SCNN1G

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

Basic information

Region (hg38): 16:23182745-23216883

Links

ENSG00000166828

∙ NCBI:6340 ∙ OMIM:600761 ∙ HGNC:10602 ∙ Uniprot:P51170 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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
pseudohypoaldosteronism, type IB1, autosomal recessive (Supportive), mode of inheritance: AR
Liddle syndrome 2 (Moderate), mode of inheritance: AD
Liddle syndrome 2 (Strong), mode of inheritance: AD
pseudohypoaldosteronism, type IB1, autosomal recessive (Strong), mode of inheritance: AR
Liddle syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pseudohypoaldosteronism, type I; Liddle syndrome 2; Bronchiectasis with or without elevated sweat chloride 3	AD/AR/Digenic (with CFTR or other SCCN1 genes)	Allergy/Immunology/Infectious; Pulmonary; Renal	In 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 morbidity	Allergy/Immunology/Infectious; Pulmonary; Renal	7046191; 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.

Liddle_syndrome_2 (131 variants)
not_provided (112 variants)
Bronchiectasis_with_or_without_elevated_sweat_chloride_3 (109 variants)
Pseudohypoaldosteronism,_type_IB3,_autosomal_recessive (96 variants)
Inborn_genetic_diseases (58 variants)
Pseudohypoaldosteronism,_type_IB1,_autosomal_recessive (36 variants)
not_specified (13 variants)
SCNN1G-related_disorder (9 variants)
Myoepithelial_tumor (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. These statistics are base on transcript: NM_000001039.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			9 clinvar	31 clinvar	1 clinvar	41
missense			145 clinvar	12 clinvar	1 clinvar	158
nonsense	3 clinvar	3 clinvar				6
start loss						0
frameshift	3 clinvar	3 clinvar				6
splice donor/acceptor (+/-2bp)	2 clinvar	2 clinvar				4
Total	8	8	154	43	2

Highest pathogenic variant AF is 6.8456e-7

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SCNN1G	protein_coding	protein_coding	ENST00000300061	12	34169

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.482	0.518	125729	0	19	125748	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.561	328	358	0.916	0.0000232	4277
Missense in Polyphen		104	145.9	0.71283		1750
Synonymous	-0.492	152	144	1.05	0.00000980	1236
Loss of Function	4.12	7	32.2	0.217	0.00000159	374

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000441	0.000441
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000528	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
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: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

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

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