Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Epithelial sodium channel, gamma subunit

The gene codes for the gamma subunit of the epithelial sodium channel, which regulates aldosteron dependend excretion of sodium in distal nephrons. Gain-of-function mutations result in Liddle syndrome whereas loss-of-function mutations lead to autosomal recessive Pseudohypoaldosternism 1.

Gene Structure

The gene locus on chromosome 16 (16p12) is in the proximity to other components of the sodium channel. The 13 exons spread over 35kb. Only the last 12 of them become translated.

Phenotype

Opposite phenotypes result depending on whether a gain- or loss-of-function mutation is present.

Pathology

The aldosteron-sensitive distal nephron consists of distal convoluted tubule (DCT), the connecting tubule (CNT), and the collecting duct (CD). This part of the nephron is characterized by the colocalization of the epithelial sodium channel (ENaC), the mineralocorticoid receptor, and the 11-beta hydroxysteroid dehydrogenase type 2. The gene codes for the gamma subunit of the channel. Gain-of-function mutations result in Liddle syndrome whereas loss-of-function mutations lead to Pseudohypoaldosteronism.

Genetests:

Clinic Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Clinic Method Genomic sequencing of the entire coding region
Turnaround 20 days
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25 days
Specimen type genomic DNA

Related Diseases:

Pseudohypoaldosteronism type1
NR3C2
SCNN1A
SCNN1B
SCNN1G
Liddle syndrome
NEDD4
NEDD4L
NR3C2
OXSR1
SCNN1B
SCNN1G
STK39
Bronchiectasis with or without elevated sweat chloride 3
SCNN1G

References:

1.

Swift PA et al. (2004) The epithelial sodium channel in hypertension: genetic heterogeneity and implications for treatment with amiloride.

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2.

Warnock DG et al. (2001) Liddle syndrome: genetics and mechanisms of Na+ channel defects.

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3.

Capasso G et al. (2005) Channels, carriers, and pumps in the pathogenesis of sodium-sensitive hypertension.

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Update: Sept. 26, 2018