251 genes

Children

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.