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 2026-10-03 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 2026-10-03 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 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 3
Gene	Authority id	Mapping file id	Evidence codes
GeneABL1	AuthorityHGNC:76	Mapping file id25 NCBI file	EvidenceTAS
GeneACTL6A	AuthorityHGNC:24124	Mapping file id86 NCBI file	EvidenceTAS
GeneACTL6B	AuthorityHGNC:160	Mapping file id51412 NCBI file	EvidenceTAS
GeneADRM1	AuthorityHGNC:15759	Mapping file id11047 NCBI file	EvidenceTAS
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
GeneARID1A	AuthorityHGNC:11110	Mapping file id8289 NCBI file	EvidenceTAS
GeneARID1B	AuthorityHGNC:18040	Mapping file id57492 NCBI file	EvidenceTAS
GeneARID2	AuthorityHGNC:18037	Mapping file id196528 NCBI file	EvidenceTAS
GeneASH2L	AuthorityHGNC:744	Mapping file id9070 NCBI file	EvidenceTAS
GeneAUTS2	AuthorityHGNC:14262	Mapping file id26053 NCBI file	EvidenceTAS
GeneAXIN1	AuthorityHGNC:903	Mapping file id8312 NCBI file	EvidenceTAS
GeneBLK	AuthorityHGNC:1057	Mapping file id640 NCBI file	EvidenceTAS
GeneBMI1	AuthorityHGNC:1066	Mapping file id648 NCBI file	EvidenceTAS
GeneCBFB	AuthorityHGNC:1539	Mapping file id865 NCBI file	EvidenceIEA, TAS
GeneCBX2	AuthorityHGNC:1552	Mapping file id84733 NCBI file	EvidenceTAS
GeneCBX4	AuthorityHGNC:1554	Mapping file id8535 NCBI file	EvidenceTAS
GeneCBX6	AuthorityHGNC:1556	Mapping file id23466 NCBI file	EvidenceTAS
GeneCBX8	AuthorityHGNC:15962	Mapping file id57332 NCBI file	EvidenceTAS
GeneCCND1	AuthorityHGNC:1582	Mapping file id595 NCBI file	EvidenceTAS
GeneCCND2	AuthorityHGNC:1583	Mapping file id894 NCBI file	EvidenceTAS
GeneCCND3	AuthorityHGNC:1585	Mapping file id896 NCBI file	EvidenceTAS
GeneCCNH	AuthorityHGNC:1594	Mapping file id902 NCBI file	EvidenceTAS
GeneCDK6	AuthorityHGNC:1777	Mapping file id1021 NCBI file	EvidenceTAS
GeneCDK7	AuthorityHGNC:1778	Mapping file id1022 NCBI file	EvidenceTAS
GeneCLDN5	AuthorityHGNC:2047	Mapping file id7122 NCBI file	EvidenceTAS
GeneCOMMD3-BMI1	AuthorityHGNC:48326	Mapping file id100532731 NCBI file	EvidenceTAS
GeneCR1	AuthorityHGNC:2334	Mapping file id1378 NCBI file	EvidenceTAS
GeneCREBBP	AuthorityHGNC:2348	Mapping file id1387 NCBI file	EvidenceTAS
GeneCSF2	AuthorityHGNC:2434	Mapping file id1437 NCBI file	EvidenceTAS
GeneCSNK2A1	AuthorityHGNC:2457	Mapping file id1457 NCBI file	EvidenceTAS
GeneCSNK2A2	AuthorityHGNC:2459	Mapping file id1459 NCBI file	EvidenceTAS
GeneCSNK2B	AuthorityHGNC:2460	Mapping file id1460 NCBI file	EvidenceTAS
GeneCTLA4	AuthorityHGNC:2505	Mapping file id1493 NCBI file	EvidenceTAS
GeneCTSK	AuthorityHGNC:2536	Mapping file id1513 NCBI file	EvidenceTAS
GeneCTSL	AuthorityHGNC:2537	Mapping file id1514 NCBI file	EvidenceTAS
GeneCTSV	AuthorityHGNC:2538	Mapping file id1515 NCBI file	EvidenceTAS
GeneDPY30	AuthorityHGNC:24590	Mapping file id84661 NCBI file	EvidenceTAS
GeneELF1	AuthorityHGNC:3316	Mapping file id1997 NCBI file	EvidenceTAS
GeneELF2	AuthorityHGNC:3317	Mapping file id1998 NCBI file	EvidenceTAS
GeneEP300	AuthorityHGNC:3373	Mapping file id2033 NCBI file	EvidenceTAS
GeneESR1	AuthorityHGNC:3467	Mapping file id2099 NCBI file	EvidenceTAS
GeneFOXP3	AuthorityHGNC:6106	Mapping file id50943 NCBI file	EvidenceTAS
GeneGATA1	AuthorityHGNC:4170	Mapping file id2623 NCBI file	EvidenceTAS
GeneGATA2	AuthorityHGNC:4171	Mapping file id2624 NCBI file	EvidenceTAS
GeneGATA3	AuthorityHGNC:4172	Mapping file id2625 NCBI file	EvidenceTAS
GeneGP1BA	AuthorityHGNC:4439	Mapping file id2811 NCBI file	EvidenceTAS
GeneGPAM	AuthorityHGNC:24865	Mapping file id57678 NCBI file	EvidenceTAS
GeneH2AB1	AuthorityHGNC:22516	Mapping file id474382 NCBI file	EvidenceIEA, TAS
GeneH2AC14	AuthorityHGNC:4727	Mapping file id8331 NCBI file	EvidenceIEA, TAS
GeneH2AC18	AuthorityHGNC:4736	Mapping file id8337 NCBI file	EvidenceIEA, TAS
GeneH2AC19	AuthorityHGNC:29668	Mapping file id723790 NCBI file	EvidenceIEA, TAS
GeneH2AC20	AuthorityHGNC:4738	Mapping file id8338 NCBI file	EvidenceIEA, TAS
GeneH2AC4	AuthorityHGNC:4734	Mapping file id8335 NCBI file	EvidenceIEA, TAS
GeneH2AC6	AuthorityHGNC:4733	Mapping file id8334 NCBI file	EvidenceIEA, TAS
GeneH2AC7	AuthorityHGNC:4729	Mapping file id3013 NCBI file	EvidenceIEA, TAS
GeneH2AC8	AuthorityHGNC:4724	Mapping file id3012 NCBI file	EvidenceIEA, TAS
GeneH2AJ	AuthorityHGNC:14456	Mapping file id55766 NCBI file	EvidenceIEA, TAS
GeneH2AX	AuthorityHGNC:4739	Mapping file id3014 NCBI file	EvidenceIEA, TAS
GeneH2AZ2	AuthorityHGNC:20664	Mapping file id94239 NCBI file	EvidenceIEA, TAS
GeneH2BC1	AuthorityHGNC:18730	Mapping file id255626 NCBI file	EvidenceIEA, TAS
GeneH2BC10	AuthorityHGNC:4756	Mapping file id8346 NCBI file	EvidenceIEA, TAS
GeneH2BC11	AuthorityHGNC:4761	Mapping file id8970 NCBI file	EvidenceIEA, TAS
GeneH2BC12	AuthorityHGNC:13954	Mapping file id85236 NCBI file	EvidenceIEA, TAS
GeneH2BC12L	AuthorityHGNC:4762	Mapping file id54145 NCBI file	EvidenceIEA, TAS
GeneH2BC13	AuthorityHGNC:4748	Mapping file id8340 NCBI file	EvidenceIEA, TAS
GeneH2BC14	AuthorityHGNC:4750	Mapping file id8342 NCBI file	EvidenceIEA, TAS
GeneH2BC15	AuthorityHGNC:4749	Mapping file id8341 NCBI file	EvidenceIEA, TAS
GeneH2BC17	AuthorityHGNC:4758	Mapping file id8348 NCBI file	EvidenceIEA, TAS
GeneH2BC21	AuthorityHGNC:4760	Mapping file id8349 NCBI file	EvidenceIEA, TAS
GeneH2BC26	AuthorityHGNC:20514	Mapping file id128312 NCBI file	EvidenceIEA, TAS
GeneH2BC3	AuthorityHGNC:4751	Mapping file id3018 NCBI file	EvidenceIEA, TAS
GeneH2BC4	AuthorityHGNC:4757	Mapping file id8347 NCBI file	EvidenceIEA, TAS
GeneH2BC5	AuthorityHGNC:4747	Mapping file id3017 NCBI file	EvidenceIEA, TAS
GeneH2BC6	AuthorityHGNC:4753	Mapping file id8344 NCBI file	EvidenceIEA, TAS
GeneH2BC7	AuthorityHGNC:4752	Mapping file id8343 NCBI file	EvidenceIEA, TAS
GeneH2BC8	AuthorityHGNC:4746	Mapping file id8339 NCBI file	EvidenceIEA, TAS
GeneH2BC9	AuthorityHGNC:4755	Mapping file id8345 NCBI file	EvidenceIEA, TAS
GeneH3-3A	AuthorityHGNC:4764	Mapping file id3020 NCBI file	EvidenceIEA, TAS
GeneH3-3B	AuthorityHGNC:4765	Mapping file id3021 NCBI file	EvidenceIEA, TAS
GeneH3C1	AuthorityHGNC:4766	Mapping file id8350 NCBI file	EvidenceIEA, TAS
GeneH3C10	AuthorityHGNC:4775	Mapping file id8357 NCBI file	EvidenceIEA, TAS
GeneH3C11	AuthorityHGNC:4771	Mapping file id8354 NCBI file	EvidenceIEA, TAS
GeneH3C12	AuthorityHGNC:4774	Mapping file id8356 NCBI file	EvidenceIEA, TAS
GeneH3C13	AuthorityHGNC:25311	Mapping file id653604 NCBI file	EvidenceIEA, TAS
GeneH3C14	AuthorityHGNC:20503	Mapping file id126961 NCBI file	EvidenceIEA, TAS
GeneH3C15	AuthorityHGNC:20505	Mapping file id333932 NCBI file	EvidenceIEA, TAS
GeneH3C2	AuthorityHGNC:4776	Mapping file id8358 NCBI file	EvidenceIEA, TAS
GeneH3C3	AuthorityHGNC:4768	Mapping file id8352 NCBI file	EvidenceIEA, TAS
GeneH3C4	AuthorityHGNC:4767	Mapping file id8351 NCBI file	EvidenceIEA, TAS
GeneH3C6	AuthorityHGNC:4769	Mapping file id8353 NCBI file	EvidenceIEA, TAS
GeneH3C7	AuthorityHGNC:4773	Mapping file id8968 NCBI file	EvidenceIEA, TAS
GeneH3C8	AuthorityHGNC:4772	Mapping file id8355 NCBI file	EvidenceIEA, TAS
GeneH4C1	AuthorityHGNC:4781	Mapping file id8359 NCBI file	EvidenceIEA, TAS
GeneH4C11	AuthorityHGNC:4785	Mapping file id8363 NCBI file	EvidenceIEA, TAS
GeneH4C12	AuthorityHGNC:4784	Mapping file id8362 NCBI file	EvidenceIEA, TAS
GeneH4C13	AuthorityHGNC:4791	Mapping file id8368 NCBI file	EvidenceIEA, TAS
GeneH4C14	AuthorityHGNC:4794	Mapping file id8370 NCBI file	EvidenceIEA, TAS

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.