SCNN1B

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

Basic information

Region (hg38): 16:23278230-23381294

Links

ENSG00000168447 ∙ ∙ OMIM:600760 ∙ HGNC:10600 ∙ Uniprot:P51168 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pseudohypoaldosteronism, type IB2; Liddle syndrome 1; Bronchiectasis with or without elevated sweat chloride 1	AD/AR/Digenic (with CFTR or other SCCN1 genes)	Allergy/Immunology/Infectious; Pulmonary; Renal	In 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 morbidity	Allergy/Immunology/Infectious; Pulmonary; Renal	7046191; 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 (8 variants)
• Liddle syndrome 1 (4 variants)
• Bronchiectasis with or without elevated sweat chloride 1;Liddle syndrome 1;Autosomal recessive pseudohypoaldosteronism type 1 (1 variants)
• 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 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	32	1	35
missense	4	2	98	11	1	116
nonsense	3	3				6
start loss						0
frameshift	3	2	2			7
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			3	3	1	7
non coding			8	26	30	64
Total	10	8	110	69	32

Highest pathogenic variant AF is 0.00000657

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)
16-23302174-G-A			Benign (Apr 22, 2022)
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)
16-23302675-C-G			Benign (May 22, 2021)
16-23302732-T-C			Benign (May 14, 2021)
16-23302926-A-T			Likely benign (May 19, 2021)
16-23303001-G-T			Benign (Apr 22, 2022)
16-23333099-AAGGAAGGAAGGGAGGGAGGGAGGGAGGGAGGGAGGGAGGAAGGAAGGAAAGAAGG-A		Schizophrenia	Uncertain significance (Nov 11, 2022)
16-23348519-T-C			Likely benign (Jan 26, 2020)
16-23348605-C-T		Liddle syndrome 1 • Autosomal recessive pseudohypoaldosteronism type 1 • Bronchiectasis with or without elevated sweat chloride 1 • SCNN1B-related disorder	Conflicting classifications of pathogenicity (Oct 21, 2022)
16-23348606-G-A		Inborn genetic diseases	Uncertain significance (Oct 24, 2023)
16-23348653-C-T			Likely benign (Apr 22, 2023)
16-23348672-C-G			Uncertain significance (Jun 09, 2022)
16-23348683-G-A		Pseudohypoaldosteronism, type IB2, autosomal recessive	Pathogenic (Aug 09, 2023)
16-23348686-C-A		Pseudohypoaldosteronism, type IB2, autosomal recessive	Pathogenic (Dec 06, 2023)
16-23348690-G-A			Uncertain significance (Jul 02, 2021)
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)
16-23348720-A-G			Uncertain significance (Nov 28, 2021)
16-23348746-A-G		not specified • Bronchiectasis with or without elevated sweat chloride 1;Liddle syndrome 1;Autosomal recessive pseudohypoaldosteronism type 1 • SCNN1B-related disorder	Benign/Likely benign (Nov 19, 2023)
16-23348752-G-A			Likely benign (Jan 01, 2024)
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)
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)
16-23348780-G-A		not specified • SCNN1B-related disorder	Likely benign (Nov 19, 2023)
16-23348786-G-A			Uncertain significance (Dec 02, 2019)
16-23348818-C-A			Likely benign (Jul 25, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SCNN1B	protein_coding	protein_coding	ENST00000343070	12	103069

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.75e-8	0.993	125701	0	47	125748	0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.212	362	374	0.969	0.0000236	4238
Missense in Polyphen		114	146.31	0.77916		1659
Synonymous	-0.873	172	158	1.09	0.0000109	1226
Loss of Function	2.45	17	32.0	0.532	0.00000159	356

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000372	0.000369
Ashkenazi Jewish	0.00109	0.00109
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000159	0.000158
Middle Eastern	0.000163	0.000163
South Asian	0.000261	0.000261
Other	0.00	0.00

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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