LARGE1

Summary

LARGE1 (LARGE xylosyl- and glucuronyltransferase 1, HGNC:6511) is a protein-coding gene on chromosome 22q12.3, encoding Xylosyl- and glucuronyltransferase LARGE1 (O95461). Bifunctional glycosyltransferase with both alpha-1,3-xylosyltransferase and beta-1,3-glucuronyltransferase activities involved in the maturation of alpha-dystroglycan (DAG1) by glycosylation leading to DAG1 binding to laminin G-like domain-containing extracellular proteins with….

This gene encodes a member of the N-acetylglucosaminyltransferase gene family. It encodes a glycosyltransferase which participates in glycosylation of alpha-dystroglycan, and may carry out the synthesis of glycoprotein and glycosphingolipid sugar chains. It may also be involved in the addition of a repeated disaccharide unit. The protein encoded by this gene is the glycotransferase that adds the final xylose and glucuronic acid to alpha-dystroglycan and thereby allows alpha-dystroglycan to bind ligands including laminin 211 and neurexin. Mutations in this gene cause several forms of congenital muscular dystrophy characterized by cognitive disability and abnormal glycosylation of alpha-dystroglycan. Alternative splicing of this gene results in multiple transcript variants that encode the same protein.

Source: NCBI Gene 9215 — RefSeq curated summary.

At a glance

• Gene–disease (curated): muscular dystrophy-dystroglycanopathy (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 23
• Clinical variants (ClinVar): 1,083 total — 63 pathogenic, 15 likely-pathogenic
• Phenotypes (HPO): 161
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_133642

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6511
Approved symbol	LARGE1
Name	LARGE xylosyl- and glucuronyltransferase 1
Location	22q12.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0609
Ensembl gene	ENSG00000133424
Ensembl biotype	protein_coding
OMIM	603590
Entrez	9215

Gene structure

Transcript identifiers

Ensembl transcripts: 54 — 44 protein_coding, 4 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay, 2 retained_intron

ENST00000354992, ENST00000397394, ENST00000402320, ENST00000413114, ENST00000421232, ENST00000421768, ENST00000423375, ENST00000430220, ENST00000432776, ENST00000434071, ENST00000476315, ENST00000608642, ENST00000609799, ENST00000610186, ENST00000674543, ENST00000674562, ENST00000674668, ENST00000674708, ENST00000674780, ENST00000674789, ENST00000674816, ENST00000674999, ENST00000675031, ENST00000675277, ENST00000675382, ENST00000675416, ENST00000676031, ENST00000676070, ENST00000676126, ENST00000676132, ENST00000676217, ENST00000676370, ENST00000899788, ENST00000899789, ENST00000899790, ENST00000899791, ENST00000899792, ENST00000899793, ENST00000899794, ENST00000899795, ENST00000911678, ENST00000911679, ENST00000911680, ENST00000911681, ENST00000911682, ENST00000966030, ENST00000966031, ENST00000966032, ENST00000966033, ENST00000966034, ENST00000966035, ENST00000966036, ENST00000966037, ENST00000966038

RefSeq mRNA: 13 — MANE Select: NM_133642 NM_001362949, NM_001362951, NM_001362953, NM_001378624, NM_001378625, NM_001378626, NM_001378627, NM_001378628, NM_001378629, NM_001378630, NM_001378631, NM_004737, NM_133642

CCDS: CCDS13912, CCDS93152, CCDS93153, CCDS93154

Canonical transcript exons

ENST00000397394 — 15 exons

Exon	Start	End
ENSE00001528530	33919995	33920476
ENSE00001596074	33283202	33283348
ENSE00001703968	33304229	33304507
ENSE00001707058	33277060	33277255
ENSE00001723191	33432161	33432265
ENSE00001729479	33316085	33316248
ENSE00001753201	33384192	33384304
ENSE00001760765	33337646	33337801
ENSE00001766035	33381919	33382044
ENSE00001776077	33604435	33604558
ENSE00001787819	33626244	33626326
ENSE00003550229	33564848	33565019
ENSE00003623417	33761371	33761558
ENSE00003789569	33650367	33650668
ENSE00003908020	33272509	33274624

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 95.04.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0765 / max 22.3554, expressed in 19 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193769	0.0668	16
193770	0.0096	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
heart left ventricle	UBERON:0002084	95.04	gold quality
cardiac ventricle	UBERON:0002082	94.90	gold quality
apex of heart	UBERON:0002098	94.13	gold quality
cortical plate	UBERON:0005343	92.96	gold quality
left ventricle myocardium	UBERON:0006566	92.75	gold quality
gastrocnemius	UBERON:0001388	92.46	gold quality
heart	UBERON:0000948	92.18	gold quality
muscle of leg	UBERON:0001383	92.18	gold quality
prefrontal cortex	UBERON:0000451	92.11	gold quality
right atrium auricular region	UBERON:0006631	91.24	gold quality
heart right ventricle	UBERON:0002080	91.19	gold quality
stromal cell of endometrium	CL:0002255	91.09	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.76	gold quality
cardiac atrium	UBERON:0002081	90.65	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.52	gold quality
muscle organ	UBERON:0001630	90.34	gold quality
right frontal lobe	UBERON:0002810	90.09	gold quality
frontal cortex	UBERON:0001870	90.00	gold quality
neocortex	UBERON:0001950	89.45	gold quality
cingulate cortex	UBERON:0003027	89.39	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.38	gold quality
anterior cingulate cortex	UBERON:0009835	89.34	gold quality
Brodmann (1909) area 10	UBERON:0013541	89.27	gold quality
frontal pole	UBERON:0002795	89.16	gold quality
sural nerve	UBERON:0015488	89.06	gold quality
Brodmann (1909) area 46	UBERON:0006483	89.05	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.72	gold quality
cerebral cortex	UBERON:0000956	88.48	gold quality
body of uterus	UBERON:0009853	88.09	gold quality
gluteal muscle	UBERON:0002000	87.87	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	57.43
E-CURD-119	yes	31.11
E-ANND-3	yes	6.52

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ASCL1, ELF5, GTF2IRD1, JUN, JUNB, MYC, NFATC2, NFIA, NFKB, SALL2, SP1, TBP, TFEB, THRA, TP53, XBP1

miRNA regulators (miRDB)

68 targeting LARGE1, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 17)

• LARGE2 was found to support the maturation of alpha-dystroglycan more effectively than LARGE. (PMID:15752776)
• LARGE repression is responsible for the defects in dystroglycan-mediated cell adhesion that are observed in epithelium-derived cancer cells and point to a defect of dystroglycan glycosylation as a factor in cancer progression (PMID:19244252)
• LARGE has a role in inducing alpha-dystroglycan hyperglycosylation in skeletal and cardiac muscle (PMID:21203384)
• This report extends our knowledge of the clinical phenotype associated with LARGE, and is the second family in which disease results from a large-scale gene rearrangement. (PMID:21248746)
• This study demonistreated that Intragenic rearrangements in LARGE gene in muscle-eye-brain disease. (PMID:21727005)
• the ligand-binding activity of alpha-dystroglycan is conferred primarily by LARGE modification at Thr-317 and -319, within the highly conserved first 18 amino acids of the mucin-like domain (PMID:21987822)
• LARGE could act as a bifunctional glycosyltransferase, with xylosyltransferase and glucuronyltransferase activities, which produced repeating units of [-3-xylose-alpha1,3-glucuronic acid-beta1-]; allowed alpha-DG to bind laminin-G domain-containing ECM ligands (PMID:22223806)
• This study suggests LARGE as the first known modifier of plasma antithrombin. (PMID:23705025)
• results reveal that the LARGE-glycan of dystroglycan serves as a tunable extracellular matrix protein scaffold, the extension of which is required for normal skeletal muscle function (PMID:24132234)
• results suggest absent alpha-DG expression & LARGE deregulation closely associated w/ nodal metastasis tongue cancer. Aberrant alpha-DG expression & glycosylation attributed to abnormal epigenetic modification of LARGE; hypermethylation of its promoter. (PMID:24629698)
• A homozygous LARGE mutation at Cys443 is identified in patients with dystroglycanopathies, whereas the mutation p.Glu509Lys in this study may confer a milder phenotype. (PMID:24709677)
• B4GAT1 is involved in the initiation of the LARGE-dependent repeating disaccharide that is necessary for extracellular matrix protein binding to O-mannosylated alpha-dystroglycan. (PMID:25279697)
• A glucuronic acid beta1,4-xylose disaccharide synthesized by B4GAT1 acts as an acceptor primer that can be elongated by LARGE with the ligand-binding heteropolysaccharide. (PMID:25279699)
• Large1 gene is a target for human papillomavirus integrations and chromosome rearrangements in oropharyngeal squamous cell carcinoma. (PMID:27636103)
• findings demonstrate that a lack of matriglycan on alpha-dystroglycan is a common feature in rhabdomyosarcoma due to the downregulation of LARGE1, and that ectopic expression of LARGE1 can restore matriglycan modifications and the ability of alpha-dystroglycan to function as an extracellular matrix receptor (PMID:31054580)
• Clinical significance of LARGE1 in progression of liver cancer and the underlying mechanism. (PMID:33588034)
• The Origins and Future of Sentinel: An Early-Warning System for Pandemic Preemption and Response. (PMID:34452470)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	large1	ENSDARG00000005126
mus_musculus	Large1	ENSMUSG00000004383
rattus_norvegicus	Large1	ENSRNOG00000013742
drosophila_melanogaster	CG11149	FBGN0031732
drosophila_melanogaster	CG9171	FBGN0031738
drosophila_melanogaster	CG15483	FBGN0032457
drosophila_melanogaster	shams	FBGN0039273
caenorhabditis_elegans	bgnt-1.8	WBGENE00008290
caenorhabditis_elegans		WBGENE00009032
caenorhabditis_elegans	bgnt-1.6	WBGENE00010167
caenorhabditis_elegans		WBGENE00010694
caenorhabditis_elegans		WBGENE00010716
caenorhabditis_elegans	bgnt-1.7	WBGENE00011779
caenorhabditis_elegans		WBGENE00015982
caenorhabditis_elegans		WBGENE00017723

Paralogs (5): GXYLT1 (ENSG00000151233), LARGE2 (ENSG00000165905), GXYLT2 (ENSG00000172986), XXYLT1 (ENSG00000173950), B4GAT1 (ENSG00000174684)

Protein

Protein identifiers

Xylosyl- and glucuronyltransferase LARGE1 — O95461 (reviewed: O95461)

Alternative names: Acetylglucosaminyltransferase-like 1A, Glycosyltransferase-like protein, LARGE xylosyl- and glucuronyltransferase 1

All UniProt accessions (17): A0A6Q8PF10, A0A6Q8PF85, A0A6Q8PFT0, A0A6Q8PFW0, A0A6Q8PFY8, A0A6Q8PG57, A0A6Q8PHF1, A0A6Q8PHK1, B0QY08, B0QYZ8, O95461, B0QYZ9, V9GY39, V9GY56, V9GYK8, X5DR28, X5DRG1

UniProt curated annotations — full annotation on UniProt →

Function. Bifunctional glycosyltransferase with both alpha-1,3-xylosyltransferase and beta-1,3-glucuronyltransferase activities involved in the maturation of alpha-dystroglycan (DAG1) by glycosylation leading to DAG1 binding to laminin G-like domain-containing extracellular proteins with high affinity. Elongates the glucuronyl-beta-1,4-xylose-beta disaccharide primer structure initiated by B4GAT1 by adding repeating units [-3-Xylose-alpha-1,3-GlcA-beta-1-] to produce a heteropolysaccharide. Requires the phosphorylation of core M3 (O-mannosyl trisaccharide) by POMK to elongate the glucuronyl-beta-1,4-xylose-beta disaccharide primer. Plays a key role in skeletal muscle function and regeneration.

Subunit / interactions. Interacts with DAG1 (via the N-terminal domain of alpha-DAG1); the interaction increases binding of DAG1 to laminin. Interacts with B4GAT1.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Ubiquitous. Highest expression in heart, brain and skeletal muscle.

Disease relevance. Muscular dystrophy-dystroglycanopathy congenital with impaired intellectual development B6 (MDDGB6) [MIM:608840] A congenital muscular dystrophy associated with profound intellectual disability, white matter changes and structural brain abnormalities. Skeletal muscle biopsies show reduced immunolabeling of alpha-dystroglycan. The disease is caused by variants affecting the gene represented in this entry. Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A6 (MDDGA6) [MIM:613154] An autosomal recessive disorder characterized by congenital muscular dystrophy associated with cobblestone lissencephaly and other brain anomalies, eye malformations, profound intellectual disability, and death usually in the first years of life. Included diseases are the more severe Walker-Warburg syndrome and the slightly less severe muscle-eye-brain disease. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 2 Mn(2+) ions per subunit. The xylosyltransferase part binds one Mn(2+) and the beta-1,3-glucuronyltransferase part binds one Mn(2+).

Pathway. Protein modification; protein glycosylation.

Similarity. In the C-terminal section; belongs to the glycosyltransferase 49 family. In the N-terminal section; belongs to the glycosyltransferase 8 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O95461-1	1	yes
O95461-2	2

RefSeq proteins (13): NP_001349878, NP_001349880, NP_001349882, NP_001365553, NP_001365554, NP_001365555, NP_001365556, NP_001365557, NP_001365558, NP_001365559, NP_001365560, NP_004728, NP_598397* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002495	Glyco_trans_8	Family
IPR029044	Nucleotide-diphossugar_trans	Homologous_superfamily
IPR051292	Xyl/GlcA_transferase	Family

Pfam: PF01501, PF13896

Enzyme classification (BRENDA):

• EC 2.4.1.B80 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)
• EC 2.4.2.B18 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

Catalyzed reactions (Rhea), 3 shown:

• 3-O-[beta-D-GlcA-(1->3)-beta-D-Xyl-(1->4)-Rib-ol-P-Rib-ol-P-3-beta-D-GalNAc-(1->3)-beta-D-GlcNAc-(1->4)-(O-6-P-alpha-D-Man)]-Thr-[protein] + UDP-alpha-D-xylose = 3-O-[alpha-D-Xyl-(1->3)-beta-D-GlcA-(1->4)-beta-D-Xyl-(1->4)-Rib-ol-P-Rib-ol-P-3-beta-D-GalNAc-(1->3)-beta-D-GlcNAc-(1->4)-(O-6-P-alpha-D-Man)]-Thr-[protein] + UDP + H(+) (RHEA:57336)
• 3-O-{(1->3)-alpha-D-Xyl-(1->3)-beta-D-GlcA-(1->-4)-beta-D-Xyl-(1->4)-Rib-ol-P-Rib-ol-P-3-beta-D-GalNAc-(1->3)-beta-D-GlcNAc-(1->4)-O-6-P-alpha-D-Man}-L-Thr-[protein] + UDP-alpha-D-glucuronate = 3-O-{beta-D-GlcA-(1->3)-alpha-D-Xyl-(1->3)-beta-D-GlcA-(1->-4)-beta-D-Xyl-(1->4)-Rib-ol-P-Rib-ol-P-3-beta-D-GalNAc-(1->3)-beta-D-GlcNAc-(1->4)-O-6-P-alpha-D-Man}-L-Thr-[protein] + UDP + H(+) (RHEA:67924)
• 3-O-{beta-D-GlcA-(1->3)-alpha-D-Xyl-(1->3)-beta-D-GlcA-(1->-4)-beta-D-Xyl-(1->4)-Rib-ol-P-Rib-ol-P-3-beta-D-GalNAc-(1->3)-beta-D-GlcNAc-(1->4)-O-6-P-alpha-D-Man}-L-Thr-[protein] + UDP-alpha-D-xylose = 3-O-{(1->3)-alpha-D-Xyl-(1->3)-beta-D-GlcA-(1->-4)-beta-D-Xyl-(1->4)-Rib-ol-P-Rib-ol-P-3-beta-D-GalNAc-(1->3)-beta-D-GlcNAc-(1->4)-O-6-P-alpha-D-Man}-L-Thr-[protein] + UDP + H(+) (RHEA:68368)

UniProt features (102 total): helix 33, strand 32, sequence variant 7, mutagenesis site 5, turn 5, binding site 4, glycosylation site 4, region of interest 4, topological domain 2, compositionally biased region 2, chain 1, splice variant 1, transmembrane region 1, coiled-coil region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7ZVJ	X-RAY DIFFRACTION	2.61
9E1T	ELECTRON MICROSCOPY	3
7UI7	ELECTRON MICROSCOPY	3.4
7UI6	ELECTRON MICROSCOPY	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95461-F1	86.15	0.70

Functional residue map

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

Ligand- & substrate-binding residues (4): 242; 244; 563; 565

Glycosylation sites (4): 97, 122, 148, 272

Mutagenesis-validated functional residues (5):

Position	Phenotype
242–244	loss of function, but does not abolish subcellular location.
242–244	glucuronyltransferase activity is present while xylosyltransferase activity is abolished.
334–336	loss of function, but does not abolish subcellular location.
563–565	xylosyltransferase activity is present while glucuronyltransferase activity is abolished.
563–565	loss of function and abolishes subcellular location.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-5083627	Defective LARGE causes MDDGA6 and MDDGB6
R-HSA-9939291	Matriglycan biosynthesis on DAG1
R-HSA-1643685	Disease
R-HSA-3781865	Diseases of glycosylation
R-HSA-3906995	Diseases associated with O-glycosylation of proteins
R-HSA-392499	Metabolism of proteins
R-HSA-5173105	O-linked glycosylation
R-HSA-5668914	Diseases of metabolism
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 647 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_POTASSIUM_ION_TRANSPORT, GOBP_NEUROMUSCULAR_JUNCTION_DEVELOPMENT, GOBP_MEMORY, GOBP_DENTATE_GYRUS_DEVELOPMENT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_COGNITION, GOBP_SKELETAL_MUSCLE_TISSUE_REGENERATION, GOBP_BEHAVIOR, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_INFLAMMATORY_RESPONSE, GOBP_SYNAPSE_ASSEMBLY, RORA1_01

GO Biological Process (73): blood vessel development (GO:0001568), behavioral fear response (GO:0001662), neuron migration (GO:0001764), N-acetylglucosamine metabolic process (GO:0006044), protein O-linked glycosylation (GO:0006493), protein targeting to membrane (GO:0006612), glycosphingolipid biosynthetic process (GO:0006688), water transport (GO:0006833), intracellular protein transport (GO:0006886), striated muscle contraction (GO:0006941), plasma membrane organization (GO:0007009), cytoskeleton organization (GO:0007010), neuromuscular synaptic transmission (GO:0007274), sensory perception of sound (GO:0007605), memory (GO:0007613), determination of adult lifespan (GO:0008340), glycoprotein biosynthetic process (GO:0009101), response to light stimulus (GO:0009416), response to mechanical stimulus (GO:0009612), gene expression (GO:0010467), negative regulation of muscle cell apoptotic process (GO:0010656), retina layer formation (GO:0010842), dentate gyrus development (GO:0021542), nerve development (GO:0021675), principal sensory nucleus of trigeminal nerve development (GO:0021740), macrophage differentiation (GO:0030225), positive regulation of Rac protein signal transduction (GO:0035022), post-embryonic hindlimb morphogenesis (GO:0035129), multicellular organism growth (GO:0035264), protein O-linked glycosylation via mannose (GO:0035269), myelination (GO:0042552), skeletal muscle tissue regeneration (GO:0043403), post-translational protein modification (GO:0043687), muscle cell cellular homeostasis (GO:0046716), astrocyte differentiation (GO:0048708), skeletal muscle fiber development (GO:0048741), neuromuscular process controlling posture (GO:0050884), synaptic assembly at neuromuscular junction (GO:0051124), localization of cell (GO:0051674), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897)

GO Molecular Function (12): acetylglucosaminyltransferase activity (GO:0008375), glucuronosyltransferase activity (GO:0015020), glycosyltransferase activity (GO:0016757), hexosyltransferase activity (GO:0016758), manganese ion binding (GO:0030145), UDP-xylosyltransferase activity (GO:0035252), xylosyltransferase activity (GO:0042285), catalytic activity (GO:0003824), protein binding (GO:0005515), UDP-glycosyltransferase activity (GO:0008194), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (6): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), neuromuscular junction (GO:0031594), protein-containing complex (GO:0032991), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Diseases associated with O-glycosylation of proteins	1
DAG1 glycosylations	1
Diseases of metabolism	1
Diseases of glycosylation	1
Post-translational protein modification	1
Disease	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
UDP-glycosyltransferase activity	3
macromolecule biosynthetic process	2
hexosyltransferase activity	2
glycosyltransferase activity	2
vasculature development	1
anatomical structure development	1
behavioral defense response	1
fear response	1
cell migration	1
generation of neurons	1
amino sugar metabolic process	1
glycoprotein biosynthetic process	1
protein targeting	1
establishment of protein localization to membrane	1
glycosphingolipid metabolic process	1
glycolipid biosynthetic process	1
sphingolipid biosynthetic process	1
fluid transport	1
intracellular protein localization	1
protein transport	1
intracellular transport	1
muscle contraction	1
endomembrane system organization	1
membrane organization	1
organelle organization	1
chemical synaptic transmission	1
sensory perception of mechanical stimulus	1
learning or memory	1
multicellular organismal process	1
glycoprotein metabolic process	1
carbohydrate derivative biosynthetic process	1
response to radiation	1
response to external stimulus	1
response to abiotic stimulus	1
transferase activity	1
transition metal ion binding	1
xylosyltransferase activity	1
pentosyltransferase activity	1
molecular_function	1
binding	1

Protein interactions and networks

STRING

498 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LARGE1	FKTN	O75072	927
LARGE1	POMGNT1	Q8WZA1	914
LARGE1	DAG1	Q14118	896
LARGE1	POMT1	Q9Y6A1	875
LARGE1	FKRP	Q9H9S5	864
LARGE1	POMT2	Q9UKY4	854
LARGE1	RXYLT1	Q9Y2B1	756
LARGE1	POMK	Q9H5K3	724
LARGE1	B3GALNT2	Q8NCR0	722
LARGE1	POMGNT2	Q8NAT1	710
LARGE1	CRPPA	A4D126	670
LARGE1	MGAT1	P26572	663
LARGE1	AGRN	O00468	571
LARGE1	GMPPB	Q9Y5P6	547
LARGE1	RNF20	Q5VTR2	535

IntAct

23 interactions, top by confidence:

A	B	Type	Score
PLAUR	XRCC3	psi-mi:“MI:0914”(association)	0.530
RANBP10	HTRA2	psi-mi:“MI:0914”(association)	0.510
HLA-DQA1	TMEM223	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
SCGB2A1	RAP1BL	psi-mi:“MI:0914”(association)	0.350
PSCA	METTL15	psi-mi:“MI:0914”(association)	0.350
KLRC1	METTL15	psi-mi:“MI:0914”(association)	0.350
RLN1	RTL8C	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
CEACAM8	PRRT4	psi-mi:“MI:0914”(association)	0.350
GPIHBP1	SAC3D1	psi-mi:“MI:0914”(association)	0.350
SLC3A2	GET1	psi-mi:“MI:0914”(association)	0.350
C1orf54	AGRN	psi-mi:“MI:0914”(association)	0.350
TMEM25	NME4	psi-mi:“MI:0914”(association)	0.350
HYOU1	SNX2	psi-mi:“MI:0914”(association)	0.350
TAFA2	ERN1	psi-mi:“MI:0914”(association)	0.350
SLC30A7	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC44A1	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
LARGE1	RANBP10	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (30): LARGE (Affinity Capture-MS), LARGE (Affinity Capture-MS), LARGE (Affinity Capture-MS), LARGE (Affinity Capture-MS), LARGE (Affinity Capture-MS), LARGE (Affinity Capture-MS), LARGE (Affinity Capture-MS), RANBP10 (Affinity Capture-MS), LARGE (Affinity Capture-MS), LARGE (Affinity Capture-MS), LARGE (Affinity Capture-MS), LARGE (Affinity Capture-MS), LARGE (Affinity Capture-MS), LARGE (Affinity Capture-MS), LARGE (Affinity Capture-MS)

ESM2 similar proteins: A0A8C2LVE3, A2BGL3, F4HXW9, O08889, O17645, O43909, O43916, O93336, O93403, O95461, P25722, P69478, P79948, Q0IIY2, Q2TBF2, Q5NDE4, Q5NDE5, Q5NDE6, Q5NDE7, Q5NDE8, Q5NVB3, Q5R621, Q5RJQ0, Q5XHM7, Q66PG1, Q66PG2, Q66PG3, Q6DBY9, Q6NVP8, Q6P9A2, Q6PA90, Q76EC5, Q76KB1, Q7LFX5, Q7LGA3, Q7LGC8, Q7T3S3, Q800H9, Q8BUB6, Q8CHI9

Diamond homologs: O95461, Q21389, Q32NJ7, Q54PG8, Q54SH2, Q5XPT3, Q66PG1, Q66PG2, Q66PG3, Q66PG4, Q6P7A1, Q6PA90, Q8N3Y3, Q9Z1M7, O43505, Q555X4, Q55FD5, Q5EA01, Q5R4S2, Q8BWP8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1083 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	63
Likely pathogenic	15
Uncertain significance	355
Likely benign	519
Benign	68

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069815	NM_133642.5(LARGE1):c.620_621del (p.Glu207fs)	Pathogenic
1073611	NC_000022.10:g.(?34022218)(34157473_?)del	Pathogenic
1073612	NC_000022.10:g.(?33828137)(34157473_?)del	Pathogenic
1073613	NC_000022.10:g.(?33960824)(34022320_?)del	Pathogenic
1369565	NM_133642.5(LARGE1):c.1209del (p.Phe404fs)	Pathogenic
1451623	NM_133642.5(LARGE1):c.1811del (p.Leu604fs)	Pathogenic
1453494	NC_000022.10:g.(?33712051)(33733807_?)del	Pathogenic
1454275	NM_133642.5(LARGE1):c.265C>T (p.Arg89Ter)	Pathogenic
1456020	NC_000022.10:g.(?33960814)(33961025_?)del	Pathogenic
1456023	NC_000022.10:g.(?33733612)(34157463_?)del	Pathogenic
1458741	NC_000022.10:g.(?33733612)(33828271_?)del	Pathogenic
1459070	NC_000022.10:g.(?34157338)(34157463_?)del	Pathogenic
1459072	NC_000022.10:g.(?33700195)(33712254_?)del	Pathogenic
1459368	NC_000022.10:g.(?33828127)(33961025_?)del	Pathogenic
1956170	NM_133642.5(LARGE1):c.1616_1620delinsG (p.Gln539fs)	Pathogenic
2425215	NC_000022.10:g.(?34022208)(34022330_?)del	Pathogenic
2425216	NC_000022.10:g.(?33559508)(33673261_?)del	Pathogenic
2425218	NC_000022.10:g.(?34000401)(34157463_?)del	Pathogenic
2425219	NC_000022.10:g.(?33960814)(34157463_?)del	Pathogenic
2425220	NC_000022.10:g.(?34000401)(34046674_?)del	Pathogenic
2425221	NC_000022.10:g.(?33777885)(33828271_?)del	Pathogenic
253645	GRCh37/hg19 22q12.3(chr22:34146948-34157735)x1	Pathogenic
2696612	NM_133642.5(LARGE1):c.941_945dup (p.Trp316fs)	Pathogenic
2702127	NM_133642.5(LARGE1):c.1390G>T (p.Glu464Ter)	Pathogenic
2739916	NM_133642.5(LARGE1):c.184_187del (p.Glu63fs)	Pathogenic
2747160	NM_133642.5(LARGE1):c.96del (p.Ser33fs)	Pathogenic
2788600	NM_133642.5(LARGE1):c.1030C>T (p.Gln344Ter)	Pathogenic
2806164	NM_133642.5(LARGE1):c.156dup (p.Arg53fs)	Pathogenic
2844016	NM_133642.5(LARGE1):c.171del (p.Ser58fs)	Pathogenic
2847272	NM_133642.5(LARGE1):c.1671del (p.Tyr558fs)	Pathogenic

SpliceAI

4136 predictions. Top by Δscore:

Variant	Effect	Δscore
22:33274620:TACTC:T	acceptor_gain	1.0000
22:33274622:CTC:C	acceptor_gain	1.0000
22:33274622:CTCCT:C	acceptor_loss	1.0000
22:33274624:CCTGG:C	acceptor_loss	1.0000
22:33274625:C:CC	acceptor_gain	1.0000
22:33274625:CTGGA:C	acceptor_loss	1.0000
22:33277057:CA:C	donor_loss	1.0000
22:33277059:C:CT	donor_loss	1.0000
22:33281715:T:A	donor_gain	1.0000
22:33283197:CTCA:C	donor_loss	1.0000
22:33283198:TCACC:T	donor_loss	1.0000
22:33283199:CAC:C	donor_loss	1.0000
22:33283200:ACCTG:A	donor_loss	1.0000
22:33283201:C:CG	donor_loss	1.0000
22:33283345:CTTC:C	acceptor_gain	1.0000
22:33316079:CCATA:C	donor_loss	1.0000
22:33316080:CATA:C	donor_loss	1.0000
22:33316081:ATACC:A	donor_loss	1.0000
22:33316082:TACCT:T	donor_loss	1.0000
22:33316244:TGGAG:T	acceptor_gain	1.0000
22:33316245:GGAG:G	acceptor_gain	1.0000
22:33316246:GAG:G	acceptor_gain	1.0000
22:33316247:AG:A	acceptor_gain	1.0000
22:33316249:C:CC	acceptor_gain	1.0000
22:33337641:CTTA:C	donor_loss	1.0000
22:33337642:TTA:T	donor_loss	1.0000
22:33337643:TAC:T	donor_loss	1.0000
22:33337644:A:AC	donor_gain	1.0000
22:33337644:AC:A	donor_loss	1.0000
22:33337645:C:CC	donor_gain	1.0000

AlphaMissense

4993 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:33274522:A:G	C726R	1.000
22:33274545:C:G	R718P	1.000
22:33274546:G:T	R718S	1.000
22:33274547:G:C	F717L	1.000
22:33274547:G:T	F717L	1.000
22:33274549:A:G	F717L	1.000
22:33274565:G:C	S711R	1.000
22:33274565:G:T	S711R	1.000
22:33274567:T:G	S711R	1.000
22:33274574:A:C	H708Q	1.000
22:33274574:A:T	H708Q	1.000
22:33274575:T:C	H708R	1.000
22:33274576:G:C	H708D	1.000
22:33274576:G:T	H708N	1.000
22:33274578:G:T	P707H	1.000
22:33274583:G:C	H705Q	1.000
22:33274583:G:T	H705Q	1.000
22:33274584:T:C	H705R	1.000
22:33274585:G:A	H705Y	1.000
22:33274585:G:C	H705D	1.000
22:33274585:G:T	H705N	1.000
22:33277090:T:A	K681N	1.000
22:33277090:T:G	K681N	1.000
22:33277091:T:A	K681I	1.000
22:33277093:G:C	N680K	1.000
22:33277093:G:T	N680K	1.000
22:33277100:C:T	G678D	1.000
22:33277102:A:C	F677L	1.000
22:33277102:A:T	F677L	1.000
22:33277103:A:C	F677C	1.000

dbSNP variants (sampled 300 via entrez): RS1000001797 (22:33629056 T>C), RS1000003824 (22:33430450 T>G), RS1000005780 (22:33180117 G>A), RS1000008628 (22:33690883 C>T), RS1000020135 (22:33828821 T>C), RS1000025102 (22:33634856 A>C), RS1000028137 (22:33131275 C>T), RS1000036705 (22:33739243 G>A), RS1000039670 (22:33447299 G>C), RS1000042794 (22:33654976 A>G), RS1000046834 (22:33356754 G>A,C), RS1000051366 (22:33215615 G>C,T), RS1000052614 (22:33465819 T>C), RS1000054439 (22:33649611 G>A), RS1000056093 (22:33471130 C>A)

Disease associations

OMIM: gene MIM:603590 | disease phenotypes: MIM:608840, MIM:613154, MIM:236670, MIM:268000

GenCC curated gene-disease

Disease	Classification	Inheritance
muscular dystrophy-dystroglycanopathy type B6	Definitive	Autosomal recessive
muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A6	Strong	Autosomal recessive
congenital muscular dystrophy with intellectual disability	Supportive	Autosomal recessive
muscular dystrophy-dystroglycanopathy, type A	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
muscular dystrophy-dystroglycanopathy	Definitive	AR

Mondo (7): muscular dystrophy-dystroglycanopathy type B6 (MONDO:0012138), muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A6 (MONDO:0013158), muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 (MONDO:0009364), muscular dystrophy (MONDO:0020121), retinitis pigmentosa (MONDO:0019200), congenital muscular dystrophy with intellectual disability (MONDO:0018278), muscular dystrophy-dystroglycanopathy, type A (MONDO:0000171)

Orphanet (5): Muscle-eye-brain disease (Orphanet:588), Walker-Warburg syndrome (Orphanet:899), Muscular dystrophy (Orphanet:98473), Retinitis pigmentosa (Orphanet:791), Congenital muscular dystrophy type 1D (Orphanet:98894)

HPO phenotypes

161 total (30 of 161 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000050	Hypoplastic male external genitalia
HP:0000054	Micropenis
HP:0000110	Renal dysplasia
HP:0000158	Macroglossia
HP:0000175	Cleft palate
HP:0000176	Submucous cleft hard palate
HP:0000193	Bifid uvula
HP:0000204	Cleft upper lip
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000298	Mask-like facies
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000411	Protruding ear
HP:0000413	Atresia of the external auditory canal
HP:0000478	Abnormality of the eye
HP:0000482	Microcornea
HP:0000485	Megalocornea
HP:0000486	Strabismus
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000519	Developmental cataract
HP:0000528	Anophthalmia
HP:0000541	Retinal detachment

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST001523_30	Visceral adipose tissue adjusted for BMI	6.000000e-06
GCST001524_32	Visceral adipose tissue/subcutaneous adipose tissue ratio	6.000000e-07
GCST001525_33	Visceral fat	8.000000e-06
GCST002097_21	Coronary artery calcification	7.000000e-06
GCST002247_4	Blood pressure measurement (cold pressor test)	3.000000e-07
GCST002830_20	Urate levels in lean individuals	7.000000e-06
GCST003262_610	Post bronchodilator FEV1	2.000000e-06
GCST003262_619	Post bronchodilator FEV1	2.000000e-06
GCST003434_6	Obsessive-compulsive symptoms	5.000000e-06
GCST003795_10	Age at first birth	3.000000e-09
GCST004029_11	Angiotensin-converting enzyme inhibitor intolerance	4.000000e-06
GCST004139_16	Bipolar disorder	9.000000e-07
GCST004162_3	Carotid plaque burden	7.000000e-06
GCST005316_258	Intelligence (MTAG)	1.000000e-08
GCST006041_34	Major depressive disorder	1.000000e-06
GCST006045_2	Age at first birth	2.000000e-06
GCST006269_1199	General cognitive ability	4.000000e-08
GCST006585_2684	Blood protein levels	1.000000e-06
GCST009028_47	Adverse response to drug	2.000000e-07
GCST009524_120	Household income (MTAG)	3.000000e-08
GCST009524_211	Household income (MTAG)	7.000000e-09
GCST009732_3	Type 2 diabetes	1.000000e-07
GCST011684_8	High density lipoprotein cholesterol levels	7.000000e-07

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004767	visceral:subcutaneous adipose tissue ratio
EFO:0004723	coronary artery calcification
EFO:0005404	response to cold pressor test
EFO:0006336	diastolic blood pressure
EFO:0004531	urate measurement
EFO:0004314	forced expiratory volume
EFO:0007802	obsessive-compulsive symptom measurement
EFO:0009101	age at first birth measurement
EFO:0005325	response to angiotensin-converting enzyme inhibitor
EFO:0006501	carotid plaque build
EFO:0004337	intelligence
EFO:0009658	adverse effect
EFO:0009695	household income
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D009136	Muscular Dystrophies	C05.651.534.500; C10.668.491.175.500; C16.320.577
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
D058494	Walker-Warburg Syndrome	C10.500.507.450.499.249.500; C11.270.881; C16.131.666.507.450.499.249.500; C16.320.577.750
C563844	Muscular Dystrophy, Congenital, Type 1D (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2146300 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

77 measured of 94 human assays (98 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
N-{4-[5-(4-methoxybenzyl)-1,2,4-oxadiazol-3-yl]phenyl}nicotinamide	EC50	1520 nM
N-[2-(dimethylamino)-2-(4-ethylphenyl)ethyl]-3-(2-fluorophenyl)-4-oxo-2-sulfanylidene-1H-quinazoline-7-carboxamide	EC50	1900 nM
4-tert-butyl-N-[4-[oxo-(3-pyridinylmethylamino)methyl]phenyl]benzamide	EC50	2480 nM
cid_720645	EC50	3340 nM
[3-(4-Chloro-phenyl)-5-methyl-pyrazolo[1,5-a]pyrimidin-7-yl]-pyridin-2-ylmethyl-amine	EC50	3480 nM
4-[(5-methyl-1,2-oxazol-3-yl)amino]naphthalene-1,2-dione	IC50	3520 nM
4-(4-chlorophenyl)-N-(4-propan-2-ylphenyl)-2,3-dihydrofuro[2,3-b]pyridine-2-carboxamide	EC50	3980 nM
MLS-0471919.0001	EC50	3990 nM
cid_3491956	EC50	4360 nM
cid_8902468	EC50	4500 nM
cid_4826888	EC50	4750 nM
4-(1H-indol-3-yl)-N-(2-phenylethyl)-1,3-thiazol-2-amine	EC50	5130 nM
4-(azepan-1-ylcarbonyl)-2-(4-ethoxyphenyl)-6,7-dimethoxy-isoquinolin-1-one	EC50	5600 nM
cid_1942203	EC50	5690 nM
N-(4,5-Dihydro-1H-imidazol-2-yl)-N’-[1-(4-pentyloxy-phenyl)-ethylidene]-hydrazine	EC50	5810 nM
N-(4-methyl-3-morpholin-4-ylsulfonylphenyl)-5-nitrothiophene-2-carboxamide	EC50	5920 nM
2-(2,3-dioxo-1-indolyl)acetic acid propan-2-yl ester	IC50	6070 nM
SMR001283653	EC50	6070 nM
SMR000594945	EC50	6110 nM
(2E)-2-[(3-methylphenyl)methylidene]-3-oxidanylidene-N-(2-pyrrolidin-1-ylethyl)-4H-1,4-benzothiazine-6-carboxamide	EC50	6280 nM
cid_1226038	EC50	6310 nM
MLS000574381	EC50	6370 nM
cid_6882316	EC50	6460 nM
N-naphthalen-1-yl-5-nitro-thiophene-2-carboxamide	EC50	6880 nM
MLS003123696	EC50	7320 nM
2-chloranyl-N-[2-[(2E)-2-[(5-nitrothiophen-2-yl)methylidene]hydrazinyl]-2-oxidanylidene-ethyl]benzamide	EC50	7480 nM
N2-(2-methoxyethyl)-N4-(2-phenoxyethyl)-6-phenylthieno[3,2-d]pyrimidine-2,4-diamine	EC50	7860 nM
4-[3-(cyclohexylmethyl)imidazo[2,1-a]isoquinolin-2-yl]benzenecarbonitrile	EC50	7970 nM
SMR000626447	EC50	8180 nM
(3Z)-3-(4-bromophenyl)sulfonylimino-2-(3-butyl-1-imidazol-3-iumyl)-4-oxo-1-naphthalenolate	IC50	8280 nM
cid_2954663	EC50	8540 nM
1-(3-chloro-4-fluorophenyl)-3-[[1-[(3-methylphenyl)methyl]piperidin-4-yl]methyl]urea	EC50	8570 nM
cid_53207487	EC50	8680 nM
N-(2-fluorophenyl)-5-nitrothiophene-2-carboxamide	EC50	8890 nM
SMR001291831	EC50	8930 nM
(E)-N-[6-(propan-2-ylsulfamoyl)-1,3-benzothiazol-2-yl]-3-(3,4,5-trimethoxyphenyl)-2-propenamide	EC50	9210 nM
SMR000652385	EC50	9360 nM
cid_5914949	EC50	9370 nM
MLS001075987	IC50	10100 nM
cid_3278258	EC50	11600 nM
ethanedioic acid;N-[3-[2-methoxy-4-[(E)-prop-1-enyl]phenoxy]propyl]cyclopentanamine	EC50	11600 nM
MLS001079090	EC50	11800 nM
cid_2922661	EC50	12200 nM
MLS000723586	EC50	12300 nM
SMR000805815	EC50	12300 nM
oxalic acid;1-[3-(4-propan-2-yloxyphenoxy)propyl]azepane	EC50	12400 nM
2-Nitro-benzoic acid 4-(3-benzotriazol-1-yl-1,4-dioxo-1,4-dihydro-naphthalen-2-ylamino)-phenyl ester	IC50	12700 nM
MLS000718125	EC50	12700 nM
4-(4-acetylphenyl)-N-(4-isopropylphenyl)piperazine-1-carboxamide	EC50	12800 nM
2-(3-benzyl-2-iminobenzimidazol-1-yl)-1-(3,4-dichlorophenyl)ethanone;hydrobromide	EC50	15500 nM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	6
Aflatoxin B1	decreases expression, affects expression	4
sodium arsenite	affects methylation, decreases expression	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
methyleugenol	decreases expression	1
bisphenol A	affects cotreatment, increases methylation	1
terbufos	increases methylation	1
beta-lapachone	decreases expression	1
butyraldehyde	decreases expression	1
bisphenol S	affects cotreatment, increases methylation	1
jinfukang	affects cotreatment, decreases expression	1
Venlafaxine Hydrochloride	decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	decreases expression	1
Cadmium	decreases expression	1
Cisplatin	decreases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Estradiol	affects cotreatment, increases expression	1
Methamphetamine	affects response to substance	1
Parathion	increases methylation	1
Rotenone	decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2114735	Functional	PubChem BioAssay. Dose response confirmation of small molecule activators of alpha dystroglycan glycosylation. (Class of assay: confirmatory)	PubChem BioAssay data set

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A1CH	HAP1 LARGE (-) POMK (-)	Cancer cell line	Male
CVCL_BX05	GM23652	Finite cell line	Female
CVCL_SV31	HAP1 LARGE (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01882400	PHASE4	COMPLETED	Assessment of Response to Treatment of Osteoporosis With Oral Bisphosphonates in Patients With Muscular Dystrophy
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT01254019	PHASE3	COMPLETED	A Clinical Study to Assess the Efficacy and Safety of GSK2402968 in Subjects With Duchenne Muscular Dystrophy
NCT01480245	PHASE3	TERMINATED	Open Label Study of GSK2402968 in Subjects With Duchenne Muscular Dystrophy
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NCT01890798	PHASE3	WITHDRAWN	Drisapersen Duchenne Muscular Dystrophy (DMD) Treatment Protocol
NCT02090959	PHASE3	TERMINATED	An Extension Study of Ataluren (PTC124) in Participants With Nonsense Mutation Dystrophinopathy
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NCT01910649	PHASE2	TERMINATED	A Phase I/II, Open Label, Escalating Dose, Pilot Study to Assess Effect, Safety, Tolerability and PK of Multiple SC Doses of Drisapersen in Patients With Duchenne Muscular Dystrophy and to Assess the Potential for IV Dosing as an Alternative Route of Administration
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NCT07287189	PHASE2	RECRUITING	Phase 2 Study of SAT-3247 in Pediatric Ambulatory Patients
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