Pathway Human Homo sapiens

Kidney development

R-HSA-9830369 in Reactome release 97: under Developmental Biology, with 46 genes placed in it by the mapping files and 3 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; neither of the other two lists holds it. Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

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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-9830369.1
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2023-12-06
Events inside: 3, counted from the record

Kidney development begins at embryonic day 8.5 (E8.5) in mouse embryos, a time after gastrulation and formation of the intermediate mesoderm (reviewed in Marcotte et al. 2014, Smyth 2021, Schnell et al. 2022). Renal progenitors are specified within the intermediate mesoderm in the region between the 6th and 8th somites. The nephric duct then begins to form by mesenchymal to epithelial transitions of the renal progenitors and grows caudally to fuse with the bladder and urethra primordium (cloaca). The nephric duct induces the formation of mesonephric tubules in the adjacent nephric cord which form the mesonephros, an embryonic kidney in mammals that regresses and is supplanted by the metanephros. (In anamniotes such as frogs and fish, the mesonephros is the adult kidney and no metanephros forms.)

In mammals, the metanephros is initiated as the caudal region of the nephric cord forms metanephric mesenchyme which then interacts with the nephric duct to induce formation of the ureteric bud, the progenitor of the ureter. Branching of the ureteric bud forms ureter tips which induce nephron formation in the surrounding metanephric mesenchyme (reviewed in El-Dahr et al. 2008, O'Brien and McMahon 2014, Desgrange and Cereghini 2015, Chambers and Wingert 2020, Schnell et al. 2022).

Induction of kidney development in the intermediate mesoderm occurs by incompletely characterized signals from the adjacent ectoderm and lateral plate mesoderm. Notably, BMP activity from the lateral plate mesoderm can induce expression of the renal markers Pax2 and Lhx1.

Foxc1 and Foxc2 expressed in the paraxial mesoderm repress Lhx1 and prevent over-expansion of the intermediate mesoderm (Wilm et al. 2004). Conversely, Nodal signaling maintains Pax2 expression and prevents over-expansion of the paraxial mesoderm (Fleming et al. 2013). The rostral-caudal position of renal development appears to specified by the rostral-caudal gradient of retinoic acid acting through HoxB4 (Preger-Ben Noon et al. 2009) and limited caudally by HoxA6.

The combined expression of Pax2, Pax8, Lhx1, and Gata3 is the earliest observed marker of the renal lineage and these transcription factors, together with Emx2, form a self-reinforcing module that drives formation of the nephric duct. Nephronectin (Npnt) from the nephric duct interacts with integrin alpha8/beta1 (Itga8) on the metanephric mesenchyme and Ret located on the nephric duct interacts with Gdnf secreted by the metanephric mesenchyme to regulate formation and branching of the ureteric bud (reviewed in Marcotte et al. 2014). Signals from the tips of the ureteric bud then induce epithelialization of the metanephric mesenchyme and formation of nephrons, the basic filtration units of the kidney comprising the glomerulus, the proximal tubule, the loop of Henle, and the distal tubule (reviewed in Desgrange and Cereghini 2015). Canonical Wnt signaling from the ureteric bud appears to be the main inductive event: Wnt9b activates Wnt4 expression to epithelialize mesenchymal pre-tubular aggregates and Wnt9b also supports expression of Six2 to maintain a nephron progenitor pool in the cap mesenchyme.

Congenital anomalies of the kidney and urinary tract (CAKUT) comprise about 30% of antnatal congenital abnormalities and cause the majority of chronic kidney disease in children (reviewed in Costigan and Rosenblum 2022). Knowledge gained from studying kidney development is being used to generate kidney organoids in vitro with a goal of producing transplantable kidney tissue (reviewed in Kalejaiye et al. 2022, Safi et al. 2022, Trush and Takasato 2022, Shi et al. 2023).

Literature Reactome attaches

Genetic controls and cellular behaviors in branching morphogenesis of the renal collecting systemWiley Interdiscip Rev Dev Biol, 2012, vol. 1, p. 693-713PubMed 22942910
Gene regulatory network of renal primordium developmentPediatr Nephrol, 2014, vol. 29, p. 637-44PubMed 24104595
Mammalian kidney development: principles, progress, and projectionsCold Spring Harb Perspect Biol, 2012, vol. 4PubMed 22550230
Advances in early kidney specification, development and patterningDevelopment, 2009, vol. 136, p. 3863-74PubMed 19906853
Nephron Patterning: Lessons from Xenopus, Zebrafish, and Mouse StudiesCells, 2015, vol. 4, p. 483-99PubMed 26378582
Development of the Mammalian KidneyCurr Top Dev Biol, 2016, vol. 117, p. 31-64PubMed 26969971
Induction and patterning of the metanephric nephronSemin Cell Dev Biol, 2014, vol. 36, p. 31-8PubMed 25194660

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-02 ET · Reactome pathway browser"Kidney development". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-9830369 with StableID: R-HSA-9830369.1 (accessed 2026-10-02 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 46 genes in this human pathway; showing 1 to 46, 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
GeneBMP4	AuthorityHGNC:1071	Mapping file id652 NCBI file	EvidenceIEA
GeneCTNNB1	AuthorityHGNC:2514	Mapping file id1499 NCBI file	EvidenceIEA
GeneDLL1	AuthorityHGNC:2908	Mapping file id28514 NCBI file	EvidenceIEA
GeneEMX2	AuthorityHGNC:3341	Mapping file id2018 NCBI file	EvidenceIEA
GeneEYA1	AuthorityHGNC:3519	Mapping file id2138 NCBI file	EvidenceIEA
GeneFGF2	AuthorityHGNC:3676	Mapping file id2247 NCBI file	EvidenceIEA
GeneFOXC1	AuthorityHGNC:3800	Mapping file id2296 NCBI file	EvidenceIEA
GeneFOXC2	AuthorityHGNC:3801	Mapping file id2303 NCBI file	EvidenceIEA
GeneGATA3	AuthorityHGNC:4172	Mapping file id2625 NCBI file	EvidenceIEA
GeneGDNF	AuthorityHGNC:4232	Mapping file id2668 NCBI file	EvidenceIEA
GeneGFRA1	AuthorityHGNC:4243	Mapping file id2674 NCBI file	EvidenceIEA
GeneGREM1	AuthorityHGNC:2001	Mapping file id26585 NCBI file	EvidenceIEA
GeneHNF1B	AuthorityHGNC:11630	Mapping file id6928 NCBI file	EvidenceIEA
GeneHNF4A	AuthorityHGNC:5024	Mapping file id3172 NCBI file	EvidenceIEA
GeneHOXA11	AuthorityHGNC:5101	Mapping file id3207 NCBI file	EvidenceIEA
GeneHOXA6	AuthorityHGNC:5107	Mapping file id3203 NCBI file	EvidenceIEA
GeneHOXB4	AuthorityHGNC:5115	Mapping file id3214 NCBI file	EvidenceIEA
GeneHOXC11	AuthorityHGNC:5123	Mapping file id3227 NCBI file	EvidenceIEA
GeneHOXD11	AuthorityHGNC:5134	Mapping file id3237 NCBI file	EvidenceIEA
GeneID4	AuthorityHGNC:5363	Mapping file id3400 NCBI file	EvidenceIEA
GeneIRX1	AuthorityHGNC:14358	Mapping file id79192 NCBI file	EvidenceIEA
GeneIRX2	AuthorityHGNC:14359	Mapping file id153572 NCBI file	EvidenceIEA
GeneITGA8	AuthorityHGNC:6144	Mapping file id8516 NCBI file	EvidenceIEA
GeneITGB1	AuthorityHGNC:6153	Mapping file id3688 NCBI file	EvidenceIEA
GeneJAG1	AuthorityHGNC:6188	Mapping file id182 NCBI file	EvidenceIEA
GeneLFNG	AuthorityHGNC:6560	Mapping file id3955 NCBI file	EvidenceIEA
GeneLHX1	AuthorityHGNC:6593	Mapping file id3975 NCBI file	EvidenceIEA
GeneMECOM	AuthorityHGNC:3498	Mapping file id2122 NCBI file	EvidenceIEA
GeneNPNT	AuthorityHGNC:27405	Mapping file id255743 NCBI file	EvidenceIEA
GeneOSR1	AuthorityHGNC:8111	Mapping file id130497 NCBI file	EvidenceIEA
GenePAX2	AuthorityHGNC:8616	Mapping file id5076 NCBI file	EvidenceIEA
GenePAX8	AuthorityHGNC:8622	Mapping file id7849 NCBI file	EvidenceIEA
GenePCDH19	AuthorityHGNC:14270	Mapping file id57526 NCBI file	EvidenceIEA
GenePLAC8	AuthorityHGNC:19254	Mapping file id51316 NCBI file	EvidenceIEA
GenePOU3F3	AuthorityHGNC:9216	Mapping file id5455 NCBI file	EvidenceIEA
GeneRET	AuthorityHGNC:9967	Mapping file id5979 NCBI file	EvidenceIEA
GeneROBO2	AuthorityHGNC:10250	Mapping file id6092 NCBI file	EvidenceIEA
GeneSALL1	AuthorityHGNC:10524	Mapping file id6299 NCBI file	EvidenceIEA
GeneSIX1	AuthorityHGNC:10887	Mapping file id6495 NCBI file	EvidenceIEA
GeneSIX2	AuthorityHGNC:10888	Mapping file id10736 NCBI file	EvidenceIEA
GeneSLIT2	AuthorityHGNC:11086	Mapping file id9353 NCBI file	EvidenceIEA
GeneWFDC2	AuthorityHGNC:15939	Mapping file id10406 NCBI file	EvidenceIEA
GeneWNT11	AuthorityHGNC:12776	Mapping file id7481 NCBI file	EvidenceIEA
GeneWNT4	AuthorityHGNC:12783	Mapping file id54361 NCBI file	EvidenceIEA
GeneWNT9B	AuthorityHGNC:12779	Mapping file id7484 NCBI file	EvidenceIEA
GeneWT1	AuthorityHGNC:12796	Mapping file id7490 NCBI file	EvidenceIEA

Evidence codes on this page: IEA, 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

Developmental BiologyR-HSA-12667381,589 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.