COLQ

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

Basic information

Region (hg38): 3:15450132-15521751

Links

ENSG00000206561 ∙ NCBI:8292 ∙ OMIM:603033 ∙ HGNC:2226 ∙ Uniprot:Q9Y215 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital myasthenic syndrome 5 (Strong), mode of inheritance: AR
• congenital myasthenic syndrome 5 (Strong), mode of inheritance: AR
• congenital myasthenic syndrome 5 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myasthenic syndrome, congenital, 5	AR	Musculoskeletal; Neurologic; Pharmacogenomic	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	Musculoskeletal; Neurologic	9758617; 9689136; 10441569; 11865139; 23108489
Endplate acetylcholinesterase deficiency has been reported as nonresponsive to treatment

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COLQ gene.

• Congenital myasthenic syndrome 5 (410 variants)
• not provided (123 variants)
• not specified (30 variants)
• Inborn genetic diseases (21 variants)
• Congenital Myasthenic Syndrome, Recessive (9 variants)
• Synaptic congenital myasthenic syndrome (8 variants)
• Congenital myasthenic syndrome (7 variants)
• Abnormality of the musculature (6 variants)
• See cases (2 variants)
• Myasthenic syndrome, slow-channel congenital (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COLQ gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	4	54	3	62
missense	5	8	157	2	3	175
nonsense	15	7				22
start loss			1			1
frameshift	15	15	1			31
inframe indel			2			2
splice donor/acceptor (+/-2bp)	3	13	1			17
splice region	3		12	14	1	30
non coding		1	36	68	61	166
Total	38	45	202	124	67

Highest pathogenic variant AF is 0.0000921

Variants in COLQ

This is a list of pathogenic ClinVar variants found in the COLQ region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-15450154-T-G		Congenital myasthenic syndrome 5	Uncertain significance (Jan 13, 2018)
3-15450236-G-A		Congenital myasthenic syndrome 5	Uncertain significance (Jan 13, 2018)
3-15450249-G-A		Congenital myasthenic syndrome 5	Benign (Jan 13, 2018)
3-15450352-A-C		Congenital myasthenic syndrome 5	Uncertain significance (Jan 12, 2018)
3-15450364-G-A		Congenital myasthenic syndrome 5	Uncertain significance (Jan 13, 2018)
3-15450367-G-A		Congenital myasthenic syndrome 5	Uncertain significance (Jan 13, 2018)
3-15450396-G-A		Congenital myasthenic syndrome 5	Uncertain significance (Jan 12, 2018)
3-15450560-C-T		Congenital myasthenic syndrome 5	Uncertain significance (Jan 12, 2018)
3-15450643-C-T		Congenital myasthenic syndrome 5	Benign (Jan 12, 2018)
3-15450645-C-T		Congenital myasthenic syndrome 5	Uncertain significance (Jan 12, 2018)
3-15450650-C-T		Congenital myasthenic syndrome 5	Benign (Jan 12, 2018)
3-15450651-G-A		Congenital myasthenic syndrome 5	Uncertain significance (Jan 12, 2018)
3-15450796-G-A		Congenital myasthenic syndrome 5	Uncertain significance (Jan 13, 2018)
3-15450893-G-A		Congenital myasthenic syndrome 5	Uncertain significance (Jan 13, 2018)
3-15450908-T-C		Congenital myasthenic syndrome 5	Uncertain significance (Jan 13, 2018)
3-15450929-C-T		Congenital myasthenic syndrome 5	Uncertain significance (Jan 13, 2018)
3-15451128-C-T		Congenital myasthenic syndrome 5	Uncertain significance (Jan 12, 2018)
3-15451129-G-A		Congenital myasthenic syndrome 5	Benign (Jan 12, 2018)
3-15451152-C-T		Congenital myasthenic syndrome 5	Benign (Jan 12, 2018)
3-15451198-T-G		Congenital myasthenic syndrome 5	Uncertain significance (Jan 13, 2018)
3-15451218-C-T		Congenital myasthenic syndrome 5	Uncertain significance (Jan 12, 2018)
3-15451219-G-A		Congenital myasthenic syndrome 5	Uncertain significance (Jan 13, 2018)
3-15451223-C-T		Congenital myasthenic syndrome 5	Uncertain significance (Jan 13, 2018)
3-15451237-G-A		Congenital myasthenic syndrome 5	Uncertain significance (Jan 13, 2018)
3-15451279-T-A		Congenital myasthenic syndrome 5	Benign (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COLQ	protein_coding	protein_coding	ENST00000383788	17	71619

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.94e-14	0.231	125658	0	90	125748	0.000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.219	274	264	1.04	0.0000152	2891
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000800	0.000799
Ashkenazi Jewish	0.00	0.00
East Asian	0.000763	0.000761
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000301	0.000299
Middle Eastern	0.000763	0.000761
South Asian	0.000428	0.000425
Other	0.000994	0.000978

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.0838
• hipred: N
• hipred_score: 0.394
• ghis: 0.441

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.722

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Colq
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); growth/size/body region phenotype

Gene ontology

• 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
• Cellular component: collagen trimer;basement membrane;extracellular space;plasma membrane;cell junction;extracellular matrix;neuromuscular junction;synaptic cleft
• Molecular function: extracellular matrix structural constituent;protein binding;heparin binding