Details for: SCNN1B

Gene ID: 6338

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: SCNN1B

Ensembl ID: ENSG00000168447

Description: sodium channel epithelial 1 subunit beta

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • ionocyte CL0005006
    CSI 23.25
    rCSI 24.92%
    PRS 91.63
  • pulmonary ionocyte CL0017000
    CSI 20.13
    rCSI 24.51%
    PRS 93.66
  • colon epithelial cell CL0011108
    CSI 8.56
    rCSI 8.97%
    PRS 88.08
  • intestine goblet cell CL0019031
    CSI 6.93
    rCSI 6.16%
    PRS 87.87
  • epithelial cell of lower respiratory tract CL0002632
    CSI 4.83
    rCSI 3.75%
    PRS 92.78
  • nasal mucosa goblet cell CL0002480
    CSI 4.57
    rCSI 5.3%
    PRS 90.81
  • secretory cell CL0000151
    CSI 3.85
    rCSI 4.01%
    PRS 89.22
  • club cell CL0000158
    CSI 3.66
    rCSI 5.36%
    PRS 85.84
  • kidney collecting duct principal cell CL1001431
    CSI 3.62
    rCSI 18.21%
    PRS 85.41
  • epithelial cell of lung CL0000082
    CSI 3.51
    rCSI 2.91%
    PRS 91.14
  • ependymal cell CL0000065
    CSI 3.33
    rCSI 6.75%
    PRS 72.93
  • brush cell of tracheobronchial tree CL0002075
    CSI 3.26
    rCSI 9.66%
    PRS 95.57
  • foveolar cell of stomach CL0002179
    CSI 2.98
    rCSI 6.34%
    PRS 92.37
  • respiratory goblet cell CL0002370
    CSI 2.75
    rCSI 29.95%
    PRS 93.02
  • duct epithelial cell CL0000068
    CSI 2.64
    rCSI 3.86%
    PRS 93.53
  • respiratory suprabasal cell CL4033048
    CSI 2.44
    rCSI 3.12%
    PRS 92
  • neural progenitor cell CL0011020
    CSI 2.41
    rCSI 10.59%
    PRS 80.05
  • kidney connecting tubule epithelial cell CL1000768
    CSI 2.37
    rCSI 6.02%
    PRS 84.13
  • lung secretory cell CL1000272
    CSI 2.07
    rCSI 5.13%
    PRS 90.9
  • enterocyte of epithelium of large intestine CL0002071
    CSI 2.07
    rCSI 10.88%
    PRS 92.22
  • renal principal cell CL0005009
    CSI 1.97
    rCSI 5.12%
    PRS 89.62
  • bronchial goblet cell CL1000312
    CSI 1.95
    rCSI 7.81%
    PRS 93.33
  • respiratory basal cell CL0002633
    CSI 1.78
    rCSI 1.85%
    PRS 91.92
  • pulmonary alveolar type 1 cell CL0002062
    CSI 1.78
    rCSI 10.26%
    PRS 87.41
  • tracheal goblet cell CL1000329
    CSI 1.69
    rCSI 3.68%
    PRS 92.59
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 1.63
    rCSI 17.25%
    PRS 86.55
  • basal cell of epithelium of trachea CL1000348
    CSI 1.58
    rCSI 11.17%
    PRS 90.95
  • transit amplifying cell CL0009010
    CSI 1.55
    rCSI 2.36%
    PRS 93.65
  • kidney connecting tubule principal cell CL4030018
    CSI 1.42
    rCSI 10.29%
    PRS 89.16
  • airway submucosal gland duct basal cell CL4033024
    CSI 1.32
    rCSI 8.44%
    PRS 91.7
  • squamous epithelial cell CL0000076
    CSI 1.3
    rCSI 3.09%
    PRS 87.7
  • lung goblet cell CL1000143
    CSI 0.9
    rCSI 10.09%
    PRS 93.88

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.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • 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 [SCNN1B](/details-gene/6338), or Sodium Channel Epithelial 1 Subunit Beta, encodes the beta subunit of the amiloride-sensitive epithelial sodium channel (ENaC). This channel is a critical component for maintaining sodium and water balance across epithelial tissues. **Overall**, the expression of [SCNN1B](/details-gene/6338) is exceptionally high in specialized epithelial cells, such as [ionocytes](/details-cell/CL0005006) in the lungs and [kidney collecting duct principal cells](/details-cell/CL1001431), underscoring its essential role in ion and fluid homeostasis in the respiratory, renal, and gastrointestinal systems. Consistent with this function, mutations in [SCNN1B](/details-gene/6338) are associated with inherited disorders of blood pressure regulation, including Liddle's syndrome ([177200](https://omim.org/entry/177200)), a form of severe hypertension, and pseudohypoaldosteronism ([600760](https://omim.org/entry/600760)), which involves salt wasting ([Link](https://doi.org/10.1016/0092-8674(94)90250-x); [Link](https://doi.org/10.1210/jcem-73-5-936)). ## Cellular Roles and Expression Landscape The expression profile of [SCNN1B](/details-gene/6338) highlights its specialized function as a cornerstone of epithelial transport physiology. **Overall**, its significance is most pronounced in cells dedicated to ion exchange. It is the top marker for [ionocyte](/details-cell/CL0005006) (CSI: 23.25) and [pulmonary ionocyte](/details-cell/CL0017000) (CSI: 20.13), rare but potent cell types responsible for regulating the composition of airway surface liquid. This gene's role extends across multiple organ systems where fluid and electrolyte balance are paramount: * **Gastrointestinal Tract:** High significance in [colon epithelial cell](/details-cell/CL0011108) and secretory cells like [intestine goblet cell](/details-cell/CL0019031) suggests a role in intestinal sodium absorption and mucus hydration. * **Respiratory System:** Beyond ionocytes, its high CSI in [epithelial cell of lower respiratory tract](/details-cell/CL0002632), [club cell](/details-cell/CL0000158), and [respiratory goblet cell](/details-cell/CL0002370) points to a broad function in maintaining airway hydration and facilitating mucociliary clearance. * **Renal System:** Its importance in [kidney collecting duct principal cell](/details-cell/CL1001431) is consistent with its well-established role in the final regulation of sodium reabsorption and blood pressure control under the influence of aldosterone. * **Other Tissues:** Notable expression in [ependymal cell](/details-cell/CL0000065) suggests a potential role in regulating cerebrospinal fluid composition. The highly specific expression pattern, concentrated in epithelial cells at the interface with the external environment or body fluids, firmly establishes [SCNN1B](/details-gene/6338) as a key mediator of organism-level homeostasis. ## Pathways and Molecular Function The functional annotations for [SCNN1B](/details-gene/6338) confirm its identity as a subunit of a transmembrane ion channel. As part of the [Sodium channel complex](/details-go/GO:0034706) located on the [Apical plasma membrane](/details-go/GO:0016324), it directly facilitates [Sodium ion import across plasma membrane](/details-go/GO:0098719) through its [Ligand-gated sodium channel activity](/details-go/GO:0015280). This core molecular function drives several critical biological processes: * **Homeostasis:** It is central to [Sodium ion homeostasis](/details-go/GO:0055078), [Potassium ion homeostasis](/details-go/GO:0055075), and [Multicellular organismal-level water homeostasis](/details-go/GO:0050891). This is consistent with its high expression in kidney and colon epithelial cells. * **Systemic Regulation:** Its activity is a key determinant in the [Regulation of blood pressure](/details-go/GO:0008217) and is modulated by the [Aldosterone metabolic process](/details-go/GO:0032341), aligning with its clinical relevance in hypertension and pseudohypoaldosteronism ([Link](https://doi.org/10.1210/jcem.87.7.8674)). * **Sensory Perception:** An intriguing role is suggested by its involvement in [Sensory perception of salty taste](/details-go/GO:0050914) and the broader [Sensory perception](/details-reactome/R-HSA-9709957) pathway. This indicates that the ENaC complex, including [SCNN1B](/details-gene/6338), functions as a salt sensor in taste buds. * **Secretory Functions:** The gene's connection to [Epithelial fluid transport](/details-go/GO:0042045) and [Mucus secretion](/details-go/GO:0070254) is consistent with its high expression in various goblet cells of the respiratory and intestinal tracts. The Reactome database reinforces these functions, placing [SCNN1B](/details-gene/6338) within the major pathways of [Ion channel transport](/details-reactome/R-HSA-983712) and [Transport of small molecules](/details-reactome/R-HSA-382551). ## Research Directions The well-defined function and highly specific expression of [SCNN1B](/details-gene/6338) provide a strong foundation for further investigation into its roles in health and disease. Based on the available data, several testable hypotheses can be proposed: 1. **Hypothesis 1:** Given its exceptionally high expression in [pulmonary ionocytes](/details-cell/CL0017000), [SCNN1B](/details-gene/6338) activity in this specific cell type is the primary determinant of airway surface liquid height and pH. Its dysregulation may be a key factor in diseases characterized by mucus dehydration, such as cystic fibrosis, independent of CFTR function. 2. **Hypothesis 2:** The expression of [SCNN1B](/details-gene/6338) in chemosensory cells like [brush cell of tracheobronchial tree](/details-cell/CL0002075) suggests it functions as a luminal sodium sensor that triggers protective airway reflexes. Increased luminal sodium could be detected by [SCNN1B](/details-gene/6338)-containing channels, leading to vagal nerve activation and subsequent bronchoconstriction or mucus secretion. A key experiment to test the second hypothesis could be performed using advanced genetic and physiological models. Specifically, one could generate a conditional knockout mouse model where [SCNN1B](/details-gene/6338) is selectively deleted in airway brush cells. By employing *in situ* calcium imaging on tracheal preparations or by making direct electrophysiological recordings from afferent nerves, researchers could assess the cellular and neural responses to perfusion with solutions of varying sodium concentrations. A loss of response in the knockout mice compared to wild-type controls would provide direct evidence for [SCNN1B](/details-gene/6338) as a crucial component of an airway sodium-sensing mechanism. **Therapeutic Potential:** [SCNN1B](/details-gene/6338) is already a clinically validated therapeutic target. Its function can be modulated for therapeutic benefit through two primary strategies: * **Inhibition:** For gain-of-function mutations causing Liddle's syndrome and potentially other forms of salt-sensitive hypertension, pharmacologic inhibition is the clear strategy. Amiloride and related potassium-sparing diuretics already target the ENaC complex. Developing more specific inhibitors of the [SCNN1B](/details-gene/6338) subunit or inhaled formulations could offer targeted treatment for respiratory conditions involving airway dehydration. * **Activation:** For loss-of-function diseases like systemic pseudohypoaldosteronism, therapeutic approaches aimed at activating the channel or restoring its function would be necessary. This is more challenging but could involve small molecule potentiators or gene therapy approaches aimed at restoring functional [SCNN1B](/details-gene/6338) expression in target tissues like the kidney or lung.

Genular Protein ID: 846169625

Symbol: SCNNB_HUMAN

Name: Amiloride-sensitive sodium channel subunit beta

UniProtKB Accession Codes:

P51168 C5HTZ2 O60891 Q96KG2 Q9UJ32 Q9UMU5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CORUM 1 CTD 1 ChEMBL 1 ChiTaRS 1 ComplexPortal 3 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 3 DrugCentral 1 ELM 1 EMBL 18 EMDB 2 Ensembl 2 ExpressionAtlas 1 GO 34 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 7 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OpenTargets 1 Orphanet 3 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PIR 1 PRINTS 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 2 RefSeq 1 SIGNOR 1 SMR 1 STRING 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 7490094

Title: Cloning, chromosomal localization, and physical linkage of the beta and gamma subunits (SCNN1B and SCNN1G) of the human epithelial amiloride-sensitive sodium channel.

PubMed ID: 7490094

DOI: 10.1006/geno.1995.1188

PubMed ID: 7762608

Title: Cloning and expression of the beta- and gamma-subunits of the human epithelial sodium channel.

PubMed ID: 7762608

DOI: 10.1152/ajpcell.1995.268.5.c1157

PubMed ID: 9813171

Title: Gene structure of the human amiloride-sensitive epithelial sodium channel beta subunit.

PubMed ID: 9813171

DOI: 10.1006/bbrc.1998.9625

PubMed ID: 12107247

Title: Novel mutations responsible for autosomal recessive multisystem pseudohypoaldosteronism and sequence variants in epithelial sodium channel alpha-, beta-, and gamma-subunit genes.

PubMed ID: 12107247

DOI: 10.1210/jcem.87.7.8674

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: 10493829

Title: Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q.

PubMed ID: 10493829

DOI: 10.1006/geno.1999.5927

PubMed ID: 7954808

Title: Liddle's syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel.

PubMed ID: 7954808

DOI: 10.1016/0092-8674(94)90250-x

PubMed ID: 1939532

Title: Type I pseudohypoaldosteronism includes two clinically and genetically distinct entities with either renal or multiple target organ defects.

PubMed ID: 1939532

DOI: 10.1210/jcem-73-5-936

PubMed ID: 7499195

Title: Molecular cloning and functional expression of a novel amiloride-sensitive Na+ channel.

PubMed ID: 7499195

DOI: 10.1074/jbc.270.46.27411

PubMed ID: 9169421

Title: Identification of novel human WW domain-containing proteins by cloning of ligand targets.

PubMed ID: 9169421

DOI: 10.1074/jbc.272.23.14611

PubMed ID: 11244092

Title: The Nedd4-like protein KIAA0439 is a potential regulator of the epithelial sodium channel.

PubMed ID: 11244092

DOI: 10.1074/jbc.c000906200

PubMed ID: 12167593

Title: Ubiquitin-protein ligase WWP2 binds to and downregulates the epithelial Na(+) channel.

PubMed ID: 12167593

DOI: 10.1152/ajprenal.00080.2002

PubMed ID: 16423824

Title: Delta-subunit confers novel biophysical features to alpha beta gamma-human epithelial sodium channel (ENaC) via a physical interaction.

PubMed ID: 16423824

DOI: 10.1074/jbc.m512293200

PubMed ID: 18634878

Title: Renin-aldosterone response, urinary Na/K ratio and growth in pseudohypoaldosteronism patients with mutations in epithelial sodium channel (ENaC) subunit genes.

PubMed ID: 18634878

DOI: 10.1016/j.jsbmb.2008.06.013

PubMed ID: 20064610

Title: Truncated beta epithelial sodium channel (ENaC) subunits responsible for multi-system pseudohypoaldosteronism support partial activity of ENaC.

PubMed ID: 20064610

DOI: 10.1016/j.jsbmb.2010.01.002

PubMed ID: 22207244

Title: Epithelial sodium channels (ENaC) are uniformly distributed on motile cilia in the oviduct and the respiratory airways.

PubMed ID: 22207244

DOI: 10.1007/s00418-011-0904-1

PubMed ID: 22493497

Title: Regulation of epithelial sodium channel trafficking by proprotein convertase subtilisin/kexin type 9 (PCSK9).

PubMed ID: 22493497

DOI: 10.1074/jbc.m112.363382

PubMed ID: 24124190

Title: Identification of the SPLUNC1 ENaC-inhibitory domain yields novel strategies to treat sodium hyperabsorption in cystic fibrosis airway epithelial cultures.

PubMed ID: 24124190

DOI: 10.1152/ajplung.00103.2013

PubMed ID: 23547933

Title: ENaC modulators and renal disease.

PubMed ID: 23547933

DOI: 10.2174/1874467211306010005

PubMed ID: 24043776

Title: Molecular basis for pH-dependent mucosal dehydration in cystic fibrosis airways.

PubMed ID: 24043776

DOI: 10.1073/pnas.1311999110

PubMed ID: 26772908

Title: Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue distribution, and associated inherited diseases.

PubMed ID: 26772908

DOI: 10.1016/j.gene.2015.12.061

PubMed ID: 7550319

Title: Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle syndrome.

PubMed ID: 7550319

DOI: 10.1038/ng0995-76

PubMed ID: 8524790

Title: A de novo missense mutation of the beta subunit of the epithelial sodium channel causes hypertension and Liddle syndrome, identifying a proline-rich segment critical for regulation of channel activity.

PubMed ID: 8524790

DOI: 10.1073/pnas.92.25.11495

PubMed ID: 8601645

Title: Liddle disease caused by a missense mutation of beta subunit of the epithelial sodium channel gene.

PubMed ID: 8601645

DOI: 10.1172/jci118606

PubMed ID: 8589714

Title: Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1.

PubMed ID: 8589714

DOI: 10.1038/ng0396-248

PubMed ID: 9674649

Title: Genetic analysis of the beta subunit of the epithelial Na+ channel in essential hypertension.

PubMed ID: 9674649

DOI: 10.1161/01.hyp.32.1.129

PubMed ID: 9626162

Title: A family with Liddle's syndrome caused by a new missense mutation in the beta subunit of the epithelial sodium channel.

PubMed ID: 9626162

DOI: 10.1210/jcem.83.6.5030

PubMed ID: 9794716

Title: Genetic analysis of the epithelial sodium channel in Liddle's syndrome.

PubMed ID: 9794716

DOI: 10.1097/00004872-199816080-00008

PubMed ID: 10404817

Title: Polymorphisms of amiloride-sensitive sodium channel subunits in five sporadic cases of pseudohypoaldosteronism: do they have pathologic potential?

PubMed ID: 10404817

DOI: 10.1210/jcem.84.7.5857

PubMed ID: 12714866

Title: A new mutation, R563Q, of the beta subunit of the epithelial sodium channel associated with low-renin, low-aldosterone hypertension.

PubMed ID: 12714866

DOI: 10.1097/00004872-200305000-00016

PubMed ID: 15853823

Title: Novel mutations in epithelial sodium channel (ENaC) subunit genes and phenotypic expression of multisystem pseudohypoaldosteronism.

PubMed ID: 15853823

DOI: 10.1111/j.1365-2265.2005.02255.x

PubMed ID: 16207733

Title: Mutations in the beta-subunit of the epithelial Na+ channel in patients with a cystic fibrosis-like syndrome.

PubMed ID: 16207733

DOI: 10.1093/hmg/ddi374

PubMed ID: 15483078

Title: Liddle's syndrome caused by a novel mutation in the proline-rich PY motif of the epithelial sodium channel beta-subunit.

PubMed ID: 15483078

DOI: 10.1210/jc.2004-1027

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

PubMed ID: 18507830

Title: Could a defective epithelial sodium channel lead to bronchiectasis.

PubMed ID: 18507830

DOI: 10.1186/1465-9921-9-46

PubMed ID: 19017867

Title: Genetic analysis of Rwandan patients with cystic fibrosis-like symptoms: identification of novel cystic fibrosis transmembrane conductance regulator and epithelial sodium channel gene variants.

PubMed ID: 19017867

DOI: 10.1378/chest.08-2246

Sequence Information:

  • Length: 640
  • Mass: 72659
  • Checksum: 5249867F0A960E0C
  • Sequence:
    • MHVKKYLLKG LHRLQKGPGY TYKELLVWYC DNTNTHGPKR IICEGPKKKA MWFLLTLLFA 
ALVCWQWGIF IRTYLSWEVS VSLSVGFKTM DFPAVTICNA SPFKYSKIKH LLKDLDELME 
AVLERILAPE LSHANATRNL NFSIWNHTPL VLIDERNPHH PMVLDLFGDN HNGLTSSSAS 
EKICNAHGCK MAMRLCSLNR TQCTFRNFTS ATQALTEWYI LQATNIFAQV PQQELVEMSY 
PGEQMILACL FGAEPCNYRN FTSIFYPHYG NCYIFNWGMT EKALPSANPG TEFGLKLILD 
IGQEDYVPFL ASTAGVRLML HEQRSYPFIR DEGIYAMSGT ETSIGVLVDK LQRMGEPYSP 
CTVNGSEVPV QNFYSDYNTT YSIQACLRSC FQDHMIRNCN CGHYLYPLPR GEKYCNNRDF 
PDWAHCYSDL QMSVAQRETC IGMCKESCND TQYKMTISMA DWPSEASEDW IFHVLSQERD 
QSTNITLSRK GIVKLNIYFQ EFNYRTIEES AANNIVWLLS NLGGQFGFWM GGSVLCLIEF 
GEIIIDFVWI TIIKLVALAK SLRQRRAQAS YAGPPPTVAE LVEAHTNFGF QPDTAPRSPN 
TGPYPSEQAL PIPGTPPPNY DSLRLQPLDV IESDSEGDAI