B4GALT1

Summary

B4GALT1 (beta-1,4-galactosyltransferase 1, HGNC:924) is a protein-coding gene on chromosome 9p21.1, encoding Beta-1,4-galactosyltransferase 1 (P15291). Galactosyltransferase acting in the Golgi stacks.

This gene is one of seven beta-1,4-galactosyltransferase (beta4GalT) genes. They encode type II membrane-bound glycoproteins that appear to have exclusive specificity for the donor substrate UDP-galactose; all transfer galactose in a beta1,4 linkage to similar acceptor sugars: GlcNAc, Glc, and Xyl. Each beta4GalT has a distinct function in the biosynthesis of different glycoconjugates and saccharide structures. As type II membrane proteins, they have an N-terminal hydrophobic signal sequence that directs the protein to the Golgi apparatus and which then remains uncleaved to function as a transmembrane anchor. By sequence similarity, the beta4GalTs form four groups: beta4GalT1 and beta4GalT2, beta4GalT3 and beta4GalT4, beta4GalT5 and beta4GalT6, and beta4GalT7. This gene is unique among the beta4GalT genes because it encodes an enzyme that participates both in glycoconjugate and lactose biosynthesis. For the first activity, the enzyme adds galactose to N-acetylglucosamine residues that are either monosaccharides or the nonreducing ends of glycoprotein carbohydrate chains. The second activity is restricted to lactating mammary tissues where the enzyme forms a heterodimer with alpha-lactalbumin to catalyze UDP-galactose + D-glucose <=> UDP + lactose. The two enzymatic forms result from alternate transcription initiation sites and post-translational processing. Two transcripts, which differ only at the 5’ end, with approximate lengths of 4.1 kb and 3.9 kb encode the same protein. The longer transcript encodes the type II membrane-bound, trans-Golgi resident protein involved in glycoconjugate biosynthesis. The shorter transcript encodes a protein which is cleaved to form the soluble lactose synthase.

Source: NCBI Gene 2683 — RefSeq curated summary.

At a glance

• Gene–disease (curated): B4GALT1-congenital disorder of glycosylation (Strong, GenCC)
• GWAS associations: 28
• Clinical variants (ClinVar): 160 total — 3 pathogenic
• Phenotypes (HPO): 44
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001497

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:924
Approved symbol	B4GALT1
Name	beta-1,4-galactosyltransferase 1
Location	9p21.1
Locus type	gene with protein product
Status	Approved
Aliases	beta4Gal-T1
Ensembl gene	ENSG00000086062
Ensembl biotype	protein_coding
OMIM	137060
Entrez	2683

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 nonsense_mediated_decay

ENST00000379731, ENST00000535206, ENST00000718311, ENST00000860371, ENST00000860372

RefSeq mRNA: 4 — MANE Select: NM_001497 NM_001378495, NM_001378496, NM_001378497, NM_001497

CCDS: CCDS6535, CCDS94396

Canonical transcript exons

ENST00000379731 — 6 exons

Exon	Start	End
ENSE00000695817	33135189	33135424
ENSE00001482335	33166758	33167336
ENSE00004034738	33115991	33116113
ENSE00004034740	33120419	33120606
ENSE00004034741	33110642	33113586
ENSE00004034742	33113774	33113878

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 97.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 130.1528 / max 13238.2613, expressed in 1823 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100437	49.8843	1731
100416	31.0560	1654
100441	26.5746	1801
100438	13.1289	1771
100440	1.8747	1075
100439	1.8052	1036
100418	1.5509	745
100442	1.1577	787
100426	0.9761	403
100425	0.6454	228

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	97.73	gold quality
stromal cell of endometrium	CL:0002255	95.79	gold quality
left uterine tube	UBERON:0001303	95.79	gold quality
minor salivary gland	UBERON:0001830	95.27	gold quality
ileal mucosa	UBERON:0000331	95.12	gold quality
gall bladder	UBERON:0002110	94.93	gold quality
right ovary	UBERON:0002118	94.86	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.65	gold quality
smooth muscle tissue	UBERON:0001135	94.57	gold quality
mucosa of transverse colon	UBERON:0004991	94.53	gold quality
tendon of biceps brachii	UBERON:0008188	94.48	gold quality
left ovary	UBERON:0002119	94.37	gold quality
left lobe of thyroid gland	UBERON:0001120	94.27	gold quality
right lobe of thyroid gland	UBERON:0001119	94.19	gold quality
saliva-secreting gland	UBERON:0001044	94.10	gold quality
epithelium of nasopharynx	UBERON:0001951	94.07	gold quality
type B pancreatic cell	CL:0000169	93.94	gold quality
thyroid gland	UBERON:0002046	93.83	gold quality
right lobe of liver	UBERON:0001114	93.81	gold quality
lower esophagus mucosa	UBERON:0035834	93.44	gold quality
right atrium auricular region	UBERON:0006631	93.42	gold quality
mouth mucosa	UBERON:0003729	93.40	gold quality
upper lobe of left lung	UBERON:0008952	93.31	gold quality
right lung	UBERON:0002167	93.23	gold quality
ovary	UBERON:0000992	93.17	gold quality
monocyte	CL:0000576	93.09	gold quality
leukocyte	CL:0000738	92.94	gold quality
popliteal artery	UBERON:0002250	92.92	gold quality
tibial artery	UBERON:0007610	92.92	gold quality
vagina	UBERON:0000996	92.85	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-7051	yes	6516.13
E-GEOD-75140	yes	244.48
E-MTAB-10287	yes	44.95
E-CURD-122	yes	12.83
E-GEOD-83139	yes	10.87
E-MTAB-9801	yes	6.17
E-MTAB-6678	yes	4.31
E-GEOD-124858	no	1534.98
E-MTAB-6075	no	795.76
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, ETS1, NR1I2, SP1, TBXT, TP63

miRNA regulators (miRDB)

138 targeting B4GALT1, 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-4262	100.00	73.26	3931
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-3529-3P	99.90	73.55	3045

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• deficiency causes a new congenital disorder of glycosylation (CDG), designated type IId (CDG-IId), a severe neurologic disease characterized by hydrocephalus, myopathy, and blood-clotting defects (PMID:11901181)
• E1AF has an essential role in the activation of the human GalT I gene in highly metastatic lung cancer cells (PMID:15611127)
• TNFalpha modulates the glycosylation of endothelial cells by a mechanism that directly enhances the stability of beta4GalT-1 mRNA transcripts (PMID:15668241)
• beta4Gal-T1 interacts preferentially with the 1,2-1,6-arm trisaccharide rather than with the 1,2-1,3-arm or 1,4-1,3-arm of a bi- or tri-antennary oligosaccharide chain of N-glycan (PMID:16157350)
• Data show that expression of a hybrid enzyme of Arabidopsis thaliana xylosyltransferase and human beta-1,4-galactosyltransferase I in tobacco causes a reduction of N-glycans with potentially immunogenic core-bound xylose and fucose residues. (PMID:16675551)
• These results demonstrated that cell surface beta1,4GT1 may negatively regulate cell survival possibly through inhibiting and modulating EGFR signaling pathway. (PMID:16786197)
• Cycling between the trans-Golgi cisterna and the trans-Golgi network of galT is signal mediated. (PMID:17021253)
• hepatitis B-induced GalT I expression might contribute to hepatitis B-mediated hepatocellular carcinoma development and progression (PMID:18929424)
• Deoxygenated disaccharide analogs as specific inhibitors of beta1-4-galactosyltransferase 1 and selectin-mediated tumor metastasis. (PMID:19106107)
• These results demonstrate that B3GNT1 and B4GALT1 physically associate in vitro and in cultured cells, providing insight into possible mechanisms for regulation of polyLacNAc production. (PMID:19261593)
• found that both the long and short isoforms of beta-1,4-GalT-I were expressed in human CD4(+) T lymphocytes, and localized in the cytoplasm and on the plasma membrane. (PMID:20202494)
• Golgi N-glycosyltransferases beta-1,2-N-acetylglucosaminyltransferase I, beta-1,2-N-acetylglucosaminyltransferase II, 1,4-galactosyltransferase I, and alpha-2,6-sialyltransferase I form both homo- and heterodimeric enzyme complexes in live cells (PMID:20378551)
• These results suggested that beta1,4-Galactosyltransferase-I may play an important role in the inflammatory processes in synovial tissue of patients with rheumatoid arthritis. (PMID:20490888)
• PKC signal transduction pathway participates in regulating beta-1, 4-GalT-I expression in endothelial cells stimulated by TNF-alpha. (PMID:20619088)
• The mutation of C80S introduces a fully occupied UDP binding site at the enzyme dimer interface that is observed to be dependent on the binding of H antigen acceptor analog. (PMID:20655926)
• B4GalTI might act as a key adhesion molecule participating in T cell-dendritic cell contacts. (PMID:20851383)
• TNF-alpha contributes to the up-regulation of beta1,4-GalT-I mRNA in human fibroblast-like synoviocytes. (PMID:20886274)
• expression of beta1,4-GalT-I increased in the cartilage and synovial tissue of osteoarthritis (OA) patients compared with healthy controls; data suggest that beta1,4-GalT-I may play an important role in the inflammatory processes in cartilage and synovial tissue of patients with OA (PMID:21750942)
• beta4Gal-T1 molecule has two different oligosaccharide binding regions for the binding of the extended oligosaccharide moiety of the acceptor substrate. (PMID:22740701)
• Osteopontin increases the expression of beta1, 4-Galactosyltransferase-I and promotes adhesion in human RL95-2 cells, the activity critical for embryo implantation. (PMID:22847114)
• the glycogene B4GALT1 represent a valuable candidate biomarker of invasive phenotype of colorectal cancer. (PMID:22927297)
• estrogen regulates the expression of B4GALT1 through the direct binding of ER-alpha to ERE; the expressed B4GALT1 plays a crucial role in the proliferation of MCF-7 cells through its activity as a membrane receptor. (PMID:22982306)
• RNAi-mediated knockdown of beta1,4GT1 increased the levels of EGFR dimerization and phosphorylation. These data suggest that cell surface beta1,4GT1 interacts with EGFR and inhibits EGFR activatio (PMID:23583406)
• B4GALT1 and B4GALT5, two members of B4GALT gene family, are involved in the development of multidrug resistance of human leukemia cells. (PMID:23744354)
• plays a role in activation of T-lymphocytes and participates in intercellular contact formation (PMID:25223470)
• HS5 cells had significantly enhanced levels of bisecting N-glycans (catalyzed by MGAT3 whereas HS27a cells had enhanced levels of Galbeta1,4GlcNAc. (PMID:25936519)
• Human chorionic gonadotropin provides a mechanism to bridge embryo to endometrium through beta1,4-GalT. (PMID:26191157)
• We suggest that the unique expression patterns for the B4GALT1 in normal and malignant tissues are controlled by a differential usage of 5’-B4GALT1 regulatory units along with a post-transcriptional regulation by the antisense RNA (PMID:26315939)
• High B4GALT1 expression is associated with aging. (PMID:26840264)
• Increased B4GALT1 expression is a potential independent adverse prognostic factor for overall survival in patients with non-metastatic clear cell renal cell carcinoma. (PMID:27092876)
• demonstrated that ZFX is aberrantly expressed in multiple human leukemic cells and it modulates the growth and drug response of leukemic cells partially via B4GALT1, which suggests that ZFX is a new regulator of leukemic cells and warrants intensive investigations on this ‘stemness’ regulator in these deadly diseases (PMID:27797721)
• Human beta-1,4-GalT1 is a constitutively expressed mesangial cell IgA receptor with an important role in both mesangial IgA clearance and the initial response to IgA deposition. (PMID:28750925)
• Study indicated that B4GALT1 may be a possible prognosticator of muscle-invasive bladder cancer, and it may be a predictive marker for the choice of adjuvant chemotherapy in pT3/4 or N+ patients. (PMID:29793447)
• Study solved the crystal structure of the wild-type human B4GalT1 homodimer and showed that B4GalT1 exists in a dynamic equilibrium between monomer and dimer. These two crystal forms revealed the unliganded B4GalT1 in both the open and the closed conformation of the Trp loop and the lid regions, responsible for donor and acceptor substrate binding, respectively. (PMID:30352055)
• beta4GalT1 promotes inflammation in human osteoarthritic fibroblast-like synoviocytes by enhancing autocrine TNF-alpha activity. (PMID:31210280)
• Reduced CETP glycosylation and activity in patients with homozygous B4GALT1 mutations. (PMID:31800099)
• B4GALT1 expression in stromal cells positively correlated with upstream c-Jun expression (PMID:32027290)
• B4GALT1-congenital disorders of glycosylation: Expansion of the phenotypic and molecular spectrum and review of the literature. (PMID:32157688)
• Study on the role and mechanism of beta4GalT1 both in vivo and in vitro glioma. (PMID:32373974)
• The AKR1C3/AR-V7 complex maintains CRPC tumour growth by repressing B4GALT1 expression. (PMID:32902124)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	b4galt1	ENSDARG00000002634
danio_rerio	b4galt1l	ENSDARG00000104404
mus_musculus	B4galt1	ENSMUSG00000028413
rattus_norvegicus	B4galt1	ENSRNOG00000059461
drosophila_melanogaster	beta4GalNAcTA	FBGN0027538
caenorhabditis_elegans	bre-4	WBGENE00000269

Paralogs (6): B4GALT7 (ENSG00000027847), B4GALT2 (ENSG00000117411), B4GALT6 (ENSG00000118276), B4GALT4 (ENSG00000121578), B4GALT5 (ENSG00000158470), B4GALT3 (ENSG00000158850)

Protein

Protein identifiers

Beta-1,4-galactosyltransferase 1 — P15291 (reviewed: P15291)

Alternative names: Beta-N-acetylglucosaminyl-glycolipid beta-1,4-galactosyltransferase, Beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase, Lactose synthase A protein, N-acetyllactosamine synthase, Nal synthase, Neolactotriaosylceramide beta-1,4-galactosyltransferase, UDP-Gal:beta-GlcNAc beta-1,4-galactosyltransferase 1, UDP-galactose:beta-N-acetylglucosamine beta-1,4-galactosyltransferase 1

All UniProt accessions (3): P15291, Q86XA6, W6MEN3

UniProt curated annotations — full annotation on UniProt →

Function. Galactosyltransferase acting in the Golgi stacks. Catalyzes the transfer of galactose (Gal) from UDP-alpha-D-galactose in beta(1->4) linkage to the non-reducing terminal N-acetylglucosamine (GlcNAc) moieties of glycolipids and complex-type N-linked glycans. Adds one Gal residue to both GlcNAc beta(1->2)-linked to the alpha(1->3) and alpha(1->6) mannose antennae of complex-type N-glycans, enabling the formation of mono- and di-galactosylated glycoforms. Galactosylates complex-type N-glycans attached on the fragment crystallizable (Fc) of immunoglobulin-gamma isotypes (IgGs), a prerequisite for antibody glycan sialylation and related anti-inflammatory effector functions. Can also transfer a Gal residue to free GlcNAc to form N-acetyllactosamine. With LALBA/alpha-lactalbumin forms the lactose synthase complex responsible for production of large amounts of lactose in the lactating mammary gland. Interaction with LALBA alters the sugar substrate specificity of the catalytic domain, enabling high affinity binding of glucose and its transformation to lactose. The cell surface form functions as a recognition molecule during a variety of cell to cell and cell to matrix interactions, like those occurring during development and egg fertilization, by binding to specific oligosaccharide ligands on opposing cells or in the extracellular matrix. Acts as a sperm receptor for ZP3 O-linked glycans on the zona pellucida leading to activation of G-protein signaling and acrosome reaction. The secreted form is proficient in galactosyltransferase activity and could be involved in glycan remodeling in biological fluids.

Subunit / interactions. Homodimer; and heterodimer with LALBA/alpha-lactalbumin to form lactose synthase. Interacts (via N-terminal cytoplasmic domain) with UBE2Q1 (via N-terminus); the interaction is direct.

Subcellular location. Golgi apparatus. Golgi stack membrane Golgi apparatus. Golgi stack membrane. Cell membrane. Cell surface. Cell projection. Filopodium Golgi apparatus. Golgi stack membrane Secreted.

Tissue specificity. Ubiquitously expressed, but at very low levels in fetal and adult brain.

Post-translational modifications. The soluble form derives from the membrane forms by proteolytic processing.

Disease relevance. Congenital disorder of glycosylation 2D (CDG2D) [MIM:607091] A multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. The disease is caused by variants affecting the gene represented in this entry. Combined low LDL and fibrinogen (CLDLFIB) [MIM:620364] An autosomal recessive condition characterized by low plasma LDL-cholesterol and fibrinogen levels, and associated with a decreased risk of coronary artery disease. Disease susceptibility may be associated with variants affecting the gene represented in this entry.

Pathway. Protein modification; protein glycosylation. Glycolipid biosynthesis.

Similarity. Belongs to the glycosyltransferase 7 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P15291-1	Long, Cell surface	yes
P15291-2	Short, Golgi complex

RefSeq proteins (4): NP_001365424, NP_001365425, NP_001365426, NP_001488* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003859	Galactosyl_T	Family
IPR027791	Galactosyl_T_C	Domain
IPR027995	Galactosyl_T_N	Domain
IPR029044	Nucleotide-diphossugar_trans	Homologous_superfamily

Pfam: PF02709, PF13733

Enzyme classification (BRENDA):

• EC 2.4.1.133 — xylosylprotein 4-beta-galactosyltransferase (BRENDA: 8 organisms, 83 substrates, 23 inhibitors, 137 Km, 56 kcat entries)
• EC 2.4.1.22 — lactose synthase (BRENDA: 22 organisms, 45 substrates, 43 inhibitors, 12 Km, 1 kcat entries)
• EC 2.4.1.38 — beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase (BRENDA: 18 organisms, 205 substrates, 71 inhibitors, 132 Km, 51 kcat entries)
• EC 2.4.1.90 — N-acetyllactosamine synthase (BRENDA: 18 organisms, 143 substrates, 60 inhibitors, 85 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
UDP-GALACTOSE	0.02–2.41	42
4-METHYLUMBELLIFERYL-BETA-D-XYLOPYRANOSIDE	0.16–4.22	29
N-ACETYLGLUCOSAMINE	0.0007–40	27
UDPGALACTOSE	0.0108–0.25	26
N-ACETYLGLUCOSAMINE	0.0039–40	20
4-METHYLUMBELLIFERYL O-BETA-D-XYLOPYRANOSIDE	0.27–4.22	10
4-NITROPHENYL-BETA-D-XYLOPYRANOSIDE	0.85–7.93	10
UDP-ALPHA-D-GALACTOSE	0.22–0.4	10
4-METHYLUMBELLIFERYL-BETA-D-XYLOPYRANOSIDE	0.35–1.06	10
GLUCOSE	1.7–1400	6
UDP-GALACTOSE	0.0105–0.31	5
UDP-GLUCOSE	0.031–0.28	5
4-NITROPHENYL O-BETA-D-XYLOPYRANOSIDE	1.27–7.93	4

Catalyzed reactions (Rhea), 12 shown:

• D-glucose + UDP-alpha-D-galactose = lactose + UDP + H(+) (RHEA:12404)
• N-acetyl-D-glucosamine + UDP-alpha-D-galactose = beta-D-galactosyl-(1->4)-N-acetyl-D-glucosamine + UDP + H(+) (RHEA:17745)
• an N-acetyl-beta-D-glucosaminyl derivative + UDP-alpha-D-galactose = a beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl derivative + UDP + H(+) (RHEA:22932)
• a beta-D-GlcNAc-(1->3)-beta-D-Gal-(1->4)-beta-D-Glc-(1<->1)-Cer(d18:1(4E)) + UDP-alpha-D-galactose = a neolactoside nLc4Cer(d18:1(4E)) + UDP + H(+) (RHEA:31499)
• a neolactoside IV(3)-beta-GlcNAc-nLc4Cer + UDP-alpha-D-galactose = a neolactoside nLc6Cer + UDP + H(+) (RHEA:62548)
• a beta-D-glucosylceramide + UDP-alpha-D-galactose = a beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide + UDP + H(+) (RHEA:62552)
• an N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[beta-D-GlcNAc-(1->4)]-[beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-[alpha-L-Fuc-(1->6)]-beta-D-GlcNAc}-L-asparaginyl-[protein] + UDP-alpha-D-galactose = an N(4)-{beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[beta-D-GlcNAc-(1->4)]-[beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-[alpha-L-Fuc-(1->6)]-beta-D-GlcNAc}-L-asparaginyl-[protein] + UDP + H(+) (RHEA:83935)
• an N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-[alpha-L-Fuc-(1->6)]-beta-D-GlcNAc}-L-asparaginyl-[protein] + UDP-alpha-D-galactose = an N(4)-{beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-[alpha-L-Fuc-(1->6)]-beta-D-GlcNAc}-L-asparaginyl-[protein] + UDP + H(+) (RHEA:83939)
• an N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[beta-D-GlcNAc-(1->4)]-[beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-[alpha-L-Fuc-(1->6)]-beta-D-GlcNAc}-L-asparaginyl-[protein] + UDP-alpha-D-galactose = an N(4)-{beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[beta-D-GlcNAc-(1->4)]-[beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-[alpha-L-Fuc-(1->6)]-beta-D-GlcNAc}-L-asparaginyl-[protein] + UDP + H(+) (RHEA:83955)
• an N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-[alpha-L-Fuc-(1->6)]-beta-D-GlcNAc}-L-asparaginyl-[protein] + UDP-alpha-D-galactose = an N(4)-{beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-[alpha-L-Fuc-(1->6)]-beta-D-GlcNAc}-L-asparaginyl-[protein] + UDP + H(+) (RHEA:83959)
• an N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-[alpha-L-Fuc-(1->6)]-beta-D-GlcNAc}-L-asparaginyl-[protein] + UDP-alpha-D-galactose = an N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-[alpha-L-Fuc-(1->6)]-beta-D-GlcNAc}-L-asparaginyl-[protein] + UDP + H(+) (RHEA:83963)
• N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-L-asparaginyl-[protein] + UDP-alpha-D-galactose = an N(4)-{beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-L-asparaginyl-[protein] + UDP + H(+) (RHEA:83975)

UniProt features (68 total): sequence conflict 11, helix 11, strand 11, binding site 9, mutagenesis site 6, sequence variant 4, turn 4, chain 2, disulfide bond 2, topological domain 2, site 1, glycosylation site 1, splice variant 1, transmembrane region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

19 structures.

PDB	Method	Resolution (Å)
2FY7	X-RAY DIFFRACTION	1.7
6FWT	X-RAY DIFFRACTION	1.84
2AGD	X-RAY DIFFRACTION	1.9
2FYA	X-RAY DIFFRACTION	1.9
2FYB	X-RAY DIFFRACTION	1.9
4EE4	X-RAY DIFFRACTION	1.95
2AE7	X-RAY DIFFRACTION	2
2AEC	X-RAY DIFFRACTION	2
2AES	X-RAY DIFFRACTION	2
2AH9	X-RAY DIFFRACTION	2
4EEA	X-RAY DIFFRACTION	2
3EE5	X-RAY DIFFRACTION	2.2
4EE5	X-RAY DIFFRACTION	2.2
4EEG	X-RAY DIFFRACTION	2.2
4EEM	X-RAY DIFFRACTION	2.2
4EE3	X-RAY DIFFRACTION	2.3
4EEO	X-RAY DIFFRACTION	2.3
6FWU	X-RAY DIFFRACTION	2.35
4L41	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P15291-F1	85.23	0.68

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 (1): 77–78 (cleavage; to produce soluble form)

Ligand- & substrate-binding residues (9): 250; 310; 312–315; 343–346; 343; 355; 183–187; 222–224; 249–250

Disulfide bonds (2): 130–172, 243–262

Glycosylation sites (1): 113

Mutagenesis-validated functional residues (6):

Position	Phenotype
282	reduction in n-acetylglucosamine binding.
285	no change in enzymatic activity.
307	reduction in n-acetylglucosamine and udp-galactose binding.
308	reduction in n-acetylglucosamine binding.
310	reduction in n-acetylglucosamine binding.
340	favors the closed conformation of the enzyme.

Function

Pathways and Gene Ontology

Reactome pathways

29 pathways

ID	Pathway
R-HSA-1912420	Pre-NOTCH Processing in Golgi
R-HSA-2022854	Keratan sulfate biosynthesis
R-HSA-2534343	Interaction With Cumulus Cells And The Zona Pellucida
R-HSA-3656244	Defective B4GALT1 causes B4GALT1-CDG (CDG-2d)
R-HSA-4793953	Defective B4GALT1 causes CDG-2d
R-HSA-5653890	Lactose synthesis
R-HSA-6798695	Neutrophil degranulation
R-HSA-975577	N-Glycan antennae elongation
R-HSA-1187000	Fertilization
R-HSA-1430728	Metabolism
R-HSA-1474165	Reproduction
R-HSA-157118	Signaling by NOTCH
R-HSA-162582	Signal Transduction
R-HSA-1630316	Glycosaminoglycan metabolism
R-HSA-1638074	Keratan sulfate/keratin metabolism
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-1912422	Pre-NOTCH Expression and Processing
R-HSA-3560782	Diseases associated with glycosaminoglycan metabolism
R-HSA-3781860	Diseases associated with N-glycosylation of proteins
R-HSA-3781865	Diseases of glycosylation
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-5668914	Diseases of metabolism
R-HSA-597592	Post-translational protein modification
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives
R-HSA-948021	Transport to the Golgi and subsequent modification
R-HSA-975576	N-glycan antennae elongation in the medial/trans-Golgi

MSigDB gene sets: 486 (showing top): RNGTGGGC_UNKNOWN, GOBP_SINGLE_FERTILIZATION, GOBP_OLIGOSACCHARIDE_METABOLIC_PROCESS, REACTOME_SIGNALING_BY_NOTCH, GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, KEGG_N_GLYCAN_BIOSYNTHESIS, GOCC_CELL_SURFACE, GNF2_PTX3

GO Biological Process (25): epithelial cell development (GO:0002064), acute inflammatory response (GO:0002526), lactose biosynthetic process (GO:0005989), galactose metabolic process (GO:0006012), protein N-linked glycosylation (GO:0006487), lipid metabolic process (GO:0006629), cell adhesion (GO:0007155), binding of sperm to zona pellucida (GO:0007339), penetration of zona pellucida (GO:0007341), oligosaccharide biosynthetic process (GO:0009312), extracellular matrix organization (GO:0030198), positive regulation of apoptotic process (GO:0043065), development of animal secondary sexual characteristics (GO:0045136), epithelial cell proliferation (GO:0050673), negative regulation of epithelial cell proliferation (GO:0050680), regulation of acrosome reaction (GO:0060046), positive regulation of epithelial cell proliferation involved in wound healing (GO:0060054), angiogenesis involved in wound healing (GO:0060055), positive regulation of circulating fibrinogen levels (GO:0061755), macrophage migration (GO:1905517), carbohydrate metabolic process (GO:0005975), obsolete protein glycosylation (GO:0006486), cell population proliferation (GO:0008283), glycoprotein biosynthetic process (GO:0009101), wound healing (GO:0042060)

GO Molecular Function (13): beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase activity (GO:0003831), N-acetyllactosamine synthase activity (GO:0003945), lactose synthase activity (GO:0004461), galactosyltransferase activity (GO:0008378), manganese ion binding (GO:0030145), UDP-galactosyltransferase activity (GO:0035250), identical protein binding (GO:0042802), alpha-tubulin binding (GO:0043014), beta-tubulin binding (GO:0048487), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), metal ion binding (GO:0046872)

GO Cellular Component (20): Golgi trans cisterna (GO:0000138), Golgi membrane (GO:0000139), obsolete extracellular space (GO:0005615), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), desmosome (GO:0030057), filopodium (GO:0030175), secretory granule membrane (GO:0030667), brush border membrane (GO:0031526), Golgi cisterna membrane (GO:0032580), protein-containing complex (GO:0032991), azurophil granule membrane (GO:0035577), extracellular exosome (GO:0070062), extracellular region (GO:0005576), cell surface (GO:0009986), endomembrane system (GO:0012505), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Metabolism of carbohydrates and carbohydrate derivatives	2
Pre-NOTCH Expression and Processing	1
Keratan sulfate/keratin metabolism	1
Fertilization	1
Diseases associated with glycosaminoglycan metabolism	1
Diseases associated with N-glycosylation of proteins	1
Innate Immune System	1
N-glycan antennae elongation in the medial/trans-Golgi	1
Reproduction	1
Signal Transduction	1
Glycosaminoglycan metabolism	1
Immune System	1
Signaling by NOTCH	1
Diseases of glycosylation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
UDP-galactosyltransferase activity	3
wound healing	2
tubulin binding	2
Golgi cisterna	2
bounding membrane of organelle	2
plasma membrane	2
epithelial cell differentiation	1
cell development	1
inflammatory response	1
lactose metabolic process	1
disaccharide biosynthetic process	1
hexose metabolic process	1
glycoprotein biosynthetic process	1
primary metabolic process	1
cellular process	1
sperm-egg recognition	1
single fertilization	1
multi-multicellular organism process	1
multicellular organismal reproductive process	1
oligosaccharide metabolic process	1
carbohydrate biosynthetic process	1
extracellular structure organization	1
external encapsulating structure organization	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
developmental process involved in reproduction	1
multicellular organism development	1
sex differentiation	1
cell population proliferation	1
negative regulation of cell population proliferation	1
epithelial cell proliferation	1
regulation of epithelial cell proliferation	1
acrosome reaction	1
regulation of reproductive process	1
positive regulation of epithelial cell proliferation	1
angiogenesis	1
regulation of circulating fibrinogen levels	1
mononuclear cell migration	1

Protein interactions and networks

STRING

1164 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
B4GALT1	LALBA	P00709	979
B4GALT1	B4GALNT2	Q8NHY0	924
B4GALT1	ST6GAL1	P15907	913
B4GALT1	FUT6	P51993	865
B4GALT1	MAN2A1	Q16706	849
B4GALT1	B3GALT1	Q9Y5Z6	847
B4GALT1	MAN2A2	P49641	822
B4GALT1	SLC35C1	Q96A29	784
B4GALT1	B3GALT2	O43825	757
B4GALT1	FUT5	Q11128	721
B4GALT1	SLC35D1	Q9NTN3	706
B4GALT1	FUT8	Q9BYC5	702
B4GALT1	SLC35D2	Q76EJ3	688
B4GALT1	ST3GAL1	Q11201	675
B4GALT1	B3GNT2	Q9NY97	672

IntAct

38 interactions, top by confidence:

A	B	Type	Score
TSPAN5	ADAM10	psi-mi:“MI:0914”(association)	0.800
FAM234B	ABCD4	psi-mi:“MI:0914”(association)	0.620
MME	TMEM223	psi-mi:“MI:0914”(association)	0.530
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
IL13RA2	METTL15	psi-mi:“MI:0914”(association)	0.530
TNF	B4GALT5	psi-mi:“MI:0914”(association)	0.530
IL27RA	B4GALT5	psi-mi:“MI:0914”(association)	0.530
TSPAN5	SC5D	psi-mi:“MI:0914”(association)	0.530
MMP10	TIMP1	psi-mi:“MI:0914”(association)	0.530
CDK5RAP3	PLD2	psi-mi:“MI:0914”(association)	0.530
B4GALT1	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
B4galt1	B4GALT1	psi-mi:“MI:0915”(physical association)	0.400
OCRL	MYO1C	psi-mi:“MI:0914”(association)	0.350
	TNFRSF10A	psi-mi:“MI:0914”(association)	0.350
Npc1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
SLC7A14	TMEM120B	psi-mi:“MI:0914”(association)	0.350
TCTN2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
CHRNB2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
CSTL1	DENND11	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
KLRC1	METTL15	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
SLC39A12		psi-mi:“MI:0914”(association)	0.350
TMEM59	GPR89A	psi-mi:“MI:0914”(association)	0.350
KIR2DL4	GPR89A	psi-mi:“MI:0914”(association)	0.350
CEACAM8	PRRT4	psi-mi:“MI:0914”(association)	0.350
IGFL3	CBX4	psi-mi:“MI:0914”(association)	0.350
HTR3C	GET1	psi-mi:“MI:0914”(association)	0.350

BioGRID (118): B4GALT1 (Affinity Capture-MS), B4GALT1 (Affinity Capture-MS), B4GALT1 (Affinity Capture-MS), B4GALT1 (Affinity Capture-MS), B4GALT1 (Affinity Capture-MS), B4GALT1 (Affinity Capture-MS), B4GALT1 (Affinity Capture-MS), B4GALT1 (Affinity Capture-MS), B4GALT1 (Affinity Capture-MS), B4GALT1 (Affinity Capture-MS), B4GALT1 (Affinity Capture-MS), B4GALT1 (Affinity Capture-MS), B4GALT1 (Affinity Capture-MS), B4GALT1 (Affinity Capture-MS), B4GALT1 (Affinity Capture-MS)

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

Diamond homologs: A0A1S6M251, A8Y1P7, O43286, O60512, O60513, O60909, O88419, P08037, P15291, P15535, P34548, Q09323, Q3YL68, Q5EA87, Q5NVN3, Q66HH1, Q6P768, Q80WN7, Q80WN8, Q80WN9, Q8R087, Q91YY2, Q9GUM2, Q9JJ04, Q9JMK0, Q9UBV7, Q9UBX8, Q9VBZ9, Q9WVK5, Q9Z2Y2, Q6ZQ11, Q86X52

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
B4GALT1	“down-regulates quantity”	UDP-D-galactose	“chemical modification”
B4GALT1	“down-regulates quantity”	D-glucopyranose	“chemical modification”
B4GALT1	“up-regulates quantity”	lactose	“chemical modification”
B4GALT1	“up-regulates quantity”	UDP(3-)	“chemical modification”
B4GALT1	“form complex”	“Lactose synthase complex”	binding

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	79
Likely benign	42
Benign	18

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
16229	NM_001497.4(B4GALT1):c.1031dup (p.Arg345fs)	Pathogenic
2502285	NM_001497.4(B4GALT1):c.1055A>G (p.Asn352Ser)	Pathogenic
998093	NM_001497.4(B4GALT1):c.579C>G (p.Tyr193Ter)	Pathogenic

SpliceAI

1074 predictions. Top by Δscore:

Variant	Effect	Δscore
9:33113585:ACC:A	acceptor_loss	1.0000
9:33113586:CCT:C	acceptor_loss	1.0000
9:33113587:CTAC:C	acceptor_loss	1.0000
9:33113588:T:A	acceptor_loss	1.0000
9:33120605:GCCTG:G	acceptor_loss	1.0000
9:33120606:CC:C	acceptor_loss	1.0000
9:33120606:CCTGG:C	acceptor_gain	1.0000
9:33120607:CTG:C	acceptor_loss	1.0000
9:33120608:T:G	acceptor_loss	1.0000
9:33120610:G:C	acceptor_gain	1.0000
9:33120610:G:GC	acceptor_gain	1.0000
9:33135183:CCTCA:C	donor_loss	1.0000
9:33135184:CTCA:C	donor_loss	1.0000
9:33135185:TCAC:T	donor_loss	1.0000
9:33135186:CACCT:C	donor_loss	1.0000
9:33135187:A:C	donor_loss	1.0000
9:33135421:CCCA:C	acceptor_gain	1.0000
9:33135422:CCA:C	acceptor_gain	1.0000
9:33135422:CCAC:C	acceptor_gain	1.0000
9:33135423:CA:C	acceptor_gain	1.0000
9:33135423:CAC:C	acceptor_gain	1.0000
9:33135425:C:CC	acceptor_gain	1.0000
9:33113582:CAAAC:C	acceptor_gain	0.9900
9:33113587:C:CC	acceptor_gain	0.9900
9:33113874:CTAAT:C	acceptor_gain	0.9900
9:33116109:GTAGG:G	acceptor_gain	0.9900
9:33116112:GG:G	acceptor_gain	0.9900
9:33116114:C:CC	acceptor_gain	0.9900
9:33120414:CTTA:C	donor_loss	0.9900
9:33120417:ACCTG:A	donor_loss	0.9900

AlphaMissense

2583 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:33115991:C:G	R320T	1.000
9:33116006:T:A	D315V	1.000
9:33116006:T:C	D315G	1.000
9:33116006:T:G	D315A	1.000
9:33116007:C:G	D315H	1.000
9:33116008:A:C	D314E	1.000
9:33116008:A:T	D314E	1.000
9:33116009:T:A	D314V	1.000
9:33116009:T:C	D314G	1.000
9:33116009:T:G	D314A	1.000
9:33116010:C:A	D314Y	1.000
9:33116010:C:G	D314H	1.000
9:33116012:T:A	E313V	1.000
9:33116020:C:A	W310C	1.000
9:33116020:C:G	W310C	1.000
9:33116022:A:G	W310R	1.000
9:33116022:A:T	W310R	1.000
9:33116045:C:T	G302E	1.000
9:33116090:C:T	G287E	1.000
9:33120503:A:G	L251P	1.000
9:33120506:T:A	D250V	1.000
9:33120512:T:A	D248V	1.000
9:33120512:T:C	D248G	1.000
9:33120512:T:G	D248A	1.000
9:33120568:A:C	N229K	1.000
9:33120568:A:T	N229K	1.000
9:33120585:G:T	R224S	1.000
9:33120586:A:C	N223K	1.000
9:33120586:A:T	N223K	1.000
9:33120589:G:C	F222L	1.000

dbSNP variants (sampled 300 via entrez): RS1000011368 (9:33179130 C>A), RS1000082987 (9:33166186 T>C), RS1000096439 (9:33151655 A>C), RS1000126402 (9:33120203 A>C), RS1000190044 (9:33132791 T>C), RS1000214701 (9:33155761 T>G), RS1000229347 (9:33118777 T>C), RS1000247465 (9:33155357 A>C,G), RS1000254732 (9:33114824 A>G), RS1000266644 (9:33182349 T>C), RS1000314343 (9:33109169 C>T), RS1000318070 (9:33182106 G>A), RS1000343113 (9:33126049 G>A,T), RS1000374883 (9:33149244 G>A), RS1000509021 (9:33162302 G>A,T)

Disease associations

OMIM: gene MIM:137060 | disease phenotypes: MIM:607091, MIM:620364

GenCC curated gene-disease

Disease	Classification	Inheritance
B4GALT1-congenital disorder of glycosylation	Strong	Autosomal recessive

Mondo (2): B4GALT1-congenital disorder of glycosylation (MONDO:0011772), combined low LDL and fibrinogen (MONDO:0957260)

Orphanet (1): B4GALT1-CDG (Orphanet:79332)

HPO phenotypes

44 total (30 of 44 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000219	Thin upper lip vermilion
HP:0000238	Hydrocephalus
HP:0000256	Macrocephaly
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000369	Low-set ears
HP:0000431	Wide nasal bridge
HP:0000545	Myopia
HP:0000821	Hypothyroidism
HP:0000969	Edema
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001305	Dandy-Walker malformation
HP:0001321	Cerebellar hypoplasia
HP:0001518	Small for gestational age
HP:0001622	Premature birth
HP:0001744	Splenomegaly
HP:0001892	Abnormal bleeding
HP:0001976	Reduced antithrombin III activity
HP:0001999	Abnormal facial shape
HP:0002014	Diarrhea
HP:0002240	Hepatomegaly
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003160	Abnormal isoelectric focusing of serum transferrin
HP:0003186	Inverted nipples
HP:0003198	Myopathy
HP:0003199	Decreased muscle mass
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003256	Abnormality of the coagulation cascade

GWAS associations

28 associations (top):

Study	Trait	p-value
GCST001791_33	Urate levels	4.000000e-07
GCST001848_19	IgG glycosylation	3.000000e-11
GCST001848_327	IgG glycosylation	3.000000e-10
GCST001848_340	IgG glycosylation	3.000000e-11
GCST001848_507	IgG glycosylation	1.000000e-10
GCST001848_676	IgG glycosylation	5.000000e-07
GCST001849_2	IgG glycosylation	5.000000e-08
GCST003123_21	Severe influenza A (H1N1) infection	9.000000e-11
GCST003124_25	Mild influenza (H1N1) infection	1.000000e-13
GCST003125_4	Influenza A (H1N1) infection	1.000000e-14
GCST004925_2	IgG N-glycosylation phenotypes (multivariate analysis)	1.000000e-10
GCST004927_8	IgG galactosylation phenotypes (multivariate analysis)	7.000000e-08
GCST004929_1	IgG fucosylation phenotypes (multivariate analysis)	5.000000e-13
GCST005999_17	Aspartate aminotransferase levels	6.000000e-14
GCST006585_2450	Blood protein levels	6.000000e-08
GCST007733_29	Serum uric acid levels	4.000000e-07
GCST007733_62	Serum uric acid levels	7.000000e-06
GCST008108_3	N-glycan levels	3.000000e-12
GCST008971_51	Urate levels	4.000000e-14
GCST008972_186	Urate levels	5.000000e-20
GCST009860_5	IgG N-glycosylation phenotypes (multivariate analysis)	9.000000e-34
GCST010637_30	Urate levels	2.000000e-09
GCST011351_12	Aspartate aminotransferase levels	1.000000e-13
GCST011369_16	Iron status biomarkers (ferritin levels)	1.000000e-11
GCST90002383_514	Hematocrit	1.000000e-10
GCST90002384_260	Hemoglobin	1.000000e-10
GCST90002403_609	Red blood cell count	2.000000e-10
GCST90011899_182	Aspartate aminotransferase levels	8.000000e-33

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0005193	serum IgG glycosylation measurement
EFO:1001488	influenza A (H1N1)
EFO:0008425	IgG galactosylation measurement
EFO:0008427	IgG fucosylation measurement
EFO:0004736	aspartate aminotransferase measurement
EFO:0004761	uric acid measurement
EFO:0004999	N-glycan measurement
EFO:0004459	ferritin measurement
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004305	erythrocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535753	Congenital disorder of glycosylation type 2D (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4384 (SINGLE PROTEIN)

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 7 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.73	Ki	1860	nM	CHEMBL2368685
5.73	Ki	1860	nM	CHEMBL1214871
5.31	Ki	4910	nM	UDP-GALACTOSE

PubChem BioAssay actives

3 with measured affinity, of 37 total; 3 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
[[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-[2-[2-[2-(naphthalen-2-ylmethoxy)ethoxy]ethoxy]ethoxymethyl]oxan-2-yl] hydrogen phosphate	499231: Inhibition of human Beta-1,4-galactosyltransferase 1	ki	1.8600	uM
[[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6-[2-[2-[2-(naphthalen-2-ylmethoxy)ethoxy]ethoxy]ethoxymethyl]oxan-2-yl] hydrogen phosphate	254502: Inhibitory constant against human galactosyltransferase using UDP-Gal	ki	1.8600	uM
[[(2R,3S,4R,5S)-5-(2,4-dioxo-1H-pyrimidin-6-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] hydrogen phosphate	254470: Inhibitory constant against human recombinant Beta-1,4-galactosyltransferase I	ki	4.9100	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	3
bisphenol A	decreases expression, increases expression	2
Acetaminophen	decreases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Diethylstilbestrol	increases expression	2
Doxorubicin	decreases expression	2
Estradiol	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
triphenyl phosphate	affects expression	1
glycidyl methacrylate	decreases expression	1
methylselenic acid	affects expression	1
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone	affects cotreatment, increases expression, decreases reaction	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sulforaphane	increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	increases expression	1
2-tert-butylhydroquinone	increases expression	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	decreases methylation	1
coumarin	increases phosphorylation	1
andrographolide	increases expression	1
4-nonylphenol	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-octylphenol	increases expression	1
paricalcitol	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
bardoxolone methyl	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1218969	Binding	Inhibition of human Beta-1,4-galactosyltransferase 1	An efficient approach to the discovery of potent inhibitors against glycosyltransferases. — J Med Chem

Cellosaurus cell lines

8 cell lines: 5 transformed cell line, 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1KW	Abcam HeLa B4GALT1 KO	Cancer cell line	Female
CVCL_SE54	HAP1 B4GALT1 (-) 1	Cancer cell line	Male
CVCL_SE55	HAP1 B4GALT1 (-) 2	Cancer cell line	Male
CVCL_VT68	CHO IM4/V/IV-G1	Transformed cell line	Female
CVCL_VT69	CHO IM4/V/IV-G2	Transformed cell line	Female
CVCL_VT70	CHO IM4/V/IV-G3	Transformed cell line	Female
CVCL_VT71	CHO IM4/V/IV-G4	Transformed cell line	Female
CVCL_VT72	CHO IM4/V/IV-G5	Transformed cell line	Female

Clinical trials (associated diseases)

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