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 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 4
Gene	Authority id	Mapping file id	Evidence codes
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	EvidenceIEA, TAS
GeneHECW1	AuthorityHGNC:22195	Mapping file id23072 NCBI file	EvidenceTAS
GeneITPR1	AuthorityHGNC:6180	Mapping file id3708 NCBI file	EvidenceIEA
GeneITPR2	AuthorityHGNC:6181	Mapping file id3709 NCBI file	EvidenceIEA
GeneITPR3	AuthorityHGNC:6182	Mapping file id3710 NCBI file	EvidenceIEA
GeneKAT5	AuthorityHGNC:5275	Mapping file id10524 NCBI file	EvidenceIEA, TAS
GeneKLHL12	AuthorityHGNC:19360	Mapping file id59349 NCBI file	EvidenceTAS
GeneKMT2B	AuthorityHGNC:15840	Mapping file id9757 NCBI file	EvidenceTAS
GeneKRAS	AuthorityHGNC:6407	Mapping file id3845 NCBI file	EvidenceTAS
GeneKREMEN1	AuthorityHGNC:17550	Mapping file id83999 NCBI file	EvidenceIEA, TAS
GeneKREMEN2	AuthorityHGNC:18797	Mapping file id79412 NCBI file	EvidenceIEA, TAS
GeneLEF1	AuthorityHGNC:6551	Mapping file id51176 NCBI file	EvidenceIEA, TAS
GeneLEO1	AuthorityHGNC:30401	Mapping file id123169 NCBI file	EvidenceTAS
GeneLGR4	AuthorityHGNC:13299	Mapping file id55366 NCBI file	EvidenceTAS
GeneLGR5	AuthorityHGNC:4504	Mapping file id8549 NCBI file	EvidenceTAS
GeneLGR6	AuthorityHGNC:19719	Mapping file id59352 NCBI file	EvidenceTAS
GeneLRP5	AuthorityHGNC:6697	Mapping file id4041 NCBI file	EvidenceIEA, TAS
GeneLRP6	AuthorityHGNC:6698	Mapping file id4040 NCBI file	EvidenceIEA, TAS
GeneMAP3K7	AuthorityHGNC:6859	Mapping file id6885 NCBI file	EvidenceTAS
GeneMEN1	AuthorityHGNC:7010	Mapping file id4221 NCBI file	EvidenceTAS
GeneMOV10	AuthorityHGNC:7200	Mapping file id4343 NCBI file	EvidenceTAS
GeneMYC	AuthorityHGNC:7553	Mapping file id4609 NCBI file	EvidenceTAS
GeneNFATC1	AuthorityHGNC:7775	Mapping file id4772 NCBI file	EvidenceTAS
GeneNLK	AuthorityHGNC:29858	Mapping file id51701 NCBI file	EvidenceTAS
GenePARD6A	AuthorityHGNC:15943	Mapping file id50855 NCBI file	EvidenceTAS
GenePDE6A	AuthorityHGNC:8785	Mapping file id5145 NCBI file	EvidenceIEA, TAS
GenePDE6B	AuthorityHGNC:8786	Mapping file id5158 NCBI file	EvidenceIEA, TAS
GenePDE6G	AuthorityHGNC:8789	Mapping file id5148 NCBI file	EvidenceIEA, TAS
GenePFN1	AuthorityHGNC:8881	Mapping file id5216 NCBI file	EvidenceTAS
GenePIP5K1B	AuthorityHGNC:8995	Mapping file id8395 NCBI file	EvidenceTAS
GenePLCB1	AuthorityHGNC:15917	Mapping file id23236 NCBI file	EvidenceTAS
GenePLCB2	AuthorityHGNC:9055	Mapping file id5330 NCBI file	EvidenceTAS
GenePLCB3	AuthorityHGNC:9056	Mapping file id5331 NCBI file	EvidenceTAS
GenePORCN	AuthorityHGNC:17652	Mapping file id64840 NCBI file	EvidenceIEA
GenePPP2CA	AuthorityHGNC:9299	Mapping file id5515 NCBI file	EvidenceIEA, TAS
GenePPP2CB	AuthorityHGNC:9300	Mapping file id5516 NCBI file	EvidenceIEA, TAS
GenePPP2R1A	AuthorityHGNC:9302	Mapping file id5518 NCBI file	EvidenceIEA, TAS
GenePPP2R1B	AuthorityHGNC:9303	Mapping file id5519 NCBI file	EvidenceIEA, TAS
GenePPP2R5A	AuthorityHGNC:9309	Mapping file id5525 NCBI file	EvidenceIEA, TAS
GenePPP2R5B	AuthorityHGNC:9310	Mapping file id5526 NCBI file	EvidenceIEA, TAS
GenePPP2R5C	AuthorityHGNC:9311	Mapping file id5527 NCBI file	EvidenceIEA, TAS
GenePPP2R5D	AuthorityHGNC:9312	Mapping file id5528 NCBI file	EvidenceIEA, TAS
GenePPP2R5E	AuthorityHGNC:9313	Mapping file id5529 NCBI file	EvidenceIEA, TAS
GenePPP3CA	AuthorityHGNC:9314	Mapping file id5530 NCBI file	EvidenceTAS
GenePPP3CB	AuthorityHGNC:9315	Mapping file id5532 NCBI file	EvidenceTAS
GenePPP3R1	AuthorityHGNC:9317	Mapping file id5534 NCBI file	EvidenceTAS
GenePRICKLE1	AuthorityHGNC:17019	Mapping file id144165 NCBI file	EvidenceTAS
GenePRKCA	AuthorityHGNC:9393	Mapping file id5578 NCBI file	EvidenceIEA, TAS
GenePRKCB	AuthorityHGNC:9395	Mapping file id5579 NCBI file	EvidenceTAS
GenePRKCG	AuthorityHGNC:9402	Mapping file id5582 NCBI file	EvidenceTAS
GenePRKG1	AuthorityHGNC:9414	Mapping file id5592 NCBI file	EvidenceIEA
GenePRKG2	AuthorityHGNC:9416	Mapping file id5593 NCBI file	EvidenceIEA
GenePSMA1	AuthorityHGNC:9530	Mapping file id5682 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

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.