B4GAT1

Summary

B4GAT1 (beta-1,4-glucuronyltransferase 1, HGNC:15685) is a protein-coding gene on chromosome 11q13.2, encoding Beta-1,4-glucuronyltransferase 1 (O43505). Beta-1,4-glucuronyltransferase involved in O-mannosylation of alpha-dystroglycan (DAG1).

This gene encodes a member of the beta-1,3-N-acetylglucosaminyltransferase family. This enzyme is a type II transmembrane protein. It is essential for the synthesis of poly-N-acetyllactosamine, a determinant for the blood group i antigen.

Source: NCBI Gene 11041 — RefSeq curated summary.

At a glance

• Gene–disease (curated): muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A13 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 311 total — 2 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 74
• MANE Select transcript: NM_006876

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15685
Approved symbol	B4GAT1
Name	beta-1,4-glucuronyltransferase 1
Location	11q13.2
Locus type	gene with protein product
Status	Approved
Aliases	IGnT, iGAT, BETA3GNTI, B3GN-T1
Ensembl gene	ENSG00000174684
Ensembl biotype	protein_coding
OMIM	605517
Entrez	11041

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000311181, ENST00000865226

RefSeq mRNA: 1 — MANE Select: NM_006876 NM_006876

CCDS: CCDS8136

Canonical transcript exons

ENST00000311181 — 2 exons

Exon	Start	End
ENSE00001189142	66345374	66346240
ENSE00001189146	66346490	66347629

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 99.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.2968 / max 354.0832, expressed in 1703 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120795	24.0658	1697
120796	0.2311	88

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.62	gold quality
middle temporal gyrus	UBERON:0002771	99.11	gold quality
pons	UBERON:0000988	98.87	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.72	gold quality
superior vestibular nucleus	UBERON:0007227	98.66	gold quality
prefrontal cortex	UBERON:0000451	98.55	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.50	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.45	gold quality
substantia nigra pars compacta	UBERON:0001965	98.43	gold quality
superior frontal gyrus	UBERON:0002661	98.37	gold quality
frontal cortex	UBERON:0001870	98.30	gold quality
frontal lobe	UBERON:0016525	98.30	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.19	gold quality
entorhinal cortex	UBERON:0002728	98.15	gold quality
ventral tegmental area	UBERON:0002691	98.13	gold quality
cerebellar vermis	UBERON:0004720	98.07	gold quality
parietal lobe	UBERON:0001872	98.06	gold quality
postcentral gyrus	UBERON:0002581	98.02	gold quality
right frontal lobe	UBERON:0002810	97.95	gold quality
occipital lobe	UBERON:0002021	97.93	gold quality
neocortex	UBERON:0001950	97.92	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.90	gold quality
primary visual cortex	UBERON:0002436	97.90	gold quality
nucleus accumbens	UBERON:0001882	97.86	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.83	gold quality
hypothalamus	UBERON:0001898	97.82	gold quality
orbitofrontal cortex	UBERON:0004167	97.81	gold quality
cerebral cortex	UBERON:0000956	97.80	gold quality
medulla oblongata	UBERON:0001896	97.65	gold quality
telencephalon	UBERON:0001893	97.59	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	9.78
E-ANND-3	yes	6.72
E-GEOD-84465	yes	6.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

69 targeting B4GAT1, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4650-5P	99.98	64.69	999
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-4756-3P	99.62	66.30	1319

Literature-anchored findings (GeneRIF, showing 5)

• These results demonstrate that B3GNT1 and B4GALT1 physically associate in vitro and in cultured cells, providing insight into possible mechanisms for regulation of polyLacNAc production. (PMID:19261593)
• These results identify a previously undescribed role of carbohydrate-dependent cell-basement membrane interaction in tumor suppression and its control by beta3GnT1 and LARGE. (PMID:19587235)
• These functional studies identify an important role of B3GNT1 in the synthesis of the uncharacterized laminin-binding glycan of alpha-dystroglycan and implicate B3GNT1 as a novel causative gene for Walker-Warburg syndrome. (PMID:23359570)
• report describes the first truncating mutation in B3GNT1 and confirms that this gene, which plays a role in alphaDG glycosylation, is a bona fide disease gene in Walker-Warburg syndrome (PMID:23877401)
• 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)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	b4gat1	ENSDARG00000077583
mus_musculus	B4gat1	ENSMUSG00000047379
rattus_norvegicus	B4gat1	ENSRNOG00000020110
drosophila_melanogaster	CG11149	FBGN0031732
drosophila_melanogaster	CG9171	FBGN0031738
drosophila_melanogaster	CG15483	FBGN0032457
caenorhabditis_elegans		WBGENE00008491

Paralogs (5): LARGE1 (ENSG00000133424), GXYLT1 (ENSG00000151233), LARGE2 (ENSG00000165905), GXYLT2 (ENSG00000172986), XXYLT1 (ENSG00000173950)

Protein

Protein identifiers

Beta-1,4-glucuronyltransferase 1 — O43505 (reviewed: O43505)

Alternative names: I-beta-1,3-N-acetylglucosaminyltransferase, N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase, Poly-N-acetyllactosamine extension enzyme, UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 1

All UniProt accessions (1): O43505

UniProt curated annotations — full annotation on UniProt →

Function. Beta-1,4-glucuronyltransferase involved in O-mannosylation of alpha-dystroglycan (DAG1). Transfers a glucuronic acid (GlcA) residue onto a xylose (Xyl) acceptor to produce the glucuronyl-beta-1,4-xylose-beta disaccharide primer, which is further elongated by LARGE1, during synthesis of phosphorylated O-mannosyl glycan. Phosphorylated O-mannosyl glycan is a carbohydrate structure present in alpha-dystroglycan (DAG1), which is required for binding laminin G-like domain-containing extracellular proteins with high affinity. Required for axon guidance; via its function in O-mannosylation of alpha-dystroglycan (DAG1).

Subunit / interactions. Interacts with LARGE1 and LARGE2.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. In the adult, highly expressed in heart, brain, skeletal muscle and kidney and to a lesser extent in placenta, pancreas, spleen, prostate, testis, ovary, small intestine and colon. Very weak expression in lung, liver, thymus and peripheral blood leukocytes. In fetal highly expressed in brain and kidney and to a lesser extent in lung and liver.

Disease relevance. Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A13 (MDDGA13) [MIM:615287] 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.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the glycosyltransferase 49 family.

RefSeq proteins (1): NP_006867* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR043189	B4GAT1	Family

Pfam: PF13896

Enzyme classification (BRENDA):

• EC 2.4.1.149 — N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase (BRENDA: 6 organisms, 107 substrates, 59 inhibitors, 27 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

10 substrates with measured Km, best-characterized 10. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
UDP-N-ACETYL-D-GLUCOSAMINE	0.129–15.97	11
N-ACETYLLACTOSAMINE	2.2–19.6	4
LACTOSE	5.2–29.8	3
GALBETA(1-4)GLCNACBETA(1-4)GLCNAC-2-AMINOPYRIDIN	0.44–0.9	2
ASIALO-ALPHA1-ACID GLYCOPROTEIN	0.6	1
GALBETA(1->4)GLCNACBETA(1->3)GALBETA(1->4)GLCNAC	1	1
GALBETA1,4(SO3-,6)-GLCNACBETA1,3-GALBETA1,4(SO3-	0.36	1
LACTONEOTETRAOSYLCERAMIDE	0.19	1
LACTONORHEXAOSYLCERAMIDE	0.19	1
NEOLACTOTETRAOSYLCERAMIDE	0.09	1

Catalyzed reactions (Rhea), 1 shown:

• 3-O-[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-glucuronate = 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 + H(+) (RHEA:46860)

UniProt features (13 total): sequence variant 3, topological domain 2, mutagenesis site 2, binding site 2, glycosylation site 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43505-F1	88.46	0.67

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 (2): 227; 229

Glycosylation sites (2): 204, 300

Mutagenesis-validated functional residues (2):

Position	Phenotype
155	in mut3; mislocalization to the endoplasmic reticulum.
227–229	in mut2; mislocalization to the endoplasmic reticulum.

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-2022854	Keratan sulfate biosynthesis
R-HSA-5083627	Defective LARGE causes MDDGA6 and MDDGB6
R-HSA-9939291	Matriglycan biosynthesis on DAG1
R-HSA-1430728	Metabolism
R-HSA-1630316	Glycosaminoglycan metabolism
R-HSA-1638074	Keratan sulfate/keratin metabolism
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
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives

MSigDB gene sets: 328 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_NEUROGENESIS, chr11q13, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_AMINOGLYCAN_BIOSYNTHETIC_PROCESS, MODULE_66, MAHAJAN_RESPONSE_TO_IL1A_DN, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_AMINOGLYCAN_METABOLIC_PROCESS, NIKOLSKY_BREAST_CANCER_11Q12_Q14_AMPLICON, GOBP_CELL_PROJECTION_ORGANIZATION, YYCATTCAWW_UNKNOWN, MODULE_11, GOBP_PROTEIN_O_LINKED_GLYCOSYLATION_VIA_N_ACETYL_GALACTOSAMINE

GO Biological Process (4): axon guidance (GO:0007411), keratan sulfate proteoglycan biosynthetic process (GO:0018146), protein O-linked glycosylation via mannose (GO:0035269), obsolete protein glycosylation (GO:0006486)

GO Molecular Function (6): N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase activity (GO:0008532), glucuronosyltransferase activity (GO:0015020), metal ion binding (GO:0046872), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (4): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Keratan sulfate/keratin metabolism	1
Diseases associated with O-glycosylation of proteins	1
DAG1 glycosylations	1
Metabolism of carbohydrates and carbohydrate derivatives	1
Glycosaminoglycan metabolism	1
Diseases of metabolism	1
Diseases of glycosylation	1
Post-translational protein modification	1
Disease	1
Metabolism of proteins	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
axonogenesis	1
neuron projection guidance	1
proteoglycan biosynthetic process	1
keratan sulfate proteoglycan metabolic process	1
protein O-linked glycosylation	1
acetylglucosaminyltransferase activity	1
UDP-glycosyltransferase activity	1
hexosyltransferase activity	1
cation binding	1
binding	1
catalytic activity	1
transferase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

584 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
B4GAT1	RXYLT1	Q9Y2B1	858
B4GAT1	POMGNT2	Q8NAT1	845
B4GAT1	POMK	Q9H5K3	845
B4GAT1	B3GALNT2	Q8NCR0	841
B4GAT1	POMT1	Q9Y6A1	802
B4GAT1	FKTN	O75072	782
B4GAT1	FKRP	Q9H9S5	763
B4GAT1	POMT2	Q9UKY4	755
B4GAT1	CRPPA	A4D126	746
B4GAT1	DAG1	Q14118	716
B4GAT1	POMGNT1	Q8WZA1	700
B4GAT1	DOLK	Q9UPQ8	622
B4GAT1	DPM1	O60762	620
B4GAT1	DPM3	Q9P2X0	597
B4GAT1	GMPPB	Q9Y5P6	580

IntAct

57 interactions, top by confidence:

A	B	Type	Score
B4GAT1	LARGE2	psi-mi:“MI:0915”(physical association)	0.560
CHST10	B4GAT1	psi-mi:“MI:0914”(association)	0.530
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
B4GAT1	ADCY6	psi-mi:“MI:0914”(association)	0.530
CENPH	PSMD11	psi-mi:“MI:0914”(association)	0.530
TMEM184A	SLC33A1	psi-mi:“MI:0914”(association)	0.530
SLC15A4	PGRMC1	psi-mi:“MI:0914”(association)	0.530
SLCO4C1	CLGN	psi-mi:“MI:0914”(association)	0.530
	B4GAT1	psi-mi:“MI:0915”(physical association)	0.400
B4GAT1	LARGE1	psi-mi:“MI:0915”(physical association)	0.400
B4GAT1	HNRNPD	psi-mi:“MI:0915”(physical association)	0.400
B4GAT1	CASP5	psi-mi:“MI:0915”(physical association)	0.400
B4GAT1	VSIG8	psi-mi:“MI:0915”(physical association)	0.400
	ESYT2	psi-mi:“MI:0914”(association)	0.350
B4GAT1	ADCY6	psi-mi:“MI:0914”(association)	0.350
BSCL2	B4GAT1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
E	SPTLC2	psi-mi:“MI:0914”(association)	0.350
CNR2	ILVBL	psi-mi:“MI:0914”(association)	0.350
POMK	ESYT2	psi-mi:“MI:0914”(association)	0.350
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
TMED10	PGRMC1	psi-mi:“MI:0914”(association)	0.350
TMED2	PGRMC1	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350

BioGRID (182): PTPN2 (Affinity Capture-MS), ATP9A (Affinity Capture-MS), SNX25 (Affinity Capture-MS), EIF2AK3 (Affinity Capture-MS), SUSD1 (Affinity Capture-MS), ADCY6 (Affinity Capture-MS), FKTN (Affinity Capture-MS), PPM1L (Affinity Capture-MS), ST7 (Affinity Capture-MS), TMEM39A (Affinity Capture-MS), PTPLB (Affinity Capture-MS), XPR1 (Affinity Capture-MS), HAPLN3 (Affinity Capture-MS), EXT1 (Affinity Capture-MS), FAR2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1S6M251, A8Y1P7, H0ZAB5, L7YAI7, O43286, O43505, O60513, O60909, O61394, O61397, O88419, P08037, P15291, P15535, P34548, P34678, P70419, Q09323, Q09363, Q14435, Q3YL68, Q5EA01, Q5EA87, Q5QQ54, Q5QQ55, Q5R4S2, Q66HH1, Q6P768, Q6WV17, Q6WV20, Q7K755, Q80WN7, Q80WN8, Q80WN9, Q8BWP8, Q8I136, Q8IA42, Q8MV48, Q8MVS5, Q91YY2

Diamond homologs: L7YAI7, O43505, Q555X4, Q5EA01, Q5R4S2, Q8BWP8, Q54SH2, Q66PG1, O95461, Q21389, Q32NJ7, Q54PG8, Q55FD5, Q5XPT3, Q66PG2, Q66PG3, Q66PG4, Q6PA90, Q9Z1M7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 67 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
SLC-mediated transmembrane transport	8	10.1×	3e-04
Transport of small molecules	9	4.8×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	5	19.5×	3e-03
transport across blood-brain barrier	5	16.0×	4e-03
monoatomic ion transport	5	13.9×	4e-03
adenylate cyclase-activating G protein-coupled receptor signaling pathway	5	10.1×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	5
Uncertain significance	173
Likely benign	114
Benign	4

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1252009	NM_006876.3(B4GAT1):c.1207G>T (p.Glu403Ter)	Pathogenic
1709842	NM_006876.3(B4GAT1):c.864T>A (p.Tyr288Ter)	Pathogenic
208399	NM_138706.5(B3GNT6):c.552C>G (p.Asp184Glu)	Likely pathogenic
242669	NM_006876.3(B4GAT1):c.1168A>G (p.Asn390Asp)	Likely pathogenic
242670	NM_006876.3(B4GAT1):c.1217C>T (p.Ala406Val)	Likely pathogenic
4849376	NM_006876.3(B4GAT1):c.686_690del (p.Asp229fs)	Likely pathogenic
503771	NM_006876.3(B4GAT1):c.1179_1181del (p.Asn393del)	Likely pathogenic

SpliceAI

320 predictions. Top by Δscore:

Variant	Effect	Δscore
11:66346236:CAGGC:C	acceptor_gain	1.0000
11:66346238:GGCC:G	acceptor_loss	1.0000
11:66346241:C:CC	acceptor_gain	1.0000
11:66346477:C:CA	donor_gain	1.0000
11:66346488:ACCT:A	donor_loss	1.0000
11:66346489:CC:C	donor_loss	1.0000
11:66346489:CCTGG:C	donor_gain	1.0000
11:66346513:A:AC	donor_gain	1.0000
11:66346514:C:CC	donor_gain	1.0000
11:66346237:AGGC:A	acceptor_gain	0.9900
11:66346239:GC:G	acceptor_gain	0.9900
11:66346240:CC:C	acceptor_gain	0.9900
11:66346242:T:A	acceptor_loss	0.9900
11:77039550:AGAT:A	acceptor_gain	0.9900
11:77039551:GAT:G	acceptor_gain	0.9900
11:77039551:GATG:G	acceptor_gain	0.9900
11:66346238:GGC:G	acceptor_gain	0.9800
11:66346244:C:CT	acceptor_gain	0.9700
11:66346245:A:T	acceptor_gain	0.9700
11:66346513:ACTG:A	donor_gain	0.9700
11:66346514:CTG:C	donor_gain	0.9700
11:66346514:CTGC:C	donor_gain	0.9700
11:77034477:AGG:A	donor_loss	0.9700
11:77034478:GGTAA:G	donor_loss	0.9700
11:77034479:G:C	donor_loss	0.9700
11:77039550:AGATG:A	acceptor_gain	0.9700
11:77039551:GATGG:G	acceptor_gain	0.9700
11:66346516:G:GA	donor_gain	0.9600
11:77039550:A:AG	acceptor_gain	0.9600
11:77039551:G:GG	acceptor_gain	0.9600

AlphaMissense

2680 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:66346634:C:A	W304C	1.000
11:66346634:C:G	W304C	1.000
11:66346908:C:A	R213M	1.000
11:66346908:C:G	R213T	1.000
11:66346916:G:C	N210K	1.000
11:66346916:G:T	N210K	1.000
11:66346187:G:C	F370L	0.999
11:66346187:G:T	F370L	0.999
11:66346189:A:G	F370L	0.999
11:66346502:G:C	N348K	0.999
11:66346502:G:T	N348K	0.999
11:66346505:G:C	F347L	0.999
11:66346505:G:T	F347L	0.999
11:66346507:A:G	F347L	0.999
11:66346520:A:C	F342L	0.999
11:66346520:A:T	F342L	0.999
11:66346521:A:C	F342C	0.999
11:66346521:A:G	F342S	0.999
11:66346522:A:G	F342L	0.999
11:66346571:C:A	W325C	0.999
11:66346571:C:G	W325C	0.999
11:66346573:A:G	W325R	0.999
11:66346573:A:T	W325R	0.999
11:66346636:A:G	W304R	0.999
11:66346636:A:T	W304R	0.999
11:66346866:T:A	D227V	0.999
11:66346907:C:A	R213S	0.999
11:66346907:C:G	R213S	0.999
11:66347198:C:A	W116C	0.999
11:66347198:C:G	W116C	0.999

dbSNP variants (sampled 300 via entrez): RS1000409141 (11:66348903 C>T), RS1000447391 (11:66348692 T>C), RS1000733603 (11:66347389 G>A), RS1000741575 (11:66348053 C>A,G,T), RS1001740342 (11:66349607 T>G), RS1001961363 (11:66348179 G>T), RS1002027365 (11:66349286 T>C), RS1003542244 (11:66347733 G>A,C), RS1003597544 (11:66348024 G>A,T), RS1003961051 (11:66348334 A>C), RS1003972164 (11:66348637 C>A,G,T), RS1005091879 (11:66348061 T>C), RS1005397679 (11:66349187 A>G), RS1005428836 (11:66348956 A>G), RS1008311913 (11:66346935 T>C)

Disease associations

OMIM: gene MIM:605517 | disease phenotypes: MIM:615287, MIM:618723, MIM:236670

GenCC curated gene-disease

Disease	Classification	Inheritance
muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A13	Strong	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 (congenital with brain and eye anomalies), type A13	Moderate	AR

Mondo (5): muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A13 (MONDO:0014120), premature ovarian failure 16 (MONDO:0032881), muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 (MONDO:0009364), childhood-onset schizophrenia (MONDO:0957430), muscular dystrophy-dystroglycanopathy, type A (MONDO:0000171)

Orphanet (3): Walker-Warburg syndrome (Orphanet:899), Muscle-eye-brain disease (Orphanet:588), Childhood-onset schizophrenia (Orphanet:641496)

HPO phenotypes

74 total (30 of 74 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000054	Micropenis
HP:0000126	Hydronephrosis
HP:0000175	Cleft palate
HP:0000176	Submucous cleft hard palate
HP:0000193	Bifid uvula
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000411	Protruding ear
HP:0000482	Microcornea
HP:0000501	Glaucoma
HP:0000518	Cataract
HP:0000528	Anophthalmia
HP:0000541	Retinal detachment
HP:0000556	Retinal dystrophy
HP:0000568	Microphthalmia
HP:0000587	Abnormal optic nerve morphology
HP:0000612	Iris coloboma
HP:0000618	Blindness
HP:0000648	Optic atrophy
HP:0000878	11 pairs of ribs
HP:0001093	Optic nerve dysplasia
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010059_2	Physiological traits	3.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
Cyclosporine	decreases expression, increases expression	4
sodium arsenite	decreases expression, increases abundance, increases expression	3
bisphenol A	increases expression, affects cotreatment, affects expression, increases abundance	2
Air Pollutants	decreases expression, increases abundance	2
Particulate Matter	decreases expression, increases abundance	2
ginger extract	affects expression, increases abundance, affects cotreatment	1
triphenyl phosphate	affects expression	1
deoxynivalenol	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
nivalenol	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Ethanol	increases expression	1
Arsenic	decreases expression, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Copper	decreases expression, affects binding	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Oils, Volatile	affects cotreatment, affects expression, increases abundance	1
Phenobarbital	affects expression	1
Plant Oils	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04001595	Not specified	UNKNOWN	Global FKRP Registry