Pathway Human Homo sapiens

Signaling by WNT

R-HSA-195721 in Reactome release 97: under Signal Transduction, with 321 genes placed in it by the mapping files and 4 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-195721 (mouse), R-RNO-195721 (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-195721.7
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2007-05-15
Last updated: 2019-12-10
Events inside: 4, counted from the record

WNT signaling pathways control a wide range of developmental and adult process in metozoans including cell proliferation, cell fate decisions, cell polarity and stem cell maintenance (reviewed in Saito-Diaz et al, 2013; MacDonald et al, 2009). The pathway is named for the WNT ligands, a large family of secreted cysteine-rich glycoproteins. At least 19 WNT members have been identified in humans and mice with distinct expression patterns during development (reviewed in Willert and Nusse, 2012). These ligands can activate at least three different downstream signaling cascades depending on which receptors they engage.

In the so-called 'canonical' WNT signaling pathway, WNT ligands bind one of the 10 human Frizzled (FZD) receptors in conjunction with the LRP5/6 co-receptors to activate a transcriptional cascade that controls processes such as cell fate, proliferation and self-renenwal of stem cells. Engagement of the FZD-LRP receptor by WNT ligand results in the stabilization and translocation of cytosolic beta-catenin to the nucleus where it is a co-activator for LEF (lymphoid enhancer-binding factor)- and TCF (T cell factor) -dependent transcription. In the absence of WNT ligand, cytosolic beta-catenin is phosphorylated by a degradation complex consisting of glycogen synthase kinase 3 (GSK3), casein kinase 1 (CK1), Axin and Adenomatous polyposis coli (APC), and subsequently ubiquitinated and degraded by the 26S proteasome (reviewed in Saito-Diaz et al, 2013; Kimmelman and Xu, 2006).

In addition to the beta-catenin-dependent transcriptional response, WNT signaling can also activate distinct non-transcriptional pathways that regulate cell migration and polarity. These beta-catenin-independent 'non-canonical' pathways signal through Frizzled receptors independently of LRP5/6, or occur through the tyrosine kinase receptors ROR and RYK (reviewed in Veeman et al, 2003; James et al, 2009). Non-canonical WNT pathways are best studied in Drosophila where the planar cell polarity (PCP) pathway controls the orientation of wing hairs and eye facets, but are also involved in processes such as convergent extension, neural tube closure, inner ear development and hair orientation in vertebrates and mammals(reviewed in Seifert and Mlodzik, 2007; Simons and Mlodzik, 2008). In the PCP pathway, binding of WNT ligand to the FZD receptor leads to activation of small Rho GTPases and JNK, which regulate the cytoskeleton and coordinate cell migration and polarity (reviewed in Lai et al, 2009; Schlessinger et al, 2009). In some cases, a FZD-WNT interaction increases intracellular calcium concentration and activates CaMK II and PKC; this WNT calcium pathway promotes cell migration and inhibits the canonical beta-catenin dependent transcriptional pathway (reviewed in Kuhl et al, 2000; Kohn and Moon, 2005; Rao et al 2010). Binding of WNT to ROR or RYK receptors also regulates cell migration, apparently through activation of JNK or SRC kinases, respectively, however the details of these pathways remain to be worked out (reviewed in Minami et al, 2010).

Although the WNT signaling pathways were originally viewed as discrete, linear pathways controlled by defined subsets of 'canonical' or 'non-canonical' ligands and receptors, the emerging evidence is challenging this notion. Instead, the specificity and the downstream response appear to depend on the particular cellular context and vary with species, tissue and stage of development (reviewed in van Amerongen and Nusse, 2009; Rao et al, 2010).

Literature Reactome attaches

beta-catenin destruction complex: insights and questions from a structural perspectiveOncogene, 2006, vol. 25, p. 7482-91PubMed 17143292
Wnt/beta-catenin signaling: components, mechanisms, and diseasesDev Cell, 2009, vol. 17, p. 9-26PubMed 19619488
The way Wnt works: Components and mechanismGrowth Factors, 2013, vol. 31, p. 1-31PubMed 23256519
Wnt proteinsCold Spring Harb Perspect Biol, 2012, vol. 4, p. a007864PubMed 22952392
Frizzled/PCP signalling: a conserved mechanism regulating cell polarity and directed motilityNat Rev Genet, 2007, vol. 8, p. 126-38PubMed 17230199
The Wnt/Ca2+ pathway: a new vertebrate Wnt signaling pathway takes shapeTrends Genet., 2000, vol. 16, p. 279-83PubMed 10858654
Wnt and calcium signaling: beta-catenin-independent pathwaysCell Calcium, 2005, vol. 38, p. 439-46PubMed 16099039

Reactome's record lists 14 orthologous events, R-MMU-195721 (Mus musculus), R-RNO-195721 (Rattus norvegicus) among the species this site serves, and 12 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-01 ET · Reactome pathway browser"Signaling by WNT". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-195721 with StableID: R-HSA-195721.7 (accessed 2026-10-01 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 321 genes in this human pathway; showing 201 to 300, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 3 of 4
Gene	Authority id	Mapping file id	Evidence codes
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
GenePYGO1	AuthorityHGNC:30256	Mapping file id26108 NCBI file	EvidenceTAS
GenePYGO2	AuthorityHGNC:30257	Mapping file id90780 NCBI file	EvidenceTAS
GeneRAC1	AuthorityHGNC:9801	Mapping file id5879 NCBI file	EvidenceTAS
GeneRAC2	AuthorityHGNC:9802	Mapping file id5880 NCBI file	EvidenceTAS
GeneRAC3	AuthorityHGNC:9803	Mapping file id5881 NCBI file	EvidenceTAS
GeneRBBP5	AuthorityHGNC:9888	Mapping file id5929 NCBI file	EvidenceTAS
GeneRBX1	AuthorityHGNC:9928	Mapping file id9978 NCBI file	EvidenceTAS
GeneRHOA	AuthorityHGNC:667	Mapping file id387 NCBI file	EvidenceTAS
GeneRNF146	AuthorityHGNC:21336	Mapping file id81847 NCBI file	EvidenceTAS
GeneRNF43	AuthorityHGNC:18505	Mapping file id54894 NCBI file	EvidenceTAS
GeneROR1	AuthorityHGNC:10256	Mapping file id4919 NCBI file	EvidenceTAS
GeneROR2	AuthorityHGNC:10257	Mapping file id4920 NCBI file	EvidenceIEA, TAS
GeneRPS27A	AuthorityHGNC:10417	Mapping file id6233 NCBI file	EvidenceTAS
GeneRSPO1	AuthorityHGNC:21679	Mapping file id284654 NCBI file	EvidenceTAS
GeneRSPO2	AuthorityHGNC:28583	Mapping file id340419 NCBI file	EvidenceTAS
GeneRSPO3	AuthorityHGNC:20866	Mapping file id84870 NCBI file	EvidenceTAS
GeneRSPO4	AuthorityHGNC:16175	Mapping file id343637 NCBI file	EvidenceTAS
GeneRUNX3	AuthorityHGNC:10473	Mapping file id864 NCBI file	EvidenceTAS
GeneRUVBL1	AuthorityHGNC:10474	Mapping file id8607 NCBI file	EvidenceIEA, TAS
GeneRYK	AuthorityHGNC:10481	Mapping file id6259 NCBI file	EvidenceIEA, TAS
GeneSCRIB	AuthorityHGNC:30377	Mapping file id23513 NCBI file	EvidenceIEA
GeneSEM1	AuthorityHGNC:10845	Mapping file id7979 NCBI file	EvidenceTAS
GeneSFRP1	AuthorityHGNC:10776	Mapping file id6422 NCBI file	EvidenceIEA
GeneSFRP2	AuthorityHGNC:10777	Mapping file id6423 NCBI file	EvidenceIEA
GeneSKP1	AuthorityHGNC:10899	Mapping file id6500 NCBI file	EvidenceTAS
GeneSMARCA4	AuthorityHGNC:11100	Mapping file id6597 NCBI file	EvidenceTAS
GeneSMURF1	AuthorityHGNC:16807	Mapping file id57154 NCBI file	EvidenceTAS
GeneSMURF2	AuthorityHGNC:16809	Mapping file id64750 NCBI file	EvidenceTAS
GeneSNX3	AuthorityHGNC:11174	Mapping file id8724 NCBI file	EvidenceTAS
GeneSOST	AuthorityHGNC:13771	Mapping file id50964 NCBI file	EvidenceIEA, TAS
GeneSOX13	AuthorityHGNC:11192	Mapping file id9580 NCBI file	EvidenceTAS
GeneSOX17	AuthorityHGNC:18122	Mapping file id64321 NCBI file	EvidenceTAS
GeneSOX2	AuthorityHGNC:11195	Mapping file id6657 NCBI file	EvidenceTAS
GeneSOX3	AuthorityHGNC:11199	Mapping file id6658 NCBI file	EvidenceTAS
GeneSOX4	AuthorityHGNC:11200	Mapping file id6659 NCBI file	EvidenceTAS
GeneSOX6	AuthorityHGNC:16421	Mapping file id55553 NCBI file	EvidenceTAS
GeneSOX7	AuthorityHGNC:18196	Mapping file id83595 NCBI file	EvidenceTAS
GeneSOX9	AuthorityHGNC:11204	Mapping file id6662 NCBI file	EvidenceTAS
GeneSRY	AuthorityHGNC:11311	Mapping file id6736 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	EvidenceIEA, TAS
GeneTLE2	AuthorityHGNC:11838	Mapping file id7089 NCBI file	EvidenceIEA, TAS
GeneTLE3	AuthorityHGNC:11839	Mapping file id7090 NCBI file	EvidenceIEA, TAS
GeneTLE4	AuthorityHGNC:11840	Mapping file id7091 NCBI file	EvidenceIEA, TAS
GeneTLE5	AuthorityHGNC:307	Mapping file id166 NCBI file	EvidenceIEA
GeneTMED5	AuthorityHGNC:24251	Mapping file id50999 NCBI file	EvidenceTAS
GeneTNKS	AuthorityHGNC:11941	Mapping file id8658 NCBI file	EvidenceTAS
GeneTNKS2	AuthorityHGNC:15677	Mapping file id80351 NCBI file	EvidenceTAS
GeneTNRC6A	AuthorityHGNC:11969	Mapping file id27327 NCBI file	EvidenceTAS
GeneTNRC6B	AuthorityHGNC:29190	Mapping file id23112 NCBI file	EvidenceTAS
GeneTNRC6C	AuthorityHGNC:29318	Mapping file id57690 NCBI file	EvidenceTAS
GeneTRRAP	AuthorityHGNC:12347	Mapping file id8295 NCBI file	EvidenceIEA, TAS
GeneUBA52	AuthorityHGNC:12458	Mapping file id7311 NCBI file	EvidenceTAS
GeneUBB	AuthorityHGNC:12463	Mapping file id7314 NCBI file	EvidenceTAS
GeneUBC	AuthorityHGNC:12468	Mapping file id7316 NCBI file	EvidenceTAS
GeneUSP34	AuthorityHGNC:20066	Mapping file id9736 NCBI file	EvidenceTAS
GeneUSP8	AuthorityHGNC:12631	Mapping file id9101 NCBI file	EvidenceTAS
GeneVANGL2	AuthorityHGNC:15511	Mapping file id57216 NCBI file	EvidenceIEA
GeneVPS26A	AuthorityHGNC:12711	Mapping file id9559 NCBI file	EvidenceTAS
GeneVPS29	AuthorityHGNC:14340	Mapping file id51699 NCBI file	EvidenceTAS
GeneVPS35	AuthorityHGNC:13487	Mapping file id55737 NCBI file	EvidenceTAS
GeneWDR5	AuthorityHGNC:12757	Mapping file id11091 NCBI file	EvidenceTAS
GeneWIF1	AuthorityHGNC:18081	Mapping file id11197 NCBI file	EvidenceIEA
GeneWLS	AuthorityHGNC:30238	Mapping file id79971 NCBI file	EvidenceTAS
GeneWNT1	AuthorityHGNC:12774	Mapping file id7471 NCBI file	EvidenceIEA, TAS
GeneWNT10A	AuthorityHGNC:13829	Mapping file id80326 NCBI file	EvidenceIEA, TAS
GeneWNT10B	AuthorityHGNC:12775	Mapping file id7480 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

Signal TransductionR-HSA-1625822,631 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.