Pathway Human Homo sapiens

WNT ligand biogenesis and trafficking

R-HSA-3238698 in Reactome release 97: under Signaling by WNT, with 26 genes placed in it by the mapping files and 0 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-3238698 (mouse), R-RNO-3238698 (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-3238698.3
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2013-06-11
Last updated: 2015-07-02
Events inside: 12, counted from the record

19 WNT proteins have been identified in human cells. The WNTs are members of a conserved metazoan family of secreted morphogens that activate several signaling pathways in the responding cell: the canonical (beta-catenin) WNT signaling cascade and several non-canonical pathways, including the planar cell polarity (PCP), the regulation of intracellular calcium signaling and activation of JNK kinases. WNT proteins exist in a gradient outside the secreting cell and are able to act over both short and long ranges to promote proliferation, changes in cell migration and polarity and tissue homeostasis, among others (reviewed in Saito-Diaz et al, 2012; Willert and Nusse, 2012).

The WNTs are ~40kDa proteins with 23 conserved cysteine residues in the N-terminal that may form intramolecular disulphide bonds. They also contain an N-terminal signal sequence and a number of N-linked glycosylation sites (Janda et al, 2012). In addition to being glycosylated, WNTs are also lipid-modified in the endoplasmic reticulum by a WNT-specific O-acyl-transferase, Porcupine (PORCN), contributing to their characteristic hydrophobicity. PORCN-dependent palmitoylation is required for the secretion of WNT as well as its signaling activity, as either depletion of PORCN or mutation of the conserved serine acylation site results in the intracellular accumulation of WNT ligand (Takada et al, 2006; Barrott et al, 2011; Biechele et al, 2011; reviewed in Willert and Nusse, 2012).

Secretion of WNT requires a number of other dedicated factors including the sorting receptor Wntless (WLS) (also knownas Evi, Sprinter, and GPR177), which binds WNT and escorts it to the cell surface (Banziger et al, 2006; Bartscherer et al, 2006; Goodman et al, 2006). A WNT-specific retromer containing SNX3 is subsequently required for the recycling of WLS back to the Golgi (reviewed in Herr et al, 2012; Johannes and Wunder, 2011). Once at the cell surface, WNT makes extensive contacts with components of the extracellular matrix such as heparan sulphate proteoglycans (HSPGs) and may be bound by any of a number of regulatory proteins, including WIFs and SFRPs. The diffusion of the WNT ligand may be aided by its packing either into WNT multimers, exosomes or onto lipoprotein particles to shield the hydrophobic lipid adducts from the aqueous extracellular environment (Gross et al, 2012; Luga et al, 2012, Korkut et al, 2009; reviewed in Willert and Nusse, 2012).

Literature Reactome attaches

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
Monounsaturated fatty acid modification of Wnt protein: its role in Wnt secretionDev. Cell, 2006, vol. 11, p. 791-801PubMed 17141155
Deletion of mouse Porcn blocks Wnt ligand secretion and reveals an ectodermal etiology of human focal dermal hypoplasia/Goltz syndromeProc. Natl. Acad. Sci. U.S.A., 2011, vol. 108, p. 12752-7PubMed 21768372
Porcupine homolog is required for canonical Wnt signaling and gastrulation in mouse embryosDev. Biol., 2011, vol. 355, p. 275-85PubMed 21554866
WNT secretion and signalling in human diseaseTrends Mol Med, 2012, vol. 18, p. 483-93PubMed 22796206
The SNXy flavours of endosomal sortingNat. Cell Biol., 2011, vol. 13, p. 884-6PubMed 21725318

Reactome's record lists 13 orthologous events, R-MMU-3238698 (Mus musculus), R-RNO-3238698 (Rattus norvegicus) among the species this site serves, and 11 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-09-30 ET · Reactome pathway browser"WNT ligand biogenesis and trafficking". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-3238698 with StableID: R-HSA-3238698.3 (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 26 genes in this human pathway; showing 1 to 26, 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
GenePORCN	AuthorityHGNC:17652	Mapping file id64840 NCBI file	EvidenceIEA
GeneSNX3	AuthorityHGNC:11174	Mapping file id8724 NCBI file	EvidenceTAS
GeneTMED5	AuthorityHGNC:24251	Mapping file id50999 NCBI file	EvidenceTAS
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
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
GeneWNT11	AuthorityHGNC:12776	Mapping file id7481 NCBI file	EvidenceIEA, TAS
GeneWNT16	AuthorityHGNC:16267	Mapping file id51384 NCBI file	EvidenceIEA, TAS
GeneWNT2	AuthorityHGNC:12780	Mapping file id7472 NCBI file	EvidenceIEA, TAS
GeneWNT2B	AuthorityHGNC:12781	Mapping file id7482 NCBI file	EvidenceIEA, TAS
GeneWNT3	AuthorityHGNC:12782	Mapping file id7473 NCBI file	EvidenceIEA, TAS
GeneWNT3A	AuthorityHGNC:15983	Mapping file id89780 NCBI file	EvidenceIEA, TAS
GeneWNT4	AuthorityHGNC:12783	Mapping file id54361 NCBI file	EvidenceIEA, TAS
GeneWNT5A	AuthorityHGNC:12784	Mapping file id7474 NCBI file	EvidenceIEA, TAS
GeneWNT5B	AuthorityHGNC:16265	Mapping file id81029 NCBI file	EvidenceIEA, TAS
GeneWNT6	AuthorityHGNC:12785	Mapping file id7475 NCBI file	EvidenceIEA, TAS
GeneWNT7A	AuthorityHGNC:12786	Mapping file id7476 NCBI file	EvidenceIEA, TAS
GeneWNT7B	AuthorityHGNC:12787	Mapping file id7477 NCBI file	EvidenceIEA, TAS
GeneWNT8A	AuthorityHGNC:12788	Mapping file id7478 NCBI file	EvidenceIEA, TAS
GeneWNT8B	AuthorityHGNC:12789	Mapping file id7479 NCBI file	EvidenceIEA, TAS
GeneWNT9A	AuthorityHGNC:12778	Mapping file id7483 NCBI file	EvidenceIEA, TAS
GeneWNT9B	AuthorityHGNC:12779	Mapping file id7484 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

Signaling by WNTR-HSA-195721321 genes

Children

None: no pathway of this release's list names this one as a parent.

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.