AGRN

Summary

AGRN (agrin, HGNC:329) is a protein-coding gene on chromosome 1p36.33, encoding Agrin (O00468). Depending on alternative splicing and post-translational modifications, it has a role in different processes, including neuromuscular junction formation and maintenance, and regulation of neurite outgrowth.

This gene encodes one of several proteins that are critical in the development of the neuromuscular junction (NMJ), as identified in mouse knock-out studies. The encoded protein contains several laminin G, Kazal type serine protease inhibitor, and epidermal growth factor domains. Additional post-translational modifications occur to add glycosaminoglycans and disulfide bonds. In one family with congenital myasthenic syndrome affecting limb-girdle muscles, a mutation in this gene was found. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 375790 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital myasthenic syndrome 8 (Definitive, ClinGen) — +2 more curated relationships
• Clinical variants (ClinVar): 2,582 total — 40 pathogenic, 24 likely-pathogenic
• Phenotypes (HPO): 105
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_198576

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:329
Approved symbol	AGRN
Name	agrin
Location	1p36.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000188157
Ensembl biotype	protein_coding
OMIM	103320
Entrez	375790

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 retained_intron, 4 protein_coding

ENST00000379370, ENST00000461111, ENST00000466223, ENST00000469403, ENST00000478677, ENST00000479707, ENST00000492947, ENST00000620552, ENST00000651234, ENST00000652369

RefSeq mRNA: 3 — MANE Select: NM_198576 NM_001305275, NM_001364727, NM_198576

CCDS: CCDS30551

Canonical transcript exons

ENST00000379370 — 36 exons

Exon	Start	End
ENSE00001367302	1050726	1050837
ENSE00001374645	1051453	1051645
ENSE00001381606	1051728	1051815
ENSE00001385905	1051253	1051369
ENSE00001605257	1043239	1043457
ENSE00001622111	1047327	1047454
ENSE00001622861	1049566	1049795
ENSE00001627476	1041478	1041702
ENSE00001641464	1048867	1049059
ENSE00001650172	1048012	1048365
ENSE00001652878	1046160	1046265
ENSE00001653556	1044109	1044257
ENSE00001657020	1050233	1050329
ENSE00001667688	1047776	1047895
ENSE00001673004	1022201	1022462
ENSE00001688790	1045161	1045277
ENSE00001693596	1050427	1050591
ENSE00001700910	1041956	1042162
ENSE00001701194	1043538	1043732
ENSE00001706121	1049236	1049451
ENSE00001737074	1045359	1045523
ENSE00001750513	1046397	1046735
ENSE00001756488	1049903	1050037
ENSE00001762402	1043823	1044023
ENSE00001773423	1044334	1044439
ENSE00001787340	1046820	1046957
ENSE00001883271	1054824	1056116
ENSE00002277560	1020120	1020373
ENSE00002692404	1053753	1053977
ENSE00003472518	1041173	1041397
ENSE00003529542	1047573	1047687
ENSE00003619422	1054448	1054551
ENSE00003635914	1035277	1035324
ENSE00003677060	1040665	1040880
ENSE00003684009	1045964	1046088
ENSE00003686258	1045733	1045876

Expression profiles

Bgee: expression breadth ubiquitous, 271 present calls, max score 98.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 44.7991 / max 520.5794, expressed in 1719 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
50	43.6748	1714
51	0.4462	247
49	0.2441	112
201306	0.1926	87
57	0.1767	67
201304	0.0402	19
201305	0.0244	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.01	gold quality
metanephros cortex	UBERON:0010533	97.82	gold quality
renal medulla	UBERON:0000362	97.07	gold quality
decidua	UBERON:0002450	96.90	gold quality
stromal cell of endometrium	CL:0002255	96.39	gold quality
left lobe of thyroid gland	UBERON:0001120	96.31	gold quality
right lobe of thyroid gland	UBERON:0001119	96.23	gold quality
thyroid gland	UBERON:0002046	95.60	gold quality
right frontal lobe	UBERON:0002810	95.27	gold quality
adult mammalian kidney	UBERON:0000082	95.02	gold quality
cortical plate	UBERON:0005343	94.13	gold quality
body of pancreas	UBERON:0001150	93.91	gold quality
ganglionic eminence	UBERON:0004023	93.66	gold quality
nasal cavity epithelium	UBERON:0005384	93.47	gold quality
apex of heart	UBERON:0002098	93.20	gold quality
anterior cingulate cortex	UBERON:0009835	93.16	gold quality
cingulate cortex	UBERON:0003027	93.15	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.08	gold quality
tendon of biceps brachii	UBERON:0008188	93.08	gold quality
mammary duct	UBERON:0001765	93.01	gold quality
minor salivary gland	UBERON:0001830	92.91	gold quality
amygdala	UBERON:0001876	92.83	gold quality
upper lobe of left lung	UBERON:0008952	92.81	gold quality
upper lobe of lung	UBERON:0008948	92.74	gold quality
right lung	UBERON:0002167	92.23	gold quality
ventricular zone	UBERON:0003053	92.13	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.01	gold quality
epithelium of mammary gland	UBERON:0003244	91.95	gold quality
cortex of kidney	UBERON:0001225	91.83	gold quality
embryo	UBERON:0000922	91.81	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.25
E-GEOD-99795	no	24.51

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI3

miRNA regulators (miRDB)

59 targeting AGRN, 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-4283	100.00	66.42	2097
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
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-6825-5P	99.96	69.81	3431
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-4498	99.47	67.42	2360

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• Agrin, a heparan sulfate proteoglycan, is a component of the basal lamina of BBB microvessels, and growing evidence suggests that it may be important for the maintenance of the BBB. (PMID:12070669)
• acts at the nerve-muscle synapse in the glomerular basal membrane and on T-lymphocytes (PMID:12073527)
• evidence for additional functions of agrin during axonal growth, establishment of the blood-brain barrier, and Alzheimer’s disease is accumulating–REVIEW (PMID:12270958)
• Thus, an agrin/MuSK complex may form part of a motor neuron stop signal involved in “reverse signaling” to the motor neuron. (PMID:15691710)
• in the NtA-laminin complex, conserved amino acids in the gamma 1 chain are prerequisite for the binding to agrin (PMID:15694127)
• agrin has a role in binding alpha-synuclein and modulating alpha-synuclein fibrillation (PMID:16037493)
• In human sperm an agrin isoform with a short NH2-terminus (agrinSN) localized in the posterior post-acrosomal, neck, and flagellar mid-piece regions. (PMID:16487930)
• agrin might play an important role in neoangiogenesis in human HCC, being a part of the newly formed vasculature. In CC, however, agrin might be involved in tumor progression (PMID:17640714)
• The agrin expression in human T cells is regulated by cell activation and IFN-alpha, and may have an important function during cell activation with potential implications for autoimmunity. (PMID:18025246)
• study concludes that Abeta can modulate the cellular expression of agrin and glypican-1, which may contribute to the accumulation of these heparan sulfate proteoglycans in Alzheimer’s disease lesions (PMID:19166823)
• agrin facilitates the discrimination of benign and malignant hepatocellular lesions (PMID:19194276)
• The agrin mutation does not interfere with its ability to induce postsynaptic structures but that it dramatically perturbs the maintenance of the neuromuscular junction. (PMID:19631309)
• different regions within the agrin protein are responsible for synapse formation at the neuromuscular junction and for process formation in central nervous system neurons (PMID:19940118)
• Agrin immunohistochemistry may facilitate determination of primary versus metastatic origin in problematic liver cancer cases. (PMID:20471664)
• study identifies a spontaneous agrin mutation that reduces the ability of z+ agrin to activate MuSK and induce AChR clustering; this results in a severe congenital myasthenic syndrome in the patient, with both pre- and postsynaptic defects at the neuromuscular junction (PMID:22205389)
• Dynamics of expression patterns of agrin in human glioblastoma (PMID:22307776)
• In contrast to wild-type neurons which form synapses and survive for prolonged periods, agrin-deficient neurons do not mature and are rapidly eliminated in the transgenic olfactory bulb. (PMID:22423096)
• MuSK myasthenia gravis IgG4 disrupts the interaction of LRP4 with MuSK but both IgG4 and IgG1-3 can disperse preformed agrin-independent AChR clusters (PMID:24244707)
• these observations indicate that agrin is another autoantigen in patients with MG and agrin autoantibodies may be pathogenic through inhibition of agrin/LRP4/MuSK signaling at the NMJ. (PMID:24632822)
• Five new recessive mutations in the gene encoding agrin are identified in patients with congenital myasthenic syndrome. (PMID:24951643)
• Among 42 hip fractured patients (age 83.7+/-8.6 years, 76.2% women), sarcopenia was diagnosed in 7 individuals (16.7%). Serum C-terminal agrin fragment (CAF) levels were significantly higher in sarcopenic relative to non-sarcopenic patients. (PMID:25304331)
• Knockdown of agrin and perlecan promoted a decrease on cell migration and adhesion, and on resistance of cells to cisplatin. (PMID:25506919)
• In patients suffering from severe sepsis and septic shock, serum levels of C-terminal agrin fragment were significantly associated with kidney function and the need for renal replacement therapy and were not influenced by severe septic conditions. (PMID:25807640)
• Agrin strongly promotes chondrocyte differentiation and cartilage formation in vivo. (PMID:26290588)
• Agrin promotes oncogenesis through YAP-dependent transcription. (PMID:28273460)
• C-terminal agrin fragment levels predict acute kidney injury after acute myocardial infarction. (PMID:28646861)
• High Agrin expression is associated with Chronic obstructive pulmonary disease. (PMID:29351440)
• The presence of agrin at locations with particular importance for the growth and stability of atherosclerotic plaques renders this molecule strategically positioned to influence plaque development and vulnerability (PMID:29405249)
• we have identified multiple pathogenic effects of the agrin V1727F mutation that decrease its functional levels and ability to bind HSPG and LRP4 coreceptors critical for MuSK signaling and synaptic differentiation (PMID:30994901)
• The current study suggests that increased maternal serum agrin is associated with intrauterine growth restriction in early-onset preeclampsia. (PMID:31018746)
• A Role of Agrin in Maintaining the Stability of Vascular Endothelial Growth Factor Receptor-2 during Tumor Angiogenesis. (PMID:31340156)
• High expression of agrin is associated with tumor progression and poor prognosis in hepatocellular carcinoma. (PMID:31698617)
• Null variants in AGRN cause lethal fetal akinesia deformation sequence. (PMID:31730230)
• Serum agrin and talin are increased in major depression while agrin and creatine phosphokinase are associated with chronic fatigue and fibromyalgia symptoms in depression. (PMID:31734845)
• agrin is highly expressed in nuclei of lung adenocarcinoma tissues and is strongly correlated with lymph node metastasis, clinical stage, and poor differentiation (PMID:31820863)
• Agrin in the Muscularis Mucosa Serves as a Biomarker Distinguishing Hyperplastic Polyps from Sessile Serrated Lesions. (PMID:31852835)
• AGRN Gene Mutation Leads to Congenital Myasthenia Syndromes: A Pediatric Case Report and Literature Review. (PMID:32221959)
• Congenital myasthenic syndrome-associated agrin variants affect clustering of acetylcholine receptors in a domain-specific manner. (PMID:32271162)
• Agrin promotes the proliferation, invasion and migration of rectal cancer cells via the WNT signaling pathway to contribute to rectal cancer progression. (PMID:32862766)
• Autoantibodies to cortactin and agrin in sera of patients with myasthenia gravis. (PMID:33962172)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	agrn	ENSDARG00000079388
mus_musculus	Agrn	ENSMUSG00000041936
rattus_norvegicus	Agrn	ENSRNOG00000020205

Paralogs (27): USH2A (ENSG00000042781), LAMC3 (ENSG00000050555), LAMA3 (ENSG00000053747), LAMC2 (ENSG00000058085), NTN1 (ENSG00000065320), NTN4 (ENSG00000074527), ATRN (ENSG00000088812), LAMB4 (ENSG00000091128), LAMB1 (ENSG00000091136), LAMA1 (ENSG00000101680), MEGF8 (ENSG00000105429), MEGF9 (ENSG00000106780), ATRNL1 (ENSG00000107518), LAMA4 (ENSG00000112769), LAMA5 (ENSG00000130702), LAMC1 (ENSG00000135862), NTN5 (ENSG00000142233), HSPG2 (ENSG00000142798), TMEFF2 (ENSG00000144339), NTN3 (ENSG00000162068), NTNG1 (ENSG00000162631), EGFLAM (ENSG00000164318), LAMB2 (ENSG00000172037), NTNG2 (ENSG00000196358), LAMA2 (ENSG00000196569), LAMB3 (ENSG00000196878), TMEFF1 (ENSG00000241697)

Protein

Protein identifiers

Agrin — O00468 (reviewed: O00468)

All UniProt accessions (4): A0A087X208, A0A494C0G5, A0A494C1I6, O00468

UniProt curated annotations — full annotation on UniProt →

Function. Depending on alternative splicing and post-translational modifications, it has a role in different processes, including neuromuscular junction formation and maintenance, and regulation of neurite outgrowth. Also involved in positive regulation of cartilage formation through alpha-dystroglycan binding and up-regulation of SOX9. Heparan sulfate basal lamina glycoprotein that plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ) and directs key events in postsynaptic differentiation. Component of the AGRN-LRP4 receptor complex that induces the phosphorylation and activation of MUSK. The activation of MUSK in myotubes induces the formation of NMJ by regulating different processes including the transcription of specific genes and the clustering of AChR in the postsynaptic membrane. Calcium ions are required for maximal AChR clustering. AGRN function in neurons is highly regulated by alternative splicing, glycan binding and proteolytic processing. Modulates calcium ion homeostasis in neurons, specifically by inducing an increase in cytoplasmic calcium ions. Functions differentially in the central nervous system (CNS) by inhibiting the alpha(3)-subtype of Na+/K+-ATPase and evoking depolarization at CNS synapses. This secreted isoform forms a bridge, after release from motor neurons, to basal lamina through binding laminin via the NtA domain. Transmembrane form that is the predominate form in neurons of the brain, induces dendritic filopodia and synapse formation in mature hippocampal neurons in large part due to the attached glycosaminoglycan chains and the action of Rho-family GTPases. Isoform 1, isoform 4 and isoform 5: neuron-specific (z+) isoforms that contain C-terminal insertions of 8-19 AA are potent activators of AChR clustering. Isoform 5, agrin (z+8), containing the 8-AA insert, forms a receptor complex in myotubules containing the neuronal AGRN, the muscle-specific kinase MUSK and LRP4, a member of the LDL receptor family. The splicing factors, NOVA1 and NOVA2, regulate AGRN splicing and production of the ‘z’ isoforms. Muscle-specific isoform, probably involved in endothelial cell differentiation. Involved in the positive regulation of cartilage formation, acting through alpha-dystroglycan binding and up-regulation of SOX9, a transcription factor that plays a key role in chondrocytes differentiation. Is involved in regulation of neurite outgrowth probably due to the presence of the glycosaminoglcan (GAG) side chains of heparan and chondroitin sulfate attached to the Ser/Thr- and Gly/Ser-rich regions. Also involved in modulation of growth factor signaling. This released fragment is important for agrin signaling and to exert a maximal dendritic filopodia-inducing effect. All ‘z’ splice variants (z+) of this fragment also show an increase in the number of filopodia.

Subunit / interactions. Monomer. Interacts (N-terminal subunit) with TGF-beta family members, BMP2 and BMP4; the interactions inhibit the activity of these growth factors. Interacts with TGFB1; the interaction enhances the activity of TGFB1. Component of the AGRN-LRP4 complex that consists of a tetramer of two AGRN-LRP4 heterodimers. Interacts (via the laminin G-like 3 domain) directly with LRP4; the interaction is required for activation of MUSK and clustering of AChR and requires the ‘z8’ insert present in the z(+8) isoforms. Interacts with DAG1; the interaction is influenced by cell surface glycosaminoglycans and by alternative splicing of AGRN, and is required for up-regulation of SOX9 and cartilage formation.

Subcellular location. Secreted. Extracellular space. Extracellular matrix Synapse. Cell membrane.

Tissue specificity. Expressed in basement membranes of lung and kidney. Muscle- and neuron-specific isoforms are found. Isoforms (y+) with the 4 AA insert and (z+8) isoforms with the 8 AA insert are all neuron-specific. Isoforms (z+11) are found in both neuronal and non-neuronal tissues. Expressed in articular cartilage.

Post-translational modifications. Contains heparan and chondroitin sulfate chains and alpha-dystroglycan as well as N-linked and O-linked oligosaccharides. Glycosaminoglycans (GAGs), present in the N-terminal 110 kDa fragment, are required for induction of filopodia in hippocampal neurons. The first cluster (Gly/Ser-rich) for GAG attachment contains heparan sulfate (HS) chains and the second cluster (Ser/Thr-rich), contains chondroitin sulfate (CS) chains. Heparin and heparin sulfate binding in the G3 domain is independent of calcium ions. Binds heparin with a stoichiometry of 2:1. Binds sialic acid with a stoichiometry of 1:1 and binding requires calcium ions. At synaptic junctions, cleaved at two conserved sites, alpha and beta, by neurotrypsin. Cleavage at the alpha-site produces the agrin N-terminal 110-kDa subunit and the agrin C-terminal 110-kDa subunit. Further cleavage of agrin C-terminal 110-kDa subunit at the beta site produces the C-terminal fragments, agrin C-terminal 90 kDa fragment and agrin C-terminal 22 kDa fragment. Excessive cleavage at the beta-site releases large amounts of the agrin C-terminal 22 kDa fragment leading to destabilization at the neuromuscular junction (NMJ).

Disease relevance. Myasthenic syndrome, congenital, 8 (CMS8) [MIM:615120] 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. CMS8 is an autosomal recessive disease characterized by prominent defects of both the pre- and postsynaptic regions. Affected individuals have onset of muscle weakness in early childhood; the severity of the weakness and muscles affected is variable. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The NtA domain, absent in TM-agrin, is required for binding laminin and connecting to basal lamina. Both laminin G-like 2 (G2) and laminin G-like 3 (G3) domains are required for alpha-dystroglycan/DAG1 binding. G3 domain is required for C-terminal heparin, heparan sulfate and sialic acid binding.

Miscellaneous. Cleaved C-terminal fragments may be used as a biomarker for sarcopenia, age-related progressive loss of skeletal muscle. Produced by usage of an alternative first exon.

Isoforms (7)

UniProt ID	Names	Canonical?
O00468-1	1, Secreted agrin, LN-agrin	yes
O00468-2	2, Transmembrane agrin, TM-agrin
O00468-3	3, Agrin z(0)
O00468-4	4, Agrin z(+11)
O00468-5	5, Agrin z(+8)
O00468-6	6, Agrin y(0)z(0)
O00468-7	7, y(0)

RefSeq proteins (3): NP_001292204, NP_001351656, NP_940978* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000082	SEA_dom	Domain
IPR000742	EGF	Domain
IPR001791	Laminin_G	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR002049	LE_dom	Domain
IPR002350	Kazal_dom	Domain
IPR003645	Fol_N	Domain
IPR003884	FacI_MAC	Domain
IPR004850	NtA_dom	Domain
IPR008993	TIMP-like_OB-fold	Homologous_superfamily
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR036058	Kazal_dom_sf	Homologous_superfamily
IPR036364	SEA_dom_sf	Homologous_superfamily
IPR050372	Neurexin-related_CASP	Family

Pfam: PF00008, PF00050, PF00053, PF00054, PF01390, PF03146, PF07648

UniProt features (134 total): disulfide bond 50, sequence variant 27, domain 20, site 7, splice variant 6, chain 5, glycosylation site 5, compositionally biased region 4, binding site 4, region of interest 2, modified residue 2, signal peptide 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8S9P	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00468-F1	69.79	0.12

Functional residue map

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

Catalytic / active sites (7): 1102–1103 (cleavage, alpha site; by neurotrypsin); 1250 (alternative splice site to produce ‘x’ isoforms); 1751 (alternative splice site to produce ‘y’ isoforms); 1862 (critical for cleavage by neurotrypsin); 1863–1864 (cleavage, beta site; by neurotrypsin); 1888 (alternative splice site to produce ‘z’ isoforms); 1892 (highly important for the agrin receptor complex activity of the ‘z(8)’ insert)

Ligand- & substrate-binding residues (4): 1940; 1957; 2007; 2009

Post-translational modifications (2): 674, 676

Disulfide bonds (50): 31–103, 152–177, 197–228, 202–221, 210–242, 270–303, 276–296, 285–317, 349–368, 357–389, 414–447, 421–440, 429–461, 490–520, 494–513, 502–534, 546–585, 555–578, 567–599, 613–650 …

Glycosylation sites (5): 135, 250, 777, 932, 1835

Function

Pathways and Gene Ontology

Reactome pathways

45 pathways

ID	Pathway
R-HSA-1971475	Glycosaminoglycan-protein linkage region biosynthesis
R-HSA-2022928	HS-GAG biosynthesis
R-HSA-2024096	HS-GAG degradation
R-HSA-216083	Integrin cell surface interactions
R-HSA-3000171	Non-integrin membrane-ECM interactions
R-HSA-3000178	ECM proteoglycans
R-HSA-3560783	Defective B4GALT7 causes EDS, progeroid type
R-HSA-3560801	Defective B3GAT3 causes JDSSDHD
R-HSA-3656237	Defective EXT2 causes exostoses 2
R-HSA-3656253	Defective EXT1 causes exostoses 1, TRPS2 and CHDS
R-HSA-419037	NCAM1 interactions
R-HSA-4420332	Defective B3GALT6 causes EDSP2 and SEMDJL1
R-HSA-9694614	Attachment and Entry
R-HSA-975634	Retinoid metabolism and transport
R-HSA-9769735	Initiation of coagulation cascade
R-HSA-9769739	Regulation of clotting cascade
R-HSA-9820960	Respiratory syncytial virus (RSV) attachment and entry
R-HSA-9833110	RSV-host interactions
R-HSA-9913351	Formation of the dystrophin-glycoprotein complex (DGC)
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-9918485	Dengue Virus Attachment and Entry
R-HSA-1266738	Developmental Biology
R-HSA-1430728	Metabolism
R-HSA-1474244	Extracellular matrix organization
R-HSA-1630316	Glycosaminoglycan metabolism
R-HSA-1638091	Heparan sulfate/heparin (HS-GAG) metabolism
R-HSA-1643685	Disease
R-HSA-1793185	Chondroitin sulfate/dermatan sulfate metabolism
R-HSA-196854	Metabolism of vitamins and cofactors
R-HSA-2187338	Visual phototransduction

MSigDB gene sets: 569 (showing top): GOBP_NEUROMUSCULAR_JUNCTION_DEVELOPMENT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, LIANG_HEMATOPOIESIS_STEM_CELL_NUMBER_SMALL_VS_HUGE_UP, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_SYNAPSE_ASSEMBLY, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_NEURON_MATURATION, GOBP_POSITIVE_REGULATION_OF_SYNAPSE_ASSEMBLY, GOBP_GROWTH, REACTOME_NCAM_SIGNALING_FOR_NEURITE_OUT_GROWTH, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS

GO Biological Process (18): chondrocyte differentiation (GO:0002062), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), G protein-coupled acetylcholine receptor signaling pathway (GO:0007213), neuromuscular junction development (GO:0007528), receptor clustering (GO:0043113), clustering of voltage-gated sodium channels (GO:0045162), positive regulation of synaptic assembly at neuromuscular junction (GO:0045887), positive regulation of transcription by RNA polymerase II (GO:0045944), filopodium assembly (GO:0046847), synapse organization (GO:0050808), cytoskeleton organization (GO:0007010), nervous system development (GO:0007399), cell differentiation (GO:0030154), positive regulation of GTPase activity (GO:0043547), positive regulation of filopodium assembly (GO:0051491), membrane organization (GO:0061024), synaptic signaling (GO:0099536)

GO Molecular Function (11): dystroglycan binding (GO:0002162), structural constituent of cytoskeleton (GO:0005200), calcium ion binding (GO:0005509), sialic acid binding (GO:0033691), chondroitin sulfate binding (GO:0035374), laminin binding (GO:0043236), heparan sulfate proteoglycan binding (GO:0043395), receptor ligand activity (GO:0048018), extracellular matrix structural constituent (GO:0005201), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (9): extracellular region (GO:0005576), basement membrane (GO:0005604), Golgi lumen (GO:0005796), plasma membrane (GO:0005886), extracellular matrix (GO:0031012), lysosomal lumen (GO:0043202), synapse (GO:0045202), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Diseases associated with glycosaminoglycan metabolism	5
Extracellular matrix organization	3
Heparan sulfate/heparin (HS-GAG) metabolism	2
Coagulation pathway	2
Respiratory Syncytial Virus Infection Pathway	2
Glycosaminoglycan metabolism	1
NCAM signaling for neurite out-growth	1
Early SARS-CoV-2 Infection Events	1
Visual phototransduction	1
Metabolism of fat-soluble vitamins	1
Non-integrin membrane-ECM interactions	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	2
protein binding	2
structural molecule activity	2
extracellular matrix	2
cellular anatomical structure	2
cell differentiation	1
cartilage development	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor signaling pathway	1
G protein-coupled acetylcholine receptor activity	1
acetylcholine receptor signaling pathway	1
synapse organization	1
plasma membrane	1
protein localization to membrane	1
neuronal ion channel clustering	1
regulation of synaptic assembly at neuromuscular junction	1
positive regulation of developmental growth	1
synaptic assembly at neuromuscular junction	1
positive regulation of synapse assembly	1
positive regulation of neuromuscular junction development	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
plasma membrane bounded cell projection assembly	1
cell junction organization	1
organelle organization	1
system development	1
cellular developmental process	1
GTPase activity	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
filopodium assembly	1
regulation of filopodium assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
cellular component organization	1
cell-cell signaling	1

Protein interactions and networks

STRING

2742 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AGRN	MUSK	O15146	999
AGRN	DAG1	Q14118	999
AGRN	LRP4	O75096	994
AGRN	DOK7	Q18PE1	991
AGRN	RAPSN	Q13702	989
AGRN	HSPG2	P98160	988
AGRN	NID1	P14543	979
AGRN	FN1	P02751	977
AGRN	DMD	P11532	912
AGRN	BST2	Q10589	884
AGRN	PTPRS	Q13332	863
AGRN	UTRN	P46939	859
AGRN	TMPRSS15	P98073	845
AGRN	FKTN	O75072	830
AGRN	ACHE	P22303	811

IntAct

88 interactions, top by confidence:

A	B	Type	Score
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
OS9	AGRN	psi-mi:“MI:0914”(association)	0.530
PDPK1	AGRN	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.530
HADHA	AGRN	psi-mi:“MI:0914”(association)	0.530
LRRTM4	AP3B1	psi-mi:“MI:0914”(association)	0.530
NOTCH2	ZNF316	psi-mi:“MI:0914”(association)	0.530
ATXN7	AGRN	psi-mi:“MI:0915”(physical association)	0.510
APP	AGRN	psi-mi:“MI:0407”(direct interaction)	0.440
AGRN	Npnt	psi-mi:“MI:0407”(direct interaction)	0.440
AGRN	PDIA3	psi-mi:“MI:0408”(disulfide bond)	0.440
AGRN	CACNA1A	psi-mi:“MI:0915”(physical association)	0.400
AGRN	HOXA1	psi-mi:“MI:0915”(physical association)	0.370
AGRN	NUFIP2	psi-mi:“MI:0915”(physical association)	0.370
DAG1	AGRN	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.350
ZFP41	AGRN	psi-mi:“MI:0914”(association)	0.350
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.350
OLFM3	AGRN	psi-mi:“MI:0914”(association)	0.350

BioGRID (287): AGRN (Affinity Capture-RNA), AGRN (Affinity Capture-RNA), AGRN (Affinity Capture-MS), AGRN (Affinity Capture-MS), AGRN (Affinity Capture-MS), AGRN (Affinity Capture-MS), AGRN (Affinity Capture-MS), AGRN (Affinity Capture-MS), AGRN (Affinity Capture-MS), AGRN (Reconstituted Complex), AGRN (Affinity Capture-MS), AGRN (Affinity Capture-MS), AGRN (Affinity Capture-MS), AGRN (Affinity Capture-RNA), AGRN (Affinity Capture-MS)

ESM2 similar proteins: A1A5Y0, A2ASQ1, O00468, O00548, O57409, O89103, O95428, P06579, P07204, P0C5J5, P15306, P20063, P25304, P31696, P97607, P97677, P98160, Q05793, Q08E66, Q14112, Q2PC93, Q501P1, Q53RD9, Q5W7P8, Q61483, Q61810, Q66PY1, Q6NUX0, Q6NZL8, Q6ZRI0, Q71U07, Q75N90, Q7T3Q2, Q8IWY4, Q8IX30, Q8JZM4, Q8NFT8, Q8R0S6, Q8R4Y4, Q8VIK5

Diamond homologs: A0JP86, A2ASQ1, G5ECE3, O00468, O00634, O09118, O15230, O75445, O75882, O95631, P02468, P11047, P15215, P19137, P24043, P25304, P25391, P31696, P34710, P97927, Q00174, Q01635, Q13751, Q13753, Q16363, Q16787, Q18823, Q19981, Q1LVF0, Q24567, Q24568, Q27262, Q2HXW4, Q2QI47, Q5RB89, Q5VV63, Q60675, Q61001, Q61087, Q61092

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
AGRN	“up-regulates activity”	CHRNB3	binding
AGRN	“up-regulates activity”	LRP4	binding
FUS	“down-regulates quantity by repression”	AGRN	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 85 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	5	13.3×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

2582 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	40
Likely pathogenic	24
Uncertain significance	1150
Likely benign	1070
Benign	123

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070058	NM_198576.4(AGRN):c.3724C>T (p.Gln1242Ter)	Pathogenic
1070394	NC_000001.10:g.(?954503)(992499_?)del	Pathogenic
1071394	NM_198576.4(AGRN):c.3973_3979dup (p.Gln1327fs)	Pathogenic
1072755	NM_198576.4(AGRN):c.543dup (p.Val182fs)	Pathogenic
1076092	NM_198576.4(AGRN):c.2002G>T (p.Glu668Ter)	Pathogenic
1180647	NM_198576.4(AGRN):c.1323G>A (p.Trp441Ter)	Pathogenic
126556	NM_198576.4(AGRN):c.1057C>T (p.Gln353Ter)	Pathogenic
1284256	NM_198576.4(AGRN):c.1385-42G>C	Pathogenic
1322937	NM_198576.4(AGRN):c.4217_4218del (p.Gln1406fs)	Pathogenic
1384683	NM_198576.4(AGRN):c.1105_1106del (p.Val369fs)	Pathogenic
1397221	NM_198576.4(AGRN):c.5753_5754del (p.Tyr1918fs)	Pathogenic
1429166	NM_198576.4(AGRN):c.4744G>A (p.Gly1582Arg)	Pathogenic
1454542	NM_198576.4(AGRN):c.5703del (p.Thr1902fs)	Pathogenic
1454812	NM_198576.4(AGRN):c.1077_1083del (p.Asp359fs)	Pathogenic
1458742	NM_198576.4(AGRN):c.5554_5555dup (p.Glu1853fs)	Pathogenic
18241	NM_198576.4(AGRN):c.5125G>C (p.Gly1709Arg)	Pathogenic
1925037	NM_198576.4(AGRN):c.4389G>A (p.Trp1463Ter)	Pathogenic
2025884	NM_198576.4(AGRN):c.2645_2654del (p.Asp882fs)	Pathogenic
2043005	NM_198576.4(AGRN):c.1668del (p.Ser557fs)	Pathogenic
2050791	NM_198576.4(AGRN):c.3497_3500del (p.Ala1166fs)	Pathogenic
243041	1p36.33 deletion (0.48 Mb)	Pathogenic
2705050	NM_198576.4(AGRN):c.1734C>A (p.Cys578Ter)	Pathogenic
2749616	NM_198576.4(AGRN):c.1197C>A (p.Cys399Ter)	Pathogenic
2912340	NM_198576.4(AGRN):c.3229del (p.Ala1077fs)	Pathogenic
3010684	NM_198576.4(AGRN):c.893_903del (p.Leu298fs)	Pathogenic
3068432	NC_000001.11:g.976618_977825del	Pathogenic
3247824	NC_000001.10:g.(?976533)(990361_?)del	Pathogenic
3255595	NM_198576.4(AGRN):c.369C>A (p.Tyr123Ter)	Pathogenic
3724686	NM_198576.4(AGRN):c.3178_3196del (p.Ser1060fs)	Pathogenic
4719352	NM_198576.4(AGRN):c.2298del (p.Cys766fs)	Pathogenic

SpliceAI

6206 predictions. Top by Δscore:

Variant	Effect	Δscore
1:1020371:AAGGT:A	donor_loss	1.0000
1:1022196:CCCAG:C	acceptor_loss	1.0000
1:1022197:CCAGG:C	acceptor_loss	1.0000
1:1022198:CA:C	acceptor_loss	1.0000
1:1022199:AGGTT:A	acceptor_loss	1.0000
1:1022200:G:GA	acceptor_loss	1.0000
1:1022441:G:GT	donor_gain	1.0000
1:1022460:AAG:A	donor_loss	1.0000
1:1022463:G:C	donor_loss	1.0000
1:1022464:T:A	donor_loss	1.0000
1:1035273:CCA:C	acceptor_loss	1.0000
1:1035274:CAG:C	acceptor_loss	1.0000
1:1035275:A:AG	acceptor_gain	1.0000
1:1035275:AGA:A	acceptor_loss	1.0000
1:1035276:G:A	acceptor_loss	1.0000
1:1035276:G:GA	acceptor_gain	1.0000
1:1035276:GAT:G	acceptor_gain	1.0000
1:1035276:GATA:G	acceptor_gain	1.0000
1:1035276:GATAA:G	acceptor_gain	1.0000
1:1035321:GATG:G	donor_gain	1.0000
1:1035325:G:GG	donor_gain	1.0000
1:1035326:T:A	donor_loss	1.0000
1:1042111:GC:G	donor_gain	1.0000
1:1042158:GTGTG:G	donor_gain	1.0000
1:1042159:TGTGG:T	donor_loss	1.0000
1:1042161:TGGTG:T	donor_loss	1.0000
1:1042162:GGT:G	donor_loss	1.0000
1:1042164:T:A	donor_loss	1.0000
1:1043449:G:GT	donor_gain	1.0000
1:1043730:GTG:G	donor_gain	1.0000

AlphaMissense

13091 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000124672 (1:1024778 G>A,C), RS1000275884 (1:1020269 G>A,C,T), RS1000278568 (1:1037802 C>T), RS1000305576 (1:1049707 C>T), RS1000350944 (1:1029144 G>A), RS1000395676 (1:1020470 GCC>G,GC), RS1000409062 (1:1024537 G>T), RS1000457624 (1:1023589 C>T), RS1000480219 (1:1053984 AG>A), RS1000535028 (1:1052972 G>A,C), RS1000626358 (1:1020024 G>A,T), RS1000640804 (1:1039145 A>G), RS1000722658 (1:1034377 G>A), RS1000804491 (1:1020576 T>C), RS1000842917 (1:1027325 C>T)

Disease associations

OMIM: gene MIM:103320 | disease phenotypes: MIM:615120, MIM:601462, MIM:208150

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital myasthenic syndrome 8	Strong	Autosomal recessive
postsynaptic congenital myasthenic syndrome	Supportive	Autosomal recessive
presynaptic congenital myasthenic syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
congenital myasthenic syndrome 8	Definitive	AR

Mondo (7): congenital myasthenic syndrome 8 (MONDO:0014052), congenital myasthenic syndrome (MONDO:0018940), neurodevelopmental disorder (MONDO:0700092), fetal akinesia deformation sequence (MONDO:0008824), presynaptic congenital myasthenic syndrome (MONDO:0700466), postsynaptic congenital myasthenic syndrome (MONDO:0020344), (MONDO:0020345)

Orphanet (2): Congenital myasthenic syndrome (Orphanet:590), Presynaptic congenital myasthenic syndromes (Orphanet:98914)

HPO phenotypes

105 total (30 of 105 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000276	Long face
HP:0000308	Microretrognathia
HP:0000369	Low-set ears
HP:0000407	Sensorineural hearing impairment
HP:0000467	Neck muscle weakness
HP:0000496	Abnormality of eye movement
HP:0000508	Ptosis
HP:0000565	Esotropia
HP:0000597	Ophthalmoparesis
HP:0000602	Ophthalmoplegia
HP:0000639	Nystagmus
HP:0000651	Diplopia
HP:0000768	Pectus carinatum
HP:0000774	Narrow chest
HP:0000961	Cyanosis
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001283	Bulbar palsy
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001315	Reduced tendon reflexes
HP:0001324	Muscle weakness
HP:0001374	Congenital hip dislocation
HP:0001382	Joint hypermobility

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D020294	Myasthenic Syndromes, Congenital	C10.668.758.800; C16.320.590
D065886	Neurodevelopmental Disorders	F03.625
C536647	Pena Shokeir syndrome, type 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL4295648 (SINGLE PROTEIN), CHEMBL4742252 (PROTEIN-PROTEIN INTERACTION), CHEMBL4748214 (PROTEIN-PROTEIN INTERACTION)

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

CTD chemical–gene interactions

85 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects cotreatment, decreases expression, increases abundance	4
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression, increases expression	3
Cadmium Chloride	decreases expression, increases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression, affects cotreatment	3
bisphenol A	increases methylation, affects expression, affects cotreatment	2
Arsenic	decreases expression, increases abundance, affects methylation, affects cotreatment	2
Dexamethasone	decreases expression, affects cotreatment	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Valproic Acid	increases expression, increases methylation	2
Cyclosporine	decreases expression, decreases methylation	2
bisphenol F	affects cotreatment, decreases expression	1
TAK-243	increases sumoylation	1
biochanin A	decreases expression	1
2,4,6-tribromophenol	increases expression	1
chloroacetaldehyde	decreases expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
deoxynivalenol	decreases expression	1
titanium dioxide	decreases methylation	1
trichostatin A	affects expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
nivalenol	decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
di-n-butylphosphoric acid	affects expression	1
Am 580	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
perfluoro-n-nonanoic acid	decreases expression	1
corosolic acid	increases expression	1
monomethylarsonous acid	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118993	Binding	Binding affinity to AGRN in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SB98	HAP1 AGRN (-) 1	Cancer cell line	Male
CVCL_SB99	HAP1 AGRN (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
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
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
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
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP