B3GALNT2

Summary

B3GALNT2 (beta-1,3-N-acetylgalactosaminyltransferase 2, HGNC:28596) is a protein-coding gene on chromosome 1q42.3, encoding UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 2 (Q8NCR0). Beta-1,3-N-acetylgalactosaminyltransferase that synthesizes a unique carbohydrate structure, GalNAc-beta-1-3GlcNAc, on N- and O-glycans.

This gene encodes a member of the glycosyltransferase 31 family. The encoded protein synthesizes GalNAc:beta-1,3GlcNAc, a novel carbohydrate structure, on N- and O-glycans. Alternatively spliced transcript variants that encode different isoforms have been described.

Source: NCBI Gene 148789 — RefSeq curated summary.

At a glance

• Gene–disease (curated): muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11 (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 707 total — 46 pathogenic, 19 likely-pathogenic
• Phenotypes (HPO): 80
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_152490

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28596
Approved symbol	B3GALNT2
Name	beta-1,3-N-acetylgalactosaminyltransferase 2
Location	1q42.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC39558
Ensembl gene	ENSG00000162885
Ensembl biotype	protein_coding
OMIM	610194
Entrez	148789

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 14 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000313984, ENST00000366600, ENST00000461994, ENST00000462374, ENST00000477694, ENST00000494378, ENST00000612859, ENST00000675193, ENST00000675555, ENST00000676288, ENST00000883743, ENST00000883744, ENST00000920822, ENST00000920823, ENST00000920824, ENST00000920825, ENST00000920826, ENST00000920827, ENST00000954792, ENST00000954793

RefSeq mRNA: 2 — MANE Select: NM_152490 NM_001277155, NM_152490

CCDS: CCDS1606, CCDS60453

Canonical transcript exons

ENST00000366600 — 12 exons

Exon	Start	End
ENSE00001167596	235489168	235489268
ENSE00001355475	235504141	235504452
ENSE00001832184	235447190	235450340
ENSE00002355794	235454156	235454315
ENSE00002359106	235453090	235453146
ENSE00003522958	235480054	235480149
ENSE00003604142	235465636	235465714
ENSE00003623506	235484322	235484515
ENSE00003647822	235458603	235458786
ENSE00003676198	235455559	235455684
ENSE00003687877	235470850	235470960
ENSE00003707487	235494681	235494828

Expression profiles

Bgee: expression breadth ubiquitous, 141 present calls, max score 93.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.4861 / max 114.2486, expressed in 1768 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
18143	6.6428	1755
18142	0.6643	337
18141	0.1791	69

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	93.59	gold quality
skeletal muscle tissue	UBERON:0001134	92.14	gold quality
adrenal tissue	UBERON:0018303	91.18	gold quality
pancreas	UBERON:0001264	90.94	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.67	gold quality
skeletal muscle organ	UBERON:0014892	90.35	gold quality
muscle of leg	UBERON:0001383	90.28	gold quality
gastrocnemius	UBERON:0001388	90.28	gold quality
muscle tissue	UBERON:0002385	89.94	gold quality
popliteal artery	UBERON:0002250	89.65	gold quality
tibial artery	UBERON:0007610	89.64	gold quality
stromal cell of endometrium	CL:0002255	89.50	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.11	gold quality
right coronary artery	UBERON:0001625	88.49	gold quality
smooth muscle tissue	UBERON:0001135	88.01	gold quality
mucosa of stomach	UBERON:0001199	87.14	gold quality
colonic epithelium	UBERON:0000397	86.74	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.70	gold quality
lower esophagus muscularis layer	UBERON:0035833	86.42	gold quality
lower esophagus	UBERON:0013473	86.41	gold quality
urinary bladder	UBERON:0001255	86.28	gold quality
endometrium	UBERON:0001295	86.28	gold quality
thoracic aorta	UBERON:0001515	85.98	gold quality
ascending aorta	UBERON:0001496	85.96	gold quality
stomach	UBERON:0000945	85.87	gold quality
islet of Langerhans	UBERON:0000006	85.80	gold quality
body of stomach	UBERON:0001161	85.70	gold quality
left coronary artery	UBERON:0001626	85.67	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.27	gold quality
descending thoracic aorta	UBERON:0002345	85.15	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

145 targeting B3GALNT2, 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-9-5P	100.00	72.28	2361
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-101-3P	99.94	75.03	2230

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 10)

• Although the GalNAcbeta1-3GlcNAcbeta1-R structure has not been reported in humans or other mammals, we have discovered a novel human glycosyltransferase producing this structure on N- and O-glycans. (PMID:14724282)
• Results demonstrate a role for B3GALNT2 in the glycosylation of alpha-DG and show that B3GALNT2 mutations can cause dystroglycanopathy with muscle and brain involvement. (PMID:23453667)
• B3GALNT2 is a gene associated with congenital muscular dystrophy with brain malformations. (PMID:24084573)
• B3GALNT2 overexpression is associated with breast cancer. (PMID:24285400)
• Mutations in B3GALNT2 give rise to a novel muscular dystrophy-dystroglycanopathies syndrome presentation, characterized by intellectual disability and seizure, but without any apparent muscular involvement. (PMID:29273094)
• B3GALNT2 reduced expression of some metabolic enzymes and thus downregulated levels of secreted acetoacetate. This relieved the activity of MIF and enhanced macrophage recruitment to promote tumor growth. (PMID:29618368)
• B3GALNT2 primarily transferred LDN to intracellular glycoproteins, thereby clearly delineating proteins that carry type-I or type-II LacdiNAcs (PMID:30898876)
• Novel mutations in B3GALNT2 gene causing alpha-dystroglycanopathy in Chinese patients. (PMID:33290285)
• Prenatal diagnosis of Walker-Warburg syndrome due to compound mutations in the B3GALNT2 gene. (PMID:35338537)
• [Genetic analysis of a Chinese family affected with alpha-dystroglycanopathy due to variant of B3GALNT2 gene]. (PMID:37368380)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	b3galnt2	ENSDARG00000046133
mus_musculus	B3galnt2	ENSMUSG00000039242
rattus_norvegicus	B3galnt2	ENSRNOG00000016855
drosophila_melanogaster	brn	FBGN0000221
caenorhabditis_elegans		WBGENE00000270
caenorhabditis_elegans		WBGENE00007096
caenorhabditis_elegans		WBGENE00017653

Paralogs (15): B3GNT7 (ENSG00000156966), B3GALT2 (ENSG00000162630), B3GALNT1 (ENSG00000169255), B3GNT2 (ENSG00000170340), B3GALT1 (ENSG00000172318), B3GALT6 (ENSG00000176022), B3GNT4 (ENSG00000176383), B3GNT5 (ENSG00000176597), B3GNT8 (ENSG00000177191), B3GNT3 (ENSG00000179913), B3GALT5 (ENSG00000183778), B3GNT6 (ENSG00000198488), B3GALT9 (ENSG00000214654), B3GALT4 (ENSG00000235863), B3GNT9 (ENSG00000237172)

Protein

Protein identifiers

UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 2 — Q8NCR0 (reviewed: Q8NCR0)

Alternative names: Beta-1,3-N-acetylgalactosaminyltransferase II

All UniProt accessions (5): A0A087WY64, A0A6Q8PEZ9, A0A6Q8PG34, A0A6Q8PGQ3, Q8NCR0

UniProt curated annotations — full annotation on UniProt →

Function. Beta-1,3-N-acetylgalactosaminyltransferase that synthesizes a unique carbohydrate structure, GalNAc-beta-1-3GlcNAc, on N- and O-glycans. Has no galactose nor galactosaminyl transferase activity toward any acceptor substrate. Involved in alpha-dystroglycan (DAG1) glycosylation: acts coordinately with GTDC2/POMGnT2 to synthesize a GalNAc-beta3-GlcNAc-beta-terminus at the 4-position of protein O-mannose in the biosynthesis of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydrate structure present in alpha-dystroglycan, which is required for binding laminin G-like domain-containing extracellular proteins with high affinity.

Subcellular location. Golgi apparatus membrane. Endoplasmic reticulum.

Tissue specificity. Expressed in all tissues examined, but at highest levels in testis, adipose tissue, skeletal muscle and ovary.

Post-translational modifications. N-glycosylated.

Disease relevance. Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A11 (MDDGA11) [MIM:615181] 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 31 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NCR0-1	1	yes
Q8NCR0-2	2

RefSeq proteins (2): NP_001264084, NP_689703* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002659	Glyco_trans_31	Family

Pfam: PF01762

Enzyme classification (BRENDA):

• EC 2.4.1.313 — protein O-mannose beta-1,3-N-acetylgalactosaminyltransferase (BRENDA: 3 organisms, 12 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 1 shown:

• 3-O-(N-acetyl-beta-D-glucosaminyl-(1->4)-alpha-D-mannosyl)-L-threonyl-[protein] + UDP-N-acetyl-alpha-D-galactosamine = 3-O-[beta-D-GalNAc-(1->3)-beta-D-GlcNAc-(1->4)-alpha-D-Man]-L-Thr-[protein] + UDP + H(+) (RHEA:37667)

UniProt features (14 total): sequence variant 5, splice variant 3, topological domain 2, glycosylation site 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NCR0-F1	86.81	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.

Glycosylation sites (2): 116, 174

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8932505	DAG1 core M3 glycosylations
R-HSA-392499	Metabolism of proteins
R-HSA-5173105	O-linked glycosylation
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 291 (showing top): AACYNNNNTTCCS_UNKNOWN, CHANDRAN_METASTASIS_DN, CAGCTG_AP4_Q5, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, TERAMOTO_OPN_TARGETS_CLUSTER_5, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, DODD_NASOPHARYNGEAL_CARCINOMA_UP, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_16D_UP, TTTGCAC_MIR19A_MIR19B, GOBP_PROTEIN_O_LINKED_GLYCOSYLATION, EVI1_04, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ORGANELLE_SUBCOMPARTMENT, GOMF_ACETYLGALACTOSAMINYLTRANSFERASE_ACTIVITY

GO Biological Process (4): protein O-linked glycosylation (GO:0006493), glycoprotein biosynthetic process (GO:0009101), obsolete protein glycosylation (GO:0006486), carbohydrate derivative biosynthetic process (GO:1901137)

GO Molecular Function (6): UDP-glycosyltransferase activity (GO:0008194), acetylgalactosaminyltransferase activity (GO:0008376), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), hexosyltransferase activity (GO:0016758)

GO Cellular Component (5): Golgi membrane (GO:0000139), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
DAG1 glycosylations	1
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glycosyltransferase activity	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
glycoprotein biosynthetic process	1
macromolecule biosynthetic process	1
glycoprotein metabolic process	1
carbohydrate derivative biosynthetic process	1
biosynthetic process	1
carbohydrate derivative metabolic process	1
UDP-glycosyltransferase activity	1
hexosyltransferase activity	1
binding	1
catalytic activity	1
transferase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

654 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
B3GALNT2	POMGNT2	Q8NAT1	899
B3GALNT2	POMK	Q9H5K3	881
B3GALNT2	RXYLT1	Q9Y2B1	876
B3GALNT2	POMT1	Q9Y6A1	855
B3GALNT2	POMT2	Q9UKY4	851
B3GALNT2	FKTN	O75072	846
B3GALNT2	B4GAT1	O43505	841
B3GALNT2	POMGNT1	Q8WZA1	835
B3GALNT2	FKRP	Q9H9S5	830
B3GALNT2	GMPPB	Q9Y5P6	792
B3GALNT2	DPM2	O94777	757
B3GALNT2	DOLK	Q9UPQ8	753
B3GALNT2	DPM3	Q9P2X0	745
B3GALNT2	DPM1	O60762	743
B3GALNT2	LARGE1	O95461	722

IntAct

43 interactions, top by confidence:

A	B	Type	Score
EIF2B2	SLC27A2	psi-mi:“MI:0914”(association)	0.640
CHST8	CANX	psi-mi:“MI:0914”(association)	0.640
B3GALNT2	TMBIM1	psi-mi:“MI:0915”(physical association)	0.560
OS9	AGRN	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
PARP16	VWA8	psi-mi:“MI:0914”(association)	0.350
TAZ	MANBA	psi-mi:“MI:0914”(association)	0.350
CHST8	CLSTN1	psi-mi:“MI:0914”(association)	0.350
IDS	COCH	psi-mi:“MI:0914”(association)	0.350
YY1AP1	CEBPZ	psi-mi:“MI:0914”(association)	0.350
KLF12	NOP56	psi-mi:“MI:0914”(association)	0.350
AMIGO1	TMEM223	psi-mi:“MI:0914”(association)	0.350
OS9	GXYLT2	psi-mi:“MI:0914”(association)	0.350
NUBP2	POTEF	psi-mi:“MI:0914”(association)	0.350
TAFAZZIN	MANBA	psi-mi:“MI:0914”(association)	0.350
CD3D	CLGN	psi-mi:“MI:0914”(association)	0.350
NRG1	CHST10	psi-mi:“MI:0914”(association)	0.350
CHST8	CALU	psi-mi:“MI:0914”(association)	0.350
SFRP4	ANKRD17	psi-mi:“MI:0914”(association)	0.350
GFRA3	B3GAT3	psi-mi:“MI:0914”(association)	0.350
CFAP69	UTRN	psi-mi:“MI:0914”(association)	0.350
IFNL3	HIKESHI	psi-mi:“MI:0914”(association)	0.350
NUBP2	TK2	psi-mi:“MI:0914”(association)	0.350

BioGRID (51): B3GALNT2 (Affinity Capture-RNA), B3GALNT2 (Affinity Capture-MS), B3GALNT2 (Affinity Capture-MS), B3GALNT2 (Affinity Capture-MS), B3GALNT2 (Affinity Capture-MS), B3GALNT2 (Affinity Capture-MS), B3GALNT2 (Affinity Capture-MS), B3GALNT2 (Synthetic Lethality), B3GALNT2 (Affinity Capture-MS), B3GALNT2 (Affinity Capture-MS), B3GALNT2 (Affinity Capture-MS), B3GALNT2 (Affinity Capture-MS), B3GALNT2 (Affinity Capture-MS), B3GALNT2 (Affinity Capture-MS), B3GALNT2 (Affinity Capture-MS)

ESM2 similar proteins: A2AFS3, B2RY83, O70472, O95803, P35790, P52848, P61812, P78539, Q01134, Q02353, Q08DW9, Q09LZ8, Q0VCJ8, Q38L25, Q3UHN9, Q4R5H6, Q4R766, Q5F450, Q5H8A4, Q5RES2, Q5RKN4, Q5U4X8, Q5VU57, Q5VV63, Q5XIC4, Q5ZIN0, Q5ZMH6, Q63769, Q6A051, Q6AYT7, Q6PC62, Q6UXG2, Q86W50, Q8BG28, Q8BWB6, Q8MJJ1, Q8N2K0, Q8NCR0, Q8WWQ2, Q92545

Diamond homologs: A7XDQ9, Q6NRQ1, Q8BG28, Q8GXG6, Q8L7F9, Q8NCR0, Q8RX55, Q91Z92, Q96L58, Q9ASW1, Q9LV16, Q502B3, Q5M900, Q864U8, Q9BYG0, Q9N491

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	46
Likely pathogenic	19
Uncertain significance	285
Likely benign	271
Benign	53

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1007494	NM_152490.5(B3GALNT2):c.1368+1G>C	Pathogenic
1071482	NM_152490.5(B3GALNT2):c.133C>T (p.Gln45Ter)	Pathogenic
1074962	NM_152490.5(B3GALNT2):c.59G>A (p.Trp20Ter)	Pathogenic
1324016	NM_152490.5(B3GALNT2):c.652-1G>C	Pathogenic
1324021	NM_152490.5(B3GALNT2):c.1177C>T (p.Arg393Ter)	Pathogenic
1324031	NM_152490.5(B3GALNT2):c.903dup (p.Asn302fs)	Pathogenic
1324035	NM_152490.5(B3GALNT2):c.1020_1021dup (p.Arg341fs)	Pathogenic
132979	NM_152490.5(B3GALNT2):c.51_73dup (p.Ser25fs)	Pathogenic
1423697	NM_152490.5(B3GALNT2):c.27C>A (p.Cys9Ter)	Pathogenic
1437368	NM_152490.5(B3GALNT2):c.753del (p.Val252fs)	Pathogenic
1451522	NM_152490.5(B3GALNT2):c.1066_1067del (p.Thr355_Asp356insTer)	Pathogenic
1455909	NM_152490.5(B3GALNT2):c.1039dup (p.Thr347fs)	Pathogenic
1459605	NC_000001.10:g.(?235628933)(235629051_?)del	Pathogenic
2034759	NM_152490.5(B3GALNT2):c.1209_1257dup (p.Lys420fs)	Pathogenic
2117097	NM_152490.5(B3GALNT2):c.1337G>A (p.Trp446Ter)	Pathogenic
2427392	NC_000001.10:g.(?235616382)(235643485_?)del	Pathogenic
2760106	NM_152490.5(B3GALNT2):c.947dup (p.Tyr317fs)	Pathogenic
2773142	NM_003193.5(TBCE):c.1355_1362del (p.Tyr452fs)	Pathogenic
2796220	NM_003193.5(TBCE):c.1301_1307del (p.Lys434fs)	Pathogenic
2834401	NM_003193.5(TBCE):c.1294del (p.Glu432fs)	Pathogenic
2980363	NM_003193.5(TBCE):c.1306_1307del (p.Gln436fs)	Pathogenic
3247815	NC_000001.10:g.(?235605109)(235613675_?)del	Pathogenic
3247816	NC_000001.10:g.(?235612376)(235616407_?)del	Pathogenic
3247948	NC_000001.10:g.(?235543365)(235612077_?)del	Pathogenic
3375162	NM_152490.5(B3GALNT2):c.1315G>T (p.Glu439Ter)	Pathogenic
3381836	NM_152490.5(B3GALNT2):c.261-2A>G	Pathogenic
3612008	NM_152490.5(B3GALNT2):c.388_395del (p.Ser130fs)	Pathogenic
3622136	NM_152490.5(B3GALNT2):c.1143G>A (p.Trp381Ter)	Pathogenic
3647322	NM_003193.5(TBCE):c.1337dup (p.Thr447fs)	Pathogenic
3655627	NM_152490.5(B3GALNT2):c.253dup (p.Ser85fs)	Pathogenic

SpliceAI

2276 predictions. Top by Δscore:

Variant	Effect	Δscore
1:235448441:G:GG	donor_gain	1.0000
1:235455553:A:C	donor_gain	1.0000
1:235455553:ACTT:A	donor_loss	1.0000
1:235455554:CTTA:C	donor_loss	1.0000
1:235455557:A:AC	donor_gain	1.0000
1:235455557:ACTTT:A	donor_gain	1.0000
1:235455558:C:CA	donor_gain	1.0000
1:235455558:CT:C	donor_gain	1.0000
1:235455558:CTTT:C	donor_gain	1.0000
1:235455558:CTTTC:C	donor_gain	1.0000
1:235455561:T:A	donor_gain	1.0000
1:235455680:CAGTC:C	acceptor_gain	1.0000
1:235455681:AGTC:A	acceptor_gain	1.0000
1:235455681:AGTCC:A	acceptor_loss	1.0000
1:235455682:GTC:G	acceptor_gain	1.0000
1:235455683:TC:T	acceptor_gain	1.0000
1:235455683:TCCT:T	acceptor_loss	1.0000
1:235455684:CCTGT:C	acceptor_gain	1.0000
1:235455685:C:CC	acceptor_gain	1.0000
1:235455685:CTGTT:C	acceptor_loss	1.0000
1:235455686:T:A	acceptor_loss	1.0000
1:235455688:T:TC	acceptor_gain	1.0000
1:235455692:C:CT	acceptor_gain	1.0000
1:235455694:C:CT	acceptor_gain	1.0000
1:235455695:A:T	acceptor_gain	1.0000
1:235458690:T:A	donor_gain	1.0000
1:235470964:T:C	acceptor_gain	1.0000
1:235470964:T:TC	acceptor_gain	1.0000
1:235480027:C:CT	donor_gain	1.0000
1:235480028:T:TT	donor_gain	1.0000

AlphaMissense

3272 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:235454237:A:C	F410L	1.000
1:235454237:A:T	F410L	1.000
1:235454239:A:G	F410L	1.000
1:235454276:C:A	W397C	1.000
1:235454276:C:G	W397C	1.000
1:235454278:A:G	W397R	1.000
1:235454278:A:T	W397R	1.000
1:235453122:A:G	W446R	0.999
1:235453122:A:T	W446R	0.999
1:235453128:C:G	G444R	0.999
1:235453132:G:C	S442R	0.999
1:235453132:G:T	S442R	0.999
1:235453134:T:G	S442R	0.999
1:235453138:A:C	D440E	0.999
1:235453138:A:T	D440E	0.999
1:235453139:T:A	D440V	0.999
1:235453139:T:C	D440G	0.999
1:235453139:T:G	D440A	0.999
1:235453140:C:G	D440H	0.999
1:235453142:T:A	E439V	0.999
1:235454238:A:C	F410C	0.999
1:235454248:A:C	Y407D	0.999
1:235454248:A:G	Y407H	0.999
1:235454295:A:T	V391D	0.999
1:235455648:C:A	K354N	0.999
1:235455648:C:G	K354N	0.999
1:235450329:C:A	W460C	0.998
1:235450329:C:G	W460C	0.998
1:235450331:A:G	W460R	0.998
1:235450331:A:T	W460R	0.998

dbSNP variants (sampled 300 via entrez): RS1000009882 (1:235474853 C>T), RS1000021061 (1:235459855 A>G), RS1000058314 (1:235504244 G>A,C), RS1000113267 (1:235480772 G>A), RS1000135798 (1:235468577 C>T), RS1000191813 (1:235468348 G>C), RS1000252706 (1:235498078 G>A), RS1000347279 (1:235503493 T>C), RS1000385743 (1:235486322 C>T), RS1000415067 (1:235462442 A>G), RS1000451544 (1:235452460 T>C), RS1000466451 (1:235474562 G>A), RS1000495812 (1:235440128 A>G,T), RS1000501373 (1:235449699 A>G), RS1000557816 (1:235499763 G>A)

Disease associations

OMIM: gene MIM:610194 | disease phenotypes: MIM:214500, MIM:615181, MIM:617207, MIM:241410, MIM:244460

GenCC curated gene-disease

Disease	Classification	Inheritance
muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11	Definitive	Autosomal recessive
muscle-eye-brain disease	Supportive	Autosomal recessive
autosomal recessive non-syndromic intellectual disability	Supportive	Autosomal recessive
muscular dystrophy-dystroglycanopathy, type A	Supportive	Autosomal recessive
intellectual disability	Limited	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 a, 11	Definitive	AR

Mondo (11): Chediak-Higashi syndrome (MONDO:0008963), muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11 (MONDO:0014071), encephalopathy, progressive, with amyotrophy and optic atrophy (MONDO:0014968), hypoparathyroidism-retardation-dysmorphism syndrome (MONDO:0009426), autosomal recessive Kenny-Caffey syndrome (MONDO:0009486), microcephaly (MONDO:0001149), muscular dystrophy-dystroglycanopathy (MONDO:0018276), intellectual disability (MONDO:0001071), muscle-eye-brain disease (MONDO:0018939), autosomal recessive non-syndromic intellectual disability (MONDO:0019502), muscular dystrophy-dystroglycanopathy, type A (MONDO:0000171)

Orphanet (7): Chédiak-Higashi syndrome (Orphanet:167), Muscle-eye-brain disease (Orphanet:588), Walker-Warburg syndrome (Orphanet:899), Sanjad-Sakati syndrome (Orphanet:2323), Kenny-Caffey syndrome (Orphanet:2333), Autosomal recessive Kenny-Caffey syndrome (Orphanet:93324), Congenital muscular dystrophy due to dystroglycanopathy (Orphanet:370953)

HPO phenotypes

80 total (30 of 80 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
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:0000486	Strabismus
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000528	Anophthalmia
HP:0000541	Retinal detachment
HP:0000545	Myopia
HP:0000556	Retinal dystrophy
HP:0000568	Microphthalmia
HP:0000587	Abnormal optic nerve morphology
HP:0000609	Optic nerve hypoplasia
HP:0000612	Iris coloboma
HP:0000618	Blindness
HP:0000648	Optic atrophy
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004904_144	Body mass index	2.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D002609	Chediak-Higashi Syndrome	C11.270.040.772; C15.378.553.774.257; C16.320.798.375; C20.673.774.257; C20.673.795.375
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
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
C537157	Hypoparathyroidism-retardation-dysmorphism syndrome (supp.)
C537021	Kenny-Caffey syndrome, Type 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	increases abundance, increases expression	2
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Cadmium	increases abundance, increases expression	1
Cyclophosphamide	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	increases expression, affects cotreatment	1
Indomethacin	affects cotreatment, decreases expression	1
Plant Extracts	increases expression, affects cotreatment	1
Theophylline	affects cotreatment, increases expression	1
Thimerosal	increases expression	1
Tretinoin	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Antirheumatic Agents	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SE43	HAP1 B3GALNT2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00176865	PHASE2	COMPLETED	Stem Cell Transplant for Immunologic or Histiocytic Disorders
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT02789332	PHASE2	COMPLETED	Assessing the Efficacy of Paclitaxel and Olaparib in Comparison to Paclitaxel / Carboplatin Followed by Epirubicin/Cyclophosphamide as Neoadjuvant Chemotherapy in Patients With HER2-negative Early Breast Cancer and Homologous Recombination Deficiency
NCT03740893	PHASE2	RECRUITING	PHOENIX DDR/Anti-PD-L1 Trial: A Pre-surgical Window of Opportunity and Post-surgical Adjuvant Biomarker Study of DNA Damage Response Inhibition With or Without Anti-PD-L1 Immunotherapy in Patients With Neoadjuvant Treatment Resistant Residual Triple Negative Breast Cancer
NCT04895046	PHASE2	WITHDRAWN	Maintenance Niraparib and Dostarlimab in Advanced Cholangiocarcinoma
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01917708	PHASE1	COMPLETED	Bone Marrow Transplant With Abatacept for Non-Malignant Diseases
NCT03415659	PHASE1	UNKNOWN	Phase I Clinical Study of HWH340 Tablet in Patients With Advanced Solid Tumors
NCT07156253	PHASE1	RECRUITING	Study of SYN818 With Olaparib for the Treatment of Locally Advanced or Metastatic Solid Tumors
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population