Pathway Human Homo sapiens

Sensory processing of sound

R-HSA-9659379 in Reactome release 97: under Sensory Perception, with 77 genes placed in it by the mapping files and 2 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-9659379.3
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2021-03-23
Events inside: 2, counted from the record

In mammals, sounds are processed in the cochlea, a spiral-shaped organ in the inner ear (reviewed in Basch et al. 2016, Fettiplace 2017, Koppl and Manley 2019). Low frequency sounds are sensed at the distal end (apex) of the cochlea; high frequency sounds are sensed at the proximal end (base) of the cochlea (reviewed in Dallos 1992, Manley 2018). Sound vibrations are transmitted from the eardrum through the three bones of the inner ear (malleus, incus, stapes) and the oval window of the cochlea to the fluids within the cochlea. Within the organ of Corti in the cochlea there are 3 rows of outer hair cells (OHCs) on the external side of the tunnel of Corti and 1 row of inner hair cells (IHCs) on the internal side (Spoendlin 1967). Each IHC synapses with approximately 20 afferent myelinated type I spiral ganglion neurons and functions as a sensory receptor to convert the energy of sound waves to secretion of glutamate neurotransmitter. Multiple OHCs synapse with each unmyelinated type II afferent neuron and OHCs are also synapsed with efferent medial olivocochlear fibers (Spoendlin 1967). The primary function of OHCs, however, is amplification of organ of Corti motions in response to sound (Ryan and Dallos 1975). Amplification is produced by changes in receptor-potential driven cell length caused by changes in the conformation of the unusual membrane protein prestin (SLC26A5, Zheng et al. 2000).

IHCs and OHCs sense the sonic vibrations by deflection of stereocilia on their apical surfaces (reviewed in Fettiplace et al. 2017, McPherson 2018). The stereocilia are arranged in rows of increasing height, with a stereocilium of one row connected to a stereocilium of another row by a tip link composed of a CDH23 dimer on the taller stereocilium joined at its N-termini to the N-termini of a PCDH15 dimer on the shorter stereocilium. CDH23 is connected to the cytoskeleton of the taller stereocilium via MYO7A (MyoVIIa), USH1C (Harmonin), and USH1G (Sans) (reviewed in Peng et al. 2011, Cosgrove and Zallocchi 2014, Barr-Gillespie 2015, Fettiplace 2017, McGrath et al. 2017, Cunningham and Müller 2019, Ó Maoiléidigh and Ricci 2019, Velez-Ortega and Frolenkov 2019) while PCDH15 on the shorter stereocilium interacts with LHFPL5, an auxiliary subunit of the mechanoelectrical transduction channel (MET channel, also known as the mechanotransduction channel), which contains at least TMC1 or TMC2, TMIE, and the auxiliary subunits LHFPL5 and CIB2 (reviewed in Fettiplace 2016, Qiu and Müller 2018, Corey et al. 2019). Deflection of stereocilia in the direction that increases tension on the tip link causes depolarization of the cell by increasing the open probability of the MET channel, which then transports calcium and potassium into the hair cell according to the gradient of those ions between the scala media (containing endolymph at 154 mM K+ and <1 mM Ca2+) at the apex of the cell and the scala tympani (containing perilymph at 7 mM K+) at the base (reviewed in Fettiplace and Kim 2014). Similarly, compression of the tip link by deflection of the stereocilia in the opposite direction decreases the open probability of the MET channel and causes hyperpolarization of the cell.

Depolarization of IHCs causes opening of voltage-gated calcium channels arrayed in stripes on the basolateral membrane close to ribbon synapses formed between the IHC and the afferent fiber of a myelinated type I spiral ganglion neuron. This results in a localized increase in cytosolic calcium ions which interact with Otoferlin (OTOF) on glutamate-containing synaptic vesicles at the ribbon structure to activate exocytosis of glutamate into the synapse formed with the afferent neuron (reviewed in Wichmann 2015, Pangrsic and Vogl 2018). Ribbon synapses are distinguished by electron-dense ribbon structures projecting from the presynaptic membrane into the cytosol and comprising at least BASSOON, RIBEYE (an isoform of CTBP2), and PICCOLINO (an isoform of PICCOLO). The ribbon structures appear to transiently bind synaptic vesicles and facilitate resupply of synaptic vesicles at active zones to refill the pool of readily releasable vesicles (reviewed in Moser et al. 2006, Moser et al. 2020).

In contrast with IHCs, OHCs mainly function in sound amplification by decreasing up to about 4% in length in response to depolarization caused by opening of the MET channel and increasing in length in response to hyperpolarization caused by channel closing, resulting in alternating compression and decompression between the reticular lamina and the basilar membrane. The changes in the length of the OHC are caused by very rapid (microseconds), voltage-sensitive changes in the conformation of the membrane protein prestin (SLC26A5). Stereociliary ATP2B2 (PMCA2) extrudes calcium ions and basally located KCNQ4 extrudes potassium ions to repolarize the OHC.

OHCs are synapsed with efferent cholinergic medial olivocochlear fibers (reviewed in Fritzsch and Elliott 2017, Fuchs and Lauer 2019). Acetylcholine released at the synapse binds an unusual, nicotine-antagonized, nicotinic receptor comprising CHRNA9 and CHRNA10. Upon binding acetylcholine, CHRNA9:CHRNA10 transports calcium ions into the OHC. The calcium activates SK2 potassium channels (KCNN2) and BK potassium channels (KCNMA1:KCNMB1) which extrude potassium ions, hyperpolarize the OHC, and inhibit activation of the OHC.

Loud sounds can cause a temporary threshold shift (temporary loss of hearing) caused by damage to stereocilia and synapses or permanent threshold shift (permanent loss of hearing) caused by damage or death of hair cells and neurons (reviewed in Kurabi et al. 2017).

Literature Reactome attaches

Hair Cell Transduction, Tuning, and Synaptic Transmission in the Mammalian CochleaCompr Physiol, 2017, vol. 7, p. 1197-1227PubMed 28915323
The physiology of mechanoelectrical transduction channels in hearingPhysiol. Rev., 2014, vol. 94, p. 951-86PubMed 24987009
Is TMC1 the Hair Cell Mechanotransducer Channel?Biophys. J., 2016, vol. 111, p. 3-9PubMed 27410728
Sensory Processing at Ribbon Synapses in the Retina and the CochleaPhysiol. Rev., 2020, vol. 100, p. 103-144PubMed 31373863
A Functional Perspective on the Evolution of the CochleaCold Spring Harb Perspect Med, 2019, vol. 9PubMed 30181353
Where hearing starts: the development of the mammalian cochleaJ. Anat., 2016, vol. 228, p. 233-54PubMed 26052920
Building and repairing the stereocilia cytoskeleton in mammalian auditory hair cellsHear. Res., 2019, vol. 376, p. 47-57PubMed 30638948

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-09-30 ET · Reactome pathway browser"Sensory processing of sound". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-9659379 with StableID: R-HSA-9659379.3 (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 77 genes in this human pathway; showing 1 to 77, 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
GeneACTB	AuthorityHGNC:132	Mapping file id60 NCBI file	EvidenceIEA
GeneACTG1	AuthorityHGNC:144	Mapping file id71 NCBI file	EvidenceIEA
GeneATP2B1	AuthorityHGNC:814	Mapping file id490 NCBI file	EvidenceIEA
GeneATP2B2	AuthorityHGNC:815	Mapping file id491 NCBI file	EvidenceIEA
GeneBSN	AuthorityHGNC:1117	Mapping file id8927 NCBI file	EvidenceIEA
GeneCABP1	AuthorityHGNC:1384	Mapping file id9478 NCBI file	EvidenceIEA
GeneCABP2	AuthorityHGNC:1385	Mapping file id51475 NCBI file	EvidenceIEA
GeneCACNA1D	AuthorityHGNC:1391	Mapping file id776 NCBI file	EvidenceIEA
GeneCACNA2D2	AuthorityHGNC:1400	Mapping file id9254 NCBI file	EvidenceIEA
GeneCACNB2	AuthorityHGNC:1402	Mapping file id783 NCBI file	EvidenceIEA
GeneCAPZA1	AuthorityHGNC:1488	Mapping file id829 NCBI file	EvidenceIEA
GeneCAPZA2	AuthorityHGNC:1490	Mapping file id830 NCBI file	EvidenceIEA
GeneCAPZB	AuthorityHGNC:1491	Mapping file id832 NCBI file	EvidenceIEA
GeneCASK	AuthorityHGNC:1497	Mapping file id8573 NCBI file	EvidenceIEA
GeneCDH23	AuthorityHGNC:13733	Mapping file id64072 NCBI file	EvidenceIEA
GeneCHRNA10	AuthorityHGNC:13800	Mapping file id57053 NCBI file	EvidenceIEA
GeneCHRNA9	AuthorityHGNC:14079	Mapping file id55584 NCBI file	EvidenceIEA
GeneCIB2	AuthorityHGNC:24579	Mapping file id10518 NCBI file	EvidenceIEA
GeneCLIC5	AuthorityHGNC:13517	Mapping file id53405 NCBI file	EvidenceIEA
GeneCTBP2	AuthorityHGNC:2495	Mapping file id1488 NCBI file	EvidenceIEA
GeneDNAJC5	AuthorityHGNC:16235	Mapping file id80331 NCBI file	EvidenceIEA
GeneEPB41L1	AuthorityHGNC:3378	Mapping file id2036 NCBI file	EvidenceIEA
GeneEPB41L3	AuthorityHGNC:3380	Mapping file id23136 NCBI file	EvidenceIEA
GeneEPS8	AuthorityHGNC:3420	Mapping file id2059 NCBI file	EvidenceIEA
GeneEPS8L2	AuthorityHGNC:21296	Mapping file id64787 NCBI file	EvidenceIEA
GeneESPN	AuthorityHGNC:13281	Mapping file id83715 NCBI file	EvidenceIEA
GeneESPNL	AuthorityHGNC:27937	Mapping file id339768 NCBI file	EvidenceIEA
GeneEZR	AuthorityHGNC:12691	Mapping file id7430 NCBI file	EvidenceIEA
GeneFSCN2	AuthorityHGNC:3960	Mapping file id25794 NCBI file	EvidenceIEA
GeneGRXCR1	AuthorityHGNC:31673	Mapping file id389207 NCBI file	EvidenceIEA
GeneGRXCR2	AuthorityHGNC:33862	Mapping file id643226 NCBI file	EvidenceIEA
GeneGSN	AuthorityHGNC:4620	Mapping file id2934 NCBI file	EvidenceIEA
GeneKCNMA1	AuthorityHGNC:6284	Mapping file id3778 NCBI file	EvidenceIEA
GeneKCNMB1	AuthorityHGNC:6285	Mapping file id3779 NCBI file	EvidenceIEA
GeneKCNN2	AuthorityHGNC:6291	Mapping file id3781 NCBI file	EvidenceIEA
GeneKCNQ4	AuthorityHGNC:6298	Mapping file id9132 NCBI file	EvidenceIEA
GeneLHFPL5	AuthorityHGNC:21253	Mapping file id222662 NCBI file	EvidenceIEA
GeneLRRC52	AuthorityHGNC:32156	Mapping file id440699 NCBI file	EvidenceIEA
GeneMPP1	AuthorityHGNC:7219	Mapping file id4354 NCBI file	EvidenceIEA
GeneMSN	AuthorityHGNC:7373	Mapping file id4478 NCBI file	EvidenceIEA
GeneMYH9	AuthorityHGNC:7579	Mapping file id4627 NCBI file	EvidenceIEA
GeneMYO15A	AuthorityHGNC:7594	Mapping file id51168 NCBI file	EvidenceIEA
GeneMYO1C	AuthorityHGNC:7597	Mapping file id4641 NCBI file	EvidenceIEA
GeneMYO3A	AuthorityHGNC:7601	Mapping file id53904 NCBI file	EvidenceIEA
GeneMYO3B	AuthorityHGNC:15576	Mapping file id140469 NCBI file	EvidenceIEA
GeneMYO7A	AuthorityHGNC:7606	Mapping file id4647 NCBI file	EvidenceIEA
GeneOTOF	AuthorityHGNC:8515	Mapping file id9381 NCBI file	EvidenceIEA
GeneOTOG	AuthorityHGNC:8516	Mapping file id340990 NCBI file	EvidenceIEA
GeneOTOGL	AuthorityHGNC:26901	Mapping file id283310 NCBI file	EvidenceIEA
GenePCDH15	AuthorityHGNC:14674	Mapping file id65217 NCBI file	EvidenceIEA
GenePCLO	AuthorityHGNC:13406	Mapping file id27445 NCBI file	EvidenceIEA
GenePJVK	AuthorityHGNC:29502	Mapping file id494513 NCBI file	EvidenceIEA
GenePLS1	AuthorityHGNC:9090	Mapping file id5357 NCBI file	EvidenceIEA
GeneRAB3A	AuthorityHGNC:9777	Mapping file id5864 NCBI file	EvidenceIEA
GeneRDX	AuthorityHGNC:9944	Mapping file id5962 NCBI file	EvidenceIEA
GeneRIPOR2	AuthorityHGNC:13872	Mapping file id9750 NCBI file	EvidenceIEA
GeneSLC17A8	AuthorityHGNC:20151	Mapping file id246213 NCBI file	EvidenceIEA
GeneSLC26A5	AuthorityHGNC:9359	Mapping file id375611 NCBI file	EvidenceIEA
GeneSNAP25	AuthorityHGNC:11132	Mapping file id6616 NCBI file	EvidenceIEA
GeneSPTAN1	AuthorityHGNC:11273	Mapping file id6709 NCBI file	EvidenceIEA
GeneSPTBN1	AuthorityHGNC:11275	Mapping file id6711 NCBI file	EvidenceIEA
GeneSTRC	AuthorityHGNC:16035	Mapping file id161497 NCBI file	EvidenceIEA
GeneSTX1A	AuthorityHGNC:11433	Mapping file id6804 NCBI file	EvidenceIEA
GeneSYN1	AuthorityHGNC:11494	Mapping file id6853 NCBI file	EvidenceIEA
GeneSYP	AuthorityHGNC:11506	Mapping file id6855 NCBI file	EvidenceIEA
GeneTMC1	AuthorityHGNC:16513	Mapping file id117531 NCBI file	EvidenceIEA
GeneTMC2	AuthorityHGNC:16527	Mapping file id117532 NCBI file	EvidenceIEA
GeneTMIE	AuthorityHGNC:30800	Mapping file id259236 NCBI file	EvidenceIEA
GeneTPRN	AuthorityHGNC:26894	Mapping file id286262 NCBI file	EvidenceIEA
GeneTRIOBP	AuthorityHGNC:17009	Mapping file id11078 NCBI file	EvidenceIEA
GeneTWF1	AuthorityHGNC:9620	Mapping file id5756 NCBI file	EvidenceIEA
GeneTWF2	AuthorityHGNC:9621	Mapping file id11344 NCBI file	EvidenceIEA
GeneUSH1C	AuthorityHGNC:12597	Mapping file id10083 NCBI file	EvidenceIEA
GeneUSH1G	AuthorityHGNC:16356	Mapping file id124590 NCBI file	EvidenceIEA
GeneVAMP2	AuthorityHGNC:12643	Mapping file id6844 NCBI file	EvidenceIEA
GeneWHRN	AuthorityHGNC:16361	Mapping file id25861 NCBI file	EvidenceIEA
GeneXIRP2	AuthorityHGNC:14303	Mapping file id129446 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

Sensory PerceptionR-HSA-9709957641 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.