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COLQ
collagen like tail subunit of asymmetric acetylcholinesterase
The COLQ gene provides instructions for the acetylcholinesterase collagenic tail peptide, a protein crucial for proper function of the neuromuscular junction. COLQ encodes a subunit that anchors acetylcholinesterase, an enzyme involved in neurotransmission, to muscle cells.
COLQ is located on the short (p) arm of chromosome 3, at band 3p25.1. Arm ratio per GRCh38 - banding schematic.
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Overview
The COLQ gene, also known as collagen like tail subunit of asymmetric acetylcholinesterase, provides the genetic blueprint for a protein called the acetylcholinesterase collagenic tail peptide. This protein plays a fundamental role in the neuromuscular junction, which is the specialised connection point between nerve cells and muscle cells where signals are transmitted to initiate muscle movement. Proper function of COLQ is vital for efficient communication between nerves and muscles.
What the gene does
The protein produced from the COLQ gene is essential for regulating nerve-to-muscle signalling by anchoring acetylcholinesterase (AChE) to the muscle cell membrane at the neuromuscular junction. The acetylcholinesterase collagenic tail peptide consists of three identical subunits. Each of these subunits binds to a bundle of four AChE proteins, effectively securing them in place. AChE is responsible for breaking down the neurotransmitter acetylcholine, thereby controlling the duration and strength of muscle contraction signals. By localising AChE, the COLQ protein ensures precise and timely termination of nerve impulses, allowing for coordinated muscle function.
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Chromosome location
The COLQ gene is situated on chromosome 3. Specifically, its chromosomal location is 3p25.1. This region of the chromosome contains the genetic information necessary for the synthesis of the acetylcholinesterase collagenic tail peptide.
Protein structure
The COLQ protein is composed of 455 amino acids. Key regions and domains include a PRAD region spanning amino acids 51-67, and a Disordered region from amino acids 90-282. It also features a Collagen-like 1 domain (amino acids 96-269) and a Collagen-like 2 domain (amino acids 277-291). Additionally, the protein contains two Heparan sulfate proteoglycan binding regions, located at amino acids 130-133 and 235-238, respectively.
Key variants
Variants within the COLQ gene can impact the production or function of the acetylcholinesterase collagenic tail peptide. These genetic changes can lead to an impaired ability of the protein to anchor acetylcholinesterase, subsequently affecting neuromuscular transmission. Understanding these variants is crucial for diagnosing associated conditions.
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.1026C>G | p.Asp342Glu | Pathogenic/Likely pathogenic | ★★☆☆ | Synaptic congenital myasthenic syndromes |
c.175C>T | p.Pro59Ser | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital myasthenic syndrome 5 |
c.241_242dup | p.Asn81fs | Pathogenic | ★★☆☆ | Congenital myasthenic syndrome 5 |
c.631C>T | p.Gln211Ter | Pathogenic | ★★☆☆ | Congenital myasthenic syndrome 5 |
c.700G>T | p.Gly234Ter | Pathogenic | ★★☆☆ | Congenital myasthenic syndrome 5 |
c.827_843del | p.Met276fs | Pathogenic/Likely pathogenic | ★★☆☆ | Synaptic congenital myasthenic syndromes |
c.893del | p.Asn298fs | Pathogenic | ★★☆☆ | Congenital myasthenic syndrome 5 |
c.955-2A>C | - | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital myasthenic syndrome 5 |
c.955-2A>T | - | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital myasthenic syndrome 5 |
c.992_998del | p.Leu331fs | Pathogenic/Likely pathogenic | ★★☆☆ | Congenital myasthenic syndrome |
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
Pathogenic variants in the COLQ gene are linked to congenital myasthenic syndromes, specifically Congenital myasthenic syndrome (COLQ). These are a group of inherited disorders characterised by muscle weakness and easy fatigability (myasthenia), typically presenting either shortly after birth or during early childhood. The autosomal recessive inheritance pattern means that an individual must inherit two copies of a pathogenic variant, one from each parent, to develop the condition.
- Congenital myasthenic syndrome (COLQ)
- Congenital myasthenic syndromes Dedicated page coming soon
Inheritance pattern
Conditions caused by pathogenic COLQ 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
The COLQ gene is included in several NHS England Genomic Medicine Service national genomic test directories, indicating its clinical relevance within the UK healthcare system. It is listed as 'green' for Arthrogryposis (R83), Congenital myaesthenic syndrome (R80), and Foetal anomalies (R21). A 'green' status signifies that there is sufficient evidence for the gene to be routinely offered on these panels.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the COLQ gene?
The COLQ gene provides instructions for a protein that anchors acetylcholinesterase (AChE) at the neuromuscular junction. This anchoring is crucial for the efficient breakdown of acetylcholine, which regulates nerve signal transmission to muscles.
Which condition is primarily associated with COLQ gene variants?
Variants in the COLQ gene are primarily associated with congenital myasthenic syndromes, a group of inherited disorders causing muscle weakness and fatigue, often starting in infancy or early childhood.
How is congenital myasthenic syndrome associated with COLQ inherited?
Congenital myasthenic syndrome related to COLQ is inherited in an autosomal recessive pattern. This means an individual must inherit two altered copies of the COLQ gene, one from each parent, to develop the condition.