Pathway Human Homo sapiens

Nephrin family interactions

R-HSA-373753 in Reactome release 97: under Cell-Cell communication, with 23 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-373753 (mouse), R-RNO-373753 (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-373753.5
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2010-09-21
Last updated: 2023-06-07
Events inside: 13, counted from the record

Nephrin (NPHS1) is a member of the Super-IgG-Molecule family and is most prominently expressed in kidney podocytes. It is a major if not the most important structural component of the slit diaphragm, a modified adherens junction in between these cells. NPHS1 has an extracellular domain that contains eight distal IgG like domains and one proximal fibronectin type III domain, a transmembrane domain and a short intracellular domain. NPHS1 molecules show both homophilic and heterophilic interactions. Among heterophilic interaction partners, slit diaphragm proteins such as Kin of IRRE-like protein 1 (KIRREL, Nephrin-like protein 1, NEPH1), KIRREL3 (NEPH2) and KIRREL2 (NEPH3) were shown to stabilize the slit diaphragm structure. Intracellularly Podocin (NPHS2), CD2 associated protein (CD2AP) and adherins junction associated proteins like IQGAP, MAGI, CASK and spectrins all interact with NPHS1. Hence it seems to play a major role in organizing the molecular structure of the slit diaphragm itself and via its binding partners links it to the actin cytoskeleton. NPHS1 tyrosine phosphorylation by the Src kinase FYN initiates the PI3K-AKT signaling cascade, which seems to promote antiapoptotic signals.

Literature Reactome attaches

Nephrin--a unique structural and signaling protein of the kidney filterTrends Mol Med, 2007, vol. 13, p. 396-403PubMed 17766183
Nephrin is specifically located at the slit diaphragm of glomerular podocytesProc Natl Acad Sci U S A, 1999, vol. 96, p. 7962-7PubMed 10393930
Unraveling the mechanisms of glomerular ultrafiltration: nephrin, a key component of the slit diaphragmJ Am Soc Nephrol, 1999, vol. 10, p. 2440-5PubMed 10541305
Hereditary proteinuria syndromes and mechanisms of proteinuriaN Engl J Med, 2006, vol. 354, p. 1387-401PubMed 16571882
Nephrin and CD2AP associate with phosphoinositide 3-OH kinase and stimulate AKT-dependent signalingMol Cell Biol, 2003, vol. 23, p. 4917-28PubMed 12832477
The slit diaphragm: a signaling platform to regulate podocyte functionCurr Opin Nephrol Hypertens, 2005, vol. 14, p. 211-6PubMed 15821412
Cell junction-associated proteins IQGAP1, MAGI-2, CASK, spectrins, and alpha-actinin are components of the nephrin multiprotein complexProc Natl Acad Sci U S A, 2005, vol. 102, p. 9814-9PubMed 15994232
Genetics of nephrotic syndrome: new insights into molecules acting at the glomerular filtration barrierJ Mol Med, 2009, vol. 87, p. 849-57PubMed 19649571

Reactome's record lists 9 orthologous events, R-RNO-373753 (Rattus norvegicus), R-MMU-373753 (Mus musculus) among the species this site serves, and 7 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-01 ET · Reactome pathway browser"Nephrin family interactions". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-373753 with StableID: R-HSA-373753.5 (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 23 genes in this human pathway; showing 1 to 23, 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
GeneACTN1	AuthorityHGNC:163	Mapping file id87 NCBI file	EvidenceIEA
GeneACTN2	AuthorityHGNC:164	Mapping file id88 NCBI file	EvidenceIEA
GeneACTN3	AuthorityHGNC:165	Mapping file id89 NCBI file	EvidenceIEA
GeneACTN4	AuthorityHGNC:166	Mapping file id81 NCBI file	EvidenceIEA
GeneCASK	AuthorityHGNC:1497	Mapping file id8573 NCBI file	EvidenceIEA
GeneCD2AP	AuthorityHGNC:14258	Mapping file id23607 NCBI file	EvidenceIEA
GeneFYN	AuthorityHGNC:4037	Mapping file id2534 NCBI file	EvidenceIEA, TAS
GeneIQGAP1	AuthorityHGNC:6110	Mapping file id8826 NCBI file	EvidenceTAS
GeneKIRREL1	AuthorityHGNC:15734	Mapping file id55243 NCBI file	EvidenceIEA, TAS
GeneKIRREL2	AuthorityHGNC:18816	Mapping file id84063 NCBI file	EvidenceTAS
GeneKIRREL3	AuthorityHGNC:23204	Mapping file id84623 NCBI file	EvidenceTAS
GeneMAGI2	AuthorityHGNC:18957	Mapping file id9863 NCBI file	EvidenceIEA
GeneNCK1	AuthorityHGNC:7664	Mapping file id4690 NCBI file	EvidenceTAS
GeneNCK2	AuthorityHGNC:7665	Mapping file id8440 NCBI file	EvidenceTAS
GeneNPHS1	AuthorityHGNC:7908	Mapping file id4868 NCBI file	EvidenceIEA, TAS
GeneNPHS2	AuthorityHGNC:13394	Mapping file id7827 NCBI file	EvidenceTAS
GenePIK3CA	AuthorityHGNC:8975	Mapping file id5290 NCBI file	EvidenceIEA
GenePIK3CB	AuthorityHGNC:8976	Mapping file id5291 NCBI file	EvidenceIEA
GenePIK3R1	AuthorityHGNC:8979	Mapping file id5295 NCBI file	EvidenceIEA
GenePIK3R2	AuthorityHGNC:8980	Mapping file id5296 NCBI file	EvidenceIEA
GeneSPTAN1	AuthorityHGNC:11273	Mapping file id6709 NCBI file	EvidenceIEA
GeneSPTBN1	AuthorityHGNC:11275	Mapping file id6711 NCBI file	EvidenceIEA
GeneWASL	AuthorityHGNC:12735	Mapping file id8976 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

Cell-Cell communicationR-HSA-1500931364 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.