Details for: SLC26A9

Gene ID: 115019

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: SLC26A9

Ensembl ID: ENSG00000174502

Description: solute carrier family 26 member 9

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • lung neuroendocrine cell CL1000223
    CSI 3.19
    rCSI 4.72%
    PRS 98.42
  • foveolar cell of stomach CL0002179
    CSI 2.24
    rCSI 4.78%
    PRS 99

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

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  • Node Size: Proportional to Target Cell CSI magnitude
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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 [SLC26A9](/details-gene/115019), or Solute Carrier Family 26 Member 9, is a protein-coding gene located on chromosome 1q32.1. It encodes a versatile anion transporter protein that functions as both a Cl-/HCO3- exchanger and a chloride channel ([Link](https://doi.org/10.1152/ajpcell.00030.2005), [Link](https://doi.org/10.1113/jphysiol.2007.135855)). Its primary role involves the transport of inorganic anions, including chloride, bicarbonate, sulfate, and oxalate, across the plasma membrane. **Overall**, expression data highlights its significant and specific role in specialized epithelial cells, particularly the [lung neuroendocrine cell](/details-cell/CL1000223) and the [foveolar cell of stomach](/details-cell/CL0002179), suggesting its importance in maintaining ion homeostasis in the respiratory and gastrointestinal tracts. ## Cellular Roles and Expression Landscape The expression profile of [SLC26A9](/details-gene/115019) indicates a highly specialized function within specific epithelial lineages. Its most significant expression is observed in [lung neuroendocrine cell](/details-cell/CL1000223) (CSI: 3.19) and [foveolar cell of stomach](/details-cell/CL0002179) (CSI: 2.24). This pattern underscores its role in tissues that require robust control of ion and fluid secretion. In the stomach, its high significance in [foveolar cell of stomach](/details-cell/CL0002179), the surface mucus-producing cells, is consistent with its function as a Cl-/HCO3- exchanger, which is critical for establishing the protective mucus-bicarbonate barrier against gastric acid ([Link](https://doi.org/10.1152/ajpcell.00030.2005)). Its activity helps regulate pH at the epithelial surface. The prominent expression in [lung neuroendocrine cell](/details-cell/CL1000223) suggests a potential role in modulating cellular excitability and hormone secretion in the pulmonary system, although this function is less characterized. The focused expression in these distinct cell types suggests that [SLC26A9](/details-gene/115019) is not a general housekeeping gene but rather a key functional component of specialized secretory epithelia. ## Pathways and Molecular Function Functionally, [SLC26A9](/details-gene/115019) is annotated as a multifunctional anion transporter. Its involvement in 'Bicarbonate transport' ([GO:0015701](https://www.ebi.ac.uk/QuickGO/term/GO:0015701)) and 'Chloride transmembrane transport' ([GO:1902476](https://www.ebi.ac.uk/QuickGO/term/GO:1902476)) are central to its physiological roles. These activities are categorized within broader Reactome pathways such as '[Multifunctional anion exchangers](/details-pathway/R-HSA-427601)' and '[SLC-mediated transmembrane transport](/details-pathway/R-HSA-425407)'. At the molecular level, it exhibits 'Chloride channel activity' ([GO:0005254](https://www.ebi.ac.uk/QuickGO/term/GO:0005254)) and 'Solute:inorganic anion antiporter activity' ([GO:0005452](https://www.ebi.ac.uk/QuickGO/term/GO:0005452)). Studies have confirmed that [SLC26A9](/details-gene/115019) can function as a constitutively active chloride channel, a property that distinguishes it from other members of the SLC26 family ([Link](https://doi.org/10.1113/jphysiol.2007.135855)). Cellular component annotations place the protein at the 'Apical plasma membrane' ([GO:0016324](https://www.ebi.ac.uk/QuickGO/term/GO:0016324)) and 'Cell surface' ([GO:0009986](https://www.ebi.ac.uk/QuickGO/term/GO:0009986)), which is consistent with its function in mediating ion flux between the cell and the extracellular environment, such as the gastric or airway lumen. ## Research Directions The specific expression and critical function of [SLC26A9](/details-gene/115019) in epithelial homeostasis present several avenues for future investigation. **Testable Hypotheses:** 1. **Gastric Mucosal Defense:** Given its function as a bicarbonate exchanger in [foveolar cell of stomach](/details-cell/CL0002179), it is hypothesized that reduced [SLC26A9](/details-gene/115019) activity or expression impairs the integrity of the gastric mucus-bicarbonate barrier, increasing susceptibility to acid-induced injury, gastritis, and peptic ulcer disease. 2. **Neuroendocrine Cell Excitability:** In [lung neuroendocrine cell](/details-cell/CL1000223), the chloride channel activity of [SLC26A9](/details-gene/115019) may be critical for regulating membrane potential and stimulus-secretion coupling. It is hypothesized that [SLC26A9](/details-gene/115019) modulates the release of neuropeptides (e.g., bombesin, calcitonin) in response to airway stimuli, thereby playing a role in pulmonary physiology and pathologies like neuroendocrine hyperplasia. **Proposed Experimental Approach:** To test the second hypothesis regarding the role of [SLC26A9](/details-gene/115019) in [lung neuroendocrine cell](/details-cell/CL1000223) function, one could utilize a human lung neuroendocrine tumor cell line (e.g., NCI-H727). [SLC26A9](/details-gene/115019) expression would first be silenced using shRNA or knocked out via CRISPR-Cas9. The impact on cellular function would then be assessed by comparing wild-type and modified cells. Key readouts would include: (1) measurement of basal and stimulated changes in membrane potential using whole-cell patch-clamp electrophysiology, and (2) quantification of neuropeptide secretion in response to depolarizing stimuli (e.g., high extracellular K+) or specific secretagogues using targeted mass spectrometry or ELISA. A significant alteration in either membrane potential or hormone release in the knockout cells would support a role for [SLC26A9](/details-gene/115019) in neuroendocrine signaling. **Therapeutic Potential:** [SLC26A9](/details-gene/115019) represents a promising therapeutic target for diseases characterized by defective epithelial ion transport. Its specific expression pattern may allow for targeted therapies with fewer off-target effects. For conditions involving fluid and mucus imbalance in the airways, such as cystic fibrosis, pharmacological **activation** of [SLC26A9](/details-gene/115019)-mediated chloride conductance could provide a therapeutic strategy to bypass the defective CFTR channel. Conversely, in pathologies associated with excessive anion secretion, such as certain forms of secretory diarrhea or gastric acid hypersecretion, selective **inhibition** of [SLC26A9](/details-gene/115019) could be beneficial. The development of small-molecule modulators targeting its channel or transporter function is a viable path for therapeutic innovation.

Genular Protein ID: 1360045468

Symbol: S26A9_HUMAN

Name: Anion transporter/exchanger protein 9

UniProtKB Accession Codes:

Q7LBE3 A7E2V6 B1AVM8 B1AVM9 B7ZKK2 Q96PK9 Q96RN0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChEBI 3 ChEMBL 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 7 EMDB 1 Ensembl 3 GO 19 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 2 Rhea 2 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 11834742

Title: Functional characterization of three novel tissue-specific anion exchangers SLC26A7, -A8, and -A9.

PubMed ID: 11834742

DOI: 10.1074/jbc.m111802200

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

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: 15800055

Title: SLC26A9 is expressed in gastric surface epithelial cells, mediates Cl-/HCO3- exchange, and is inhibited by NH4+.

PubMed ID: 15800055

DOI: 10.1152/ajpcell.00030.2005

PubMed ID: 17673510

Title: SLC26A9 is a Cl(-) channel regulated by the WNK kinases.

PubMed ID: 17673510

DOI: 10.1113/jphysiol.2007.135855

PubMed ID: 26801567

Title: Generation and functional characterization of epithelial cells with stable expression of SLC26A9 Cl- channels.

PubMed ID: 26801567

DOI: 10.1152/ajplung.00321.2015

PubMed ID: 22544634

Title: Functional analysis of nonsynonymous single nucleotide polymorphisms in human SLC26A9.

PubMed ID: 22544634

DOI: 10.1002/humu.22107

PubMed ID: 32818062

Title: Structural insights into the gating mechanism of human SLC26A9 mediated by its C-terminal sequence.

PubMed ID: 32818062

DOI: 10.1038/s41421-020-00193-7

Sequence Information:

  • Length: 791
  • Mass: 86988
  • Checksum: DC651F4E8DF2BF77
  • Sequence:
    • MSQPRPRYVV DRAAYSLTLF DDEFEKKDRT YPVGEKLRNA FRCSSAKIKA VVFGLLPVLS 
WLPKYKIKDY IIPDLLGGLS GGSIQVPQGM AFALLANLPA VNGLYSSFFP LLTYFFLGGV 
HQMVPGTFAV ISILVGNICL QLAPESKFQV FNNATNESYV DTAAMEAERL HVSATLACLT 
AIIQMGLGFM QFGFVAIYLS ESFIRGFMTA AGLQILISVL KYIFGLTIPS YTGPGSIVFT 
FIDICKNLPH TNIASLIFAL ISGAFLVLVK ELNARYMHKI RFPIPTEMIV VVVATAISGG 
CKMPKKYHMQ IVGEIQRGFP TPVSPVVSQW KDMIGTAFSL AIVSYVINLA MGRTLANKHG 
YDVDSNQEMI ALGCSNFFGS FFKIHVICCA LSVTLAVDGA GGKSQVASLC VSLVVMITML 
VLGIYLYPLP KSVLGALIAV NLKNSLKQLT DPYYLWRKSK LDCCIWVVSF LSSFFLSLPY 
GVAVGVAFSV LVVVFQTQFR NGYALAQVMD TDIYVNPKTY NRAQDIQGIK IITYCSPLYF 
ANSEIFRQKV IAKTGMDPQK VLLAKQKYLK KQEKRRMRPT QQRRSLFMKT KTVSLQELQQ 
DFENAPPTDP NNNQTPANGT SVSYITFSPD SSSPAQSEPP ASAEAPGEPS DMLASVPPFV 
TFHTLILDMS GVSFVDLMGI KALAKLSSTY GKIGVKVFLV NIHAQVYNDI SHGGVFEDGS 
LECKHVFPSI HDAVLFAQAN ARDVTPGHNF QGAPGDAELS LYDSEEDIRS YWDLEQEMFG 
SMFHAETLTA L

Genular Protein ID: 3441920835

Symbol: B3KXK1_HUMAN

Name: N/A

UniProtKB Accession Codes:

B3KXK1

Database IDs:

ARBA 5 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 5 Gene3D 1 InterPro 4 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 2 PeptideAtlas 1 Pfam 2 PharmGKB 1 RefSeq 1 SAM 2 SUPFAM 1

Sequence Information:

  • Length: 459
  • Mass: 50415
  • Checksum: A2BA138AD9F3DFC8
  • Sequence:
    • MIGTAFSLAI VSYVINLAMG RTLANKHGYD VDSNQEMIAL GCSNFFGSFF KIHVICCALS 
VTLAVDGAGG KSQVASLCVS LVVMITMLVL GIYLYPLPKS VLGALIAVNL KNSLKQLTDP 
YYLWRKSKLG CCIWVVSFLS SFFLSLPYGV AVGVAFSVLV VVFQTQFRNG YALAQVMDTD 
IYVNPKTYNR AQDIQGIKII TYCSPLYFAN SEIFRQKVIA KTGMDPQKVL LAKQKYLKKQ 
EKRRMRPTQQ RRSLFMKTKT VSLQELQQDF ENAPPTDPNN NQTPANGTSV SYITFSPDSS 
SPAQSEPPAS AEAPGEPSDM LASVPPFVTF HTLILDMSGV SFVDLMGIKA LAKLSSTYGK 
IGVKVFLVNI HAQVYNDISH GGVFEDGSLE CKHVFPSIHD AVLFAQANAR DVTPGHNFQG 
APGDAELSLY DSEEDIRSYW DLEQEMFGSM FHAETLTAL