Details for: SLC26A5

Gene ID: 375611

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: SLC26A5

Ensembl ID: ENSG00000170615

Description: solute carrier family 26 member 5

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • pulmonary alveolar type 2 cell CL0002063
    CSI 12.76
    rCSI 19.79%
    PRS 96.75
  • conventional dendritic cell CL0000990
    CSI 11.59
    rCSI 9.67%
    PRS 91.08
  • innate lymphoid cell CL0001065
    CSI 10.2
    rCSI 21.07%
    PRS 91.51
  • endothelial cell of pericentral hepatic sinusoid CL0019022
    CSI 8.18
    rCSI 25.19%
    PRS 97.11
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 6.46
    rCSI 7.83%
    PRS 82.16
  • lung ciliated cell CL1000271
    CSI 6.36
    rCSI 7.35%
    PRS 93.62
  • cerebellar granule cell CL0001031
    CSI 5.21
    rCSI 7.65%
    PRS 93.73
  • lung secretory cell CL1000272
    CSI 4.26
    rCSI 10.54%
    PRS 97.71
  • Bergmann glial cell CL0000644
    CSI 4.02
    rCSI 5.5%
    PRS 92.61
  • retinal bipolar neuron CL0000748
    CSI 3.82
    rCSI 7.16%
    PRS 92.24
  • ependymal cell CL0000065
    CSI 3.26
    rCSI 6.61%
    PRS 85.8
  • cytotoxic T cell CL0000910
    CSI 3.11
    rCSI 17.81%
    PRS 93.86
  • cerebral cortex endothelial cell CL1001602
    CSI 3.06
    rCSI 5.3%
    PRS 94.45
  • chondrocyte CL0000138
    CSI 3.03
    rCSI 4.81%
    PRS 94.32
  • basal cell of epidermis CL0002187
    CSI 2.73
    rCSI 4.85%
    PRS 75.76
  • melanocyte of skin CL1000458
    CSI 2.3
    rCSI 3.14%
    PRS 76.39
  • pulmonary alveolar type 1 cell CL0002062
    CSI 1.71
    rCSI 9.88%
    PRS 95.09
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.61
    rCSI 2.59%
    PRS 91.16
  • helper T cell CL0000912
    CSI 1.56
    rCSI 2.21%
    PRS 92.12
  • retinal ganglion cell CL0000740
    CSI 1.44
    rCSI 3.18%
    PRS 91.12
  • suprabasal keratinocyte CL4033013
    CSI 0.95
    rCSI 1.55%
    PRS 76.61
  • ON parasol ganglion cell CL4033052
    CSI 0.56
    rCSI 7.88%
    PRS 91.68
  • ON midget ganglion cell CL4033046
    CSI 0.36
    rCSI 7.41%
    PRS 91.34
  • OFF midget ganglion cell CL4033047
    CSI 0.36
    rCSI 7.34%
    PRS 91.61

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [SLC26A5](/details-gene/375611), also known as prestin, is a protein-coding gene located on chromosome 7q22.1. It is a member of the solute carrier family 26 and functions primarily as an anion transporter, facilitating the exchange of chloride, bicarbonate, sulfate, and other anions across the plasma membrane. Its most well-characterized role is as the motor protein in cochlear outer hair cells, where its electromotive activity is essential for sound amplification and the sensory perception of sound ([Link](https://doi.org/10.1016/j.cell.2021.07.034)). Mutations in [SLC26A5](/details-gene/375611) are a known cause of non-syndromic hearing loss ([Link](https://doi.org/10.1093/hmg/ddg127)). While its function in the auditory system is well-established, expression data reveals significant roles in a diverse range of other cell types. **Overall**, it shows the highest significance in [pulmonary alveolar type 2 cell](/details-cell/CL0002063), [conventional dendritic cell](/details-cell/CL0000990), and [innate lymphoid cell](/details-cell/CL0001065), suggesting that its physiological functions may extend far beyond hearing, potentially encompassing roles in lung homeostasis and immune regulation. ## Cellular Roles and Expression Landscape The expression profile of [SLC26A5](/details-gene/375611) indicates a broader functional context than its classical role in the auditory system would suggest. The **Overall** analysis identifies [pulmonary alveolar type 2 cell](/details-cell/CL0002063) (CSI: 12.76) as the cell type where it has the highest significance, pointing towards a previously underappreciated role in the respiratory system. This is further supported by its notable significance in other lung-resident cells, including [lung ciliated cell](/details-cell/CL1000271) and [lung secretory cell](/details-cell/CL1000272). A second major functional axis appears to be within the immune system. [SLC26A5](/details-gene/375611) is a significant marker in several key immune populations, including [conventional dendritic cell](/details-cell/CL0000990) (CSI: 11.59), [innate lymphoid cell](/details-cell/CL0001065) (CSI: 10.20), and [cytotoxic T cell](/details-cell/CL0000910). This pattern suggests a potential involvement in modulating immune cell activity through ion transport, which is critical for processes like cell motility, activation, and volume regulation. Furthermore, the gene shows notable expression in various neural and glial cell types, such as [cerebellar granule cell](/details-cell/CL0001031), [Bergmann glial cell](/details-cell/CL0000644), and [retinal bipolar neuron](/details-cell/CL0000748), as well as in endothelial cells. This diverse expression landscape suggests that the anion transport capabilities of [SLC26A5](/details-gene/375611) may be utilized by a wide variety of tissues for maintaining cellular homeostasis. ## Pathways and Molecular Function The molecular functions of [SLC26A5](/details-gene/375611) are centered on its activity as a transmembrane anion transporter. Gene Ontology annotations highlight its role in [chloride transmembrane transporter activity](/details-go/GO:0015108), [bicarbonate transmembrane transporter activity](/details-go/GO:0015106), and [sulfate transmembrane transporter activity](/details-go/GO:0015116). This transport activity is fundamental to its well-documented role in the auditory system, as detailed in Reactome pathways like '[Sensory processing of sound by outer hair cells of the cochlea](/details-pathway/R-HSA-9662361)'. In this context, voltage-dependent conformational changes in [SLC26A5](/details-gene/375611) drive the rapid cell length changes (electromotility) necessary for cochlear amplification. Consistent with its high significance in non-auditory cells, its molecular functions are likely relevant to other biological processes. Its role in [bicarbonate transport](/details-go/GO:0015701) and [chloride transport](/details-go/GO:0006821) is highly relevant for [pulmonary alveolar type 2 cell](/details-cell/CL0002063), where such ion exchange is critical for regulating alveolar fluid balance and pH. Furthermore, its annotated involvement in the '[Positive regulation of cell motility](/details-go/GO:2000147)' and '[Regulation of cell shape](/details-go/GO:0008360)' may explain its significance in migratory immune cells like [conventional dendritic cell](/details-cell/CL0000990), where ion fluxes are essential for cytoskeletal dynamics and cell movement. ## Research Directions The most compelling area for future research is to elucidate the functional roles of [SLC26A5](/details-gene/375611) outside of the cochlea, particularly in the pulmonary and immune systems where it demonstrates high significance. The disjunct between its well-defined role in hearing and its widespread, significant expression in other tissues suggests a moonlighting functionality that is currently uncharacterized. Based on the available data, several testable hypotheses can be proposed: 1. In [pulmonary alveolar type 2 cell](/details-cell/CL0002063), [SLC26A5](/details-gene/375611) functions as a key anion exchanger that regulates the composition of the alveolar lining fluid, thereby influencing surfactant function and gas exchange. Its dysfunction could contribute to pulmonary edema or other respiratory pathologies. 2. In antigen-presenting cells such as [conventional dendritic cell](/details-cell/CL0000990), [SLC26A5](/details-gene/375611)-mediated ion transport is crucial for regulating endosomal pH, a process vital for efficient antigen processing and presentation to T cells. To test the first hypothesis regarding its pulmonary role, a compelling experimental approach would be to utilize a lung organoid model or primary cultures of human [pulmonary alveolar type 2 cell](/details-cell/CL0002063). Using CRISPR-Cas9 to knock out [SLC26A5](/details-gene/375611) in these cells, one could measure changes in transepithelial ion transport, alveolar fluid clearance rates, and the secretion profile of surfactant proteins (e.g., SP-B, SP-C) using electrophysiological assays and mass spectrometry, respectively. From a therapeutic perspective, [SLC26A5](/details-gene/375611) is already a target of interest for gene therapy approaches aimed at restoring function and treating certain forms of congenital deafness ([Link](https://doi.org/10.1093/hmg/ddg127)). However, the discovery of its high significance in critical cell types such as pulmonary and immune cells introduces a major consideration for safety and off-target effects. Any therapeutic strategy, particularly one involving systemic delivery or activation of the gene, must be preceded by a thorough investigation of its function in these other vital tissues to avoid unintended consequences on lung or immune homeostasis.

Genular Protein ID: 2566945520

Symbol: S26A5_HUMAN

Name: Solute carrier family 26 member 5

UniProtKB Accession Codes:

P58743 Q496J2 Q7Z7F3 Q86UF8 Q86UF9 Q86UG0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 5 CDD 1 CTD 1 ChEBI 3 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 9 EMDB 4 Ensembl 7 ExpressionAtlas 1 GO 29 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 4 PDBsum 4 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 Reactome 1 RefSeq 7 Rhea 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12719379

Title: Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss.

PubMed ID: 12719379

DOI: 10.1093/hmg/ddg127

PubMed ID: 12853948

Title: The DNA sequence of human chromosome 7.

PubMed ID: 12853948

DOI: 10.1038/nature01782

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 34390643

Title: Molecular mechanism of prestin electromotive signal amplification.

PubMed ID: 34390643

DOI: 10.1016/j.cell.2021.07.034

Sequence Information:

  • Length: 744
  • Mass: 81264
  • Checksum: 9E64BE6DB2DC065E
  • Sequence:
    • MDHAEENEIL AATQRYYVER PIFSHPVLQE RLHTKDKVPD SIADKLKQAF TCTPKKIRNI 
IYMFLPITKW LPAYKFKEYV LGDLVSGIST GVLQLPQGLA FAMLAAVPPI FGLYSSFYPV 
IMYCFLGTSR HISIGPFAVI SLMIGGVAVR LVPDDIVIPG GVNATNGTEA RDALRVKVAM 
SVTLLSGIIQ FCLGVCRFGF VAIYLTEPLV RGFTTAAAVH VFTSMLKYLF GVKTKRYSGI 
FSVVYSTVAV LQNVKNLNVC SLGVGLMVFG LLLGGKEFNE RFKEKLPAPI PLEFFAVVMG 
TGISAGFNLK ESYNVDVVGT LPLGLLPPAN PDTSLFHLVY VDAIAIAIVG FSVTISMAKT 
LANKHGYQVD GNQELIALGL CNSIGSLFQT FSISCSLSRS LVQEGTGGKT QLAGCLASLM 
ILLVILATGF LFESLPQAVL SAIVIVNLKG MFMQFSDLPF FWRTSKIELT IWLTTFVSSL 
FLGLDYGLIT AVIIALLTVI YRTQSPSYKV LGKLPETDVY IDIDAYEEVK EIPGIKIFQI 
NAPIYYANSD LYSNALKRKT GVNPAVIMGA RRKAMRKYAK EVGNANMANA TVVKADAEVD 
GEDATKPEEE DGEVKYPPIV IKSTFPEEMQ RFMPPGDNVH TVILDFTQVN FIDSVGVKTL 
AGIVKEYGDV GIYVYLAGCS AQVVNDLTRN RFFENPALWE LLFHSIHDAV LGSQLREALA 
EQEASAPPSQ EDLEPNATPA TPEA