B3GNT6

Summary

B3GNT6 (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 6, HGNC:24141) is a protein-coding gene on chromosome 11q13.5, encoding Acetylgalactosaminyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase (Q6ZMB0). Beta-1,3-N-acetylglucosaminyltransferase that synthesizes the core 3 structure of the O-glycan, an important precursor in the biosynthesis of mucin-type glycoproteins.

The protein encoded by this gene is a beta-1,3-N-acetylglucosaminyltransferase that adds an N-acetylglucosamine moiety to N-acetylgalactosamine-modified serine or threonine. The encoded enzyme is responsible for creating the core 3 structure of O-glycans, which are important components of mucin-type glycoproteins.

Source: NCBI Gene 192134 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 62 total — 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_138706

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24141
Approved symbol	B3GNT6
Name	UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 6
Location	11q13.5
Locus type	gene with protein product
Status	Approved
Aliases	B3Gn-T6
Ensembl gene	ENSG00000198488
Ensembl biotype	protein_coding
OMIM	615315
Entrez	192134

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000528622, ENST00000622824, ENST00000854987, ENST00000854988

RefSeq mRNA: 1 — MANE Select: NM_138706 NM_138706

CCDS: CCDS53681

Canonical transcript exons

ENST00000622824 — 2 exons

Exon	Start	End
ENSE00002183823	77034398	77034478
ENSE00003721473	77039552	77041973

Expression profiles

Bgee: expression breadth broad, 76 present calls, max score 82.25.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1044 / max 26.8905, expressed in 23 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115967	0.0814	21
115968	0.0230	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
rectum	UBERON:0001052	82.25	gold quality
mucosa of sigmoid colon	UBERON:0004993	82.22	gold quality
mucosa of transverse colon	UBERON:0004991	82.17	gold quality
colonic mucosa	UBERON:0000317	81.97	gold quality
lower esophagus mucosa	UBERON:0035834	81.13	gold quality
esophagus squamous epithelium	UBERON:0006920	72.70	silver quality
transverse colon	UBERON:0001157	72.12	gold quality
buccal mucosa cell	CL:0002336	70.97	gold quality
tendon of biceps brachii	UBERON:0008188	69.14	gold quality
parotid gland	UBERON:0001831	68.47	gold quality
palpebral conjunctiva	UBERON:0001812	67.19	gold quality
duodenum	UBERON:0002114	67.14	gold quality
jejunal mucosa	UBERON:0000399	66.80	gold quality
heart right ventricle	UBERON:0002080	65.91	gold quality
vermiform appendix	UBERON:0001154	65.73	gold quality
superficial temporal artery	UBERON:0001614	65.23	gold quality
small intestine Peyer’s patch	UBERON:0003454	64.89	gold quality
superior surface of tongue	UBERON:0007371	64.84	gold quality
gingival epithelium	UBERON:0001949	64.82	gold quality
small intestine	UBERON:0002108	64.60	gold quality
caecum	UBERON:0001153	64.48	gold quality
esophagus mucosa	UBERON:0002469	64.11	gold quality
secondary oocyte	CL:0000655	63.36	silver quality
trachea	UBERON:0003126	63.09	gold quality
sperm	CL:0000019	62.77	gold quality
stomach	UBERON:0000945	62.57	gold quality
medial globus pallidus	UBERON:0002477	62.49	gold quality
body of stomach	UBERON:0001161	62.42	gold quality
gingiva	UBERON:0001828	62.21	gold quality
oral cavity	UBERON:0000167	62.20	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting B3GNT6, 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-574-5P	100.00	66.01	989
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-4709-3P	98.88	68.04	1594
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-92A-1-5P	98.28	64.51	631
HSA-MIR-6819-5P	97.96	66.59	1071
HSA-MIR-4708-5P	97.77	67.82	831
HSA-MIR-6737-5P	97.75	66.54	1044
HSA-MIR-6812-5P	97.56	65.39	1059
HSA-MIR-6500-3P	97.42	67.20	867
HSA-MIR-505-5P	97.01	65.54	778
HSA-MIR-6806-5P	96.37	68.74	587
HSA-MIR-764	94.16	64.85	656
HSA-MIR-4737	89.94	65.03	82
HSA-MIR-6771-5P	86.50	65.30	81

Literature-anchored findings (GeneRIF, showing 4)

• expression was markedly down-regulated in gastric and colorectal carcinomas (PMID:15755813)
• alpha2beta1 integrin acquired core3 O-glycans in cells expressing core3 synthase with decreased maturation of beta1 integrin, leading to decreased levels of the alpha2beta1 integrin complex (PMID:19395705)
• Clinicopathological significance of core 3 O-glycan synthetic enzyme, beta1,3-N-acetylglucosaminyltransferase 6 in pancreatic ductal adenocarcinoma. (PMID:33253272)
• Downregulation of B3GNT6 is a predictor of poor outcomes in patients with colorectal cancer. (PMID:35387659)

Cross-species orthologs

21 orthologs

Organism	Symbol	Gene ID
danio_rerio	b3gnt7l	ENSDARG00000053133
danio_rerio	b3galt10.1	ENSDARG00000061432
danio_rerio	b3galt10.2	ENSDARG00000061496
danio_rerio	zgc:194679	ENSDARG00000073723
danio_rerio		ENSDARG00000088591
danio_rerio	si:dkey-175m17.6	ENSDARG00000088601
danio_rerio	si:dkey-160o24.3	ENSDARG00000089094
danio_rerio	b3galt8	ENSDARG00000097795
		ENSDARG00000104926
danio_rerio		ENSDARG00000109569
danio_rerio	b3galt11	ENSDARG00000114948
mus_musculus	B3gnt6	ENSMUSG00000074004
rattus_norvegicus	B3gnt6	ENSRNOG00000014471
drosophila_melanogaster	brn	FBGN0000221
drosophila_melanogaster	CG30036	FBGN0050036
drosophila_melanogaster	CG30037	FBGN0050037
drosophila_melanogaster	GalT1	FBGN0053145
caenorhabditis_elegans		WBGENE00000270
caenorhabditis_elegans		WBGENE00007096
caenorhabditis_elegans		WBGENE00017653
caenorhabditis_elegans		WBGENE00044630

Paralogs (15): B3GNT7 (ENSG00000156966), B3GALT2 (ENSG00000162630), B3GALNT2 (ENSG00000162885), B3GALNT1 (ENSG00000169255), B3GNT2 (ENSG00000170340), B3GALT1 (ENSG00000172318), B3GALT6 (ENSG00000176022), B3GNT4 (ENSG00000176383), B3GNT5 (ENSG00000176597), B3GNT8 (ENSG00000177191), B3GNT3 (ENSG00000179913), B3GALT5 (ENSG00000183778), B3GALT9 (ENSG00000214654), B3GALT4 (ENSG00000235863), B3GNT9 (ENSG00000237172)

Protein

Protein identifiers

Acetylgalactosaminyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase — Q6ZMB0 (reviewed: Q6ZMB0)

Alternative names: Core 3 synthase, UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 6

All UniProt accessions (3): A8K9Q8, E9PJ79, Q6ZMB0

UniProt curated annotations — full annotation on UniProt →

Function. Beta-1,3-N-acetylglucosaminyltransferase that synthesizes the core 3 structure of the O-glycan, an important precursor in the biosynthesis of mucin-type glycoproteins. Plays an important role in the synthesis of mucin-type O-glycans in digestive organs.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Present in stomach and colon (at protein level). Restricted in the stomach, colon and small intestine, where core 3 structure is present.

Induction. Down-regulated in gastric and colorectal carcinomas, suggesting that it may be used as a marker for distinguishing between benign adenomas and premalignant lesions (at protein level).

Pathway. Protein modification; protein glycosylation.

Miscellaneous. Injection into nude mice significantly suppress lung metastasis, indicating that the core structures of O-glycans are profoundly involved in the metastatic capacity of cancer cells.

Similarity. Belongs to the glycosyltransferase 31 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6ZMB0-1	1	yes
Q6ZMB0-2	2
Q6ZMB0-3	3

RefSeq proteins (1): NP_619651* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002659	Glyco_trans_31	Family

Pfam: PF01762

Enzyme classification (BRENDA):

• EC 2.4.1.147 — acetylgalactosaminyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase (BRENDA: 8 organisms, 36 substrates, 11 inhibitors, 3 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
N-ACETYL-ALPHA-D-GALACTOSAMINYL-OVINE SUBMAXILLA	3.2	1
N-ACETYL-D-GALACTOSAMINYL-ALPHA-BENZYL	2	1
N-ACETYL-D-GALACTOSAMINYL-ALPHA-PHENYL	5	1

Catalyzed reactions (Rhea), 2 shown:

• a 3-O-[N-acetyl-alpha-D-galactosaminyl]-L-threonyl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = a 3-O-[N-acetyl-beta-D-glucosaminyl-(1->3)-N-acetyl-alpha-D-galactosaminyl]-L-threonyl-[protein] + UDP + H(+) (RHEA:46880)
• a 3-O-[N-acetyl-alpha-D-galactosaminyl]-L-seryl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = 3-O-[N-acetyl-beta-D-glucosaminyl-(1->3)-N-acetyl-alpha-D-galactosaminyl]-L-seryl-[protein] + UDP + H(+) (RHEA:46884)

UniProt features (13 total): splice variant 3, glycosylation site 3, topological domain 2, sequence conflict 2, chain 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZMB0-F1	87.19	0.75

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 (3): 73, 77, 196

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: 62 (showing top): chr11q13, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_AMINOGLYCAN_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_AMINOGLYCAN_METABOLIC_PROCESS, NIKOLSKY_BREAST_CANCER_11Q12_Q14_AMPLICON, YYCATTCAWW_UNKNOWN, GOBP_PROTEIN_O_LINKED_GLYCOSYLATION_VIA_N_ACETYL_GALACTOSAMINE, GOBP_PROTEIN_O_LINKED_GLYCOSYLATION, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS, CTGAGCC_MIR24, GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_UP, GOMF_HEXOSYLTRANSFERASE_ACTIVITY, GOMF_BETA_1_3_GALACTOSYLTRANSFERASE_ACTIVITY, GOMF_GLYCOSYLTRANSFERASE_ACTIVITY

GO Biological Process (6): protein O-linked glycosylation (GO:0006493), glycoprotein biosynthetic process (GO:0009101), protein O-linked glycosylation via N-acetylgalactosamine (GO:0016266), poly-N-acetyllactosamine biosynthetic process (GO:0030311), obsolete protein glycosylation (GO:0006486), obsolete core 3 and core 4 O-glycan biosynthetic process (GO:0016269)

GO Molecular Function (8): UDP-glycosyltransferase activity (GO:0008194), galactosyltransferase activity (GO:0008378), N-acetyl-beta-D-glucosaminide beta-(1,3)-galactosyltransferase activity (GO:0008499), beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase activity (GO:0047223), acetylgalactosaminyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase activity (GO:0047224), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), hexosyltransferase activity (GO:0016758)

GO Cellular Component (3): Golgi membrane (GO:0000139), membrane (GO:0016020), Golgi apparatus (GO:0005794)

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

Protein interactions and networks

STRING

300 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
B3GNT6	C1GALT1	Q9NS00	739
B3GNT6	C1GALT1C1	Q96EU7	711
B3GNT6	GCNT1	Q02742	693
B3GNT6	GCNT3	O95395	689
B3GNT6	GCNT4	Q9P109	607
B3GNT6	ST6GALNAC1	Q9NSC7	596
B3GNT6	ST3GAL1	Q11201	570
B3GNT6	EEF1A2	P54266	521
B3GNT6	CHST4	Q8NCG5	479
B3GNT6	GALNT6	Q8NCL4	433
B3GNT6	ST6GALNAC2	Q9UJ37	432
B3GNT6	B4GALT4	O60513	420
B3GNT6	GALNT2	Q10471	403
B3GNT6	C1GALT1C1L	P0DN25	403
B3GNT6	MUC1	P13931	398

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A7MB73, G3MZR2, O00587, O09008, O19058, P17405, P21217, P22083, P51993, P56433, P56434, Q05923, Q0VD19, Q10979, Q11126, Q11127, Q11128, Q11130, Q11131, Q17QZ8, Q32NY4, Q5GFD5, Q5T4B2, Q62994, Q659K9, Q6IQX7, Q6UX72, Q6ZMB0, Q712G6, Q8HYJ3, Q8HYJ4, Q8HYJ5, Q8HYJ6, Q8HYJ7, Q8HZR3, Q8IZ52, Q8N3Y3, Q8NET6, Q8NI29, Q8VD52

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	61
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
208399	NM_138706.5(B3GNT6):c.552C>G (p.Asp184Glu)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2468 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:77039948:C:A	R133S	0.996
11:77039971:G:C	W140C	0.996
11:77039971:G:T	W140C	0.996
11:77040151:G:C	K200N	0.996
11:77040151:G:T	K200N	0.996
11:77040014:T:C	F155L	0.995
11:77040015:T:C	F155S	0.995
11:77040015:T:G	F155C	0.995
11:77040016:T:A	F155L	0.995
11:77040016:T:G	F155L	0.995
11:77040477:A:T	D309V	0.995
11:77040478:C:A	D309E	0.995
11:77040478:C:G	D309E	0.995
11:77039969:T:A	W140R	0.994
11:77039969:T:C	W140R	0.994
11:77040119:T:C	F190L	0.994
11:77040121:C:A	F190L	0.994
11:77040121:C:G	F190L	0.994
11:77040216:A:T	D222V	0.994
11:77040222:A:T	D224V	0.994
11:77040477:A:G	D309G	0.994
11:77040391:C:G	C280W	0.993
11:77040652:G:C	W367C	0.993
11:77040652:G:T	W367C	0.993
11:77039923:G:C	K124N	0.992
11:77039923:G:T	K124N	0.992
11:77040474:A:T	D308V	0.992
11:77040476:G:C	D309H	0.992
11:77040617:C:G	H356D	0.992
11:77040344:T:C	F265L	0.991

dbSNP variants (sampled 300 via entrez): RS1000965618 (11:77040762 A>G), RS1000981132 (11:77035139 C>T), RS1000996913 (11:77040992 A>G,T), RS1001329034 (11:77042079 C>T), RS1001718521 (11:77036651 A>G), RS1002849931 (11:77037687 G>A), RS1003290035 (11:77038291 G>A), RS1003592564 (11:77039488 G>A,C,T), RS1003826808 (11:77033255 A>G), RS1004122714 (11:77037680 G>A), RS1005233120 (11:77039125 G>A), RS1005806934 (11:77039450 G>A,C), RS1006067578 (11:77034494 G>A,C), RS1007834733 (11:77035765 G>A), RS1007988656 (11:77036969 A>C)

Disease associations

OMIM: gene MIM:615315 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): childhood-onset schizophrenia (MONDO:0957430)

Orphanet (1): Childhood-onset schizophrenia (Orphanet:641496)

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2321631 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation	2
Estradiol	affects binding, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
propionaldehyde	decreases expression	1
CGP 52608	affects binding, increases reaction	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
abrine	decreases expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	increases expression	1
Valproic Acid	increases methylation	1
Mifepristone	decreases expression	1
Sodium Selenite	increases expression	1
Okadaic Acid	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2329323	Binding	Inhibition of human B3GnT6 using GalNAcalpha-Bn as substrate at 0.5 mM after 1 hr in presence of phosphatidylcholine	Selective inhibition of glycosyltransferases by bivalent imidazolium salts. — Bioorg Med Chem

Clinical trials (associated diseases)

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