COLQ

protein-coding

collagen like tail subunit of asymmetric acetylcholinesterase, the group of MicroRNA protein coding host genes

Gene summary

This 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]

MANE transcript

NM_005677.4

Inheritance

ClinVar variants

P:121U:196B:99

Top phenotype

Myasthenic syndrome, congenital, 5

gnomAD constraint

pLI —, LoF o/e 0.78

Max pathogenic AF

—

Genomic locus

chr3:15,450,133-15,521,751

External References & Databases

Ensembl (ENSG00000206561)

Transcript & Mutation Effects

hg38 • Region Span ~71.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital myasthenic syndrome 5STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011281

Submitter: Genomics England PanelApp

congenital myasthenic syndrome 5STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011281

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Myasthenic syndrome, congenital, 5AR

Manifestation: Musculoskeletal; Neurologic

Intervention: Musculoskeletal; Neurologic; Pharmacogenomic

Rationale: Most individuals with CMS benefit from AChE inhibitors and/or potassium channel blocker 3,4-diaminopyridine (3,4-DAP), though caution must be used in giving 3,4-DAP to young children and individuals with fast-channel syndromes; Some individuals with Slow-channel congenital myasthenic syndrome,are treated with quinidine, which has some major side effects and may be detrimental in individuals with AChR deficiency; Additional neurologic monitoring in pregnancy may be beneficial

Comments: Endplate acetylcholinesterase deficiency has been reported as nonresponsive to treatment

Refs: 9758617; 9689136; 10441569; 11865139; 23108489

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to COLQ variants in ClinVar

9 Conditions Cataloged

Congenital myasthenic syndrome 5Total: 473

not providedTotal: 84

Inborn genetic diseasesTotal: 67

not specifiedTotal: 37

Congenital myasthenic syndromeTotal: 19

COLQ-related disorderTotal: 15

Synaptic congenital myasthenic syndromesTotal: 8

Abnormality of the musculatureTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005677.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous		1 clinvar	5 clinvar	89 clinvar		95
missense	6 clinvar	15 clinvar	184 clinvar	8 clinvar	2 clinvar	215
nonsense	21 clinvar	10 clinvar				31
start loss			1 clinvar			1
frameshift	19 clinvar	20 clinvar	1 clinvar			40
splice donor/acceptor (+/-2bp)	7 clinvar	22 clinvar	5 clinvar			34
Total	53	68	196	97	2	416

Highest pathogenic variant AF is 0.00006815999

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005677.4	RefSeq	NP_005668.2	17	MANE Select
ENST00000383788.10	Ensembl	ENSP00000373298.3	17	MANE Select
NM_080538.2	RefSeq	NP_536799.1	17	Standard
NM_080539.4	RefSeq	NP_536800.2	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

acetylcholine catabolic process in synaptic cleft
regulation of synaptic growth at neuromuscular junction
extracellular matrix organization
skeletal muscle acetylcholine-gated channel clustering
establishment of protein localization to membrane

Molecular Function

extracellular matrix structural constituent
protein binding
heparin binding

Cellular Component

collagen trimer
basement membrane
extracellular space
plasma membrane
cell junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000383788
Coding exons: 17
Length: 71619
Individuals with no LoFs: 125658
Homozygous LoFs: 0
Heterozygous LoFs: 90
Defined: 125748
p: 0.000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.219	274	264	1.04	0.0000152	2891
Missense (PolyPhen)		36	28.558	1.2606		344
Synonymous	0.00920	97	97.1	0.999	0.00000631	917
Loss of Function	1.11	24	30.6	0.783	0.00000190	337

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00049	0.00049	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00076	0.00076	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00030	0.00030	rare
South Asian	0.00043	0.00042	rare
Other	0.00099	0.00098	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Anchors the catalytic subunits of asymmetric AChE to the synaptic basal lamina.;
Disease: DISEASE: Myasthenic syndrome, congenital, 5 (CMS5) [MIM:603034]: A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS5 inheritance is autosomal recessive. {ECO:0000269|PubMed:10665486, ECO:0000269|PubMed:11865139, ECO:0000269|PubMed:24938146, ECO:0000269|PubMed:9758617}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.226

Intolerance Scores

LoFtool: 0.0780
RVIS EVS: -0.53
RVIS percentile EVS: 20.7

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.722

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium