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GeneBe

SCNN1B

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

Basic information

Region (hg38): 16:23278230-23381294

Links

ENSG00000168447OMIM:600760HGNC:10600Uniprot:P51168AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

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

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Pseudohypoaldosteronism, type IB2; Liddle syndrome 1; Bronchiectasis with or without elevated sweat chloride 1AD/AR/Digenic (with CFTR or other SCCN1 genes)Allergy/Immunology/Infectious; Pulmonary; RenalIn Pseudohypoaldosteronism, type IB2, 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 1, 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; 6262354; 3550146; 264740; 7954808; 8524790; 8589714; 10202170; 16207733; 18507830; 19017867; 32840096

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SCNN1B gene.

  • not provided (177 variants)
  • Liddle syndrome 1 (70 variants)
  • Bronchiectasis with or without elevated sweat chloride 1 (70 variants)
  • Autosomal recessive pseudohypoaldosteronism type 1 (64 variants)
  • Inborn genetic diseases (32 variants)
  • not specified (28 variants)
  • Autosomal recessive pseudohypoaldosteronism type 1;Bronchiectasis with or without elevated sweat chloride 1;Liddle syndrome 1 (6 variants)
  • Bronchiectasis with or without elevated sweat chloride 1;Liddle syndrome 1;Autosomal recessive pseudohypoaldosteronism type 1 (6 variants)
  • Bronchiectasis with or without elevated sweat chloride 1;Autosomal recessive pseudohypoaldosteronism type 1;Liddle syndrome 1 (5 variants)
  • Pseudohypoaldosteronism, type IB2, autosomal recessive (3 variants)
  • SCNN1B-related condition (2 variants)
  • Liddle syndrome 1;Bronchiectasis with or without elevated sweat chloride 1;Autosomal recessive pseudohypoaldosteronism type 1 (2 variants)
  • Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young (1 variants)
  • Low renin, low aldosterone hypertension (1 variants)
  • Liddle syndrome 1;Autosomal recessive pseudohypoaldosteronism type 1;Bronchiectasis with or without elevated sweat chloride 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SCNN1B 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
2
clinvar
23
clinvar
1
clinvar
26
missense
4
clinvar
2
clinvar
83
clinvar
10
clinvar
1
clinvar
100
nonsense
3
clinvar
2
clinvar
5
start loss
0
frameshift
3
clinvar
2
clinvar
2
clinvar
7
inframe indel
0
splice donor/acceptor (+/-2bp)
1
clinvar
1
splice region
3
2
1
6
non coding
8
clinvar
22
clinvar
30
clinvar
60
Total 10 7 95 55 32

Highest pathogenic variant AF is 0.000158

Variants in SCNN1B

This is a list of pathogenic ClinVar variants found in the SCNN1B region.

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

Position Type Phenotype Significance ClinVar
16-23301864-G-A Benign (May 19, 2021)1233203
16-23302174-G-A Benign (Apr 22, 2022)1678733
16-23302296-C-G Bronchiectasis with or without elevated sweat chloride 1 • Autosomal recessive pseudohypoaldosteronism type 1 • Liddle syndrome 1 Likely benign (Jun 14, 2016)318400
16-23302675-C-G Benign (May 22, 2021)1251381
16-23302732-T-C Benign (May 14, 2021)1261922
16-23302926-A-T Likely benign (May 19, 2021)1326456
16-23303001-G-T Benign (Apr 22, 2022)1678734
16-23333099-AAGGAAGGAAGGGAGGGAGGGAGGGAGGGAGGGAGGGAGGAAGGAAGGAAAGAAGG-A Schizophrenia Uncertain significance (Nov 11, 2022)1801431
16-23348519-T-C Likely benign (Jan 26, 2020)1220444
16-23348605-C-T Liddle syndrome 1 • Autosomal recessive pseudohypoaldosteronism type 1 • Bronchiectasis with or without elevated sweat chloride 1 • SCNN1B-related condition Conflicting classifications of pathogenicity (Oct 21, 2022)887418
16-23348606-G-A Inborn genetic diseases Uncertain significance (Oct 24, 2023)2354048
16-23348653-C-T Likely benign (Apr 22, 2023)2716725
16-23348672-C-G Uncertain significance (Jun 09, 2022)1976055
16-23348683-G-A Pseudohypoaldosteronism, type IB2, autosomal recessive Pathogenic (Aug 09, 2023)2577438
16-23348686-C-A Pseudohypoaldosteronism, type IB2, autosomal recessive Pathogenic (Dec 06, 2023)2664488
16-23348690-G-A Uncertain significance (Jul 02, 2021)1678510
16-23348708-G-A Liddle syndrome 1 • Bronchiectasis with or without elevated sweat chloride 1 • Pseudohypoaldosteronism, type IB2, autosomal recessive • Autosomal recessive pseudohypoaldosteronism type 1 Conflicting classifications of pathogenicity (Sep 06, 2017)8832
16-23348720-A-G Uncertain significance (Nov 28, 2021)1417002
16-23348746-A-G not specified • Liddle syndrome 1;Bronchiectasis with or without elevated sweat chloride 1;Autosomal recessive pseudohypoaldosteronism type 1 • SCNN1B-related condition Benign/Likely benign (Nov 19, 2023)789831
16-23348752-G-A Likely benign (Jan 01, 2024)3025040
16-23348758-C-T Bronchiectasis with or without elevated sweat chloride 1 • Autosomal recessive pseudohypoaldosteronism type 1 • Liddle syndrome 1 Uncertain significance (Jan 12, 2018)318418
16-23348776-C-T Bronchiectasis with or without elevated sweat chloride 1;Liddle syndrome 1;Autosomal recessive pseudohypoaldosteronism type 1 Likely benign (Apr 07, 2023)740204
16-23348780-G-A not specified • SCNN1B-related condition Likely benign (Nov 19, 2023)789832
16-23348786-G-A Uncertain significance (Dec 02, 2019)995267
16-23348818-C-A Likely benign (Jul 25, 2022)2416759

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SCNN1Bprotein_codingprotein_codingENST00000343070 12103069
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
5.75e-80.9931257010471257480.000187
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.2123623740.9690.00002364238
Missense in Polyphen114146.310.779161659
Synonymous-0.8731721581.090.00001091226
Loss of Function2.451732.00.5320.00000159356

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0003720.000369
Ashkenazi Jewish0.001090.00109
East Asian0.0001630.000163
Finnish0.00004620.0000462
European (Non-Finnish)0.0001590.000158
Middle Eastern0.0001630.000163
South Asian0.0002610.000261
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:7762608, ECO:0000303|PubMed:7490094}.;
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:8589714}. 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: 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:15483078, ECO:0000269|PubMed:7550319, ECO:0000269|PubMed:8524790, ECO:0000269|PubMed:8601645, ECO:0000269|PubMed:9626162, ECO:0000269|PubMed:9794716}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Bronchiectasis with or without elevated sweat chloride 1 (BESC1) [MIM:211400]: 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:16207733, 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
0.269

Intolerance Scores

loftool
0.552
rvis_EVS
0.16
rvis_percentile_EVS
64.92

Haploinsufficiency Scores

pHI
0.678
hipred
Y
hipred_score
0.660
ghis
0.463

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.721

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Scnn1b
Phenotype
homeostasis/metabolism phenotype; normal 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); 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; digestive/alimentary phenotype; skeleton phenotype; renal/urinary system phenotype;

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
plasma membrane;integral component of plasma membrane;external side of plasma membrane;apical plasma membrane;cytoplasmic vesicle membrane;sodium channel complex;extracellular exosome
Molecular function
protein binding;ligand-gated sodium channel activity;WW domain binding