B3GNT8

Summary

B3GNT8 (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 8, HGNC:24139) is a protein-coding gene on chromosome 19q13.2, encoding N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 8 (Q7Z7M8). Beta-1,3-N-acetylglucosaminyltransferase that functions in the elongation of specific branch structures of multiantennary N-glycans.

Enables protein N-acetylglucosaminyltransferase activity. Involved in poly-N-acetyllactosamine biosynthetic process. Located in extracellular exosome.

Source: NCBI Gene 374907 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 102 total — 1 pathogenic
• MANE Select transcript: NM_001385648

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24139
Approved symbol	B3GNT8
Name	UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 8
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	BGALT15, beta3Gn-T8
Ensembl gene	ENSG00000177191
Ensembl biotype	protein_coding
OMIM	615357
Entrez	374907

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000321702, ENST00000601379, ENST00000601616, ENST00000691102

RefSeq mRNA: 2 — MANE Select: NM_001385648 NM_001385648, NM_198540

CCDS: CCDS12582

Canonical transcript exons

ENST00000691102 — 2 exons

Exon	Start	End
ENSE00001242804	41425359	41426810
ENSE00003934322	41427284	41427374

Expression profiles

Bgee: expression breadth ubiquitous, 170 present calls, max score 96.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.4211 / max 103.9666, expressed in 1053 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181060	2.2841	860
181059	0.6767	290
181061	0.3723	145
181062	0.0880	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	96.56	gold quality
mucosa of transverse colon	UBERON:0004991	91.03	gold quality
esophagus mucosa	UBERON:0002469	90.25	gold quality
blood	UBERON:0000178	89.32	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.80	gold quality
apex of heart	UBERON:0002098	84.35	gold quality
duodenum	UBERON:0002114	83.40	gold quality
leukocyte	CL:0000738	83.31	gold quality
monocyte	CL:0000576	83.20	gold quality
ileal mucosa	UBERON:0000331	82.38	gold quality
transverse colon	UBERON:0001157	81.54	gold quality
esophagus	UBERON:0001043	81.29	gold quality
upper lobe of left lung	UBERON:0008952	80.59	gold quality
granulocyte	CL:0000094	80.24	gold quality
small intestine Peyer’s patch	UBERON:0003454	80.20	gold quality
kidney epithelium	UBERON:0004819	80.02	gold quality
small intestine	UBERON:0002108	79.80	gold quality
upper lobe of lung	UBERON:0008948	79.74	gold quality
vagina	UBERON:0000996	79.28	gold quality
bone marrow	UBERON:0002371	78.42	gold quality
rectum	UBERON:0001052	78.37	gold quality
right lung	UBERON:0002167	77.64	gold quality
intestine	UBERON:0000160	77.05	gold quality
heart left ventricle	UBERON:0002084	76.78	gold quality
colon	UBERON:0001155	76.76	gold quality
large intestine	UBERON:0000059	76.69	gold quality
cardiac ventricle	UBERON:0002082	76.66	gold quality
left ventricle myocardium	UBERON:0006566	76.44	gold quality
esophagus squamous epithelium	UBERON:0006920	76.37	gold quality
jejunal mucosa	UBERON:0000399	76.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.39
E-CURD-112	no	2.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting B3GNT8, 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-607	99.97	73.62	5593
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-3661	97.83	67.30	705
HSA-MIR-631	97.05	66.93	602
HSA-MIR-6806-5P	96.37	68.74	587

Literature-anchored findings (GeneRIF, showing 13)

• highly expressed in lung, throat and ileum, whereas the expression level was low in tongue, breast, uteri, testis. In addition, it was also demonstrated that B3GALT7 is differentially transcribed in human tumor cell lines. (PMID:15486459)
• The cloning of a novel beta1,3-N-acetylglucosaminyltransferase that is upregulated in a human colon cancer cell line. (PMID:15620693)
• up-regulation of beta3Gn-T8 in differentiated cells increases poly-N-acetyllactosamine chains by activating intrinsic beta3Gn-T2. (PMID:18826941)
• These results reveal a new mechanism by which beta3Gn-T8 can regulate MMP-2 and TIMP-2. (PMID:20963502)
• The down-regulation of beta3Gn-T8 caused significant inhibition of tumor cell growth in vitro. (PMID:21468598)
• High beta3Gn-T8 expression is associated with laryngeal carcinoma. (PMID:22901175)
• we suggest that beta3GnT8 plays a key role in the metastasis of colorectal cancer cells by altering the beta1,6-branched polylactosamine sugars of CD147. (PMID:24573103)
• The results demonstrated a critical role of beta3GnT8 in the metastatic potential of glioma cells, indicating that manipulating beta3GnT8 expression may have therapeutic potential for the treatment of malignant glioma. (PMID:24715095)
• Study shows that beta3GnT8 is involved in the regulation of CD147 N-glycosylation and further influences MMP-2 expression in tumor cells suggesting that it may play an important role in the CD147 signaling as an upstream modulator of MMP-2 in tumor cells. (PMID:24970053)
• In conclusion, the alteration of b3GnT8 in colorectal cancer cells correlates with tumor sensitivity to the chemotherapeutic drug and has significant implication for the development of new treatment strategies. (PMID:25269761)
• Cjun plays a significant role in regulating the expression of beta3GnT8 in the SGC7901 cell line. (PMID:27459970)
• These results revealed that b3GnT8 may play a key role in the development of oxaliplatin resistance in colon cancer cells possibly through the alteration of the glycosylation of integrin beta1. These findings may be valuable for overcoming drug resistance in colon cancer (PMID:29393491)
• Nglycosylation and receptor tyrosine kinase signaling affect claudin3 levels in colorectal cancer cells. (PMID:32945502)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	b3gnt2l	ENSDARG00000068219
mus_musculus	B3gnt8	ENSMUSG00000059479
rattus_norvegicus	B3gnt8	ENSRNOG00000068024
drosophila_melanogaster	brn	FBGN0000221
caenorhabditis_elegans		WBGENE00000270
caenorhabditis_elegans		WBGENE00007096
caenorhabditis_elegans		WBGENE00017653

Paralogs (15): B3GNT7 (ENSG00000156966), B3GALT2 (ENSG00000162630), B3GALNT2 (ENSG00000162885), B3GALNT1 (ENSG00000169255), B3GNT2 (ENSG00000170340), B3GALT1 (ENSG00000172318), B3GALT6 (ENSG00000176022), B3GNT4 (ENSG00000176383), B3GNT5 (ENSG00000176597), B3GNT3 (ENSG00000179913), B3GALT5 (ENSG00000183778), B3GNT6 (ENSG00000198488), B3GALT9 (ENSG00000214654), B3GALT4 (ENSG00000235863), B3GNT9 (ENSG00000237172)

Protein

Protein identifiers

N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 8 — Q7Z7M8 (reviewed: Q7Z7M8)

Alternative names: UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 8

All UniProt accessions (1): Q7Z7M8

UniProt curated annotations — full annotation on UniProt →

Function. Beta-1,3-N-acetylglucosaminyltransferase that functions in the elongation of specific branch structures of multiantennary N-glycans. Has strong activity towards tetraantennary N-glycans and 2,6 triantennary glycans.

Subunit / interactions. Interacts with B3GNT2; this interaction greatly increases B3GNT2 catalytic activity, independently of B3GNT8 enzymatic activity.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Highly expressed in small intestine, pancreas, spleen, bone marrow, lung, throat, and ileum, and weakly in fetal brain, cerebellum, heart, liver, tongue, breast, uteri, and testis. Not detected in colon. Differentially expressed in human tumor cell lines.

Induction. Up-regulated in colon cancer.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the glycosyltransferase 31 family.

RefSeq proteins (2): NP_001372577, NP_940942 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002659	Glyco_trans_31	Family

Pfam: PF01762

Catalyzed reactions (Rhea), 1 shown:

• a beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl derivative + UDP-N-acetyl-alpha-D-glucosamine = an N-acetyl-beta-D-glucosaminyl-(1->3)-beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl derivative + UDP + H(+) (RHEA:14389)

UniProt features (9 total): topological domain 2, chain 1, transmembrane region 1, region of interest 1, compositionally biased region 1, glycosylation site 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z7M8-F1	88.18	0.69

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 (1): 57

Mutagenesis-validated functional residues (1):

Position	Phenotype
246	loss of enzymatic activity, no loss of b3gnt2-binding and activation.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-913709	O-linked glycosylation of mucins
R-HSA-392499	Metabolism of proteins
R-HSA-5173105	O-linked glycosylation
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 123 (showing top): GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_AMINOGLYCAN_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_AMINOGLYCAN_METABOLIC_PROCESS, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, BOYLAN_MULTIPLE_MYELOMA_C_CLUSTER_UP, GOMF_HEXOSYLTRANSFERASE_ACTIVITY, GOMF_GLYCOSYLTRANSFERASE_ACTIVITY, GOMF_UDP_GLYCOSYLTRANSFERASE_ACTIVITY, GOMF_ACETYLGLUCOSAMINYLTRANSFERASE_ACTIVITY, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, MEISSNER_BRAIN_HCP_WITH_H3K4ME2, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, MIKKELSEN_MEF_HCP_WITH_H3_UNMETHYLATED, LI_INDUCED_T_TO_NATURAL_KILLER_UP

GO Biological Process (5): protein O-linked glycosylation (GO:0006493), poly-N-acetyllactosamine biosynthetic process (GO:0030311), obsolete protein glycosylation (GO:0006486), protein O-linked glycosylation via N-acetylgalactosamine (GO:0016266), carbohydrate derivative biosynthetic process (GO:1901137)

GO Molecular Function (7): N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase activity (GO:0008532), protein N-acetylglucosaminyltransferase activity (GO:0016262), protein binding (GO:0005515), N-acetyl-beta-D-glucosaminide beta-(1,3)-galactosyltransferase activity (GO:0008499), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), hexosyltransferase activity (GO:0016758)

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

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
O-linked glycosylation	1
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
acetylglucosaminyltransferase activity	2
glycoprotein biosynthetic process	1
aminoglycan biosynthetic process	1
poly-N-acetyllactosamine metabolic process	1
protein O-linked glycosylation	1
biosynthetic process	1
carbohydrate derivative metabolic process	1
catalytic activity, acting on a protein	1
binding	1
UDP-galactosyltransferase activity	1
beta-1,3-galactosyltransferase activity	1
catalytic activity	1
transferase activity	1
glycosyltransferase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
extracellular vesicle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

384 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
B3GNT8	C1GALT1	Q9NS00	419
B3GNT8	MGAT5	Q09328	410
B3GNT8	GALNT16	Q8N428	404
B3GNT8	ST8SIA3	O43173	389
B3GNT8	B4GAT1	O43505	385
B3GNT8	ST6GAL1	P15907	384
B3GNT8	ST6GALNAC6	Q969X2	376
B3GNT8	ST8SIA5	O15466	367
B3GNT8	FUT5	Q11128	358
B3GNT8	B4GALNT3	Q6L9W6	349
B3GNT8	MGAT5B	Q3V5L5	349
B3GNT8	SPPL3	Q8TCT6	332
B3GNT8	ST6GALNAC3	Q8NDV1	331
B3GNT8	ST6GALNAC2	Q9UJ37	328
B3GNT8	B4GALT7	Q9UBV7	326

IntAct

5 interactions, top by confidence:

A	B	Type	Score
B3GNT2	B3GNT8	psi-mi:“MI:0915”(physical association)	0.660
B3GNT2	B3GNT8	psi-mi:“MI:0559”(glycosylation reaction)	0.660
B3GNT2	B3GNT8	psi-mi:“MI:0559”(glycosylation reaction)	0.440
B3GNT8	GSDME	psi-mi:“MI:0914”(association)	0.350

BioGRID (21): RHBDD1 (Affinity Capture-MS), ATRIP (Affinity Capture-MS), LNPEP (Affinity Capture-MS), XPO7 (Affinity Capture-MS), ANKRD13A (Affinity Capture-MS), INTS2 (Affinity Capture-MS), TNPO3 (Affinity Capture-MS), MMS22L (Affinity Capture-MS), INTS12 (Affinity Capture-MS), HEATR3 (Affinity Capture-MS), DFNA5 (Affinity Capture-MS), PDS5B (Affinity Capture-MS), PDS5A (Affinity Capture-MS), GLMN (Affinity Capture-MS), ATR (Affinity Capture-MS)

ESM2 similar proteins: A7MBM2, D3KCC4, E9PY61, L5KLU7, O95382, P04087, P32958, Q03395, Q08E36, Q0V8J4, Q14296, Q1KZG0, Q49LS1, Q5GH72, Q642B3, Q643R3, Q66K66, Q674R7, Q6EBV9, Q6F5E8, Q6MG64, Q6NUI2, Q6P5W5, Q6PRD1, Q6ZMH5, Q7TNJ2, Q7Z7M1, Q7Z7M8, Q86WK7, Q8BG75, Q8BP97, Q8CG70, Q8CIP5, Q8IUH8, Q8IVL6, Q8IZF5, Q8IZY2, Q8K1S7, Q8N2G8, Q8NCW0

Diamond homologs: O43825, O54904, O54905, O75752, O88178, Q1RLK6, Q3USF0, Q5HZL5, Q5R5Y3, Q5RAL7, Q5XJP0, Q66H69, Q6AY39, Q6DE15, Q6P3P5, Q6ZMB0, Q793U7, Q7JK24, Q7JK25, Q7JK26, Q7T3S5, Q7Z7M8, Q864U6, Q864U8, Q8BGY6, Q8K0J2, Q8NFL0, Q8R3I9, Q920V1, Q99NB2, Q9BYG0, Q9C0J1, Q9JI67, Q9MYM7, Q9N293, Q9N294, Q9N295, Q9NY97, Q9Y2C3, Q9Y5Z6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	78
Likely benign	7
Benign	12

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3248403	NC_000019.9:g.(?41916522)(41932683_?)del	Pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000365979 (19:41427387 GGCCCAGCCCT>G), RS1001105930 (19:41428635 A>G), RS1001772971 (19:41428245 G>T), RS1002080193 (19:41429744 CTT>C), RS1002298479 (19:41429959 A>C), RS1002472833 (19:41424970 C>T), RS1003085384 (19:41427066 T>C), RS1003147227 (19:41426929 C>A,T), RS1003709277 (19:41425301 G>A), RS1003811937 (19:41430726 G>A), RS1004082527 (19:41426023 G>A), RS1005573987 (19:41425822 C>T), RS1005860127 (19:41427004 A>C), RS1006624418 (19:41427101 C>G), RS1007139932 (19:41429122 A>C)

Disease associations

OMIM: gene MIM:615357 | disease phenotypes: MIM:248600

GenCC curated gene-disease

Mondo (1): maple syrup urine disease (MONDO:0009563)

Orphanet (1): Maple syrup urine disease (Orphanet:511)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008375	Maple Syrup Urine Disease	C10.228.140.163.100.520; C16.320.565.100.608; C16.320.565.189.520; C18.452.132.100.520; C18.452.648.100.608; C18.452.648.189.520

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, decreases expression	4
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Estradiol	affects cotreatment, increases expression	1
Lipopolysaccharides	increases expression, affects cotreatment, decreases expression, affects response to substance	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01529060	PHASE2/PHASE3	COMPLETED	Phenylbutyrate Therapy for Maple Syrup Urine Disease
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT04248062	Not specified	COMPLETED	Patient and Observer Reported Outcome Measurements in Inborn Errors of Metabolism
NCT04602325	Not specified	RECRUITING	Systemic Biomarkers of Brain Injury From Hyperammonemia
NCT04828863	Not specified	COMPLETED	Neurocognitive Outcomes and Quality of Life in Adults With Maple Syrup Urine Disease (MSUD)
NCT05051657	Not specified	COMPLETED	Evaluation of the Express Plus Range
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT05910151	Not specified	UNKNOWN	Selective Screening of Children for Hereditary Metabolic Diseases by Tandem Mass Spectrometry in Kazakhstan
NCT06298292	Not specified	NOT_YET_RECRUITING	Acceptability/Tolerance of Protein Substitutes in Tablet Form for the Dietary Management of Rare Aminoacidopathies
NCT06581991	Not specified	NOT_YET_RECRUITING	Liquid Valine and Isoleucine in Maple Syrup Urine Disease
NCT06664840	Not specified	NOT_YET_RECRUITING	MyRareDiet A Novel Diet Tracking Tool