SCNN1G Gene

HGNC Family	Ion channels
Name	sodium channel, non voltage gated 1 gamma subunit
Description	Nonvoltage-gated, amiloride-sensitive, sodium channels control fluid and electrolyte transport across epithelia in many organs. These channels are heteromeric complexes consisting of 3 subunits: alpha, beta, and gamma. This gene encodes the gamma subunit, and mutations in this gene have been associated with Liddle syndrome. [provided by RefSeq, Apr 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSCNN1G, the gene encoding the gamma‐subunit of the epithelial sodium channel (ENaC), is pivotal for regulating sodium reabsorption in high‐resistance epithelia that control extracellular fluid volume and blood pressure. Multiple studies have shown that the γ‐subunit undergoes proteolytic processing – initiated by furin during biosynthesis and subsequently augmented by various extracellular proteases (e.g., prostasin, plasmin, cathepsin‐S, and meprin β) – which cleaves inhibitory peptides from its ectodomain, thereby increasing channel open probability and enhancing channel activity. In addition, post‐translational modifications such as palmitoylation at specific cysteine residues of the γ‐subunit further stabilize its open conformation and modulate gating (see, e.g., protease‐dependent cleavage and palmitoylation studies;."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic studies highlight that variations in SCNN1G, including polymorphisms in its promoter region and missense mutations, directly influence ENaC function and are linked to clinical phenotypes such as Liddle’s syndrome, altered blood pressure regulation, and modified diuretic responsiveness. For instance, promoter polymorphisms have been associated with lower systolic and pulse pressures, while gain‐of‐function mutations (e.g., the L511Q variant) enhance channel open probability and reduce sodium self‐inhibition. Moreover, defects in ubiquitin‐mediated regulation mediated by interactions with ligases (such as Nedd4‑2 and its modulators) further underscore the role of the γ‐subunit in fine‐tuning ENaC surface expression and activity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its molecular regulation, the function of SCNN1G impacts diverse physiological processes. In renal, pulmonary, and other epithelia, the γ‐subunit not only governs Na⁺ absorption and fluid balance but also contributes to tissue‐specific roles, such as modulating airway surface liquid volume and influencing cell migration in glioblastoma. Furthermore, in pathophysiological settings—including proteinuric kidney diseases—enhanced proteolytic cleavage of the γ‐subunit has been correlated with aberrant ENaC activation, which may contribute to hypertension and edema."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "15"}]}, {"type": "t", "text": " \n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "James B Bruns, Marcelo D Carattino, Shaohu Sheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epithelial Na+ channels are fully activated by furin- and prostasin-dependent release of an inhibitory peptide from the gamma-subunit."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M610636200"}], "href": "https://doi.org/10.1074/jbc.M610636200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17199078"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17199078"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Christopher J Passero, Gunhild M Mueller, Helbert Rondon-Berrios, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plasmin activates epithelial Na+ channels by cleaving the gamma subunit."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M805676200"}], "href": "https://doi.org/10.1074/jbc.M805676200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18981180"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18981180"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Silke Haerteis, Matteus Krappitz, Marko Bertog, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proteolytic activation of the epithelial sodium channel (ENaC) by the cysteine protease cathepsin-S."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pflugers Arch (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00424-012-1138-3"}], "href": "https://doi.org/10.1007/s00424-012-1138-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22864553"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22864553"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Agustin Garcia-Caballero, Susan S Ishmael, Yan Dang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of the epithelial sodium channel by the metalloprotease meprin β subunit."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Channels (Austin) (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/chan.5.1.13759"}], "href": "https://doi.org/10.4161/chan.5.1.13759"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20953144"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20953144"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Rikke M Zachar, Karsten Skjødt, Niels Marcussen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The epithelial sodium channel γ-subunit is processed proteolytically in human kidney."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Soc Nephrol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1681/ASN.2013111173"}], "href": "https://doi.org/10.1681/ASN.2013111173"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25060057"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25060057"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Anindit Mukherjee, Gunhild M Mueller, Carol L Kinlough, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cysteine palmitoylation of the γ subunit has a dominant role in modulating activity of the epithelial sodium channel."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.526020"}], "href": "https://doi.org/10.1074/jbc.M113.526020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24692558"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24692558"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "N Iwai, S Baba, T Mannami, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of sodium channel gamma-subunit promoter variant with blood pressure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hypertension (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.hyp.38.1.86"}], "href": "https://doi.org/10.1161/01.hyp.38.1.86"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11463765"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11463765"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Dominik Wiemuth, Ying Ke, Meino Rohlfs, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epithelial sodium channel (ENaC) is multi-ubiquitinated at the cell surface."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20060747"}], "href": "https://doi.org/10.1042/BJ20060747"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17381423"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17381423"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Kazunori Nagaki, Hisao Yamamura, Shoichi Shimada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "14-3-3 Mediates phosphorylation-dependent inhibition of the interaction between the ubiquitin E3 ligase Nedd4-2 and epithelial Na+ channels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi052640q"}], "href": "https://doi.org/10.1021/bi052640q"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16716084"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16716084"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Cara J Büsst, Katrina J Scurrah, Justine A Ellis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Selective genotyping reveals association between the epithelial sodium channel gamma-subunit and systolic blood pressure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hypertension (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/HYPERTENSIONAHA.107.089128"}], "href": "https://doi.org/10.1161/HYPERTENSIONAHA.107.089128"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17698725"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17698725"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Jingxin Chen, Thomas R Kleyman, Shaohu Sheng "}, {"type": "b", "children": [{"type": "t", "text": "Gain-of-function variant of the human epithelial sodium channel."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00563.2012"}], "href": "https://doi.org/10.1152/ajprenal.00563.2012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23136006"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23136006"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Per Svenningsen, Claus Bistrup, Ulla G Friis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plasmin in nephrotic urine activates the epithelial sodium channel."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Soc Nephrol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1681/ASN.2008040364"}], "href": "https://doi.org/10.1681/ASN.2008040364"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19073825"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19073825"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Niren Kapoor, Rafal Bartoszewski, Yawar J Qadri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of ASIC1 and epithelial sodium channel subunits inhibits glioblastoma whole cell current and cell migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.037390"}], "href": "https://doi.org/10.1074/jbc.M109.037390"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19561078"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19561078"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Daniel M Collier, Peter M Snyder "}, {"type": "b", "children": [{"type": "t", "text": "Extracellular protons regulate human ENaC by modulating Na+ self-inhibition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M806954200"}], "href": "https://doi.org/10.1074/jbc.M806954200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18990692"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18990692"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Gitte R Hinrichs, Jannie S Michelsen, Rikke Zachar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Albuminuria in kidney transplant recipients is associated with increased urinary serine proteases and activation of the epithelial sodium channel."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00545.2017"}], "href": "https://doi.org/10.1152/ajprenal.00545.2017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29363322"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29363322"}]}]}]}
Synonyms	PHA1, ENACGAMMA, LDLS2, SCNEG, BESC3, ENACG
Proteins	SCNNG_HUMAN
NCBI Gene ID	6340
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SCNN1G has 5,482 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 113 datasets.

Click the + buttons to view associations for SCNN1G from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SCNN1G Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by SCNN1G gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SCNN1G gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of SCNN1G gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of SCNN1G gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SCNN1G gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of SCNN1G gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SCNN1G gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SCNN1G gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SCNN1G gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of SCNN1G gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with SCNN1G gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SCNN1G gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SCNN1G gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of SCNN1G gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with SCNN1G gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of SCNN1G gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SCNN1G protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SCNN1G protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with SCNN1G protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with SCNN1G protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of SCNN1G gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SCNN1G gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SCNN1G gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SCNN1G gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by SCNN1G gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving SCNN1G gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving SCNN1G gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with SCNN1G gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with SCNN1G gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with SCNN1G gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with SCNN1G gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SCNN1G gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for SCNN1G protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at SCNN1G gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SCNN1G gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SCNN1G gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing SCNN1G from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with SCNN1G gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with SCNN1G gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of SCNN1G gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.