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GeneBe

SCNN1G

sodium channel epithelial 1 subunit gamma, the group of Sodium channels epithelial

Basic information

Region (hg38): 16:23182744-23216883

Links

ENSG00000166828NCBI:6340OMIM:600761HGNC:10602Uniprot:P51170AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • bronchiectasis with or without elevated sweat chloride 3 (Strong), mode of inheritance: AD
  • Liddle syndrome 2 (Strong), mode of inheritance: AD
  • Liddle syndrome (Supportive), mode of inheritance: AD
  • autosomal recessive pseudohypoaldosteronism type 1 (Supportive), mode of inheritance: AR
  • Liddle syndrome 2 (Moderate), mode of inheritance: AD
  • Liddle syndrome 2 (Strong), mode of inheritance: AD
  • autosomal recessive pseudohypoaldosteronism type 1 (Strong), mode of inheritance: AR
  • Liddle syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Pseudohypoaldosteronism, type I; Liddle syndrome 2; Bronchiectasis with or without elevated sweat chloride 3AD/AR/Digenic (with CFTR or other SCCN1 genes)Allergy/Immunology/Infectious; Pulmonary; RenalIn Pseudohypoaldosteronism, type I, treatment with electrolyte replacement and control of hyperkalemia can be effective; In Liddle syndrome, certain medications (eg, amiloride, triamterene, but not spironolactone) and dietary sodium restriction can effectively treat hypertension and hypokalemia; In Bronchiectasis with or without elevated sweat chloride 3, as in cystic fibrosis, early and aggressive pulmonary and other management (eg, related to prophylaxis and management of respiratory infections) may decrease morbidityAllergy/Immunology/Infectious; Pulmonary; Renal7046191; 3550146; 3550146; 7550319; 8640238; 9649551; 10202170; 18507830; 19017867; 33690157

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SCNN1G gene.

  • not provided (113 variants)
  • Autosomal recessive pseudohypoaldosteronism type 1 (74 variants)
  • Liddle syndrome 2 (70 variants)
  • not specified (16 variants)
  • Bronchiectasis with or without elevated sweat chloride 3 (16 variants)
  • Inborn genetic diseases (14 variants)
  • Bronchiectasis with or without elevated sweat chloride 3;Liddle syndrome 2;Autosomal recessive pseudohypoaldosteronism type 1 (3 variants)
  • Bronchiectasis with or without elevated sweat chloride 3;Autosomal recessive pseudohypoaldosteronism type 1;Liddle syndrome 2 (3 variants)
  • SCNN1G-related condition (3 variants)
  • Autosomal recessive pseudohypoaldosteronism type 1;Liddle syndrome 2;Bronchiectasis with or without elevated sweat chloride 3 (2 variants)
  • Liddle syndrome 1 (2 variants)
  • Autosomal recessive pseudohypoaldosteronism type 1;Bronchiectasis with or without elevated sweat chloride 3;Liddle syndrome 2 (2 variants)
  • Liddle syndrome 2;Autosomal recessive pseudohypoaldosteronism type 1;Bronchiectasis with or without elevated sweat chloride 3 (1 variants)
  • Liddle syndrome 2;Bronchiectasis with or without elevated sweat chloride 3;Autosomal recessive pseudohypoaldosteronism type 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SCNN1G gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
7
clinvar
11
clinvar
4
clinvar
22
missense
47
clinvar
3
clinvar
50
nonsense
1
clinvar
2
clinvar
3
start loss
0
frameshift
1
clinvar
2
clinvar
3
inframe indel
1
clinvar
1
splice donor/acceptor (+/-2bp)
2
clinvar
2
splice region
2
2
4
non coding
12
clinvar
16
clinvar
42
clinvar
70
Total 2 6 67 30 46

Variants in SCNN1G

This is a list of pathogenic ClinVar variants found in the SCNN1G region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
16-23185981-C-T Benign (Nov 12, 2018)1283927
16-23185983-CACGGCTAGG-C Likely benign (Sep 10, 2020)1699900
16-23185994-CTGG-C Likely benign (Sep 10, 2020)1699901
16-23186224-C-G Liddle syndrome 2 • Autosomal recessive pseudohypoaldosteronism type 1 Benign (Nov 12, 2018)318343
16-23186241-A-G Autosomal recessive pseudohypoaldosteronism type 1 • Liddle syndrome 2 Benign (Nov 12, 2018)318344
16-23186249-G-A Liddle syndrome 2 • Autosomal recessive pseudohypoaldosteronism type 1 Conflicting classifications of pathogenicity (Jan 12, 2018)318345
16-23186316-G-T Likely benign (Nov 10, 2022)2986564
16-23186319-C-T Liddle syndrome 2 • Autosomal recessive pseudohypoaldosteronism type 1 Uncertain significance (Feb 02, 2018)885119
16-23186403-C-G Uncertain significance (Jan 16, 2024)2878213
16-23186403-C-T Autosomal recessive pseudohypoaldosteronism type 1 • Liddle syndrome 2 Conflicting classifications of pathogenicity (Jan 03, 2024)886034
16-23186410-T-TC Autosomal recessive pseudohypoaldosteronism type 1;Bronchiectasis with or without elevated sweat chloride 3;Liddle syndrome 2 Likely pathogenic (Jun 20, 2019)804476
16-23186414-G-GCGGC Pathogenic (May 16, 2016)280615
16-23186430-C-T Likely benign (Dec 20, 2017)730497
16-23186472-C-G Bronchiectasis with or without elevated sweat chloride 3 Uncertain significance (Dec 05, 2022)2443054
16-23186606-G-C Likely benign (Oct 13, 2023)1990292
16-23186733-C-T Benign (Nov 12, 2018)1277809
16-23186852-C-T Benign (Nov 12, 2018)1286975
16-23186868-G-A Benign (Nov 12, 2018)1265535
16-23189132-T-A Benign (Feb 04, 2020)1236992
16-23189272-T-C Benign (Nov 12, 2018)1266779
16-23189354-C-T Likely benign (Jun 05, 2022)1650245
16-23189370-G-A Pseudohypoaldosteronism, type IB3, autosomal recessive Pathogenic (Jun 01, 1996)8826
16-23189379-C-G Inborn genetic diseases Uncertain significance (May 23, 2023)2549831
16-23189380-C-A SCNN1G-related condition Likely benign (Feb 21, 2019)3058747
16-23189385-G-C Inborn genetic diseases Uncertain significance (Jul 26, 2022)2408769

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SCNN1Gprotein_codingprotein_codingENST00000300061 1234169
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.4820.5181257290191257480.0000756
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.5613283580.9160.00002324277
Missense in Polyphen104145.90.712831750
Synonymous-0.4921521441.050.000009801236
Loss of Function4.12732.20.2170.00000159374

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0004410.000441
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.00004620.0000462
European (Non-Finnish)0.00005280.0000439
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Plays an essential role in electrolyte and blood pressure homeostasis, but also in airway surface liquid homeostasis, which is important for proper clearance of mucus. Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. Also plays a role in taste perception. {ECO:0000269|PubMed:24124190, ECO:0000303|PubMed:7490094}.;
Disease
DISEASE: Liddle syndrome (LIDLS) [MIM:177200]: An autosomal dominant disorder characterized by hypertension, hypokalemic alkalosis, and suppression of plasma renin activity and aldosterone secretion. {ECO:0000269|PubMed:7550319}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Bronchiectasis with or without elevated sweat chloride 3 (BESC3) [MIM:613071]: A debilitating respiratory disease characterized by chronic, abnormal dilatation of the bronchi and other cystic fibrosis-like symptoms in the absence of known causes of bronchiectasis (cystic fibrosis, autoimmune diseases, ciliary dyskinesia, common variable immunodeficiency, foreign body obstruction). Clinical features include sub-normal lung function, sinopulmonary infections, chronic productive cough, excessive sputum production, and elevated sweat chloride in some cases. {ECO:0000269|PubMed:18507830, ECO:0000269|PubMed:19017867}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Aldosterone-regulated sodium reabsorption - Homo sapiens (human);Taste transduction - Homo sapiens (human);Diuretics Pathway, Pharmacodynamics;Polythiazide Action Pathway;Methyclothiazide Action Pathway;Bumetanide Action Pathway;Spironolactone Action Pathway;Eplerenone Action Pathway;Triamterene Action Pathway;Amiloride Action Pathway;Ethacrynic Acid Action Pathway;Quinethazone Action Pathway;Bendroflumethiazide Action Pathway;Chlorthalidone Action Pathway;Trichlormethiazide Action Pathway;Iminoglycinuria;Lysinuric Protein Intolerance;Blue diaper syndrome;Lysinuric protein intolerance (LPI);Cystinuria;Indapamide Action Pathway;Furosemide Action Pathway;Torsemide Action Pathway;Hartnup Disorder;Glucose Transporter Defect (SGLT2);Kidney Function;Glucose Transporter Defect (SGLT2);Metolazone Action Pathway;Hydrochlorothiazide Action Pathway;Cyclothiazide Action Pathway;Hydroflumethiazide Action Pathway;Chlorothiazide Action Pathway;Stimuli-sensing channels;Ion channel transport;Transport of small molecules (Consensus)

Recessive Scores

pRec
0.453

Intolerance Scores

loftool
0.565
rvis_EVS
-0.95
rvis_percentile_EVS
9.21

Haploinsufficiency Scores

pHI
0.692
hipred
Y
hipred_score
0.701
ghis
0.512

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.893

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Scnn1g
Phenotype
homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; renal/urinary system phenotype; digestive/alimentary phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);

Gene ontology

Biological process
sodium ion transport;excretion;sodium ion transmembrane transport;multicellular organismal water homeostasis;response to stimulus;sensory perception of taste;sodium ion homeostasis
Cellular component
nucleoplasm;plasma membrane;integral component of plasma membrane;external side of plasma membrane;apical plasma membrane;sodium channel complex;extracellular exosome
Molecular function
ion channel activity;sodium channel activity;protein binding;ligand-gated sodium channel activity;WW domain binding