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CHRNE
cholinergic receptor nicotinic epsilon subunit
The CHRNE gene provides instructions for a subunit of the adult acetylcholine receptor, which is vital for proper communication between nerves and muscles. The CHRNE gene encodes the epsilon subunit of the nicotinic acetylcholine receptor (AChR), a protein complex crucial for neuromuscular signalling.
CHRNE is located on the short (p) arm of chromosome 17, at band 17p13.2. Arm ratio per GRCh38 - banding schematic.
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Overview
The CHRNE gene, or cholinergic receptor nicotinic epsilon subunit, is essential for the formation of the adult-type acetylcholine receptor (AChR). This receptor plays a critical role in neuromuscular junctions, facilitating communication between nerve cells and skeletal muscles. Proper functioning of CHRNE is therefore fundamental for muscle movement and strength.
What the gene does
The CHRNE gene provides the genetic blueprint for the epsilon (ε) subunit, one of five subunits that assemble to form the complete acetylcholine receptor (AChR) protein. This receptor is embedded in the surface of skeletal muscle cells and is central to the process of neuromuscular transmission. At the neuromuscular junction, nerve cells release acetylcholine, a neurotransmitter, which binds to the AChR on muscle cells. This binding triggers a signal that leads to muscle contraction.
The AChR protein undergoes maturation, with the ε subunit replacing the gamma (γ) subunit around the 33rd week of pregnancy to form the adult-specific AChR. This transition from a foetal to an adult receptor type is crucial for mature muscle function. The assembled AChR protein is transported to the muscle cell surface where it carries out its role in facilitating muscle movement.
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Chromosome location
The CHRNE gene is located on chromosome 17, specifically at position 17p13.2. This region denotes the short arm of chromosome 17, band 13.2.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variants within the CHRNE gene can alter the structure or function of the epsilon subunit, leading to impaired acetylcholine receptor activity. These genetic changes can affect how the receptor assembles, its stability, or its ability to bind acetylcholine and transmit signals effectively. The consequences often manifest as issues with neuromuscular communication.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1002_1008dup | p.Ala337fs | Pathogenic | ★★☆☆ | Congenital myasthenic syndrome |
c.1116_1128del | p.Ser373fs | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital myasthenic syndrome |
c.1248_1266dup | p.Cys423fs | Pathogenic | ★★☆☆ | Congenital myasthenic syndrome 4A |
c.1251_1266dup | p.Cys423fs | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital myasthenic syndrome |
c.1255G>T | p.Glu419Ter | Pathogenic | ★★☆☆ | Congenital myasthenic syndrome 4A |
c.1258del | p.Val420fs | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital myasthenic syndrome |
c.1379G>A | p.Trp460Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital myasthenic syndrome 4A |
c.1381_1390del | p.Ala461fs | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital myasthenic syndrome 4B |
c.1383_1393del | p.Ala462fs | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital myasthenic syndrome 4A |
c.988C>T | p.Gln330Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital myasthenic syndrome 4A |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variants in the CHRNE gene are primarily associated with congenital myasthenic syndromes. These are a diverse group of inherited conditions characterised by muscle weakness and fatigue, typically manifesting shortly after birth or in early childhood. The underlying cause is a disruption in the communication between nerves and muscles, often due to abnormalities in the acetylcholine receptor where the CHRNE protein plays a key role.
- Congenital myasthenic syndromes Dedicated page coming soon
Inheritance pattern
Conditions caused by pathogenic CHRNE variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
In the UK, the CHRNE gene is included on several NHS Genomic Medicine Service national test panels. These include panels for Arthrogryposis (R83), Congenital myaesthenic syndrome (R80), and Foetal anomalies (R21), indicating its recognition as a gene with clinical significance for these conditions within the NHS.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the CHRNE gene?
The CHRNE gene provides instructions for making the epsilon subunit of the adult acetylcholine receptor (AChR), which is crucial for nerve-to-muscle communication and proper skeletal muscle function.
What happens if there are variants in the CHRNE gene?
Variants in the CHRNE gene can disrupt the normal function of the acetylcholine receptor, leading to impaired signalling between nerves and muscles. This can result in conditions like congenital myasthenic syndromes, characterised by muscle weakness.
Are CHRNE-related conditions inherited?
Yes, conditions associated with CHRNE variants, such as congenital myasthenic syndromes, are typically inherited in an autosomal recessive manner. This means an individual must inherit two copies of the variant gene (one from each parent) to develop the condition.