Pathway Human Homo sapiens

Hedgehog 'off' state

R-HSA-5610787 in Reactome release 97: under Signaling by Hedgehog, with 100 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: R-MMU-5610787 (mouse), R-RNO-5610787 (rat). Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

Scripts are off

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-5610787.3
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2014-09-30
Last updated: 2014-12-08
Events inside: 19, counted from the record

Hedgehog is a secreted morphogen that has evolutionarily conserved roles in body organization by regulating the activity of the Ci/Gli transcription factor family. In Drosophila in the absence of Hh signaling, full-length Ci is partially degraded by the proteasome to generate a truncated repressor form that translocates to the nucleus to represses Hh-responsive genes. Binding of Hh ligand to the Patched (PTC) receptor allows the 7-pass transmembrane protein Smoothened (SMO) to be activated in an unknown manner, disrupting the partial proteolysis of Ci and allowing the full length activator form to accumulate (reviewed in Ingham et al, 2011; Briscoe and Therond, 2013).

While many of the core components of Hh signaling are conserved from flies to humans, the pathways do show points of significant divergence. Notably, the human genome encodes three Ci homologues, GLI1, 2 and 3 that each play slightly different roles in regulating Hh responsive genes. GLI3 is the primary repressor of Hh signaling in vertebrates, and is converted to the truncated GLI3R repressor form in the absence of Hh. GLI2 is a potent activator of transcription in the presence of Hh but contributes only minimally to the repression function. While a minor fraction of GLI2 protein is processed into the repressor form in the absence of Hh, the majority is either fully degraded by the proteasome or sequestered in the full-length form in the cytosol by protein-protein interactions. GLI1 lacks the repression domain and appears to be an obligate transcriptional activator (reviewed in Briscoe and Therond, 2013).

Vertebrate but not fly Hh signaling also depends on the movement of pathway components through the primary cilium. The primary cilium is a non-motile microtubule based structure whose construction and maintenance depends on intraflagellar transport (IFT). Anterograde IFT moves molecules from the ciliary base along the axoneme to the ciliary tip in a manner that requires the microtubule-plus-end directed kinesin KIF3 motor complex and the IFT-B protein complex, while retrograde IFT back to the ciliary base depends on the minus-end directed dynein motor and the IFT-A complex. Genetic screens have identified a number of cilia-related proteins that are required both to maintain Hh in the 'off' state and to transduce the signal when the pathway is activated (reviewed in Hui and Angers, 2011; Goetz and Anderson, 2010).

Literature Reactome attaches

Mechanisms and functions of Hedgehog signalling across the metazoaNat. Rev. Genet., 2011, vol. 12, p. 393-406PubMed 21502959
Gli proteins in development and diseaseAnnu. Rev. Cell Dev. Biol., 2011, vol. 27, p. 513-37PubMed 21801010
The primary cilium: a signalling centre during vertebrate developmentNat. Rev. Genet., 2010, vol. 11, p. 331-44PubMed 20395968
The mechanisms of Hedgehog signalling and its roles in development and diseaseNat. Rev. Mol. Cell Biol., 2013, vol. 14, p. 416-29PubMed 23719536

Reactome's record lists 14 orthologous events, R-RNO-5610787 (Rattus norvegicus), R-MMU-5610787 (Mus musculus) 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"Hedgehog 'off' state". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-5610787 with StableID: R-HSA-5610787.3 (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 100 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 1
Gene	Authority id	Mapping file id	Evidence codes
GeneADCY1	AuthorityHGNC:232	Mapping file id107 NCBI file	EvidenceTAS
GeneADCY10	AuthorityHGNC:21285	Mapping file id55811 NCBI file	EvidenceTAS
GeneADCY2	AuthorityHGNC:233	Mapping file id108 NCBI file	EvidenceTAS
GeneADCY3	AuthorityHGNC:234	Mapping file id109 NCBI file	EvidenceTAS
GeneADCY4	AuthorityHGNC:235	Mapping file id196883 NCBI file	EvidenceTAS
GeneADCY5	AuthorityHGNC:236	Mapping file id111 NCBI file	EvidenceTAS
GeneADCY6	AuthorityHGNC:237	Mapping file id112 NCBI file	EvidenceTAS
GeneADCY7	AuthorityHGNC:238	Mapping file id113 NCBI file	EvidenceTAS
GeneADCY8	AuthorityHGNC:239	Mapping file id114 NCBI file	EvidenceTAS
GeneADCY9	AuthorityHGNC:240	Mapping file id115 NCBI file	EvidenceTAS
GeneADRM1	AuthorityHGNC:15759	Mapping file id11047 NCBI file	EvidenceIEA, TAS
GeneBTRC	AuthorityHGNC:1144	Mapping file id8945 NCBI file	EvidenceIEA, TAS
GeneCSNK1A1	AuthorityHGNC:2451	Mapping file id1452 NCBI file	EvidenceIEA, TAS
GeneCUL1	AuthorityHGNC:2551	Mapping file id8454 NCBI file	EvidenceIEA, TAS
GeneDYNC2H1	AuthorityHGNC:2962	Mapping file id79659 NCBI file	EvidenceTAS
GeneFUZ	AuthorityHGNC:26219	Mapping file id80199 NCBI file	EvidenceTAS
GeneGLI1	AuthorityHGNC:4317	Mapping file id2735 NCBI file	EvidenceIEA, TAS
GeneGLI2	AuthorityHGNC:4318	Mapping file id2736 NCBI file	EvidenceIEA, TAS
GeneGLI3	AuthorityHGNC:4319	Mapping file id2737 NCBI file	EvidenceTAS
GeneGNAS	AuthorityHGNC:4392	Mapping file id2778 NCBI file	EvidenceTAS
GeneGPR161	AuthorityHGNC:23694	Mapping file id23432 NCBI file	EvidenceTAS
GeneGSK3B	AuthorityHGNC:4617	Mapping file id2932 NCBI file	EvidenceIEA, TAS
GeneIFT122	AuthorityHGNC:13556	Mapping file id55764 NCBI file	EvidenceTAS
GeneIFT140	AuthorityHGNC:29077	Mapping file id9742 NCBI file	EvidenceTAS
GeneIFT172	AuthorityHGNC:30391	Mapping file id26160 NCBI file	EvidenceTAS
GeneIFT52	AuthorityHGNC:15901	Mapping file id51098 NCBI file	EvidenceTAS
GeneIFT57	AuthorityHGNC:17367	Mapping file id55081 NCBI file	EvidenceTAS
GeneIFT88	AuthorityHGNC:20606	Mapping file id8100 NCBI file	EvidenceTAS
GeneINTU	AuthorityHGNC:29239	Mapping file id27152 NCBI file	EvidenceTAS
GeneITCH	AuthorityHGNC:13890	Mapping file id83737 NCBI file	EvidenceTAS
GeneKIF3A	AuthorityHGNC:6319	Mapping file id11127 NCBI file	EvidenceTAS
GeneKIF7	AuthorityHGNC:30497	Mapping file id374654 NCBI file	EvidenceTAS
GeneMKS1	AuthorityHGNC:7121	Mapping file id54903 NCBI file	EvidenceTAS
GeneNUMB	AuthorityHGNC:8060	Mapping file id8650 NCBI file	EvidenceTAS
GeneOFD1	AuthorityHGNC:2567	Mapping file id8481 NCBI file	EvidenceTAS
GenePRKACA	AuthorityHGNC:9380	Mapping file id5566 NCBI file	EvidenceIEA, TAS
GenePRKACB	AuthorityHGNC:9381	Mapping file id5567 NCBI file	EvidenceIEA, TAS
GenePRKACG	AuthorityHGNC:9382	Mapping file id5568 NCBI file	EvidenceIEA, TAS
GenePRKAR1A	AuthorityHGNC:9388	Mapping file id5573 NCBI file	EvidenceTAS
GenePRKAR1B	AuthorityHGNC:9390	Mapping file id5575 NCBI file	EvidenceTAS
GenePRKAR2A	AuthorityHGNC:9391	Mapping file id5576 NCBI file	EvidenceTAS
GenePRKAR2B	AuthorityHGNC:9392	Mapping file id5577 NCBI file	EvidenceTAS
GenePSMA1	AuthorityHGNC:9530	Mapping file id5682 NCBI file	EvidenceIEA, TAS
GenePSMA2	AuthorityHGNC:9531	Mapping file id5683 NCBI file	EvidenceIEA, TAS
GenePSMA3	AuthorityHGNC:9532	Mapping file id5684 NCBI file	EvidenceIEA, TAS
GenePSMA4	AuthorityHGNC:9533	Mapping file id5685 NCBI file	EvidenceIEA, TAS
GenePSMA5	AuthorityHGNC:9534	Mapping file id5686 NCBI file	EvidenceIEA, TAS
GenePSMA6	AuthorityHGNC:9535	Mapping file id5687 NCBI file	EvidenceIEA, TAS
GenePSMA7	AuthorityHGNC:9536	Mapping file id5688 NCBI file	EvidenceIEA, TAS
GenePSMB1	AuthorityHGNC:9537	Mapping file id5689 NCBI file	EvidenceIEA, TAS
GenePSMB2	AuthorityHGNC:9539	Mapping file id5690 NCBI file	EvidenceIEA, TAS
GenePSMB3	AuthorityHGNC:9540	Mapping file id5691 NCBI file	EvidenceIEA, TAS
GenePSMB4	AuthorityHGNC:9541	Mapping file id5692 NCBI file	EvidenceIEA, TAS
GenePSMB5	AuthorityHGNC:9542	Mapping file id5693 NCBI file	EvidenceIEA, TAS
GenePSMB6	AuthorityHGNC:9543	Mapping file id5694 NCBI file	EvidenceIEA, TAS
GenePSMB7	AuthorityHGNC:9544	Mapping file id5695 NCBI file	EvidenceIEA, TAS
GenePSMC1	AuthorityHGNC:9547	Mapping file id5700 NCBI file	EvidenceIEA, TAS
GenePSMC2	AuthorityHGNC:9548	Mapping file id5701 NCBI file	EvidenceIEA, TAS
GenePSMC3	AuthorityHGNC:9549	Mapping file id5702 NCBI file	EvidenceIEA, TAS
GenePSMC4	AuthorityHGNC:9551	Mapping file id5704 NCBI file	EvidenceIEA, TAS
GenePSMC5	AuthorityHGNC:9552	Mapping file id5705 NCBI file	EvidenceIEA, TAS
GenePSMC6	AuthorityHGNC:9553	Mapping file id5706 NCBI file	EvidenceIEA, TAS
GenePSMD1	AuthorityHGNC:9554	Mapping file id5707 NCBI file	EvidenceIEA, TAS
GenePSMD11	AuthorityHGNC:9556	Mapping file id5717 NCBI file	EvidenceIEA, TAS
GenePSMD12	AuthorityHGNC:9557	Mapping file id5718 NCBI file	EvidenceIEA, TAS
GenePSMD13	AuthorityHGNC:9558	Mapping file id5719 NCBI file	EvidenceIEA, TAS
GenePSMD14	AuthorityHGNC:16889	Mapping file id10213 NCBI file	EvidenceIEA, TAS
GenePSMD2	AuthorityHGNC:9559	Mapping file id5708 NCBI file	EvidenceIEA, TAS
GenePSMD3	AuthorityHGNC:9560	Mapping file id5709 NCBI file	EvidenceIEA, TAS
GenePSMD6	AuthorityHGNC:9564	Mapping file id9861 NCBI file	EvidenceIEA, TAS
GenePSMD7	AuthorityHGNC:9565	Mapping file id5713 NCBI file	EvidenceIEA, TAS
GenePSMD8	AuthorityHGNC:9566	Mapping file id5714 NCBI file	EvidenceIEA, TAS
GenePTCH1	AuthorityHGNC:9585	Mapping file id5727 NCBI file	EvidenceTAS
GeneRBX1	AuthorityHGNC:9928	Mapping file id9978 NCBI file	EvidenceIEA, TAS
GeneRPGRIP1L	AuthorityHGNC:29168	Mapping file id23322 NCBI file	EvidenceTAS
GeneRPS27A	AuthorityHGNC:10417	Mapping file id6233 NCBI file	EvidenceIEA, TAS
GeneSEM1	AuthorityHGNC:10845	Mapping file id7979 NCBI file	EvidenceIEA, TAS
GeneSKP1	AuthorityHGNC:10899	Mapping file id6500 NCBI file	EvidenceIEA, TAS
GeneSMO	AuthorityHGNC:11119	Mapping file id6608 NCBI file	EvidenceTAS
GeneSUFU	AuthorityHGNC:16466	Mapping file id51684 NCBI file	EvidenceIEA, TAS
GeneTTC21B	AuthorityHGNC:25660	Mapping file id79809 NCBI file	EvidenceTAS
GeneTUBA1A	AuthorityHGNC:20766	Mapping file id7846 NCBI file	EvidenceTAS
GeneTUBA1B	AuthorityHGNC:18809	Mapping file id10376 NCBI file	EvidenceTAS
GeneTUBA1C	AuthorityHGNC:20768	Mapping file id84790 NCBI file	EvidenceTAS
GeneTUBA3C	AuthorityHGNC:12408	Mapping file id7278 NCBI file	EvidenceTAS
GeneTUBA3D	AuthorityHGNC:24071	Mapping file id113457 NCBI file	EvidenceTAS
GeneTUBA4A	AuthorityHGNC:12407	Mapping file id7277 NCBI file	EvidenceTAS
GeneTUBB1	AuthorityHGNC:16257	Mapping file id81027 NCBI file	EvidenceTAS
GeneTUBB2A	AuthorityHGNC:12412	Mapping file id7280 NCBI file	EvidenceTAS
GeneTUBB2B	AuthorityHGNC:30829	Mapping file id347733 NCBI file	EvidenceTAS
GeneTUBB3	AuthorityHGNC:20772	Mapping file id10381 NCBI file	EvidenceTAS
GeneTUBB4A	AuthorityHGNC:20774	Mapping file id10382 NCBI file	EvidenceTAS
GeneTUBB4B	AuthorityHGNC:20771	Mapping file id10383 NCBI file	EvidenceTAS
GeneTUBB6	AuthorityHGNC:20776	Mapping file id84617 NCBI file	EvidenceTAS
GeneTULP3	AuthorityHGNC:12425	Mapping file id7289 NCBI file	EvidenceTAS
GeneUBA52	AuthorityHGNC:12458	Mapping file id7311 NCBI file	EvidenceIEA, TAS
GeneUBB	AuthorityHGNC:12463	Mapping file id7314 NCBI file	EvidenceIEA, TAS
GeneUBC	AuthorityHGNC:12468	Mapping file id7316 NCBI file	EvidenceIEA, TAS
GeneWDR19	AuthorityHGNC:18340	Mapping file id57728 NCBI file	EvidenceTAS
GeneWDR35	AuthorityHGNC:29250	Mapping file id57539 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

Signaling by HedgehogR-HSA-5358351137 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.