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CHRNG
cholinergic receptor nicotinic gamma subunit
The CHRNG gene provides instructions for the gamma subunit of the acetylcholine receptor, a protein vital for nerve-muscle communication during foetal development. The CHRNG gene plays a critical role in early development by encoding a component of the foetal acetylcholine receptor.
CHRNG is located on the long (q) arm of chromosome 2, at band 2q37.1. Arm ratio per GRCh38 - banding schematic.
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Overview
The CHRNG gene, also known as cholinergic receptor nicotinic gamma subunit, contains the genetic blueprint for a specific component of the acetylcholine receptor (AChR) protein. This receptor is located on the surface of skeletal muscle cells and is fundamental for the signalling pathways that coordinate nerve and muscle activity, which is necessary for bodily movement.
Critically, the gamma subunit produced by CHRNG is present exclusively in the foetal form of the AChR protein. Towards the end of pregnancy, this gamma subunit is typically replaced by another subunit (epsilon), forming the adult version of the receptor.
What the gene does
The CHRNG gene provides the genetic instructions for synthesising the gamma (γ) protein subunit of the acetylcholine receptor (AChR). The AChR is a complex protein composed of five distinct subunits that are assembled together. It functions as a ligand-gated ion channel embedded within the cell membrane of skeletal muscle cells.
Upon binding of the neurotransmitter acetylcholine, the receptor undergoes a conformational change, opening an ion channel that allows ions to flow into the muscle cell, triggering muscle contraction. The γ subunit is a defining characteristic of the foetal AChR. During the third trimester of pregnancy (around 33 weeks), the γ subunit is exchanged for an epsilon (ε) subunit, encoded by the CHRNE gene, to form the mature adult-type AChR. This transition is important for the functional maturation of the neuromuscular junction.
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Chromosome location
The CHRNG gene is located on chromosome 2, specifically at position 2q37.1. This indicates it resides on the long arm (q) of chromosome 2, within region 37, band 1.
Protein structure
The CHRNG gene encodes a protein that is 517 amino acids long. Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variants within the CHRNG gene can encompass a range of genetic alterations, including substitutions, insertions, or deletions of DNA building blocks. These changes can lead to an impaired or entirely absent gamma subunit, affecting the proper assembly and function of the foetal acetylcholine receptor.
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.137_141del | p.Arg46fs | Pathogenic/Likely pathogenic | ★★☆☆ | Lethal multiple pterygium syndrome |
c.202C>T | p.Arg68Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Lethal multiple pterygium syndrome |
c.240+1del | - | Pathogenic/Likely pathogenic | ★★☆☆ | Autosomal recessive multiple pterygium syndrome |
c.274C>T | p.Arg92Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Autosomal recessive multiple pterygium syndrome |
c.350+2T>C | - | Pathogenic/Likely pathogenic | ★★☆☆ | Autosomal recessive multiple pterygium syndrome |
c.402del | p.Asp135fs | Pathogenic/Likely pathogenic | ★★☆☆ | Lethal multiple pterygium syndrome |
c.420G>A | p.Trp140Ter | Pathogenic | ★★☆☆ | Autosomal recessive multiple pterygium syndrome |
c.532_533del | p.Glu177_Ile178insTer | Pathogenic/Likely pathogenic | ★★☆☆ | Lethal multiple pterygium syndrome |
c.56-1G>A | - | Pathogenic | ★★☆☆ | Autosomal recessive multiple pterygium syndrome |
c.562C>T | p.Gln188Ter | Pathogenic | ★★☆☆ | CHRNG-related disorder |
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 CHRNG gene are associated with conditions that primarily affect muscle development and function, particularly during foetal life. One such condition is multiple pterygium syndrome, which is characterised by skin webbing (pterygium) and reduced or absent muscle movement (akinesia) before birth.
No disease links recorded for this gene in our reference set.
UK clinical status
The CHRNG gene is recognised within several NHS Genomic Medicine Service clinical panels in the UK. These include panels for arthrogryposis, clefting, congenital myasthenic syndrome (R80), developmental disorders (DDG2P), foetal anomalies (R21), and foetal hydrops.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary role of the CHRNG gene?
The CHRNG gene provides instructions for the gamma subunit of the foetal acetylcholine receptor, which is essential for transmitting signals between nerves and muscles to facilitate movement during foetal development.
How does the CHRNG gene relate to the adult acetylcholine receptor?
The gamma subunit produced by CHRNG is specific to the foetal acetylcholine receptor. As pregnancy progresses, this gamma subunit is replaced by an epsilon subunit to form the adult version of the receptor.
What happens if there are variants in the CHRNG gene?
Variants in the CHRNG gene can lead to an impaired or missing gamma subunit, which can affect the proper function of the foetal acetylcholine receptor. This is associated with conditions like multiple pterygium syndrome, characterised by reduced muscle movement and skin webbing prenatally.
References
- Michalk A, Stricker S, Becker J. Acetylcholine receptor pathway mutations explain various fetal akinesia deformation sequence disorders. American journal of human genetics. 2008. PMID: 18252226
- Hoffmann K, Muller JS, Stricker S. Escobar syndrome is a prenatal myasthenia caused by disruption of the acetylcholine receptor fetal gamma subunit. American journal of human genetics. 2006. PMID: 16826520
- Morgan NV, Brueton LA, Cox P. Mutations in the embryonal subunit of the acetylcholine receptor (CHRNG) cause lethal and Escobar variants of multiple pterygium syndrome. American journal of human genetics. 2006. PMID: 16826531