Pathway Human Homo sapiens

Transcriptional regulation of multiciliogenesis

R-HSA-9945556 in Reactome release 97: under Assembly of the 9+2 motile cilia, with 32 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-9945556 (mouse), R-RNO-9945556 (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-9945556.1
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2026-06-17
Events inside: 33, counted from the record

Multiciliated cells (MCCs) are characterized by the presence of multiple motile cilia at the cell surface and are found in developing renal system, in the terminally differentiated epithelial tissues of the respiratory and reproductive systems and in the brain ependyma (reviewed in Shahid and Singh, 2018; Arbi et al, 2018; Lewis and Stracker, 2021; Lyu et al, 2024). Motile cilia are also found individually, for instance in the sperm flagellum. Multiciliation arises as a result of a programmed overriding of the "once-per-cell-cycle" regulation of centrosome duplication, resulting in the generation of multiple centrioles that are converted to basal bodies that anchor the cilia and scaffold the assembly of the so-called "9+2" microtubule based axoneme (reviewed in Shahid and Singh, 2018; Arbi et al, 2018; Lewis and Stracker, 2021; Lyu et al, 2024; Rayamaji and Roy, 2025). Multiciliation is transcriptionally regulated by a hierarchical network of factors, with central roles for the geminin family proteins (GEMC1 and MCIDAS), DNA-binding transcription factors E2F4 and E2F5, the TP53-related protein TP73 and downstream effectors such as MYB, FOXJ1 and RFX family transcription factors that together regulate the expression of numerous structural and regulatory proteins involved in centriole amplification and ciliogenesis (reviewed in Choksi et al, 2014; Nemajerova et al, 2018; Shahid and Singh, 2018; Cumplido-Laso et al, 2023; Lewis and Stracker, 2021; Arbi et al, 2018; Lyu et al, 2024). It has recently been recognized that multiciliation is driven by a variant cell-cycle regulated by in part by cyclin CCNO in addition to other canonical cell cycle regulators (Khoury et al, 2025; Choksi et al, 2024).

Literature Reactome attaches

Emerging Picture of Deuterosome-Dependent Centriole Amplification in MCCsCells, 2018, vol. 7PubMed 30262752
Controlling centriole numbers: Geminin family members as master regulators of centriole amplification and multiciliogenesisChromosoma, 2018, vol. 127, p. 151-174PubMed 29243212
Transcriptional regulation of multiciliated cell differentiationSemin Cell Dev Biol, 2021, vol. 110, p. 51-60PubMed 32362381
Formation and function of multiciliated cellsJ Cell Biol, 2024, vol. 223PubMed 38032388
Multiciliated cells: Development, functions and disease relevanceSemin Cell Dev Biol, 2025, vol. 175, p. 103660PubMed 41067115
Switching on cilia: transcriptional networks regulating ciliogenesisDevelopment, 2014, vol. 141, p. 1427-41PubMed 24644260
Non-oncogenic roles of TAp73: from multiciliogenesis to metabolismCell Death Differ, 2018, vol. 25, p. 144-153PubMed 29077094
Transcriptional Regulation of Airway Epithelial Cell Differentiation: Insights into the Notch Pathway and BeyondInt J Mol Sci, 2023, vol. 24PubMed 37834236
Cyclin O controls entry into the cell-cycle variant required for multiciliated cell differentiationCell Rep, 2025, vol. 44, p. 115117PubMed 39740663
An alternative cell cycle coordinates multiciliated cell differentiationNature, 2024, vol. 630, p. 214-221PubMed 38811726

Reactome's record lists 10 orthologous events, R-MMU-9945556 (Mus musculus), R-RNO-9945556 (Rattus norvegicus) among the species this site serves, and 8 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-09-30 ET · Reactome pathway browser"Transcriptional regulation of multiciliogenesis". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-9945556 with StableID: R-HSA-9945556.1 (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 32 genes in this human pathway; showing 1 to 32, 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
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
GeneCCDC78	AuthorityHGNC:14153	Mapping file idENSG00000162004 Ensembl file	EvidenceTAS
GeneCCNO	AuthorityHGNC:18576	Mapping file id10309 NCBI file	EvidenceTAS
GeneDEUP1	AuthorityHGNC:26344	Mapping file id159989 NCBI file	EvidenceTAS
GeneDLL1	AuthorityHGNC:2908	Mapping file id28514 NCBI file	EvidenceTAS
GeneE2F4	AuthorityHGNC:3118	Mapping file id1874 NCBI file	EvidenceIEA, TAS
GeneE2F5	AuthorityHGNC:3119	Mapping file id1875 NCBI file	EvidenceIEA, TAS
GeneFOXJ1	AuthorityHGNC:3816	Mapping file id2302 NCBI file	EvidenceTAS
GeneGMNC	AuthorityHGNC:40049	Mapping file id647309 NCBI file	EvidenceTAS
GeneGMNN	AuthorityHGNC:17493	Mapping file id51053 NCBI file	EvidenceTAS
GeneGRHL1	AuthorityHGNC:17923	Mapping file id29841 NCBI file	EvidenceTAS
GeneGRHL2	AuthorityHGNC:2799	Mapping file id79977 NCBI file	EvidenceTAS
GeneGRHL3	AuthorityHGNC:25839	Mapping file id57822 NCBI file	EvidenceTAS
GeneMCIDAS	AuthorityHGNC:40050	Mapping file id345643 NCBI file	EvidenceIEA, TAS
GeneMIR34B	AuthorityHGNC:31636	Mapping file idENSG00000207811 Ensembl file	EvidenceTAS
GeneMIR34C	AuthorityHGNC:31637	Mapping file idENSG00000207562 Ensembl file	EvidenceTAS
GeneMIR449A	AuthorityHGNC:27645	Mapping file idENSG00000198983 Ensembl file	EvidenceTAS
GeneMIR449B	AuthorityHGNC:32794	Mapping file idENSG00000207728 Ensembl file	EvidenceTAS
GeneMIR449C	AuthorityHGNC:37302	Mapping file idENSG00000251856 Ensembl file	EvidenceTAS
GeneMOV10	AuthorityHGNC:7200	Mapping file id4343 NCBI file	EvidenceTAS
GeneMYB	AuthorityHGNC:7545	Mapping file id4602 NCBI file	EvidenceTAS
GeneNOTCH1	AuthorityHGNC:7881	Mapping file id4851 NCBI file	EvidenceTAS
GeneRFX2	AuthorityHGNC:9983	Mapping file id5990 NCBI file	EvidenceTAS
GeneRFX3	AuthorityHGNC:9984	Mapping file id5991 NCBI file	EvidenceTAS
GeneTFDP1	AuthorityHGNC:11749	Mapping file id7027 NCBI file	EvidenceIEA, TAS
GeneTNRC6A	AuthorityHGNC:11969	Mapping file id27327 NCBI file	EvidenceTAS
GeneTNRC6B	AuthorityHGNC:29190	Mapping file id23112 NCBI file	EvidenceTAS
GeneTNRC6C	AuthorityHGNC:29318	Mapping file id57690 NCBI file	EvidenceTAS
GeneTP73	AuthorityHGNC:12003	Mapping file id7161 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

Assembly of the 9+2 motile ciliaR-HSA-997592432 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.