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GeneBe

SCNN1A

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

Basic information

Region (hg38): 12:6346842-6377730

Previous symbols: [ "SCNN1" ]

Links

ENSG00000111319OMIM:600228HGNC:10599Uniprot:P37088AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

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

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Pseudohypoaldosteronism, type IB1; Liddle syndrome 3; Bronchiectasis with or without elevated sweat chloride 2AD/AR/Digenic (with CFTR or other SCCN1 genes)Allergy/Immunology/Infectious; Pulmonary; RenalIn Pseudohypoaldosteronism, type 1B1, 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 2, 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; Renal8589714; 9654209; 10202170; 9462466; 19017867

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SCNN1A gene.

  • not provided (128 variants)
  • Autosomal recessive pseudohypoaldosteronism type 1 (95 variants)
  • Bronchiectasis with or without elevated sweat chloride 2 (86 variants)
  • Inborn genetic diseases (32 variants)
  • not specified (18 variants)
  • Autosomal recessive pseudohypoaldosteronism type 1;Bronchiectasis with or without elevated sweat chloride 2;Liddle syndrome 3 (10 variants)
  • Liddle syndrome 3;Bronchiectasis with or without elevated sweat chloride 2;Autosomal recessive pseudohypoaldosteronism type 1 (4 variants)
  • Bronchiectasis with or without elevated sweat chloride 2;Liddle syndrome 3;Autosomal recessive pseudohypoaldosteronism type 1 (4 variants)
  • Liddle syndrome 3 (3 variants)
  • SCNN1A-Related Disorders (2 variants)
  • Bronchiectasis with or without elevated sweat chloride 2;Autosomal recessive pseudohypoaldosteronism type 1;Liddle syndrome 3 (2 variants)
  • SCNN1A-related condition (2 variants)
  • Idiopathic bronchiectasis (1 variants)
  • Autosomal recessive pseudohypoaldosteronism type 1;Liddle syndrome 3;Bronchiectasis with or without elevated sweat chloride 2 (1 variants)
  • Neurodevelopmental delay (1 variants)
  • Familial Periodic Fever (1 variants)
  • 6 conditions (1 variants)
  • Bronchiectasis with or without elevated sweat chloride 1 (1 variants)
  • Pseudohypoaldosteronism (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SCNN1A 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
6
clinvar
18
clinvar
1
clinvar
25
missense
1
clinvar
57
clinvar
8
clinvar
3
clinvar
69
nonsense
1
clinvar
1
clinvar
2
start loss
1
clinvar
1
frameshift
6
clinvar
3
clinvar
9
inframe indel
1
clinvar
3
clinvar
4
splice donor/acceptor (+/-2bp)
2
clinvar
2
clinvar
1
clinvar
5
splice region
3
5
1
9
non coding
1
clinvar
21
clinvar
26
clinvar
20
clinvar
68
Total 10 8 89 52 24

Highest pathogenic variant AF is 0.0000395

Variants in SCNN1A

This is a list of pathogenic ClinVar variants found in the SCNN1A region.

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

Position Type Phenotype Significance ClinVar
12-6346853-C-A Bronchiectasis with or without elevated sweat chloride 2 • Autosomal recessive pseudohypoaldosteronism type 1 Uncertain significance (Apr 20, 2018)883854
12-6346853-CAACA-C Autosomal recessive pseudohypoaldosteronism type 1 • Familial Periodic Fever • Bronchiectasis with or without elevated sweat chloride 1 Benign/Likely benign (May 22, 2021)310117
12-6346953-G-A Bronchiectasis with or without elevated sweat chloride 2 • Autosomal recessive pseudohypoaldosteronism type 1 Benign/Likely benign (Jan 12, 2018)310118
12-6346959-T-C Autosomal recessive pseudohypoaldosteronism type 1 • Bronchiectasis with or without elevated sweat chloride 2 Conflicting classifications of pathogenicity (May 19, 2021)310119
12-6347023-G-A Autosomal recessive pseudohypoaldosteronism type 1 Likely benign (Apr 27, 2017)310120
12-6347137-A-C Autosomal recessive pseudohypoaldosteronism type 1 • Bronchiectasis with or without elevated sweat chloride 2 Uncertain significance (Jan 13, 2018)310121
12-6347146-T-C Bronchiectasis with or without elevated sweat chloride 2 • Autosomal recessive pseudohypoaldosteronism type 1 Uncertain significance (Jan 12, 2018)880565
12-6347207-A-G Autosomal recessive pseudohypoaldosteronism type 1 • Bronchiectasis with or without elevated sweat chloride 2 Uncertain significance (Jan 12, 2018)880566
12-6347240-C-A Autosomal recessive pseudohypoaldosteronism type 1 • Bronchiectasis with or without elevated sweat chloride 2 Benign/Likely benign (May 16, 2021)310122
12-6347283-G-C Autosomal recessive pseudohypoaldosteronism type 1 • Bronchiectasis with or without elevated sweat chloride 2 Uncertain significance (Jan 13, 2018)310123
12-6347293-T-G Autosomal recessive pseudohypoaldosteronism type 1 • Bronchiectasis with or without elevated sweat chloride 2 Uncertain significance (Jan 12, 2018)310124
12-6347331-C-T Autosomal recessive pseudohypoaldosteronism type 1 • Bronchiectasis with or without elevated sweat chloride 2 Uncertain significance (Jan 12, 2018)881985
12-6347364-A-C Autosomal recessive pseudohypoaldosteronism type 1 • Bronchiectasis with or without elevated sweat chloride 2 Benign/Likely benign (Jan 13, 2018)883146
12-6347405-G-A Bronchiectasis with or without elevated sweat chloride 2 • Autosomal recessive pseudohypoaldosteronism type 1 Uncertain significance (Jan 12, 2018)883147
12-6347406-G-T Autosomal recessive pseudohypoaldosteronism type 1 • Bronchiectasis with or without elevated sweat chloride 2 Conflicting classifications of pathogenicity (Jan 12, 2018)883148
12-6347458-G-A Bronchiectasis with or without elevated sweat chloride 2 • Autosomal recessive pseudohypoaldosteronism type 1 Uncertain significance (Jan 13, 2018)310125
12-6347487-C-T Bronchiectasis with or without elevated sweat chloride 2 • Autosomal recessive pseudohypoaldosteronism type 1 Uncertain significance (Jan 13, 2018)883925
12-6347521-T-C Bronchiectasis with or without elevated sweat chloride 2 • Autosomal recessive pseudohypoaldosteronism type 1 Uncertain significance (Jan 12, 2018)883926
12-6347577-G-A Bronchiectasis with or without elevated sweat chloride 2 • Autosomal recessive pseudohypoaldosteronism type 1 Conflicting classifications of pathogenicity (Apr 01, 2023)310126
12-6347693-A-G Autosomal recessive pseudohypoaldosteronism type 1 • Bronchiectasis with or without elevated sweat chloride 2 Uncertain significance (Jan 12, 2018)883927
12-6347759-C-T Autosomal recessive pseudohypoaldosteronism type 1 • Bronchiectasis with or without elevated sweat chloride 2 Uncertain significance (Jan 13, 2018)310127
12-6347760-G-A Autosomal recessive pseudohypoaldosteronism type 1 • Bronchiectasis with or without elevated sweat chloride 2 Conflicting classifications of pathogenicity (Jan 13, 2018)310128
12-6347803-A-G Bronchiectasis with or without elevated sweat chloride 2 • Autosomal recessive pseudohypoaldosteronism type 1 Benign/Likely benign (Mar 07, 2020)310129
12-6347804-T-C Autosomal recessive pseudohypoaldosteronism type 1 • Bronchiectasis with or without elevated sweat chloride 2 Uncertain significance (Jan 13, 2018)880643
12-6347869-C-T Bronchiectasis with or without elevated sweat chloride 2 • Autosomal recessive pseudohypoaldosteronism type 1 Likely benign (Apr 27, 2017)310130

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SCNN1Aprotein_codingprotein_codingENST00000360168 1230888
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.08e-110.90812562601221257480.000485
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.4904434151.070.00002434728
Missense in Polyphen146151.710.962361768
Synonymous-0.4051821751.040.00001071457
Loss of Function1.972335.70.6440.00000222362

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0006560.000656
Ashkenazi Jewish0.0006950.000695
East Asian0.001360.00136
Finnish0.00009240.0000924
European (Non-Finnish)0.0005470.000510
Middle Eastern0.001360.00136
South Asian0.0002950.000294
Other0.0004980.000489

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 eccrine sweat glands. Also plays a role in taste perception. {ECO:0000269|PubMed:24124190, ECO:0000269|PubMed:8278374}.;
Disease
DISEASE: Pseudohypoaldosteronism 1, autosomal recessive (PHA1B) [MIM:264350]: A rare salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. PHA1B is a severe form involving multiple organ systems, and characterized by an often fulminant presentation in the neonatal period with dehydration, hyponatremia, hyperkalemia, metabolic acidosis, failure to thrive and weight loss. {ECO:0000269|PubMed:10586178, ECO:0000269|PubMed:15853823, ECO:0000269|PubMed:18634878}. Note=The disease is caused by mutations affecting the gene represented in this entry. The degree of channel function impairment differentially affects the renin-aldosterone system and urinary Na/K ratios, resulting in distinct genotype-phenotype relationships in PHA1 patients. Loss-of-function mutations are associated with a severe clinical course and age-dependent hyperactivation of the renin-aldosterone system. This feature is not observed in patients with missense mutations that reduce but do not eliminate channel function. Markedly reduced channel activity results in impaired linear growth and delayed puberty (PubMed:18634878). {ECO:0000269|PubMed:18634878}.; DISEASE: Bronchiectasis with or without elevated sweat chloride 2 (BESC2) [MIM:613021]: 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:19462466}. 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;Glucocorticoid Receptor Pathway;Nuclear Receptors Meta-Pathway;Stimuli-sensing channels;Ion channel transport;Transport of small molecules (Consensus)

Recessive Scores

pRec
0.290

Intolerance Scores

loftool
0.952
rvis_EVS
0.27
rvis_percentile_EVS
70.64

Haploinsufficiency Scores

pHI
0.970
hipred
Y
hipred_score
0.595
ghis
0.567

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.644

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Scnn1a
Phenotype
respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); normal phenotype; digestive/alimentary phenotype; renal/urinary system phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype;

Gene ontology

Biological process
sodium ion transmembrane transport;multicellular organismal water homeostasis;response to stimulus;sensory perception of taste;sodium ion homeostasis
Cellular component
acrosomal vesicle;cytoplasm;plasma membrane;integral component of plasma membrane;apical plasma membrane;motile cilium;sodium channel complex;ciliary membrane;extracellular exosome;sperm principal piece
Molecular function
protein binding;ligand-gated sodium channel activity;WW domain binding