B3GAT3

Summary

B3GAT3 (beta-1,3-glucuronyltransferase 3, HGNC:923) is a protein-coding gene on chromosome 11q12.3, encoding Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 3 (O94766). Glycosaminoglycans biosynthesis. It is a selective cancer dependency (DepMap: 11.8% of cell lines).

The protein encoded by this gene is a member of the glucuronyltransferase gene family, enzymes that exhibit strict acceptor specificity, recognizing nonreducing terminal sugars and their anomeric linkages. This gene product catalyzes the formation of the glycosaminoglycan-protein linkage by way of a glucuronyl transfer reaction in the final step of the biosynthesis of the linkage region of proteoglycans. A pseudogene of this gene has been identified on chromosome 3.

Source: NCBI Gene 26229 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Larsen-like syndrome, B3GAT3 type (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 5
• Clinical variants (ClinVar): 310 total — 15 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 82
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 11.8% of screened cell lines
• MANE Select transcript: NM_012200

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:923
Approved symbol	B3GAT3
Name	beta-1,3-glucuronyltransferase 3
Location	11q12.3
Locus type	gene with protein product
Status	Approved
Aliases	GlcAT-I
Ensembl gene	ENSG00000149541
Ensembl biotype	protein_coding
OMIM	606374
Entrez	26229

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000265471, ENST00000531383, ENST00000532585, ENST00000533303, ENST00000534026, ENST00000534715, ENST00000879248, ENST00000953336, ENST00000953337

RefSeq mRNA: 4 — MANE Select: NM_012200 NM_001288721, NM_001288722, NM_001288723, NM_012200

CCDS: CCDS76417, CCDS76418, CCDS8025

Canonical transcript exons

ENST00000265471 — 5 exons

Exon	Start	End
ENSE00001293049	62615296	62615799
ENSE00002142592	62621866	62621986
ENSE00003468930	62620497	62620671
ENSE00003562283	62616987	62617347
ENSE00003584650	62616506	62616796

Expression profiles

Bgee: expression breadth ubiquitous, 215 present calls, max score 95.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.6237 / max 217.0966, expressed in 1818 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120168	17.9318	1808
120170	4.1037	1395
120167	1.6518	1227
120171	0.5490	241
120166	0.2886	84
120169	0.0988	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	95.94	gold quality
adenohypophysis	UBERON:0002196	95.75	gold quality
cerebellar hemisphere	UBERON:0002245	95.73	gold quality
cerebellar cortex	UBERON:0002129	95.63	gold quality
granulocyte	CL:0000094	95.42	gold quality
right frontal lobe	UBERON:0002810	95.28	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.25	gold quality
anterior cingulate cortex	UBERON:0009835	95.17	gold quality
cingulate cortex	UBERON:0003027	95.08	gold quality
prefrontal cortex	UBERON:0000451	94.39	gold quality
pituitary gland	UBERON:0000007	94.15	gold quality
nucleus accumbens	UBERON:0001882	94.11	gold quality
cerebellum	UBERON:0002037	93.76	gold quality
caudate nucleus	UBERON:0001873	93.51	gold quality
amygdala	UBERON:0001876	93.46	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.46	gold quality
putamen	UBERON:0001874	93.40	gold quality
tibial nerve	UBERON:0001323	93.39	gold quality
nerve	UBERON:0001021	93.38	gold quality
right uterine tube	UBERON:0001302	93.35	gold quality
metanephros cortex	UBERON:0010533	93.18	gold quality
spinal cord	UBERON:0002240	93.14	gold quality
mucosa of transverse colon	UBERON:0004991	93.08	gold quality
left uterine tube	UBERON:0001303	93.00	gold quality
skin of abdomen	UBERON:0001416	92.91	gold quality
endocervix	UBERON:0000458	92.70	gold quality
skin of leg	UBERON:0001511	92.66	gold quality
right lobe of thyroid gland	UBERON:0001119	92.64	gold quality
ascending aorta	UBERON:0001496	92.53	gold quality
thoracic aorta	UBERON:0001515	92.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR2, ETS1, NFAT5, NFATC1, NFATC3, NFATC4, SP1, STAT1, TP53

miRNA regulators (miRDB)

21 targeting B3GAT3, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-6529-3P	98.68	66.76	1020
HSA-MIR-4457	98.09	67.12	1274
HSA-MIR-1271-3P	97.56	64.85	865
HSA-MIR-550A-3-5P	97.56	65.35	823
HSA-MIR-550A-5P	97.56	65.35	823
HSA-MIR-1227-3P	97.36	66.94	834
HSA-MIR-6849-3P	97.25	64.57	1371
HSA-MIR-4433A-5P	96.79	65.01	599

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 11.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 9)

• functional glycosyltransferase signature sequence of the human beta 1,3-glucuronosyltransferase is a XDD motif (PMID:12794088)
• we evaluated the consequences of C-4/C-6 sulfation of Galbeta1-3Gal (Gal2-Gal1) on the activity and specificity of beta1,3-glucuronosyltransferase I (PMID:15522873)
• GlcAT-I has a role in controlling and reversing articular cartilage defects (PMID:15601778)
• A comparison of substrate specificity of beta1,3-glucuronosyltransferases revealed that GlcAT-I was selective toward Galbeta1,3Gal, whereas GlcAT-P presented a broader profile. (PMID:17567734)
• 2-o-phosphorylation of xylose and 6-o-sulfation of galactose in the protein linkage region of glycosaminoglycans influence the glucuronyltransferase-I activity involved in the linkage region synthesis (PMID:18400750)
• Reduced GlcAT-I activity impairs skeletal as well as heart development and results in variable combinations of heart malformations. (PMID:21763480)
• Since the phenotype of the Nias patients differs from the Larsen-like syndrome described for patients with mutation p.(Arg277Gln), we suggest mutation B3GAT3:p.(Pro140Leu) to cause a different type of GAG linkeropathy showing no involvement of the heart. (PMID:25893793)
• We identified a novel B3GAT3-related disorder with craniosynostosis and bone fragility, due to a unique homozygous mutation in B3GAT3. This syndrome should be considered in the prenatal period in light of the severe outcome and as an alternative diagnosis to Antley-Bixler or Shprintzen-Goldberg syndrome. (PMID:28771243)
• Pseudodiastrophic dysplasia expands the known phenotypic spectrum of defects in proteoglycan biosynthesis. (PMID:31988067)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	b3gat3	ENSDARG00000001939
mus_musculus	B3gat3	ENSMUSG00000071649
drosophila_melanogaster	GlcAT-I	FBGN0066114

Paralogs (2): B3GAT1 (ENSG00000109956), B3GAT2 (ENSG00000112309)

Protein

Protein identifiers

Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 3 — O94766 (reviewed: O94766)

Alternative names: Beta-1,3-glucuronyltransferase 3, Glucuronosyltransferase I, UDP-GlcUA:Gal beta-1,3-Gal-R glucuronyltransferase

All UniProt accessions (4): O94766, E9PNA1, E9PQ60, G3V150

UniProt curated annotations — full annotation on UniProt →

Function. Glycosaminoglycans biosynthesis. Involved in forming the linkage tetrasaccharide present in heparan sulfate and chondroitin sulfate. Transfers a glucuronic acid moiety from the uridine diphosphate-glucuronic acid (UDP-GlcUA) to the common linkage region trisaccharide Gal-beta-1,3-Gal-beta-1,4-Xyl covalently bound to a Ser residue at the glycosaminylglycan attachment site of proteoglycans. Can also play a role in the biosynthesis of l2/HNK-1 carbohydrate epitope on glycoproteins. Shows strict specificity for Gal-beta-1,3-Gal-beta-1,4-Xyl, exhibiting negligible incorporation into other galactoside substrates including Galbeta1-3Gal beta1-O-benzyl, Galbeta1-4GlcNAc and Galbeta1-4Glc. Stimulates 2-phosphoxylose phosphatase activity of PXYLP1 in presence of uridine diphosphate-glucuronic acid (UDP-GlcUA) during completion of linkage region formation.

Subunit / interactions. Homodimer; disulfide-linked. Interacts with PXYLP1; the interaction increases the 2-phosphoxylose phosphatase activity of PXYLP1 during completion of linkage region formation in a B3GAT3-mediated manner.

Subcellular location. Golgi apparatus membrane. Golgi apparatus. cis-Golgi network.

Tissue specificity. Ubiquitous (but weakly expressed in all tissues examined).

Post-translational modifications. N-glycosylated.

Disease relevance. Multiple joint dislocations, short stature, and craniofacial dysmorphism with or without congenital heart defects (JDSCD) [MIM:245600] An autosomal recessive disease characterized by dysmorphic facies, bilateral dislocations of the elbows, hips, and knees, clubfeet, and short stature, as well as cardiovascular defects. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by EDTA.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the glycosyltransferase 43 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O94766-1	1	yes
O94766-2	2

RefSeq proteins (4): NP_001275650, NP_001275651, NP_001275652, NP_036332* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005027	Glyco_trans_43	Family
IPR029044	Nucleotide-diphossugar_trans	Homologous_superfamily

Pfam: PF03360

Enzyme classification (BRENDA):

• EC 2.4.1.135 — galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase (BRENDA: 8 organisms, 54 substrates, 4 inhibitors, 31 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

17 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
UDP-GLUCURONATE	0.04–1.27	10
UDPGLUCURONATE	0.0003–0.287	4
UDP-GLCA	0.0499–0.059	2
3-BETA-GALACTOSYL-GALACTOSE	0.0091	1
GALBETA(1-3)GAL(6-O-SULFATE)BETA(1-4)XYL(2-O-PHO	0.035	1
GALBETA(1-3)GAL(6-O-SULFATE)BETA(1-4)XYLBETA1-O-	0.049	1
GALBETA(1-3)GALBETA(1-4)XYL	0.0804	1
GALBETA(1-3)GALBETA(1-4)XYL(2-O-PHOSPHATE)BETA1-	0.025	1
GALBETA(1-3)GALBETA(1-4)XYLBETA1-O-SER	0.046	1
GALBETA1,3GALBETA-O-NAPHTHALENEMETHANOL	0.67	1
GALBETA1,3GALNACBETA-O-NAPHTHALENEMETHANOL	3.2	1
GALBETA1,3GLCNACBETA-O-NAPHTHALENEMETHANOL	2.9	1
GALBETA1,4GLCNACBETA-O-NAPHTHALENEMETHANOL	1.8	1
GALBETA1-3GAL	4.48	1
UDP-GLCNAC	0.108	1

Catalyzed reactions (Rhea), 1 shown:

• 3-O-(beta-D-galactosyl-(1->3)-beta-D-galactosyl-(1->4)-beta-D-xylosyl)-L-seryl-[protein] + UDP-alpha-D-glucuronate = 3-O-(beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-seryl-[protein] + UDP + H(+) (RHEA:24168)

UniProt features (50 total): strand 11, helix 10, binding site 7, sequence variant 3, mutagenesis site 3, topological domain 2, site 2, region of interest 2, turn 2, chain 1, glycosylation site 1, disulfide bond 1, splice variant 1, transmembrane region 1, sequence conflict 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3CU0	X-RAY DIFFRACTION	1.9
1KWS	X-RAY DIFFRACTION	2.1
1FGG	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94766-F1	92.67	0.80

Functional residue map

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

Catalytic / active sites (3): 227 (interaction with galactose moiety of substrate glycoprotein); 318 (interaction with galactose moiety of substrate glycoprotein); 281 (proton donor/acceptor)

Ligand- & substrate-binding residues (7): 156; 161; 194–196; 196; 308–310; 82–84; 113

Disulfide bonds (1): 33

Glycosylation sites (1): 300

Mutagenesis-validated functional residues (3):

Position	Phenotype
33	loss of dimer formation and reduced activity.
281	absence of enzymatic activity in presence of uridine diphosphate-glucuronic acid (udp-glcua). does not increase pxylp1-i
301	enzyme inactivation and loss of glycosylation.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-1971475	Glycosaminoglycan-protein linkage region biosynthesis
R-HSA-3560801	Defective B3GAT3 causes JDSSDHD
R-HSA-1430728	Metabolism
R-HSA-1630316	Glycosaminoglycan metabolism
R-HSA-1638091	Heparan sulfate/heparin (HS-GAG) metabolism
R-HSA-1643685	Disease
R-HSA-1793185	Chondroitin sulfate/dermatan sulfate metabolism
R-HSA-3560782	Diseases associated with glycosaminoglycan metabolism
R-HSA-3781865	Diseases of glycosylation
R-HSA-5668914	Diseases of metabolism
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives

MSigDB gene sets: 376 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_AMINOGLYCAN_BIOSYNTHETIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_TRANSPORT, GOBP_CHONDROITIN_SULFATE_PROTEOGLYCAN_BIOSYNTHETIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_HEPARAN_SULFATE_PROTEOGLYCAN_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, GOBP_AMINOGLYCAN_METABOLIC_PROCESS

GO Biological Process (8): carbohydrate metabolic process (GO:0005975), glycosaminoglycan biosynthetic process (GO:0006024), heparan sulfate proteoglycan biosynthetic process (GO:0015012), positive regulation of catalytic activity (GO:0043085), chondroitin sulfate proteoglycan biosynthetic process (GO:0050650), dermatan sulfate proteoglycan biosynthetic process (GO:0050651), positive regulation of intracellular protein transport (GO:0090316), obsolete protein glycosylation (GO:0006486)

GO Molecular Function (6): galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase activity (GO:0015018), glucuronosyltransferase activity (GO:0015020), metal ion binding (GO:0046872), protein phosphatase activator activity (GO:0072542), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (5): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), cis-Golgi network (GO:0005801), membrane (GO:0016020), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Glycosaminoglycan metabolism	3
Diseases associated with glycosaminoglycan metabolism	1
Metabolism of carbohydrates and carbohydrate derivatives	1
Diseases of glycosylation	1
Diseases of metabolism	1
Disease	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
proteoglycan biosynthetic process	3
protein O-linked glycosylation via xylose	3
catalytic activity	2
Golgi apparatus	2
intracellular membrane-bounded organelle	2
primary metabolic process	1
aminoglycan biosynthetic process	1
glycosaminoglycan metabolic process	1
heparan sulfate proteoglycan metabolic process	1
positive regulation of molecular function	1
regulation of catalytic activity	1
chondroitin sulfate proteoglycan metabolic process	1
dermatan sulfate proteoglycan metabolic process	1
intracellular protein transport	1
positive regulation of intracellular transport	1
regulation of intracellular protein transport	1
positive regulation of protein transport	1
glucuronosyltransferase activity	1
UDP-glycosyltransferase activity	1
hexosyltransferase activity	1
cation binding	1
phosphoprotein phosphatase activity	1
phosphatase activator activity	1
protein phosphatase regulator activity	1
binding	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

1048 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
B3GAT3	B4GALT7	Q9UBV7	864
B3GAT3	B3GALT6	Q96L58	816
B3GAT3	XYLT1	Q86Y38	782
B3GAT3	SLC35B2	Q8TB61	769
B3GAT3	EXTL3	O43909	747
B3GAT3	XYLT2	Q9H1B5	745
B3GAT3	PXYLP1	Q8TE99	743
B3GAT3	FAM20B	O75063	688
B3GAT3	EXT2	Q93063	657
B3GAT3	EXT1	Q16394	652
B3GAT3	UXS1	Q8NBZ7	648
B3GAT3	CHPF	Q8IZ52	645
B3GAT3	CHPF2	Q9P2E5	638
B3GAT3	CSGALNACT2	Q8N6G5	638
B3GAT3	HS2ST1	Q7LGA3	630
B3GAT3	CSGALNACT1	Q8TDX6	630

IntAct

125 interactions, top by confidence:

A	B	Type	Score
B3GAT3	GOLIM4	psi-mi:“MI:0914”(association)	0.640
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
SLC39A5	FAM171A2	psi-mi:“MI:0914”(association)	0.640
GAA	B3GAT3	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
SLC22A9	GPR89A	psi-mi:“MI:0914”(association)	0.530
PBXIP1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
CSGALNACT2	GOLIM4	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
PBXIP1	KCNN4	psi-mi:“MI:0914”(association)	0.530
EDA	AP3B1	psi-mi:“MI:0914”(association)	0.530
KCNK16	B3GAT3	psi-mi:“MI:0914”(association)	0.530
LDLRAD1	ADAM10	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
SLC30A4	OPA1	psi-mi:“MI:0914”(association)	0.530
SLC31A1	PRORP	psi-mi:“MI:0914”(association)	0.530
TMEM106A	B4GALT3	psi-mi:“MI:0914”(association)	0.530
TMEM171	B3GAT3	psi-mi:“MI:0914”(association)	0.530
ANKH	FAM234B	psi-mi:“MI:0914”(association)	0.530
B3GAT3	POMK	psi-mi:“MI:0915”(physical association)	0.500
ORF8	B3GAT3	psi-mi:“MI:0915”(physical association)	0.400
B3GAT3	CCR2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (160): B3GAT3 (Affinity Capture-MS), KIAA1468 (Affinity Capture-MS), JPH1 (Affinity Capture-MS), GOLIM4 (Affinity Capture-MS), NLGN2 (Affinity Capture-MS), COLEC12 (Affinity Capture-MS), LEMD3 (Affinity Capture-MS), CKAP4 (Affinity Capture-MS), DNAAF5 (Affinity Capture-MS), HEATR3 (Affinity Capture-MS), PBXIP1 (Affinity Capture-MS), HMGCR (Affinity Capture-MS), SEC62 (Affinity Capture-MS), HAUS7 (Affinity Capture-MS), WDR13 (Affinity Capture-MS)

ESM2 similar proteins: A0A4Z3, A1Y9I9, A4FUH1, B6CZ46, B6CZ56, B6CZ62, D3ZNQ3, G3V9Q9, O43505, O60512, O60909, O94766, P14616, P14617, P58158, Q09326, Q10469, Q2NKH9, Q2YDM8, Q3V1N9, Q3V5L5, Q4R5T7, Q5EA01, Q5EB73, Q5JU69, Q5M936, Q5NVN3, Q5R4S2, Q5R868, Q5YB40, Q5ZLK4, Q64716, Q6AYR4, Q765H6, Q7Z4J2, Q8BGT9, Q8BWP8, Q8IXK2, Q8NCL4, Q8R1J9

Diamond homologs: O35789, O94766, O97422, P58158, P59270, Q09363, Q10N05, Q5CAZ6, Q5CB03, Q5CB04, Q5QM25, Q5ZCC5, Q653F4, Q6AT32, Q7XTB2, Q8L707, Q8S626, Q9CW73, Q9NPZ5, Q9P2W7, Q9SXC4, Q9VLA1, Q9VTG7, Q9WU47, Q9Z137, Q9FH90, B9FCV3, Q6Z3Y6, Q75L84, Q9ZQC6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 148 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
Metal ion SLC transporters	6	37.2×	2e-06
R-HSA-425366	8	14.9×	7e-06
SLC-mediated transmembrane transport	11	6.7×	7e-05
Class A/1 (Rhodopsin-like receptors)	8	6.1×	4e-03
GPCR ligand binding	8	5.3×	9e-03
Transport of small molecules	13	3.4×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
zinc ion transmembrane transport	7	38.1×	4e-07
intracellular zinc ion homeostasis	7	26.1×	4e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	8
Uncertain significance	138
Likely benign	116
Benign	10

Top pathogenic / likely-pathogenic (23)

Variant ID	HGVS	Classification
1204070	NM_012200.4(B3GAT3):c.671T>A (p.Leu224Gln)	Pathogenic
1252005	NM_012200.4(B3GAT3):c.245C>T (p.Pro82Leu)	Pathogenic
1991628	NM_012200.4(B3GAT3):c.604G>T (p.Glu202Ter)	Pathogenic
1995805	NM_012200.4(B3GAT3):c.135del (p.Gln46fs)	Pathogenic
1998893	NM_012200.4(B3GAT3):c.126_154dup (p.Ser52delinsCysSerTyrGlyArgArgIleTer)	Pathogenic
225764	NM_012200.4(B3GAT3):c.419C>T (p.Pro140Leu)	Pathogenic
225924	NM_012200.4(B3GAT3):c.667G>A (p.Gly223Ser)	Pathogenic
2797326	NM_012200.4(B3GAT3):c.36C>A (p.Tyr12Ter)	Pathogenic
2844231	NM_012200.4(B3GAT3):c.150del (p.Ile51fs)	Pathogenic
2996858	NM_012200.4(B3GAT3):c.298_301del (p.Leu100fs)	Pathogenic
3681718	NM_012200.4(B3GAT3):c.231_234del (p.Ile77fs)	Pathogenic
3685902	NM_012200.4(B3GAT3):c.246del (p.Thr83fs)	Pathogenic
4715364	NM_012200.4(B3GAT3):c.631del (p.Arg211fs)	Pathogenic
4813555	NM_012200.4(B3GAT3):c.277C>G (p.Leu93Val)	Pathogenic
978467	NM_012200.4(B3GAT3):c.889C>T (p.Arg297Trp)	Pathogenic
1503077	NM_012200.4(B3GAT3):c.619-1G>A	Likely pathogenic
2137125	NM_012200.4(B3GAT3):c.1A>G (p.Met1Val)	Likely pathogenic
2578426	NM_012200.4(B3GAT3):c.986C>G (p.Ser329Ter)	Likely pathogenic
2906193	NM_012200.4(B3GAT3):c.82+1G>A	Likely pathogenic
3599828	NM_012200.4(B3GAT3):c.729G>A (p.Trp243Ter)	Likely pathogenic
3706964	NM_012200.4(B3GAT3):c.2T>G (p.Met1Arg)	Likely pathogenic
427040	NM_012200.4(B3GAT3):c.331G>A (p.Val111Met)	Likely pathogenic
4713959	NM_012200.4(B3GAT3):c.257+1G>A	Likely pathogenic

SpliceAI

994 predictions. Top by Δscore:

Variant	Effect	Δscore
11:62616988:T:TA	donor_gain	1.0000
11:62621865:CCGAG:C	donor_gain	1.0000
11:62616500:CCTT:C	donor_loss	0.9900
11:62616503:TACCC:T	donor_loss	0.9900
11:62616504:A:AG	donor_loss	0.9900
11:62616585:C:T	acceptor_gain	0.9900
11:62616593:G:T	acceptor_gain	0.9900
11:62616981:GCTCA:G	donor_loss	0.9900
11:62616982:CTCA:C	donor_loss	0.9900
11:62616983:TCACC:T	donor_loss	0.9900
11:62616984:CACC:C	donor_loss	0.9900
11:62616985:ACCT:A	donor_gain	0.9900
11:62616986:CCTC:C	donor_gain	0.9900
11:62617343:CCAGC:C	acceptor_gain	0.9900
11:62617344:CAGCC:C	acceptor_gain	0.9900
11:62617348:C:CC	acceptor_gain	0.9900
11:62620641:C:CT	acceptor_gain	0.9900
11:62620641:C:T	acceptor_gain	0.9900
11:62621869:G:C	donor_gain	0.9900
11:62615797:TACC:T	acceptor_loss	0.9800
11:62615798:ACCTG:A	acceptor_loss	0.9800
11:62615799:CCT:C	acceptor_loss	0.9800
11:62615800:CT:C	acceptor_loss	0.9800
11:62615801:T:G	acceptor_loss	0.9800
11:62616504:A:AC	donor_gain	0.9800
11:62616505:C:CC	donor_gain	0.9800
11:62616585:C:CT	acceptor_gain	0.9800
11:62616592:CGG:C	acceptor_gain	0.9800
11:62616808:C:CT	acceptor_gain	0.9800
11:62617344:CAGC:C	acceptor_gain	0.9800

AlphaMissense

2106 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:62617018:T:A	D196V	1.000
11:62615785:A:C	H308Q	0.999
11:62615785:A:T	H308Q	0.999
11:62615787:G:C	H308D	0.999
11:62615788:C:A	W307C	0.999
11:62615788:C:G	W307C	0.999
11:62615790:A:G	W307R	0.999
11:62615790:A:T	W307R	0.999
11:62616675:C:A	R247M	0.999
11:62616698:G:C	F239L	0.999
11:62616698:G:T	F239L	0.999
11:62616700:A:G	F239L	0.999
11:62616769:A:G	W216R	0.999
11:62616769:A:T	W216R	0.999
11:62617018:T:G	D196A	0.999
11:62617024:T:A	D194V	0.999
11:62620497:C:A	R86M	0.999
11:62615787:G:T	H308N	0.998
11:62616647:A:C	F256L	0.998
11:62616647:A:T	F256L	0.998
11:62616648:A:G	F256S	0.998
11:62616649:A:G	F256L	0.998
11:62616660:T:A	D252V	0.998
11:62617014:G:C	N197K	0.998
11:62617014:G:T	N197K	0.998
11:62617017:G:C	D196E	0.998
11:62617017:G:T	D196E	0.998
11:62617019:C:G	D196H	0.998
11:62617021:T:A	D195V	0.998
11:62617027:G:T	A193D	0.998

dbSNP variants (sampled 300 via entrez): RS1000058901 (11:62620010 T>C), RS1000536338 (11:62619795 C>T), RS1000920122 (11:62622199 G>A,C,T), RS1000979000 (11:62615308 T>C,G), RS1001072827 (11:62621474 A>C), RS1001922183 (11:62615238 C>G), RS1002271199 (11:62614980 G>C), RS1002331425 (11:62621627 G>A), RS1002382290 (11:62621882 G>A), RS1002709423 (11:62620392 T>C), RS1003121729 (11:62623415 G>A), RS1003195125 (11:62623214 C>G,T), RS1003226353 (11:62622944 T>A,G), RS1003399067 (11:62615146 G>A), RS1004010386 (11:62619198 A>G)

Disease associations

OMIM: gene MIM:606374 | disease phenotypes: MIM:245600

GenCC curated gene-disease

Disease	Classification	Inheritance
Larsen-like syndrome, B3GAT3 type	Strong	Autosomal recessive
complex neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (2): Larsen-like syndrome, B3GAT3 type (MONDO:0009511), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (1): Larsen-like syndrome, B3GAT3 type (Orphanet:284139)

HPO phenotypes

82 total (30 of 82 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000238	Hydrocephalus
HP:0000248	Brachycephaly
HP:0000274	Small face
HP:0000308	Microretrognathia
HP:0000316	Hypertelorism
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000465	Webbed neck
HP:0000470	Short neck
HP:0000494	Downslanted palpebral fissures
HP:0000520	Proptosis
HP:0000540	Hypermetropia
HP:0000565	Esotropia
HP:0000574	Thick eyebrow
HP:0000592	Blue sclerae
HP:0000646	Amblyopia
HP:0000691	Microdontia
HP:0000768	Pectus carinatum
HP:0000774	Narrow chest
HP:0000776	Congenital diaphragmatic hernia
HP:0000878	11 pairs of ribs
HP:0000926	Platyspondyly
HP:0000938	Osteopenia
HP:0000939	Osteoporosis

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST005956_12	Waist-to-hip ratio adjusted for BMI	2.000000e-06
GCST005956_2	Waist-to-hip ratio adjusted for BMI	1.000000e-08
GCST005962_37	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	5.000000e-07
GCST005962_51	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-07
GCST90000025_160	Appendicular lean mass	8.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537874	Larsen syndrome, recessive type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3958 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.40	Kd	3962	nM	CHEMBL5558191
5.18	Kd	6619	nM	CHEMBL5558191

PubChem BioAssay actives

2 with measured affinity, of 9 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
methyl 3-[2-[[1-(2-chloro-4-methylphenyl)-2-oxopyrrolidin-3-yl]amino]-2-oxoacetyl]-1H-indole-5-carboxylate	2066380: Binding affinity to CM5 sensor chip immobilized human B3GAT3 assessed as dissociation constant by SPR analysis	kd	3.9620	uM

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression, increases expression	3
sodium arsenite	increases expression, decreases expression	2
aristolochic acid I	increases expression	1
cobaltous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	affects cotreatment, decreases expression	1
Diacetyl	decreases activity, decreases reaction	1
Doxorubicin	increases expression	1
Ivermectin	decreases expression	1
Quercetin	increases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tretinoin	affects cotreatment, decreases expression	1
Uridine Diphosphate Glucuronic Acid	affects binding, decreases activity, decreases reaction	1
Valproic Acid	increases expression, increases methylation	1
Mifepristone	decreases expression	1
Lactic Acid	increases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5505201	Binding	Binding affinity to CM5 sensor chip immobilized human B3GAT3 assessed as dissociation constant by SPR analysis	Discovery of Novel 2-Oxoacetamide Derivatives as B3GAT3 Inhibitors for the Treatment of Hepatocellular Carcinoma. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder