COLQ

Summary

COLQ (collagen like tail subunit of asymmetric acetylcholinesterase, HGNC:2226) is a protein-coding gene on chromosome 3p25.1, encoding Acetylcholinesterase collagenic tail peptide (Q9Y215). Anchors the catalytic subunits of asymmetric AChE to the synaptic basal membrane, and is therefore involved in the down-regulation of colinergic synaptic transmission.

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.

Source: NCBI Gene 8292 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital myasthenic syndrome 5 (Strong, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 672 total — 58 pathogenic, 47 likely-pathogenic
• Phenotypes (HPO): 67
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_005677

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2226
Approved symbol	COLQ
Name	collagen like tail subunit of asymmetric acetylcholinesterase
Location	3p25.1
Locus type	gene with protein product
Status	Approved
Aliases	EAD
Ensembl gene	ENSG00000206561
Ensembl biotype	protein_coding
OMIM	603033
Entrez	8292

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 15 protein_coding, 5 retained_intron, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000383781, ENST00000383786, ENST00000383788, ENST00000603469, ENST00000603752, ENST00000603808, ENST00000604401, ENST00000605797, ENST00000679838, ENST00000680240, ENST00000680545, ENST00000680897, ENST00000681097, ENST00000681222, ENST00000874202, ENST00000874203, ENST00000874204, ENST00000874205, ENST00000959102, ENST00000959103, ENST00000959104, ENST00000959105, ENST00000959106, ENST00000959107

RefSeq mRNA: 3 — MANE Select: NM_005677 NM_005677, NM_080538, NM_080539

CCDS: CCDS33709, CCDS43057, CCDS46768

Canonical transcript exons

ENST00000383788 — 17 exons

Exon	Start	End
ENSE00001498669	15474228	15474272
ENSE00001498670	15474925	15474951
ENSE00001498671	15475425	15475487
ENSE00001498672	15477126	15477197
ENSE00001498673	15478977	15479003
ENSE00001498674	15479338	15479382
ENSE00001498675	15488206	15488307
ENSE00001498676	15489525	15489637
ENSE00001644936	15470536	15470616
ENSE00002084171	15474000	15474035
ENSE00003459962	15450133	15451713
ENSE00003480220	15458186	15458325
ENSE00003482531	15466341	15466437
ENSE00003535621	15456460	15456579
ENSE00003575027	15455899	15456019
ENSE00003644987	15453829	15453931
ENSE00003846195	15521520	15521706

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 93.04.

FANTOM5 (CAGE): breadth broad, TPM avg 0.9258 / max 99.7913, expressed in 239 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41282	0.3964	128
41281	0.2593	65
41283	0.2428	93
41280	0.0273	15

Top tissues by expression

272 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	93.04	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.02	gold quality
granulocyte	CL:0000094	86.85	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	86.31	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.81	gold quality
apex of heart	UBERON:0002098	83.69	gold quality
right atrium auricular region	UBERON:0006631	82.17	gold quality
sural nerve	UBERON:0015488	81.97	gold quality
cerebellar hemisphere	UBERON:0002245	81.85	gold quality
cerebellar cortex	UBERON:0002129	81.69	gold quality
right hemisphere of cerebellum	UBERON:0014890	81.36	gold quality
diaphragm	UBERON:0001103	81.20	gold quality
cardiac atrium	UBERON:0002081	81.06	gold quality
cerebellum	UBERON:0002037	79.90	gold quality
muscle of leg	UBERON:0001383	79.49	gold quality
right frontal lobe	UBERON:0002810	79.13	gold quality
gastrocnemius	UBERON:0001388	79.05	gold quality
descending thoracic aorta	UBERON:0002345	79.01	gold quality
heart left ventricle	UBERON:0002084	78.92	gold quality
ascending aorta	UBERON:0001496	78.69	gold quality
thoracic aorta	UBERON:0001515	78.56	gold quality
cardiac ventricle	UBERON:0002082	78.40	gold quality
heart	UBERON:0000948	78.36	gold quality
anterior cingulate cortex	UBERON:0009835	77.90	gold quality
cingulate cortex	UBERON:0003027	77.78	gold quality
muscle organ	UBERON:0001630	77.36	gold quality
nucleus accumbens	UBERON:0001882	77.28	gold quality
aorta	UBERON:0000947	77.27	gold quality
skeletal muscle tissue	UBERON:0001134	76.66	gold quality
caudate nucleus	UBERON:0001873	76.61	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.26
E-MTAB-6678	yes	5.06
E-MTAB-6386	no	9.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

84 targeting COLQ, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-543	99.52	69.03	2595

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 23)

• Three novel colq protein mutations in eight kinships. (PMID:11865139)
• Both patients presented a novel splicing mutation (IVS1-1G–>A) affecting the exon encoding the proline-rich attachment domain (PRAD), which interacts with acetylcholinesterase. (PMID:12609505)
• muscle fiber type-specific expression pattern of ColQ transcripts was regulated by a slow upsteam regulatory element (SURE) and a fast intronic regulatory element (FIRE) (PMID:16256971)
• we found familial occurrence of congenital ptosis in heterozygous carriers of 950delC. (PMID:17300939)
• Twenty different mutations of the COLQ gene have been identified in our patients: The mutations are missense (6), splice-site (3), in-frame deletion (1), non-sense (4) and frameshift (6). The majority of the mutations are protein truncating. (PMID:18180250)
• two siblings have identical novel heterozygous mutations but different phenotypic expressions. (PMID:20370815)
• Long-term follow-up of patients with COLQ mutations showed no genotype-phenotype correlation, 80% of patients were ambulant and 87% of patients had no respiratory trouble in spite of severe relapses. (PMID:22088788)
• This study presented that four cases illustrate the clinical spectrum of the recurrent homozygous W148X mutation in the COLQ gene. (PMID:22490774)
• We proved that the missense mutations in ColQ-CTD cause endplate AChE deficiency by compromising ColQ-MuSK interaction at the NMJ. (PMID:23553736)
• findings suggest that the impaired attachment of COOH-terminal mutants causing EP AChE deficiency is in part independent of MuSK, and that the COOH-terminus of ColQ may interact with other proteins at the BL (PMID:24281389)
• study identified the molecular cause underlying congenital myasthenic syndrome in two patients in a Syrian family, a novel missense mutation, homozygous single nucleotide substitution (c.1010T>C) in the COLQ gene (PMID:24938146)
• Global splicing analysis with RNA-seq revealed that exons carrying the hnRNP H-binding GGGGG motif are predisposed to be skipped compared to those carrying the SRSF1-binding GGAGG motif in both human and mouse brains. (PMID:26282582)
• Mutations in RAPSN and COLQ are the most common causes of congenital myasthenic syndrome in Israel. (PMID:28024842)
• COLQ rs7609897-T association with diverticular disease in Iceland and Denmark population. (PMID:28585551)
• To study cholinesterase distribution in patients with COLQ gene mutation, immunohistochemical staining and indirect immunofluorescence method was used to detect cholinesterase lack of disease in patients with resectable pancreatic or lung tissue samples, confirmed cholinesterase distribution in nerve fibers surrounding the vessels. Expression of cholinesterase in mutant patients was significantly higher than wildtype. (PMID:29630557)
• This data highlight COLQ (R410W) as a variant to initially test for in patients who have isolated limb-girdle myasthenia and are not responsive to acetylcholine receptor inhibitors, especially those from southern India. (PMID:30124556)
• The First Case of Congenital Myasthenic Syndrome Caused by a Large Homozygous Deletion in the C-Terminal Region of COLQ (Collagen Like Tail Subunit of Asymmetric Acetylcholinesterase) Protein. (PMID:33353066)
• COLQ and ARHGAP15 are Associated with Diverticular Disease and are Expressed in the Colon. (PMID:34225052)
• Congenital myasthenic syndrome by mutation of the ColQ gene: Phenotypic and evolutionary profile of three Algerian families. (PMID:36764859)
• The collagen ColQ binds to LRP4 and regulates the activation of the Muscle-Specific Kinase-LRP4 receptor complex by agrin at the neuromuscular junction. (PMID:37356721)
• Delineation of molecular characteristics of congenital myasthenic syndromes in Indian families and review of literature. (PMID:37646703)
• Molecular Analysis of a Congenital Myasthenic Syndrome Due to a Pathogenic Variant Affecting the C-Terminus of ColQ. (PMID:38003406)
• COLQ-Congenital myasthenic syndrome in an Iranian cohort: the clinical and genetics spectrum. (PMID:38475910)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	colq	ENSDARG00000019692
danio_rerio	wu:fc38h03	ENSDARG00000074216
mus_musculus	Colq	ENSMUSG00000057606
rattus_norvegicus	Colq	ENSRNOG00000019615

Paralogs (37): COL9A2 (ENSG00000049089), COL23A1 (ENSG00000050767), COL11A1 (ENSG00000060718), COL17A1 (ENSG00000065618), COL5A3 (ENSG00000080573), COL4A4 (ENSG00000081052), COL16A1 (ENSG00000084636), COL9A3 (ENSG00000092758), COL20A1 (ENSG00000101203), COL1A1 (ENSG00000108821), COL9A1 (ENSG00000112280), COL7A1 (ENSG00000114270), COL21A1 (ENSG00000124749), COL5A1 (ENSG00000130635), COL4A2 (ENSG00000134871), COL2A1 (ENSG00000139219), COL6A1 (ENSG00000142156), COL6A2 (ENSG00000142173), EDA (ENSG00000158813), COL26A1 (ENSG00000160963), COL1A2 (ENSG00000164692), COL3A1 (ENSG00000168542), COL4A3 (ENSG00000169031), COL22A1 (ENSG00000169436), COL24A1 (ENSG00000171502), COL18A1 (ENSG00000182871), EMID1 (ENSG00000186998), COL4A1 (ENSG00000187498), COL4A5 (ENSG00000188153), COL25A1 (ENSG00000188517), COL27A1 (ENSG00000196739), COL13A1 (ENSG00000197467), COL4A6 (ENSG00000197565), COL11A2 (ENSG00000204248), COL5A2 (ENSG00000204262), COL15A1 (ENSG00000204291), COL28A1 (ENSG00000215018)

Protein

Protein identifiers

Acetylcholinesterase collagenic tail peptide — Q9Y215 (reviewed: Q9Y215)

Alternative names: AChE Q subunit, Acetylcholinesterase-associated collagen

All UniProt accessions (4): A0A0C4DGS2, A0A7P0T9V6, Q9Y215, S4R408

UniProt curated annotations — full annotation on UniProt →

Function. Anchors the catalytic subunits of asymmetric AChE to the synaptic basal membrane, and is therefore involved in the down-regulation of colinergic synaptic transmission.

Subunit / interactions. Homotrimer. Component of the asymmetric form of AChE, a disulfide-bonded oligomer composed of the collagenic subunits (Q) and a variable number of asymmetric catalytic subunits (T). The N-terminal of a collagenic subunit (Q) associates with the C-terminal of a catalytic subunit (T). Interacts with HSPG2. Interacts with MUSK.

Subcellular location. Synapse.

Tissue specificity. Found at the end plate of skeletal muscle.

Post-translational modifications. The triple-helical tail is stabilized by disulfide bonds at each end.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The proline-rich attachment domain (PRAD) binds the AChE catalytic subunits.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the COLQ family.

Isoforms (8)

UniProt ID	Names	Canonical?
Q9Y215-1	I	yes
Q9Y215-2	II
Q9Y215-3	III
Q9Y215-4	IV
Q9Y215-5	V
Q9Y215-6	VI
Q9Y215-7	VII
Q9Y215-8	VIII

RefSeq proteins (3): NP_005668, NP_536799, NP_536800 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008160	Collagen	Repeat
IPR011936	Myxo_disulph_rpt	Repeat
IPR050149	Collagen_superfamily	Family

Pfam: PF01391

UniProt features (45 total): sequence variant 12, splice variant 10, compositionally biased region 5, disulfide bond 5, sequence conflict 5, region of interest 4, domain 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1VZJ	X-RAY DIFFRACTION	2.35

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y215-F1	55.25	0.03

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (5): 51, 52, 93, 291, 293

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 298 (showing top): MORF_RAGE, GOBP_NEUROMUSCULAR_JUNCTION_DEVELOPMENT, RNGTGGGC_UNKNOWN, MORF_FLT1, MORF_MSH3, GOBP_SYNAPSE_ASSEMBLY, RORA1_01, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOCC_COLLAGEN_TRIMER, MORF_ATRX, GOBP_GROWTH, GOBP_SYNAPTIC_TRANSMISSION_CHOLINERGIC, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, TGACCTY_ERR1_Q2, MORF_ESR1

GO Biological Process (6): acetylcholine catabolic process in synaptic cleft (GO:0001507), regulation of synaptic assembly at neuromuscular junction (GO:0008582), negative regulation of synaptic transmission, cholinergic (GO:0032223), protein localization to synapse (GO:0035418), skeletal muscle acetylcholine-gated channel clustering (GO:0071340), establishment of protein localization to membrane (GO:0090150)

GO Molecular Function (4): heparin binding (GO:0008201), molecular adaptor activity (GO:0060090), extracellular matrix structural constituent (GO:0005201), protein binding (GO:0005515)

GO Cellular Component (9): collagen trimer (GO:0005581), basement membrane (GO:0005604), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), cell junction (GO:0030054), extracellular matrix (GO:0031012), neuromuscular junction (GO:0031594), synaptic cleft (GO:0043083), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
synaptic transmission, cholinergic	2
binding	2
extracellular matrix	2
cellular anatomical structure	2
acetylcholine catabolic process	1
synaptic cleft	1
regulation of developmental growth	1
synaptic assembly at neuromuscular junction	1
regulation of synapse assembly	1
regulation of neuromuscular junction development	1
regulation of synaptic transmission, cholinergic	1
negative regulation of synaptic transmission	1
protein localization to cell junction	1
postsynaptic membrane organization	1
neuromuscular junction development	1
receptor clustering	1
establishment of protein localization	1
localization within membrane	1
glycosaminoglycan binding	1
sulfur compound binding	1
molecular_function	1
structural molecule activity	1
protein-containing complex	1
membrane	1
cell periphery	1
external encapsulating structure	1
synapse	1
extracellular region	1
cell junction	1

Protein interactions and networks

STRING

1078 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COLQ	MUSK	O15146	985
COLQ	ACHE	P22303	981
COLQ	BCHE	P06276	967
COLQ	DOK7	Q18PE1	943
COLQ	RAPSN	Q13702	879
COLQ	HSPG2	P98160	868
COLQ	CHRNE	Q04844	867
COLQ	AGRN	O00468	810
COLQ	PRIMA1	Q86XR5	809
COLQ	CHRNB1	P11230	796
COLQ	SCN4A	P35499	781
COLQ	CHRNA1	P02708	741
COLQ	CHRND	Q07001	701
COLQ	GFPT1	Q06210	671
COLQ	ALG14	Q96F25	657

IntAct

8 interactions, top by confidence:

A	B	Type	Score
ACHE	COLQ	psi-mi:“MI:0407”(direct interaction)	0.560
COLQ	ACHE	psi-mi:“MI:0407”(direct interaction)	0.560
SGTB	COLQ	psi-mi:“MI:0915”(physical association)	0.560
COLQ	PLOD3	psi-mi:“MI:0914”(association)	0.530
COLQ	PLOD2	psi-mi:“MI:0914”(association)	0.350
COLQ	POTEF	psi-mi:“MI:0914”(association)	0.350
COLQ	SGTB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (46): P3H2 (Affinity Capture-MS), FN1 (Affinity Capture-MS), TRIM68 (Affinity Capture-MS), LEPREL2 (Affinity Capture-MS), BCHE (Affinity Capture-MS), CRTAP (Affinity Capture-MS), COLGALT2 (Affinity Capture-MS), FBLN1 (Affinity Capture-MS), P3H4 (Affinity Capture-MS), PLOD1 (Affinity Capture-MS), PLOD2 (Affinity Capture-MS), P4HA1 (Affinity Capture-MS), P3H1 (Affinity Capture-MS), TEX15 (Affinity Capture-MS), COL4A2 (Affinity Capture-MS)

ESM2 similar proteins: A0A060WQA3, A0MSJ1, A5PN28, A6NHN0, A8WGB1, A8WR59, B2RNN3, B7Z0K8, C7DZK3, O35167, O35348, O76368, O88207, P0C862, P12107, P13942, P20908, P20909, P23805, P25067, P25318, P25940, P42916, P83371, P98085, Q03637, Q07092, Q07563, Q0II24, Q0VF58, Q17RW2, Q30D77, Q32S24, Q3MI99, Q4ZJM7, Q4ZJN1, Q60467, Q61245, Q64739, Q6UXH8

Diamond homologs: O35167, O35348, Q03637, Q9Y215, Q8R4K8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

672 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	58
Likely pathogenic	47
Uncertain significance	246
Likely benign	198
Benign	75

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069916	NM_005677.4(COLQ):c.361G>T (p.Glu121Ter)	Pathogenic
1069918	NM_005677.4(COLQ):c.798del (p.Gly267fs)	Pathogenic
1070410	NM_005677.4(COLQ):c.1111C>T (p.Gln371Ter)	Pathogenic
1071042	NM_005677.4(COLQ):c.377del (p.Gly126fs)	Pathogenic
1299712	NM_005677.4:c.(814+1_815-1)_(954+1_955-1)del	Pathogenic
1335503	NM_005677.4(COLQ):c.283C>T (p.Gln95Ter)	Pathogenic
1356041	NM_005677.4(COLQ):c.1005_1008del (p.Asn335fs)	Pathogenic
1383050	NM_005677.4(COLQ):c.700G>T (p.Gly234Ter)	Pathogenic
1416795	NM_005677.4(COLQ):c.1195+2T>C	Pathogenic
1448843	NM_005677.4(COLQ):c.893del (p.Asn298fs)	Pathogenic
1679827	NM_005677.4(COLQ):c.1061G>A (p.Trp354Ter)	Pathogenic
1685664	NM_005677.4(COLQ):c.1195+2T>G	Pathogenic
2017269	NM_005677.4(COLQ):c.109dup (p.Leu37fs)	Pathogenic
2018622	NM_005677.4(COLQ):c.682G>T (p.Gly228Ter)	Pathogenic
2203311	NM_005677.4(COLQ):c.176C>A (p.Pro59Gln)	Pathogenic
2435808	NM_005677.4(COLQ):c.241_242dup (p.Asn81fs)	Pathogenic
2444318	NM_005677.4(COLQ):c.109del (p.Leu37fs)	Pathogenic
2576518	NM_005677.4(COLQ):c.815G>A (p.Gly272Glu)	Pathogenic
2576520	NM_005677.4:c.188_321del	Pathogenic
2579192	GRCh38/hg38 3p25.1(chr3:15488109-15489735)x0	Pathogenic
2680856	NM_005677.4(COLQ):c.631C>T (p.Gln211Ter)	Pathogenic
2680858	NM_005677.4(COLQ):c.706C>T (p.Arg236Ter)	Pathogenic
2716578	NM_005677.4(COLQ):c.118del (p.Leu40fs)	Pathogenic
280125	NM_005677.4(COLQ):c.679C>T (p.Arg227Ter)	Pathogenic
2910166	NM_005677.4(COLQ):c.847G>T (p.Gly283Ter)	Pathogenic
3064097	NM_005677.4(COLQ):c.865G>T (p.Gly289Ter)	Pathogenic
3246896	NC_000003.11:g.(?15497386)(15498106_?)del	Pathogenic
3703618	NM_005677.4(COLQ):c.1307_1314del (p.Gly436fs)	Pathogenic
3711709	NM_005677.4(COLQ):c.824del (p.Ile275fs)	Pathogenic
3776181	NM_005677.4(COLQ):c.394-1G>A	Pathogenic

SpliceAI

2719 predictions. Top by Δscore:

Variant	Effect	Δscore
3:15455893:A:AC	donor_gain	1.0000
3:15455894:C:CC	donor_gain	1.0000
3:15470531:CTTAC:C	donor_loss	1.0000
3:15470532:TTAC:T	donor_loss	1.0000
3:15470533:TACCT:T	donor_loss	1.0000
3:15470535:CCTG:C	donor_gain	1.0000
3:15470612:TCACC:T	acceptor_gain	1.0000
3:15470613:CACCC:C	acceptor_gain	1.0000
3:15470614:ACC:A	acceptor_gain	1.0000
3:15470615:CC:C	acceptor_gain	1.0000
3:15470615:CCC:C	acceptor_gain	1.0000
3:15470615:CCCT:C	acceptor_loss	1.0000
3:15470616:CC:C	acceptor_gain	1.0000
3:15470616:CCTG:C	acceptor_loss	1.0000
3:15470617:C:CC	acceptor_gain	1.0000
3:15470617:C:CG	acceptor_loss	1.0000
3:15470618:T:A	acceptor_loss	1.0000
3:15521515:TTTAC:T	donor_loss	1.0000
3:15521516:TTA:T	donor_loss	1.0000
3:15521517:TACCT:T	donor_loss	1.0000
3:15521518:A:AT	donor_loss	1.0000
3:15451711:GACC:G	acceptor_loss	0.9900
3:15451713:CCTG:C	acceptor_loss	0.9900
3:15451714:C:A	acceptor_loss	0.9900
3:15451715:T:C	acceptor_loss	0.9900
3:15453823:CCCTA:C	donor_loss	0.9900
3:15453824:CCTA:C	donor_loss	0.9900
3:15453825:CTAC:C	donor_loss	0.9900
3:15453826:TACCC:T	donor_loss	0.9900
3:15453827:A:AC	donor_gain	0.9900

AlphaMissense

2918 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:15456474:A:G	W354R	0.997
3:15456474:A:T	W354R	0.997
3:15456472:C:A	W354C	0.996
3:15456472:C:G	W354C	0.996
3:15451693:C:G	C440S	0.995
3:15451694:A:T	C440S	0.995
3:15456521:G:T	A338D	0.994
3:15453877:C:G	C417S	0.992
3:15453878:A:T	C417S	0.992
3:15451694:A:G	C440R	0.991
3:15451660:C:G	C451S	0.990
3:15451661:A:T	C451S	0.990
3:15451680:G:C	C444W	0.990
3:15451692:G:C	C440W	0.990
3:15453847:C:G	C427S	0.990
3:15453847:C:T	C427Y	0.990
3:15453848:A:T	C427S	0.990
3:15456518:A:G	F339S	0.989
3:15451659:G:C	C451W	0.988
3:15453848:A:G	C427R	0.988
3:15453913:C:G	C405S	0.988
3:15453914:A:T	C405S	0.988
3:15451661:A:G	C451R	0.987
3:15451681:C:G	C444S	0.987
3:15451681:C:T	C444Y	0.987
3:15451682:A:G	C444R	0.987
3:15451682:A:T	C444S	0.987
3:15455937:C:G	C386S	0.987
3:15455938:A:T	C386S	0.987
3:15451660:C:T	C451Y	0.986

dbSNP variants (sampled 300 via entrez): RS1000095028 (3:15510233 T>C), RS1000097828 (3:15467958 A>T), RS1000134817 (3:15469643 T>G), RS1000142379 (3:15463217 G>C), RS1000227168 (3:15486124 G>A), RS1000240311 (3:15475707 A>G), RS1000249520 (3:15456849 G>C), RS1000303256 (3:15483244 C>T), RS1000445694 (3:15450600 C>G), RS1000509115 (3:15463036 C>G,T), RS1000524447 (3:15507819 T>C), RS1000529852 (3:15469852 A>G), RS1000539400 (3:15459064 G>A), RS1000679630 (3:15498909 G>A,T), RS1000687119 (3:15458752 G>T)

Disease associations

OMIM: gene MIM:603033 | disease phenotypes: MIM:603034, MIM:601462

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital myasthenic syndrome 5	Strong	Autosomal recessive

Mondo (2): congenital myasthenic syndrome 5 (MONDO:0011281), congenital myasthenic syndrome (MONDO:0018940)

Orphanet (2): Congenital myasthenic syndrome (Orphanet:590), Synaptic congenital myasthenic syndrome (Orphanet:98915)

HPO phenotypes

67 total (30 of 67 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000207	Triangular mouth
HP:0000218	High palate
HP:0000303	Mandibular prognathia
HP:0000467	Neck muscle weakness
HP:0000508	Ptosis
HP:0000597	Ophthalmoparesis
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001284	Areflexia
HP:0001290	Generalized hypotonia
HP:0001324	Muscle weakness
HP:0001488	Bilateral ptosis
HP:0001612	Weak cry
HP:0001667	Right ventricular hypertrophy
HP:0001762	Talipes equinovarus
HP:0001999	Abnormal facial shape
HP:0002015	Dysphagia
HP:0002033	Poor suck
HP:0002092	Pulmonary arterial hypertension
HP:0002093	Respiratory insufficiency
HP:0002098	Respiratory distress
HP:0002359	Frequent falls
HP:0002421	Poor head control
HP:0002460	Distal muscle weakness
HP:0002515	Waddling gait
HP:0002643	Neonatal respiratory distress

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006479_106	Diverticular disease	3.000000e-18
GCST008256_9	Diverticulitis	2.000000e-09
GCST008257_2	Diverticular disease	2.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009959	diverticular disease

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D020294	Myasthenic Syndromes, Congenital	C10.668.758.800; C16.320.590
C566415	Endplate Acetylcholinesterase Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, affects methylation, decreases expression	3
sotorasib	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
kojic acid	increases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Latex	increases expression	1
Methapyrilene	increases methylation	1
N-Nitrosopyrrolidine	decreases expression	1
Polychlorinated Biphenyls	affects expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	decreases expression	1
Acrylamide	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A1QD	REGUi009-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

12 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01203592	PHASE1	COMPLETED	Efficacy of Albuterol in the Treatment of Congenital Myasthenic Syndromes
NCT06436742	PHASE1	RECRUITING	A Phase 1b Study to Investigate Safety and Tolerability of ARGX-119 in Adult Participants With DOK7-Congenital Myasthenic Syndromes (CMS)
NCT07226726	PHASE1	RECRUITING	Patients With Congenital Myasthenic Syndrome Will be Treated With Mesenchymal Stem Cell Exosome Solution
NCT00872950	Not specified	APPROVED_FOR_MARKETING	3,4-Diaminopyridine Use in Lambert-Eaton Myasthenic Syndrome(LEMS) and Congenital Myasthenic Syndromes (CMS)
NCT01403402	Not specified	RECRUITING	Congenital Muscle Disease Study of Patient and Family Reported Medical Information
NCT01474980	Not specified	COMPLETED	Pregnancy Outcomes in Congenital Myasthenie Syndrome
NCT02012933	Not specified	NO_LONGER_AVAILABLE	3,4-Diaminopyridine for Lambert-Eaton Myasthenic Syndrome (LEMS) and Congenital Myasthenia (CM)
NCT02189720	Not specified	APPROVED_FOR_MARKETING	Expanded Access Study Amifampridine Phosphate in Lambert-Eaton Myasthenic Syndrome (LEMS),Congenital Myasthenic Syndrome
NCT03062631	Not specified	NO_LONGER_AVAILABLE	Treatment Use of 3,4 Diaminopyridine in Congenital Myasthenia
NCT05408702	Not specified	COMPLETED	Exercise in Autoimmune Myasthenia Gravis and Myasthenic Syndromes
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT06078553	Not specified	RECRUITING	A Natural History Study in Participants With Congenital Myasthenic Syndromes (CMS) Due to Mutations in DOK7, MUSK, AGRN, or LRP4