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 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 4
Gene	Authority id	Mapping file id	Evidence codes
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
GeneAKT1	AuthorityHGNC:391	Mapping file id207 NCBI file	EvidenceTAS
GeneAKT2	AuthorityHGNC:392	Mapping file id208 NCBI file	EvidenceTAS
GeneAMER1	AuthorityHGNC:26837	Mapping file id139285 NCBI file	EvidenceIEA, TAS
GeneAP2A1	AuthorityHGNC:561	Mapping file id160 NCBI file	EvidenceTAS
GeneAP2A2	AuthorityHGNC:562	Mapping file id161 NCBI file	EvidenceTAS
GeneAP2B1	AuthorityHGNC:563	Mapping file id163 NCBI file	EvidenceTAS
GeneAP2M1	AuthorityHGNC:564	Mapping file id1173 NCBI file	EvidenceTAS
GeneAP2S1	AuthorityHGNC:565	Mapping file id1175 NCBI file	EvidenceTAS
GeneAPC	AuthorityHGNC:583	Mapping file id324 NCBI file	EvidenceIEA, TAS
GeneARRB2	AuthorityHGNC:712	Mapping file id409 NCBI file	EvidenceTAS
GeneASH2L	AuthorityHGNC:744	Mapping file id9070 NCBI file	EvidenceTAS
GeneAXIN1	AuthorityHGNC:903	Mapping file id8312 NCBI file	EvidenceIEA, TAS
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
GeneBTRC	AuthorityHGNC:1144	Mapping file id8945 NCBI file	EvidenceTAS
GeneCALM1	AuthorityHGNC:1442	Mapping file id801 NCBI file	EvidenceTAS
GeneCALM2	AuthorityHGNC:1445	Mapping file id805 NCBI file	EvidenceTAS
GeneCALM3	AuthorityHGNC:1449	Mapping file id808 NCBI file	EvidenceTAS
GeneCAMK2A	AuthorityHGNC:1460	Mapping file id815 NCBI file	EvidenceTAS
GeneCAV1	AuthorityHGNC:1527	Mapping file id857 NCBI file	EvidenceTAS
GeneCBY1	AuthorityHGNC:1307	Mapping file id25776 NCBI file	EvidenceTAS
GeneCCDC88C	AuthorityHGNC:19967	Mapping file id440193 NCBI file	EvidenceIEA
GeneCDC73	AuthorityHGNC:16783	Mapping file id79577 NCBI file	EvidenceTAS
GeneCHD8	AuthorityHGNC:20153	Mapping file id57680 NCBI file	EvidenceTAS
GeneCLTA	AuthorityHGNC:2090	Mapping file id1211 NCBI file	EvidenceTAS
GeneCLTB	AuthorityHGNC:2091	Mapping file id1212 NCBI file	EvidenceTAS
GeneCLTC	AuthorityHGNC:2092	Mapping file id1213 NCBI file	EvidenceTAS
GeneCREBBP	AuthorityHGNC:2348	Mapping file id1387 NCBI file	EvidenceTAS
GeneCSNK1A1	AuthorityHGNC:2451	Mapping file id1452 NCBI file	EvidenceIEA, TAS
GeneCSNK1E	AuthorityHGNC:2453	Mapping file id1454 NCBI file	EvidenceTAS
GeneCSNK1G2	AuthorityHGNC:2455	Mapping file id1455 NCBI file	EvidenceIEA
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
GeneCTBP1	AuthorityHGNC:2494	Mapping file id1487 NCBI file	EvidenceTAS
GeneCTBP2	AuthorityHGNC:2495	Mapping file id1488 NCBI file	EvidenceTAS
GeneCTNNB1	AuthorityHGNC:2514	Mapping file id1499 NCBI file	EvidenceIEA, TAS
GeneCTNNBIP1	AuthorityHGNC:16913	Mapping file id56998 NCBI file	EvidenceTAS
GeneCUL1	AuthorityHGNC:2551	Mapping file id8454 NCBI file	EvidenceTAS
GeneCUL3	AuthorityHGNC:2553	Mapping file id8452 NCBI file	EvidenceTAS
GeneCXXC4	AuthorityHGNC:24593	Mapping file idENSG00000168772 Ensembl file	EvidenceIEA
GeneDAAM1	AuthorityHGNC:18142	Mapping file id23002 NCBI file	EvidenceTAS
GeneDACT1	AuthorityHGNC:17748	Mapping file id51339 NCBI file	EvidenceTAS
GeneDKK1	AuthorityHGNC:2891	Mapping file id22943 NCBI file	EvidenceIEA, TAS
GeneDKK2	AuthorityHGNC:2892	Mapping file id27123 NCBI file	EvidenceIEA, TAS
GeneDKK4	AuthorityHGNC:2894	Mapping file id27121 NCBI file	EvidenceIEA, TAS
GeneDPY30	AuthorityHGNC:24590	Mapping file id84661 NCBI file	EvidenceTAS
GeneDVL1	AuthorityHGNC:3084	Mapping file id1855 NCBI file	EvidenceIEA, TAS
GeneDVL2	AuthorityHGNC:3086	Mapping file id1856 NCBI file	EvidenceIEA, TAS
GeneDVL3	AuthorityHGNC:3087	Mapping file id1857 NCBI file	EvidenceIEA, TAS
GeneEP300	AuthorityHGNC:3373	Mapping file id2033 NCBI file	EvidenceTAS
GeneFRAT1	AuthorityHGNC:3944	Mapping file id10023 NCBI file	EvidenceTAS
GeneFRAT2	AuthorityHGNC:16048	Mapping file id23401 NCBI file	EvidenceTAS
GeneFZD1	AuthorityHGNC:4038	Mapping file id8321 NCBI file	EvidenceIEA, TAS
GeneFZD2	AuthorityHGNC:4040	Mapping file id2535 NCBI file	EvidenceIEA, TAS
GeneFZD3	AuthorityHGNC:4041	Mapping file id7976 NCBI file	EvidenceIEA, TAS
GeneFZD4	AuthorityHGNC:4042	Mapping file id8322 NCBI file	EvidenceIEA, TAS
GeneFZD5	AuthorityHGNC:4043	Mapping file id7855 NCBI file	EvidenceIEA, TAS
GeneFZD6	AuthorityHGNC:4044	Mapping file id8323 NCBI file	EvidenceIEA, TAS
GeneFZD7	AuthorityHGNC:4045	Mapping file id8324 NCBI file	EvidenceIEA, TAS
GeneFZD8	AuthorityHGNC:4046	Mapping file id8325 NCBI file	EvidenceTAS
GeneGNAO1	AuthorityHGNC:4389	Mapping file id2775 NCBI file	EvidenceIEA, TAS
GeneGNAT2	AuthorityHGNC:4394	Mapping file id2780 NCBI file	EvidenceIEA, TAS
GeneGNB1	AuthorityHGNC:4396	Mapping file id2782 NCBI file	EvidenceIEA, TAS
GeneGNB2	AuthorityHGNC:4398	Mapping file id2783 NCBI file	EvidenceIEA, TAS
GeneGNB3	AuthorityHGNC:4400	Mapping file id2784 NCBI file	EvidenceIEA, TAS
GeneGNB4	AuthorityHGNC:20731	Mapping file id59345 NCBI file	EvidenceIEA, TAS
GeneGNB5	AuthorityHGNC:4401	Mapping file id10681 NCBI file	EvidenceIEA, TAS
GeneGNG10	AuthorityHGNC:4402	Mapping file id2790 NCBI file	EvidenceIEA, TAS
GeneGNG11	AuthorityHGNC:4403	Mapping file id2791 NCBI file	EvidenceIEA, TAS
GeneGNG12	AuthorityHGNC:19663	Mapping file id55970 NCBI file	EvidenceIEA, TAS
GeneGNG13	AuthorityHGNC:14131	Mapping file id51764 NCBI file	EvidenceIEA, TAS
GeneGNG2	AuthorityHGNC:4404	Mapping file id54331 NCBI file	EvidenceIEA, TAS
GeneGNG3	AuthorityHGNC:4405	Mapping file id2785 NCBI file	EvidenceIEA, TAS
GeneGNG4	AuthorityHGNC:4407	Mapping file id2786 NCBI file	EvidenceIEA, TAS
GeneGNG5	AuthorityHGNC:4408	Mapping file id2787 NCBI file	EvidenceIEA, TAS
GeneGNG7	AuthorityHGNC:4410	Mapping file id2788 NCBI file	EvidenceIEA, TAS
GeneGNG8	AuthorityHGNC:19664	Mapping file id94235 NCBI file	EvidenceIEA, TAS
GeneGNGT1	AuthorityHGNC:4411	Mapping file id2792 NCBI file	EvidenceIEA, TAS
GeneGNGT2	AuthorityHGNC:4412	Mapping file id2793 NCBI file	EvidenceIEA, TAS
GeneGSK3B	AuthorityHGNC:4617	Mapping file id2932 NCBI file	EvidenceIEA, TAS
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

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.