COLQ
Collagen-Like Tail Subunit of Asymmetric Acetylcholinesterase
Gene Summary
RefSeq / NCBIThis gene encodes the subunit of a collagen-like molecule associated with acetylcholinesterase in skeletal muscle. Each molecule is composed of three identical subunits. Each subunit contains a proline-rich attachment domain (PRAD) that binds an acetylcholinesterase tetramer to anchor the catalytic subunit of the enzyme to the basal lamina. Mutations in this gene are associated with endplate acetylcholinesterase deficiency. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Clinical Phenotype
Congenital myasthenic syndrome (CMS) due to acetylcholinesterase (AChE) deficiency at the neuromuscular junction. Fatigable proximal weakness from infancy or early childhood, with pupillary abnormalities. May worsen with acetylcholinesterase inhibitors (pyridostigmine).
Molecular Mechanism
COLQ encodes the collagen tail that anchors asymmetric acetylcholinesterase to the basal lamina of the NMJ. Without the anchor, AChE is absent from the synapse. ACh accumulates, overstimulating and eventually desensitizing the postsynaptic nicotinic receptor — mimicking a cholinergic crisis.
Clinical Hallmarks & Key Evidence
COLQ-CMS is uniquely worsened by pyridostigmine (AChE inhibitor) — because there is already no AChE; adding more inhibition causes toxic ACh accumulation and clinical deterioration.
Ohno K et al. Hum Mol Genet. 1998;7(5):807-19.
Ephedrine and albuterol are the primary treatments for COLQ-CMS, likely by upregulating AChR or improving NMJ development — bypassing the absent AChE.
Liewluck T et al. Neurology. 2011;77(20):1806-8.
Repetitive nerve stimulation in COLQ-CMS shows a characteristic 'double CMAP' (repetitive compound muscle action potential after a single stimulus) due to re-firing from prolonged end-plate potentials.
Engel AG et al. Prog Neurobiol. 2015;131:140-58.
External Resources
Gene data compiled from the Washington University Neuromuscular Disease Center, NCBI Gene, and OMIM. For clinical use, always refer to primary sources.