Pathway Human Homo sapiens

Formation of the beta-catenin:TCF transactivating complex

R-HSA-201722 in Reactome release 97: under TCF dependent signaling in response to WNT, with 93 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: R-MMU-201722 (mouse), R-RNO-201722 (rat). Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

Scripts are off

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-201722.8
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2014-03-12
Last updated: 2018-03-26
Events inside: 10, counted from the record

Once in the nucleus, beta-catenin is recruited to WNT target genes through interaction with TCF/LEF transcription factors. This family, which consists of TCF7 (also known as TCF1), TCF7L1 (also known as TCF3), TCF7L2 (also known as TCF4) and TCF7L3 (also known as LEF1), are HMG-containing transcription factors that bind to the WNT responsive elements in target gene promoters (reviewed in Brantjes et al, 2002). In the absence of WNT signal, TCF/LEF proteins recruit Groucho/TLE repressors to inhibit transcription; upon WNT stimulation, beta-catenin can displace Groucho/TLE from TCF/LEF proteins to initiate transcriptional activation (reviewed in Chen and Courey, 2000). Although this model for WNT-dependent activation of target genes is widely accepted, it is important to note that TCF/LEF proteins are not redundant and can contribute to WNT target gene expression in a number of different ways (reviewed in Brantjes et al, 2002; MacDonald et al, 2009). In particular, TCF7L1 (TCF3) is thought to have a more pronounced repressor function than other TCF/LEF family members. A couple of recent studies in Xenopus and mammalian cells show that WNT- and beta-catenin-dependent phosphorylation of TCF7L1(TCF3) promotes its dissociation from the promoter of target genes and allows gene expression through relief of this repression activity (Hikasa et al, 2010; Hikasa et al, 2011).

The role of beta-catenin at WNT promoters hinges upon its ability to act as a scaffold for the recruitment of other proteins. The structure of beta-catenin consists of 12 imperfect ARM repeats (R1-12) flanked by an N-terminal and C-terminal extension (NTD and CTD respectively), with a conserved Helix C located between R12 and the CTD. Nuclear beta-catenin interacts with TCF/LEF at WNT target genes through ARM domains 3-9 (Graham et al, 2000; Poy et al, 2001; Xing et al, 2008). The N and the C terminal regions are important for the recruitment of transcriptional activator and repressors that contribute to WNT target gene expression (reviewed in Mosimann et al, 2009; Valenta et al, 2012). The N-terminal ARM domains 1-4 recruit the WNT-pathway specific activators BCL9:PYGO while the C-terminal region (R11-CTD) interacts with a wide range of general transcriptional activators that are involved in chromatin remodelling and transcription initiation. These include HATs such as P300, CBP and TIP60, histone methyltransferases such as MLL1 and 2, SWI/SNF factors BRG1 and ISWI and components of the PAF complex (reviewed in Mosimann et al, 2009; Valenta et al, 2012). Although many binding partners have been identified for the C-terminal region of beta-catenin, in many cases the timing and relationship of these interactions and indeed, the exact complex composition remains to be elucidated. Moreover, because many of the interacting partners appear to bind to overlapping regions of beta-catenin, it is unlikely that they all bind simultaneously. For simplicity, the interactions have been depicted as though they occur independently of one another; more accurately they are likely to cycle successively on and off beta-catenin to promote an active chromatin structure (reviewed in Willert and Jones, 2006; Valenta et al, 2012).

Literature Reactome attaches

Beta-catenin hits chromatin: regulation of Wnt target gene activationNat. Rev. Mol. Cell Biol., 2009, vol. 10, p. 276-86PubMed 19305417
The many faces and functions of ?-cateninEMBO J., 2012, vol. 31, p. 2714-36PubMed 22617422
Wnt signaling: is the party in the nucleus?Genes Dev., 2006, vol. 20, p. 1394-404PubMed 16751178
Crystal structure of a beta-catenin/Tcf complexCell, 2000, vol. 103, p. 885-96PubMed 11136974
Structure of a human Tcf4-beta-catenin complexNat Struct Biol, 2001, vol. 8, p. 1053-7PubMed 11713476
Crystal structure of a full-length beta-cateninStructure, 2008, vol. 16, p. 478-87PubMed 18334222
TCF: Lady Justice casting the final verdict on the outcome of Wnt signallingBiol. Chem., 2002, vol. 383, p. 255-61PubMed 11934263

Reactome's record lists 10 orthologous events, R-MMU-201722 (Mus musculus), R-RNO-201722 (Rattus norvegicus) 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 2026-09-30 ET · Reactome pathway browser"Formation of the beta-catenin:TCF transactivating complex". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-201722 with StableID: R-HSA-201722.8 (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 93 genes in this human pathway; showing 1 to 93, 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
GeneASH2L	AuthorityHGNC:744	Mapping file id9070 NCBI file	EvidenceTAS
GeneAXIN2	AuthorityHGNC:904	Mapping file id8313 NCBI file	EvidenceTAS
GeneBCL9	AuthorityHGNC:1008	Mapping file id607 NCBI file	EvidenceTAS
GeneBCL9L	AuthorityHGNC:23688	Mapping file id283149 NCBI file	EvidenceTAS
GeneCDC73	AuthorityHGNC:16783	Mapping file id79577 NCBI file	EvidenceTAS
GeneCREBBP	AuthorityHGNC:2348	Mapping file id1387 NCBI file	EvidenceTAS
GeneCTNNB1	AuthorityHGNC:2514	Mapping file id1499 NCBI file	EvidenceIEA, TAS
GeneDPY30	AuthorityHGNC:24590	Mapping file id84661 NCBI file	EvidenceTAS
GeneEP300	AuthorityHGNC:3373	Mapping file id2033 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	EvidenceTAS
GeneH3-3B	AuthorityHGNC:4765	Mapping file id3021 NCBI file	EvidenceTAS
GeneH3-4	AuthorityHGNC:4778	Mapping file id8290 NCBI file	EvidenceIEA, TAS
GeneH3C1	AuthorityHGNC:4766	Mapping file id8350 NCBI file	EvidenceTAS
GeneH3C10	AuthorityHGNC:4775	Mapping file id8357 NCBI file	EvidenceTAS
GeneH3C11	AuthorityHGNC:4771	Mapping file id8354 NCBI file	EvidenceTAS
GeneH3C12	AuthorityHGNC:4774	Mapping file id8356 NCBI file	EvidenceTAS
GeneH3C13	AuthorityHGNC:25311	Mapping file id653604 NCBI file	EvidenceTAS
GeneH3C14	AuthorityHGNC:20503	Mapping file id126961 NCBI file	EvidenceTAS
GeneH3C15	AuthorityHGNC:20505	Mapping file id333932 NCBI file	EvidenceTAS
GeneH3C2	AuthorityHGNC:4776	Mapping file id8358 NCBI file	EvidenceTAS
GeneH3C3	AuthorityHGNC:4768	Mapping file id8352 NCBI file	EvidenceTAS
GeneH3C4	AuthorityHGNC:4767	Mapping file id8351 NCBI file	EvidenceTAS
GeneH3C6	AuthorityHGNC:4769	Mapping file id8353 NCBI file	EvidenceTAS
GeneH3C7	AuthorityHGNC:4773	Mapping file id8968 NCBI file	EvidenceTAS
GeneH3C8	AuthorityHGNC:4772	Mapping file id8355 NCBI file	EvidenceTAS
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
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
GeneKAT5	AuthorityHGNC:5275	Mapping file id10524 NCBI file	EvidenceIEA, TAS
GeneKMT2B	AuthorityHGNC:15840	Mapping file id9757 NCBI file	EvidenceTAS
GeneLEF1	AuthorityHGNC:6551	Mapping file id51176 NCBI file	EvidenceIEA, TAS
GeneLEO1	AuthorityHGNC:30401	Mapping file id123169 NCBI file	EvidenceTAS
GeneMEN1	AuthorityHGNC:7010	Mapping file id4221 NCBI file	EvidenceTAS
GeneMYC	AuthorityHGNC:7553	Mapping file id4609 NCBI file	EvidenceTAS
GenePYGO1	AuthorityHGNC:30256	Mapping file id26108 NCBI file	EvidenceTAS
GenePYGO2	AuthorityHGNC:30257	Mapping file id90780 NCBI file	EvidenceTAS
GeneRBBP5	AuthorityHGNC:9888	Mapping file id5929 NCBI file	EvidenceTAS
GeneRUNX3	AuthorityHGNC:10473	Mapping file id864 NCBI file	EvidenceTAS
GeneRUVBL1	AuthorityHGNC:10474	Mapping file id8607 NCBI file	EvidenceIEA, TAS
GeneSMARCA4	AuthorityHGNC:11100	Mapping file id6597 NCBI file	EvidenceTAS
GeneTCF4	AuthorityHGNC:11634	Mapping file idENSG00000196628 Ensembl file	EvidenceIEA
GeneTCF7	AuthorityHGNC:11639	Mapping file id6932 NCBI file	EvidenceIEA, TAS
GeneTCF7L1	AuthorityHGNC:11640	Mapping file id83439 NCBI file	EvidenceIEA, TAS
GeneTCF7L2	AuthorityHGNC:11641	Mapping file id6934 NCBI file	EvidenceIEA, TAS
GeneTERT	AuthorityHGNC:11730	Mapping file id7015 NCBI file	EvidenceTAS
GeneTLE1	AuthorityHGNC:11837	Mapping file id7088 NCBI file	EvidenceTAS
GeneTLE2	AuthorityHGNC:11838	Mapping file id7089 NCBI file	EvidenceTAS
GeneTLE3	AuthorityHGNC:11839	Mapping file id7090 NCBI file	EvidenceTAS
GeneTLE4	AuthorityHGNC:11840	Mapping file id7091 NCBI file	EvidenceTAS
GeneTRRAP	AuthorityHGNC:12347	Mapping file id8295 NCBI file	EvidenceIEA, TAS
GeneWDR5	AuthorityHGNC:12757	Mapping file id11091 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

TCF dependent signaling in response to WNTR-HSA-201681222 genes

Children

Binding of TCF/LEF:CTNNB1 to target gene promotersR-HSA-44113648 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.