ST6GAL1

Summary

ST6GAL1 (ST6 beta-galactoside alpha-2,6-sialyltransferase 1, HGNC:10860) is a protein-coding gene on chromosome 3q27.3, encoding Beta-galactoside alpha-2,6-sialyltransferase 1 (P15907). Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates.

This gene encodes a member of glycosyltransferase family 29. The encoded protein is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates. The protein, which is normally found in the Golgi but can be proteolytically processed to a soluble form, is involved in the generation of the cell-surface carbohydrate determinants and differentiation antigens HB-6, CD75, and CD76. This gene has been incorrectly referred to as CD75. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 6480 — RefSeq curated summary.

At a glance

• GWAS associations: 58
• Clinical variants (ClinVar): 39 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_173216

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10860
Approved symbol	ST6GAL1
Name	ST6 beta-galactoside alpha-2,6-sialyltransferase 1
Location	3q27.3
Locus type	gene with protein product
Status	Approved
Aliases	CDw75
Ensembl gene	ENSG00000073849
Ensembl biotype	protein_coding
OMIM	109675
Entrez	6480

Gene structure

Transcript identifiers

Ensembl transcripts: 71 — 64 protein_coding, 3 protein_coding_CDS_not_defined, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000169298, ENST00000416235, ENST00000417392, ENST00000423451, ENST00000427315, ENST00000430309, ENST00000438590, ENST00000440338, ENST00000442023, ENST00000446170, ENST00000448044, ENST00000448408, ENST00000448449, ENST00000455441, ENST00000457772, ENST00000458216, ENST00000463542, ENST00000464827, ENST00000468614, ENST00000470633, ENST00000485105, ENST00000676633, ENST00000676786, ENST00000677292, ENST00000879710, ENST00000879711, ENST00000879712, ENST00000879713, ENST00000879714, ENST00000879715, ENST00000879716, ENST00000879717, ENST00000879718, ENST00000879719, ENST00000879720, ENST00000879721, ENST00000879722, ENST00000879723, ENST00000879724, ENST00000879725, ENST00000879726, ENST00000879727, ENST00000879728, ENST00000879729, ENST00000879730, ENST00000879731, ENST00000879732, ENST00000879733, ENST00000879734, ENST00000879735, ENST00000879736, ENST00000879737, ENST00000912779, ENST00000912780, ENST00000912781, ENST00000912782, ENST00000912783, ENST00000912784, ENST00000912785, ENST00000912786, ENST00000955782, ENST00000955783, ENST00000955784, ENST00000955785, ENST00000955786, ENST00000955787, ENST00000955788, ENST00000955789, ENST00000955790, ENST00000955791, ENST00000955792

RefSeq mRNA: 4 — MANE Select: NM_173216 NM_001353916, NM_003032, NM_173216, NM_173217

CCDS: CCDS3285, CCDS46973

Canonical transcript exons

ENST00000169298 — 8 exons

Exon	Start	End
ENSE00001140520	187042654	187043310
ENSE00001379394	187038742	187038873
ENSE00001392050	187075562	187078553
ENSE00001400329	186963785	186963926
ENSE00001924789	186930526	186930834
ENSE00003465070	187051249	187051346
ENSE00003607959	187074159	187074333
ENSE00003673469	187072849	187072947

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.6375 / max 1136.1428, expressed in 1471 samples.

FANTOM5 promoters (27 alternative TSS)

Promoter ID	TPM avg	Samples expressed
40342	21.1427	1439
40356	1.9956	194
40341	1.9760	815
40351	1.4821	167
40359	1.4385	38
40343	0.9054	486
40360	0.4959	25
40339	0.3255	163
40344	0.2673	123
40358	0.2472	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
liver	UBERON:0002107	98.90	gold quality
right lobe of liver	UBERON:0001114	98.89	gold quality
renal medulla	UBERON:0000362	98.25	gold quality
lymph node	UBERON:0000029	97.98	gold quality
bone marrow cell	CL:0002092	97.53	gold quality
epithelium of nasopharynx	UBERON:0001951	97.38	gold quality
nasopharynx	UBERON:0001728	97.36	gold quality
nasal cavity epithelium	UBERON:0005384	97.18	gold quality
urethra	UBERON:0000057	96.98	gold quality
epithelium of bronchus	UBERON:0002031	96.73	gold quality
bronchus	UBERON:0002185	96.73	gold quality
bronchial epithelial cell	CL:0002328	96.59	gold quality
trachea	UBERON:0003126	96.03	gold quality
thymus	UBERON:0002370	95.93	gold quality
colonic epithelium	UBERON:0000397	95.62	gold quality
tonsil	UBERON:0002372	95.60	gold quality
vermiform appendix	UBERON:0001154	95.59	gold quality
spleen	UBERON:0002106	95.45	gold quality
caecum	UBERON:0001153	95.36	gold quality
granulocyte	CL:0000094	95.10	gold quality
inferior vagus X ganglion	UBERON:0005363	95.04	gold quality
pylorus	UBERON:0001166	94.80	gold quality
rectum	UBERON:0001052	94.71	gold quality
trabecular bone tissue	UBERON:0002483	94.12	gold quality
adult mammalian kidney	UBERON:0000082	94.04	gold quality
kidney	UBERON:0002113	93.90	gold quality
nasal cavity mucosa	UBERON:0001826	93.87	gold quality
trigeminal ganglion	UBERON:0001675	93.68	gold quality
corpus callosum	UBERON:0002336	93.56	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.52	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-30	yes	1346.02
E-HCAD-25	yes	708.82
E-HCAD-35	yes	49.26
E-ANND-3	yes	34.22
E-CURD-119	yes	31.57
E-CURD-122	yes	20.53
E-GEOD-125970	yes	6.91

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, DBP, HNF1A, POU2F1, SP1

miRNA regulators (miRDB)

87 targeting ST6GAL1, 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-4533	100.00	69.48	2758
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-1251-3P	99.64	67.21	1408

Literature-anchored findings (GeneRIF, showing 40)

• ST6Gal I sialyltransferase has a role in regulating galectin-1-induced CD45 clustering, phosphatase modulation, and T cell death (PMID:12499376)
• Expression of alpha 2,6-sialyltransferase ST6Gal I is enhanced in cervical squamous cell carcinoma. (PMID:12798701)
• Transcriptional activation of beta-galactoside alpha2,6-sialyltransferase in colon adenocarcinoma cells. (PMID:12878221)
• High levels of ST6GAL-I in the tumor tissue correlated with secondary local tumor recurrence (p = 0.005; p = 0.012). (PMID:12931020)
• specific kinase enzymes have important roles in the expression and catalytic activity of the alpha2,6 STN (ST6N) isozyme (PMID:12943659)
• Neoplastic transformation but not cirrhosis can alter the process of alpha2,6-sialylation of liver glycoproteins. (PMID:14514712)
• sialyltransferases expression and activity are increased in Grave’s disease (PMID:16053379)
• the presence of alpha2,6-linked sialic acid added by ST6Gal.I on membrane glycoconjugates increases the binding to extracellular matrix components, resulting in a membrane stabilization of beta1 integrins, further strengthening the binding (PMID:16192407)
• ST6Gal I is upregulated in tumor and transitional tissues from colorectal cancer patients (PMID:16319516)
• siRNA targeting to ST6Gal I can effectively downregulate the ST6Gal I expression in HeLa cell and further lead to the decline of cell adhesion and invasiveness to ECM. (PMID:17441333)
• Appearance of asialoconjugates in alcoholics is possibly due to the down-regulation of ST6GalI gene expression. (PMID:17697868)
• soluble ST6Gal I produced by BACE1 plays, at least in part, a role in the sialylation of soluble glycoproteins (PMID:17897958)
• Proteolytic shedding of ST6Gal-I by BACE1 regulates the glycosylation and function of alpha4beta1 integrins (PMID:18650447)
• Alcohol-mediated down-regulation of hepatic ST6Gal1 gene leads to defective intracellular lipid and lipoprotein transport, which in turn may contribute to alcoholic steatosis. (PMID:19013288)
• There are two possible mechanisms for the upregulation of plasma ST6Gal I in hepatopathological situations: one accompanied by acute phase reactions to increase hepatic ST6Gal I expression and the other triggered by oxidative stress in the liver. (PMID:19150807)
• Activity of alpha2,6-sialyltransferase and its gene expression in peripheral B lymphocytes in patients with IgA nephropathy. (PMID:19170967)
• DBA.44(CD76) patterns of expression would help the pathologist to recognize the morphological pattern of the different subgroups of splenic marginal zone lymphomas (PMID:19413643)
• ST6Gal I and ST3Gal V were positively correlated with the high risk of pediatric acute leukemia. (PMID:19709745)
• enhanced tumour ST6Gal I activity and an increased CDw75 expression may play a role in malignant transformation of colorectal cancer (PMID:20003255)
• Adhesion of ST6Gal I-mediated human colon cancer cells to fibronectin contributes to cell survival by integrin beta1-mediated paxillin and AKT activation. (PMID:20127017)
• ST6Gal I is responsible for ST2H antigen biosynthesis in human colon cancer cells. (PMID:20656882)
• These results indicated that gastric cancer tissues expressed high levels of alpha 2,3-linked sialic acid residues, ST3Gal IV, and ST6Gal I. (PMID:21140242)
• the occurrence of CD75s- and iso-CD75s-gangliosides in tumor tissues is largely independent of the transcriptional expression of ST6GAL1 and ST3GAL6 (PMID:21147760)
• Sialylation of the Fas death receptor by ST6Gal-I provides protection against Fas-mediated apoptosis in colon carcinoma cells. (PMID:21550977)
• CDw75 expression in colorectal tumoural tissue was correlated with growth pattern (p = 0.044), Dukes stage (p = 0.002), TNM stage (p = 0.020) and distant metastasis (p = 0.005). (PMID:21778787)
• ST6Gal-I regulates macrophage apoptosis via alpha2-6 sialylation of the TNFR1 death receptor. (PMID:21930713)
• Our results suggest that soluble ST6Gal may participate in cancer progression and metastasis prior to being secreted from cancer cells (PMID:22449099)
• ST6Gal-I protein expression is upregulated in epithelial tumors. (PMID:23358684)
• the suppressive role of Necl-2 in the HRG-induced ErbB2/ErbB3 signaling is regulated by miR-199a at least through the reduction of the ST6GAL1-catalyzed sialylation of Necl-2 (PMID:23504322)
• the high expression of ST3Gal I and ST6Gal I, in skin tumors, is associated with tumors with greater potential for invasion and metastasis, as in the case of squamous cell carcinoma, and this may be related to their behavior. (PMID:23549466)
• A large glycan from a symmetry mate localizes to the active site of ST6Gal-I in an orientation compatible with catalysis. The glycan binding mode can be generalized to any glycoprotein that is a substrate of ST6Gal-I. (PMID:23999306)
• The study detected only one allele of each polymorphism in the ST6GAL1P1 promoter. (PMID:24606438)
• ST6GAL1 promotes TGF-beta-dependent epithelial-mesenchymal transition (PMID:25344606)
• Study characterizes ST6GAL1 expression loss caused by aberrant ST6GAL1 promoter methylation potentially indicating a tumor suppressive role in bladder carcinogenesis. (PMID:25465919)
• The lymphocyte levels of NEU1 and ST6GAL1 mRNA expression are significantly increased in erythremia. (PMID:25566667)
• Sialylation by beta-galactoside alpha-2,6-sialyltransferase regulates cell adhesion and invasion in human anaplastic large cell lymphoma. (PMID:25573487)
• CDX2 transcriptionally regulates ST6GalNAc-I gene expression, specifically in the preneoplastic intestinal metaplasia lesion. (PMID:25867765)
• These results suggest a role for ST6Gal-I to promote the growth and invasion of osteosarcoma cells. (PMID:26054692)
• Data indicate that O-glycan-specific alpha2,6 sialyltransferase regulate cancer growth and metastasis by regulating galectins Gal-1- and Gal-3-binding moieties on O-glycans. (PMID:26224120)
• Expression levels of sialyltransferases ST3GAL1 and ST3GAL4 were upregulated in the HRMECs after high-glucose stimulation. (PMID:26258617)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	st6gal1	ENSDARG00000044514
mus_musculus	St6gal1	ENSMUSG00000022885
rattus_norvegicus	St6gal1	ENSRNOG00000001823

Paralogs (14): ST3GAL1 (ENSG00000008513), ST3GAL6 (ENSG00000064225), ST6GALNAC1 (ENSG00000070526), ST6GALNAC2 (ENSG00000070731), ST3GAL4 (ENSG00000110080), ST3GAL5 (ENSG00000115525), ST6GALNAC5 (ENSG00000117069), C20orf173 (ENSG00000125975), ST3GAL3 (ENSG00000126091), ST6GALNAC4 (ENSG00000136840), ST6GAL2 (ENSG00000144057), ST3GAL2 (ENSG00000157350), ST6GALNAC6 (ENSG00000160408), ST6GALNAC3 (ENSG00000184005)

Protein

Protein identifiers

Beta-galactoside alpha-2,6-sialyltransferase 1 — P15907 (reviewed: P15907)

Alternative names: CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,6-sialyltransferase 1, ST6Gal I, Sialyltransferase 1

All UniProt accessions (14): P15907, C9IYS8, C9J6X5, C9JAT4, C9JFM4, C9JH16, C9JI90, C9JKG0, C9JPG6, C9JR47, C9JTR0, C9JVK7, C9K0R8, H7C472

UniProt curated annotations — full annotation on UniProt →

Function. Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates. In B lymphocytes, generates neuraminidase-sensitive lymphocyte cell-surface differentiation antigens, such as CDw75, HB-6 and CD76. Sialylates complex-type N-glycans attached on the fragment crystallizable (Fc) of IgGs confering anti-inflammatory effector functions. Preferentially monosialylates the alpha(1->3) mannose antenna of Fc glycoforms with subsequent disialylation occurring at a much slower rate.

Subunit / interactions. Monomer and homodimer.

Subcellular location. Golgi apparatus. Golgi stack membrane. Secreted.

Post-translational modifications. N-glycosylated.

Activity regulation. Inhibited by CTP.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the glycosyltransferase 29 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P15907-1	1	yes
P15907-2	2

RefSeq proteins (4): NP_001340845, NP_003023, NP_775323, NP_775324 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001675	Glyco_trans_29	Family
IPR012163	Sialyl_trans	Family
IPR038578	GT29-like_sf	Homologous_superfamily

Pfam: PF00777

Enzyme classification (BRENDA):

• EC 2.4.99.1 — beta-galactoside alpha-(2,6)-sialyltransferase (BRENDA: 0 organisms, 0 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 10 shown:

• a beta-D-galactoside + CMP-N-acetyl-beta-neuraminate = an N-acetyl-alpha-neuraminyl-(2->6)-beta-D-galactosyl derivative + CMP + H(+) (RHEA:52104)
• 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)-beta-D-GlcNAc}-L-asparaginyl-[protein] + CMP-N-acetyl-beta-neuraminate = an N(4)-{alpha-Neu5Ac-(2->6)-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)-beta-D-GlcNAc}-L-asparaginyl-[protein] + CMP + H(+) (RHEA:82947)
• 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] + CMP-N-acetyl-beta-neuraminate = an N(4)-{alpha-Neu5Ac-(2->6)-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] + CMP + H(+) (RHEA:83927)
• an N(4)-{alpha-Neu5Ac-(2->6)-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] + CMP-N-acetyl-beta-neuraminate = an N(4)-{alpha-Neu5Ac-(2->6)-beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[alpha-Neu5Ac-(2->6)-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] + CMP + H(+) (RHEA:83931)
• 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] + CMP-N-acetyl-beta-neuraminate = an N(4)-{alpha-Neu5Ac-(2->6)-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] + CMP + H(+) (RHEA:84035)
• an N(4)-{alpha-Neu5Ac-(2->6)-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] + CMP-N-acetyl-beta-neuraminate = an N(4)-{alpha-Neu5Ac-(2->6)-beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[beta-D-GlcNAc-(1->4)]-[alpha-Neu5Ac-(2->6)-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] + CMP + H(+) (RHEA:84039)
• an N(4)-{alpha-Neu5Ac-(2->6)-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)-beta-D-GlcNAc}-L-asparaginyl-[protein] + CMP-N-acetyl-beta-neuraminate = an N(4)-{alpha-Neu5Ac-(2->6)-beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[alpha-Neu5Ac-(2->6)-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)-beta-D-GlcNAc}-L-asparaginyl-[protein] + CMP + H(+) (RHEA:84119)
• 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] + CMP-N-acetyl-beta-neuraminate = an N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[alpha-Neu5Ac-(2->6)-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] + CMP + H(+) (RHEA:85275)
• 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] + CMP-N-acetyl-beta-neuraminate = an N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[beta-D-GlcNAc-(1->4)]-[alpha-Neu5Ac-(2->6)-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] + CMP + H(+) (RHEA:85395)
• an N(4)-{beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[beta-D-GlcNAc-(1->4)]-[alpha-Neu5Ac-(2->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] + CMP-N-acetyl-beta-neuraminate = an N(4)-{alpha-Neu5Ac-(2->6)-beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[beta-D-GlcNAc-(1->4)]-[alpha-Neu5Ac-(2->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] + CMP + H(+) (RHEA:85403)

UniProt features (57 total): helix 19, binding site 10, strand 9, turn 4, disulfide bond 3, sequence conflict 3, topological domain 2, glycosylation site 2, chain 1, modified residue 1, transmembrane region 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6QVS	X-RAY DIFFRACTION	1.6
6QVT	X-RAY DIFFRACTION	1.7
4JS1	X-RAY DIFFRACTION	2.09
4JS2	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P15907-F1	88.69	0.79

Functional residue map

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

Ligand- & substrate-binding residues (10): 365; 369; 370; 376; 189; 212; 233; 322–324; 353; 354

Post-translational modifications (1): 369

Disulfide bonds (3): 142–406, 184–335, 353–364

Glycosylation sites (2): 149, 161

Mutagenesis-validated functional residues (1):

Position	Phenotype
24	no effect on dimerization and on location at the golgi stack.

Function

Pathways and Gene Ontology

Reactome pathways

24 pathways

ID	Pathway
R-HSA-4085001	Sialic acid metabolism
R-HSA-9683673	Maturation of protein 3a
R-HSA-9694548	Maturation of spike protein
R-HSA-9694719	Maturation of protein 3a
R-HSA-975577	N-Glycan antennae elongation
R-HSA-977068	Termination of O-glycan biosynthesis
R-HSA-1643685	Disease
R-HSA-392499	Metabolism of proteins
R-HSA-446193	Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-446219	Synthesis of substrates in N-glycan biosythesis
R-HSA-5173105	O-linked glycosylation
R-HSA-5663205	Infectious disease
R-HSA-597592	Post-translational protein modification
R-HSA-913709	O-linked glycosylation of mucins
R-HSA-948021	Transport to the Golgi and subsequent modification
R-HSA-9678108	SARS-CoV-1 Infection
R-HSA-9679506	SARS-CoV Infections
R-HSA-9683701	Translation of Structural Proteins
R-HSA-9694516	SARS-CoV-2 Infection
R-HSA-9694635	Translation of Structural Proteins
R-HSA-975576	N-glycan antennae elongation in the medial/trans-Golgi
R-HSA-9772573	Late SARS-CoV-2 Infection Events
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 375 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, MODULE_52, LOPEZ_MESOTHELIOMA_SURVIVAL_OVERALL_UP, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, MODULE_45, KEGG_N_GLYCAN_BIOSYNTHESIS, USF_C, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, MODULE_75, ROZANOV_MMP14_TARGETS_UP, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_DN

GO Biological Process (6): N-acetylneuraminate metabolic process (GO:0006054), protein O-linked glycosylation via N-acetylgalactosamine (GO:0016266), obsolete protein N-linked glycosylation via asparagine (GO:0018279), viral protein processing (GO:0019082), sialylation (GO:0097503), obsolete protein glycosylation (GO:0006486)

GO Molecular Function (6): beta-galactoside alpha-2,6-sialyltransferase activity (GO:0003835), sialyltransferase activity (GO:0008373), protein homodimerization activity (GO:0042803), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (5): Golgi membrane (GO:0000139), extracellular region (GO:0005576), Golgi apparatus (GO:0005794), Golgi cisterna membrane (GO:0032580), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Translation of Structural Proteins	2
Asparagine N-linked glycosylation	2
Post-translational protein modification	2
SARS-CoV Infections	2
Synthesis of substrates in N-glycan biosythesis	1
Translation of Structural Proteins	1
N-glycan antennae elongation in the medial/trans-Golgi	1
O-linked glycosylation of mucins	1
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1
Disease	1
Metabolism of proteins	1
O-linked glycosylation	1
Viral Infection Pathways	1
SARS-CoV-1 Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
amino sugar metabolic process	1
carboxylic acid metabolic process	1
protein O-linked glycosylation	1
viral process	1
viral gene expression	1
macromolecule modification	1
sialyltransferase activity	1
glycosyltransferase activity	1
identical protein binding	1
protein dimerization activity	1
binding	1
catalytic activity	1
transferase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
Golgi cisterna	1

Protein interactions and networks

STRING

1256 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ST6GAL1	B4GALT1	P15291	913
ST6GAL1	MGAT5	Q09328	732
ST6GAL1	FUT8	Q9BYC5	732
ST6GAL1	HLA-B	P01889	641
ST6GAL1	GCNT1	Q02742	605
ST6GAL1	MGAT3	Q09327	604
ST6GAL1	C1GALT1	Q9NS00	603
ST6GAL1	MAN2A1	Q16706	583
ST6GAL1	B3GNT2	Q9NY97	582
ST6GAL1	FUT1	P19526	581
ST6GAL1	MGAT1	P26572	566
ST6GAL1	HSPA1L	P34931	556
ST6GAL1	FUT6	P51993	556
ST6GAL1	COG4	Q9H9E3	556
ST6GAL1	SIGLEC9	Q9Y336	548

IntAct

9 interactions, top by confidence:

A	B	Type	Score
ST6GAL1	ATP2A1	psi-mi:“MI:0915”(physical association)	0.400
BMP2K	ST6GAL1	psi-mi:“MI:0915”(physical association)	0.370
ST6GAL1		psi-mi:“MI:0915”(physical association)	0.370
ST6GAL1	HLA-C	psi-mi:“MI:0914”(association)	0.350
CD81	STX3	psi-mi:“MI:0914”(association)	0.350
ST6GAL1	HLA-B	psi-mi:“MI:0914”(association)	0.350
SLC30A7	ESYT2	psi-mi:“MI:0914”(association)	0.350
ST6GAL1	acs	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (45): KIAA1244 (Affinity Capture-MS), ATRIP (Affinity Capture-MS), WAPAL (Affinity Capture-MS), ZYG11B (Affinity Capture-MS), GLMN (Affinity Capture-MS), HOOK2 (Affinity Capture-MS), SAAL1 (Affinity Capture-MS), USP28 (Affinity Capture-MS), PRMT9 (Affinity Capture-MS), TNPO3 (Affinity Capture-MS), INTS3 (Affinity Capture-MS), INTS12 (Affinity Capture-MS), PIP4K2A (Affinity Capture-MS), ERGIC2 (Affinity Capture-MS), HLA-C (Affinity Capture-MS)

ESM2 similar proteins: A2A699, A2BD09, A5D7T4, A8MVW0, B0BN44, O77681, O88829, P0CG36, P0CG37, P15907, P51693, P59383, P61132, P70277, P97325, Q03157, Q07105, Q11203, Q3UPI1, Q3UY90, Q5K027, Q5QQ37, Q64685, Q66NC0, Q68BL7, Q6P7B4, Q6UWH4, Q701R2, Q701R3, Q701R4, Q70D51, Q766D5, Q76K27, Q76KP1, Q80WV3, Q866Y3, Q86VZ4, Q8BHP7, Q8CB67, Q8VCS0

Diamond homologs: A2WX64, A2XVC2, A2ZI41, A5D7T4, O35696, O43173, P13721, P15907, P61130, P61131, P61643, P61644, P61645, P61943, P70277, Q02745, Q07977, Q08E15, Q11200, Q11201, Q11204, Q11205, Q11206, Q16842, Q2QXM3, Q2R2B1, Q5K027, Q5QQ37, Q5RE85, Q64685, Q64689, Q64690, Q6H8M7, Q6KB54, Q6KB58, Q6KB59, Q6ZH45, Q6ZXC9, Q701R0, Q701R1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ST6GAL1	“down-regulates activity”	CD22	glycosylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	27
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
814507	GRCh37/hg19 3q27.2-27.3(chr3:185879162-187446035)x1	Pathogenic

SpliceAI

2148 predictions. Top by Δscore:

Variant	Effect	Δscore
3:186930831:GCGA:G	donor_gain	1.0000
3:186930835:G:GG	donor_gain	1.0000
3:186942425:GTT:G	donor_gain	1.0000
3:186942428:G:GG	donor_gain	1.0000
3:186972044:GGCTC:G	donor_gain	1.0000
3:186972045:GCTC:G	donor_gain	1.0000
3:186972048:C:G	donor_gain	1.0000
3:187051239:T:TA	acceptor_gain	1.0000
3:187051247:A:AC	acceptor_loss	1.0000
3:187051247:A:AG	acceptor_gain	1.0000
3:187051247:AGAT:A	acceptor_gain	1.0000
3:187051248:G:GA	acceptor_gain	1.0000
3:187051248:GAT:G	acceptor_gain	1.0000
3:187051248:GATG:G	acceptor_gain	1.0000
3:187051342:CTCAG:C	donor_loss	1.0000
3:187051343:TCAG:T	donor_loss	1.0000
3:187051344:CAGG:C	donor_loss	1.0000
3:187051345:AGGTA:A	donor_loss	1.0000
3:187051346:GGTA:G	donor_loss	1.0000
3:187051347:G:A	donor_loss	1.0000
3:187072847:A:AG	acceptor_gain	1.0000
3:187072847:AGTT:A	acceptor_gain	1.0000
3:187072847:AGTTG:A	acceptor_gain	1.0000
3:187072848:G:GT	acceptor_gain	1.0000
3:187072848:GT:G	acceptor_gain	1.0000
3:187072848:GTT:G	acceptor_gain	1.0000
3:187072848:GTTG:G	acceptor_gain	1.0000
3:187072848:GTTGG:G	acceptor_gain	1.0000
3:187072949:T:G	donor_loss	1.0000
3:187074157:A:AG	acceptor_gain	1.0000

AlphaMissense

2703 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:187051340:C:A	N233K	0.998
3:187051340:C:G	N233K	0.998
3:187075639:T:A	C353S	0.998
3:187075640:G:C	C353S	0.998
3:187075672:T:A	C364S	0.998
3:187075673:G:A	C364Y	0.998
3:187075673:G:C	C364S	0.998
3:187075690:C:G	H370D	0.998
3:187051330:G:C	R230P	0.997
3:187072912:T:A	W257R	0.997
3:187072912:T:C	W257R	0.997
3:187075639:T:C	C353R	0.997
3:187075640:G:A	C353Y	0.997
3:187075641:C:G	C353W	0.997
3:187075672:T:C	C364R	0.997
3:187075674:C:G	C364W	0.997
3:187075692:C:A	H370Q	0.997
3:187075692:C:G	H370Q	0.997
3:187075706:A:T	E375V	0.997
3:187043253:T:A	C184S	0.996
3:187043254:G:C	C184S	0.996
3:187043260:T:A	V186D	0.996
3:187051270:G:C	R210T	0.996
3:187051277:T:A	N212K	0.996
3:187051277:T:G	N212K	0.996
3:187051312:G:T	G224V	0.996
3:187072914:G:C	W257C	0.996
3:187072914:G:T	W257C	0.996
3:187074159:T:A	W269R	0.996
3:187074159:T:C	W269R	0.996

dbSNP variants (sampled 300 via entrez): RS1000008282 (3:187003743 G>C), RS1000015928 (3:187000174 C>T), RS1000018891 (3:187013564 T>C), RS1000031685 (3:187045928 G>A), RS1000065591 (3:187052066 A>G), RS1000071644 (3:186988013 C>T), RS1000091986 (3:187013362 G>A,C,T), RS1000100841 (3:187052260 A>G,T), RS1000120374 (3:186941252 G>A), RS1000126465 (3:186965006 C>T), RS1000140966 (3:187069135 C>T), RS1000150896 (3:187058366 G>A), RS1000165680 (3:187027335 A>T), RS1000170938 (3:187030183 C>G,T), RS1000195455 (3:186980916 C>T)

Disease associations

OMIM: gene MIM:109675 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

58 associations (top):

Study	Trait	p-value
GCST000415_1	Drug-induced liver injury (flucloxacillin)	1.000000e-08
GCST000903_1	Response to methylphenidate treatment in attention-deficit/hyperactivity disorder (blood pressure)	5.000000e-06
GCST001213_2	Type 2 diabetes	3.000000e-08
GCST001674_4	Esophageal cancer (squamous cell)	6.000000e-14
GCST001848_111	IgG glycosylation	6.000000e-17
GCST001848_18	IgG glycosylation	1.000000e-08
GCST001848_271	IgG glycosylation	4.000000e-07
GCST001848_273	IgG glycosylation	3.000000e-37
GCST001848_286	IgG glycosylation	9.000000e-07
GCST001848_292	IgG glycosylation	6.000000e-11
GCST001848_319	IgG glycosylation	9.000000e-15
GCST001848_326	IgG glycosylation	4.000000e-31
GCST001848_330	IgG glycosylation	4.000000e-16
GCST001848_339	IgG glycosylation	2.000000e-13
GCST001848_36	IgG glycosylation	2.000000e-45
GCST001848_405	IgG glycosylation	5.000000e-06
GCST001848_446	IgG glycosylation	5.000000e-44
GCST001848_450	IgG glycosylation	7.000000e-17
GCST001848_483	IgG glycosylation	5.000000e-06
GCST001848_496	IgG glycosylation	9.000000e-07
GCST001848_536	IgG glycosylation	8.000000e-17
GCST001848_541	IgG glycosylation	5.000000e-08
GCST001848_543	IgG glycosylation	5.000000e-17
GCST001848_549	IgG glycosylation	5.000000e-08
GCST001848_614	IgG glycosylation	6.000000e-75
GCST001848_663	IgG glycosylation	9.000000e-37
GCST001848_668	IgG glycosylation	2.000000e-20
GCST001848_675	IgG glycosylation	3.000000e-40
GCST001848_8	IgG glycosylation	5.000000e-19
GCST001848_86	IgG glycosylation	2.000000e-06

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0005193	serum IgG glycosylation measurement
EFO:0007710	cognitive decline measurement
EFO:0008423	IgG monogalactosylation measurement
EFO:0008424	IgG digalactosylation measurement
EFO:0008425	IgG galactosylation measurement
EFO:0008426	IgG bisecting N-acetyl glucosamine measurement
EFO:0008427	IgG fucosylation measurement
EFO:0008428	IgG sialylation measurement
EFO:0008429	IgG disialylation measurement
EFO:0008430	IgG monosialylation measurement
EFO:0005128	albumin:globulin ratio measurement
EFO:0004999	N-glycan measurement
EFO:0010050	thyroglobulin measurement
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density
EFO:0007991	eosinophil percentage of leukocytes
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3596075 (SINGLE PROTEIN)

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

ChEMBL bioactivities

56 potent at pChembl≥5 of 69 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.05	Kd	9	nM	CHEMBL4795501
7.80	Ki	16	nM	CHEMBL4065191
7.72	Ki	19	nM	CHEMBL3629697
7.72	Ki	19	nM	CHEMBL4102509
7.72	Ki	19	nM	CHEMBL4117853
7.70	Ki	20	nM	CHEMBL4091389
7.66	Kd	22	nM	CHEMBL4794815
7.55	Ki	28	nM	CHEMBL3629696
7.54	Ki	29	nM	CHEMBL3629698
7.35	Ki	45	nM	CHEMBL4091389
7.22	Ki	60	nM	CHEMBL4063545
6.97	Ki	106	nM	CHEMBL4097206
6.91	Ki	122	nM	CHEMBL4097206
6.78	Ki	165	nM	CHEMBL4063545
6.76	Ki	174	nM	CHEMBL4065191
6.70	Ki	200	nM	CHEMBL4081024
6.65	Ki	224	nM	CHEMBL4083608
6.36	Ki	436	nM	CHEMBL3629692
6.32	Ki	477	nM	CHEMBL3629696
6.21	IC50	610	nM	CHEMBL1170899
6.16	Ki	690	nM	CHEMBL3629698
6.06	Ki	865	nM	CHEMBL3629694
6.00	Ki	1000	nM	CHEMBL4081024
5.96	Ki	1100	nM	CHEMBL4745184
5.82	IC50	1500	nM	CHEMBL3596261
5.82	Ki	1510	nM	CHEMBL3629693
5.82	IC50	1500	nM	CHEMBL5641631
5.79	Ki	1629	nM	CHEMBL3629692
5.47	Ki	3400	nM	CHEMBL5175639
5.44	IC50	3600	nM	CHEMBL4780118
5.38	IC50	4200	nM	CHEMBL4785533
5.37	Ki	4314	nM	CHEMBL3629691
5.36	IC50	4330	nM	CHEMBL4798770
5.34	IC50	4600	nM	CHEMBL4776137
5.31	IC50	4900	nM	CHEMBL4785375
5.30	IC50	5000	nM	CHEMBL4795609
5.30	IC50	5000	nM	CHEMBL4793980
5.29	IC50	5100	nM	CHEMBL4797927
5.27	IC50	5400	nM	CHEMBL4793269
5.25	IC50	5600	nM	CHEMBL4800187
5.24	IC50	5700	nM	CHEMBL4786588
5.24	IC50	5700	nM	CHEMBL4777310
5.23	Ki	5852	nM	CHEMBL3629689
5.22	Ki	6000	nM	CHEMBL5185498
5.17	IC50	6700	nM	CHEMBL4781666
5.17	Ki	6700	nM	CHEMBL5175639
5.15	IC50	7100	nM	CHEMBL222556
5.14	IC50	7200	nM	CHEMBL4790244
5.12	IC50	7500	nM	CHEMBL122701
5.12	IC50	7500	nM	CHEMBL4779174

PubChem BioAssay actives

51 with measured affinity, of 195 total; 39 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
pentasodium;4-[[3-[(S)-[[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl]oxy-phosphonatomethyl]phenyl]carbamoyl]-2-(3-oxido-6-oxoxanthen-9-yl)benzoate	1720631: Displacement of fluorescent probe from human ST6Gal-1 by fluorescence polarization assay	kd	0.0090	uM
trisodium;[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl (2-benzamido-1-phosphonatoethyl) phosphate	1438637: Inhibition of recombinant human N-terminal His-tagged ST6Gal-1 (44 to 406 residues) using CMP-Neu5Ac as substrate after 20 mins by UV/RP-HPLC method	ki	0.0160	uM
trisodium;[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl [(3-phenoxyphenyl)-phosphonatomethyl] phosphate	1253004: Competitive inhibition of human recombinant ST6Gal-1 using CMP-Neu5Ac and p-nitrophenyl LacNAc as donar and acceptor by Lineweaver-Burk double reciprocal plot analysis	ki	0.0190	uM
trisodium;[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl [(R)-(3-phenoxyphenyl)-phosphonatomethyl] phosphate	1438637: Inhibition of recombinant human N-terminal His-tagged ST6Gal-1 (44 to 406 residues) using CMP-Neu5Ac as substrate after 20 mins by UV/RP-HPLC method	ki	0.0190	uM
[(R)-[[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-(3-phenoxyphenyl)methyl]phosphonic acid	1853254: Inhibition of human ST6Gal I	ki	0.0190	uM
trisodium;[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl (2-oxo-1-phosphonato-2-piperidin-1-ylethyl) phosphate	1438637: Inhibition of recombinant human N-terminal His-tagged ST6Gal-1 (44 to 406 residues) using CMP-Neu5Ac as substrate after 20 mins by UV/RP-HPLC method	ki	0.0200	uM
pentasodium;4-[[3-[(R)-[[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl]oxy-phosphonatomethyl]phenyl]carbamoyl]-2-(3-oxido-6-oxoxanthen-9-yl)benzoate	1720631: Displacement of fluorescent probe from human ST6Gal-1 by fluorescence polarization assay	kd	0.0220	uM
trisodium;[(2S,3S)-3-(acetamidomethyl)-2-phenylmethoxy-1-phosphonatocyclopentyl] [(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate	1253004: Competitive inhibition of human recombinant ST6Gal-1 using CMP-Neu5Ac and p-nitrophenyl LacNAc as donar and acceptor by Lineweaver-Burk double reciprocal plot analysis	ki	0.0280	uM
trisodium;[[(2R,3R,4S)-3-acetamido-4-hydroxy-2-phenoxy-3,4-dihydro-2H-pyran-6-yl]-phosphonatomethyl] [(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate	1438637: Inhibition of recombinant human N-terminal His-tagged ST6Gal-1 (44 to 406 residues) using CMP-Neu5Ac as substrate after 20 mins by UV/RP-HPLC method	ki	0.0290	uM
trisodium;[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl (2-oxo-1-phosphonato-2-pyrrolidin-1-ylethyl) phosphate	1438637: Inhibition of recombinant human N-terminal His-tagged ST6Gal-1 (44 to 406 residues) using CMP-Neu5Ac as substrate after 20 mins by UV/RP-HPLC method	ki	0.0600	uM
trisodium;[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl (2-anilino-2-oxo-1-phosphonatoethyl) phosphate	1438637: Inhibition of recombinant human N-terminal His-tagged ST6Gal-1 (44 to 406 residues) using CMP-Neu5Ac as substrate after 20 mins by UV/RP-HPLC method	ki	0.1060	uM
trisodium;[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl [phenyl(phosphonato)methyl] phosphate	1438637: Inhibition of recombinant human N-terminal His-tagged ST6Gal-1 (44 to 406 residues) using CMP-Neu5Ac as substrate after 20 mins by UV/RP-HPLC method	ki	0.2000	uM
trisodium;[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl [2-(2,5-dioxopyrrolidin-1-yl)-1-phosphonatoethyl] phosphate	1438637: Inhibition of recombinant human N-terminal His-tagged ST6Gal-1 (44 to 406 residues) using CMP-Neu5Ac as substrate after 20 mins by UV/RP-HPLC method	ki	0.2240	uM
trisodium;[[(1S,3S,4R)-3-acetamido-4-phenylmethoxycyclopentyl]-phosphonatomethyl] [(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate	1253004: Competitive inhibition of human recombinant ST6Gal-1 using CMP-Neu5Ac and p-nitrophenyl LacNAc as donar and acceptor by Lineweaver-Burk double reciprocal plot analysis	ki	0.4360	uM
trisodium;[[(1R,3S,4R)-3-(acetamidomethyl)-4-phenylmethoxycyclopentyl]-phosphonatomethyl] [(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate	1253004: Competitive inhibition of human recombinant ST6Gal-1 using CMP-Neu5Ac and p-nitrophenyl LacNAc as donar and acceptor by Lineweaver-Burk double reciprocal plot analysis	ki	0.8650	uM
disodium;[(4-fluorophenyl)-phosphonatomethyl] N-[[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl]carbamate	1720626: Inhibition of recombinant human N-terminal 6His-tagged ST6Gal-1 (Glu44 to Cys406 residues)	ki	1.1000	uM
(4S)-5-[[(3R,5R,8R,9S,10S,13R,14S,17R)-17-[(2R)-4-carboxybutan-2-yl]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-4-[(4-nitro-2,1,3-benzoxadiazol-7-yl)amino]-5-oxopentanoic acid	1744186: Inhibition of human alpha-2,6-ST6GAL1 assessed as reduction in sialylated-product formation using Gal-beta1-4GlcNac and CMP-NeuSAc incubated for 15 mins by reverse-phase HPLC analysis	ic50	1.5000	uM
(4R)-4-[(3R,5R,8R,9S,10S,13R,14S,17R)-3-[(2S)-3-carboxy-2-[(4-nitro-2,1,3-benzoxadiazol-7-yl)amino]propanoyl]oxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid	2144163: Inhibition of ST6GAL1 (unknown origin)	ic50	1.5000	uM
trisodium;[[(1R,3S,4R)-3-acetamido-4-phenylmethoxycyclopentyl]-phosphonatomethyl] [(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate	1253004: Competitive inhibition of human recombinant ST6Gal-1 using CMP-Neu5Ac and p-nitrophenyl LacNAc as donar and acceptor by Lineweaver-Burk double reciprocal plot analysis	ki	1.5100	uM
disodium;1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[[1-[phosphonato-[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]triazol-4-yl]methoxymethyl]oxolan-2-yl]pyrimidine-2,4-dione	1853256: Inhibition of recombinant human ST6Gal I incubated for 1 hrs in the presence of CMP-Neu5Ac as donor and LacNAc as acceptor by luminescence based CMP-Glo assay	ki	3.4000	uM
(3S)-4-[[(3R,5R,8R,9S,10S,13R,14S,17R)-17-[(2R)-5-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]-5-oxopentan-2-yl]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-3-[(4-nitro-2,1,3-benzoxadiazol-7-yl)amino]-4-oxobutanoic acid	1744186: Inhibition of human alpha-2,6-ST6GAL1 assessed as reduction in sialylated-product formation using Gal-beta1-4GlcNac and CMP-NeuSAc incubated for 15 mins by reverse-phase HPLC analysis	ic50	3.6000	uM
(3S)-4-[[(3R,5R,8R,9S,10S,13R,14S,17R)-17-[(2R)-5-(2-azidoethoxy)-5-oxopentan-2-yl]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-3-[(4-nitro-2,1,3-benzoxadiazol-7-yl)amino]-4-oxobutanoic acid	1744186: Inhibition of human alpha-2,6-ST6GAL1 assessed as reduction in sialylated-product formation using Gal-beta1-4GlcNac and CMP-NeuSAc incubated for 15 mins by reverse-phase HPLC analysis	ic50	4.2000	uM
trisodium;[[(1S,3S,4R)-3-acetamido-4-hydroxycyclopentyl]-phosphonatomethyl] [(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate	1253004: Competitive inhibition of human recombinant ST6Gal-1 using CMP-Neu5Ac and p-nitrophenyl LacNAc as donar and acceptor by Lineweaver-Burk double reciprocal plot analysis	ki	4.3140	uM
(3S)-4-[[(3R,5R,8R,9S,10S,13R,14S,17R)-17-[(2R)-5-[2-(2-azidoethoxy)ethoxy]-5-oxopentan-2-yl]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-3-[(4-nitro-2,1,3-benzoxadiazol-7-yl)amino]-4-oxobutanoic acid	1744186: Inhibition of human alpha-2,6-ST6GAL1 assessed as reduction in sialylated-product formation using Gal-beta1-4GlcNac and CMP-NeuSAc incubated for 15 mins by reverse-phase HPLC analysis	ic50	4.3300	uM
(3S)-4-[[(3R,5R,8R,9S,10S,13R,14S,17R)-17-[(2R)-5-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]-5-oxopentan-2-yl]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-3-[[2-(7-methoxy-2-oxochromen-4-yl)acetyl]amino]-4-oxobutanoic acid	1744186: Inhibition of human alpha-2,6-ST6GAL1 assessed as reduction in sialylated-product formation using Gal-beta1-4GlcNac and CMP-NeuSAc incubated for 15 mins by reverse-phase HPLC analysis	ic50	4.6000	uM
(3S)-4-[[(3R,5R,8R,9S,10S,13R,14S,17R)-17-[(2R)-5-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethoxy]-5-oxopentan-2-yl]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-3-[(4-nitro-2,1,3-benzoxadiazol-7-yl)amino]-4-oxobutanoic acid	1744186: Inhibition of human alpha-2,6-ST6GAL1 assessed as reduction in sialylated-product formation using Gal-beta1-4GlcNac and CMP-NeuSAc incubated for 15 mins by reverse-phase HPLC analysis	ic50	4.9000	uM
(3S)-4-[[(3R,5R,8R,9S,10S,13R,14S,17R)-17-[(2R)-5-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethoxy]-5-oxopentan-2-yl]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-3-[[2-(7-methoxy-2-oxochromen-4-yl)acetyl]amino]-4-oxobutanoic acid	1744186: Inhibition of human alpha-2,6-ST6GAL1 assessed as reduction in sialylated-product formation using Gal-beta1-4GlcNac and CMP-NeuSAc incubated for 15 mins by reverse-phase HPLC analysis	ic50	5.0000	uM
(3S)-4-[[(3R,5R,8R,9S,10S,13R,14S,17R)-17-[(2R)-5-[2-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethoxy]ethoxy]-5-oxopentan-2-yl]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-3-[(4-nitro-2,1,3-benzoxadiazol-7-yl)amino]-4-oxobutanoic acid	1744186: Inhibition of human alpha-2,6-ST6GAL1 assessed as reduction in sialylated-product formation using Gal-beta1-4GlcNac and CMP-NeuSAc incubated for 15 mins by reverse-phase HPLC analysis	ic50	5.0000	uM
(3S)-4-[[(3R,5R,8R,9S,10S,13R,14S,17R)-17-[(2R)-5-[2-(2-azidoethoxy)ethoxy]-5-oxopentan-2-yl]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-3-[[2-(7-methoxy-2-oxochromen-4-yl)acetyl]amino]-4-oxobutanoic acid	1744186: Inhibition of human alpha-2,6-ST6GAL1 assessed as reduction in sialylated-product formation using Gal-beta1-4GlcNac and CMP-NeuSAc incubated for 15 mins by reverse-phase HPLC analysis	ic50	5.1000	uM
(3S)-4-[[(3R,5R,8R,9S,10S,13R,14S,17R)-17-[(2R)-5-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]-5-oxopentan-2-yl]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-3-[(4-nitrobenzoyl)amino]-4-oxobutanoic acid	1744186: Inhibition of human alpha-2,6-ST6GAL1 assessed as reduction in sialylated-product formation using Gal-beta1-4GlcNac and CMP-NeuSAc incubated for 15 mins by reverse-phase HPLC analysis	ic50	5.4000	uM
(3S)-4-[[(3R,5R,8R,9S,10S,13R,14S,17R)-17-[(2R)-5-(2-azidoethoxy)-5-oxopentan-2-yl]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-3-[[2-(7-methoxy-2-oxochromen-4-yl)acetyl]amino]-4-oxobutanoic acid	1744186: Inhibition of human alpha-2,6-ST6GAL1 assessed as reduction in sialylated-product formation using Gal-beta1-4GlcNac and CMP-NeuSAc incubated for 15 mins by reverse-phase HPLC analysis	ic50	5.6000	uM
(3S)-4-[[(3R,5R,8R,9S,10S,13R,14S,17R)-17-[(2R)-5-[2-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethoxy]ethoxy]-5-oxopentan-2-yl]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-3-[[2-(7-methoxy-2-oxochromen-4-yl)acetyl]amino]-4-oxobutanoic acid	1744186: Inhibition of human alpha-2,6-ST6GAL1 assessed as reduction in sialylated-product formation using Gal-beta1-4GlcNac and CMP-NeuSAc incubated for 15 mins by reverse-phase HPLC analysis	ic50	5.7000	uM
(3S)-4-[[(3R,5R,8R,9S,10S,13R,14S,17R)-17-[(2R)-5-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethoxy]-5-oxopentan-2-yl]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-3-[(4-nitrobenzoyl)amino]-4-oxobutanoic acid	1744186: Inhibition of human alpha-2,6-ST6GAL1 assessed as reduction in sialylated-product formation using Gal-beta1-4GlcNac and CMP-NeuSAc incubated for 15 mins by reverse-phase HPLC analysis	ic50	5.7000	uM
trisodium;[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl [cyclopentyl(phosphonato)methyl] phosphate	1253004: Competitive inhibition of human recombinant ST6Gal-1 using CMP-Neu5Ac and p-nitrophenyl LacNAc as donar and acceptor by Lineweaver-Burk double reciprocal plot analysis	ki	5.8520	uM
disodium;1-[(2R,3R,4S,5R)-5-[[1-[(4-fluoro-3-phenoxyphenyl)-phosphonatomethyl]triazol-4-yl]methoxymethyl]-3,4-dihydroxyoxolan-2-yl]pyrimidine-2,4-dione	1853256: Inhibition of recombinant human ST6Gal I incubated for 1 hrs in the presence of CMP-Neu5Ac as donor and LacNAc as acceptor by luminescence based CMP-Glo assay	ki	6.0000	uM
(3S)-4-[[(3R,5R,8R,9S,10S,13R,14S,17R)-17-[(2R)-5-[2-(2-azidoethoxy)ethoxy]-5-oxopentan-2-yl]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-3-[(4-nitrobenzoyl)amino]-4-oxobutanoic acid	1744186: Inhibition of human alpha-2,6-ST6GAL1 assessed as reduction in sialylated-product formation using Gal-beta1-4GlcNac and CMP-NeuSAc incubated for 15 mins by reverse-phase HPLC analysis	ic50	6.7000	uM
(3S)-4-[[(3R,5R,8R,9S,10S,13R,14S,17R)-17-[(2R)-5-(2-azidoethoxy)-5-oxopentan-2-yl]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-3-[(4-nitrobenzoyl)amino]-4-oxobutanoic acid	1744186: Inhibition of human alpha-2,6-ST6GAL1 assessed as reduction in sialylated-product formation using Gal-beta1-4GlcNac and CMP-NeuSAc incubated for 15 mins by reverse-phase HPLC analysis	ic50	7.2000	uM
(3S)-4-[[(3R,5R,8R,9S,10S,13R,14S,17R)-17-[(2R)-5-[2-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethoxy]ethoxy]-5-oxopentan-2-yl]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-3-[(4-nitrobenzoyl)amino]-4-oxobutanoic acid	1744186: Inhibition of human alpha-2,6-ST6GAL1 assessed as reduction in sialylated-product formation using Gal-beta1-4GlcNac and CMP-NeuSAc incubated for 15 mins by reverse-phase HPLC analysis	ic50	7.5000	uM
disodium;[1-benzothiophen-2-yl(phosphonato)methyl] N-[[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl]carbamate	1720626: Inhibition of recombinant human N-terminal 6His-tagged ST6Gal-1 (Glu44 to Cys406 residues)	ki	8.5000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases methylation, affects methylation, decreases expression, affects cotreatment, increases abundance (+1 more)	6
Benzo(a)pyrene	decreases methylation, increases methylation, affects methylation, decreases expression	5
Air Pollutants	decreases expression, increases abundance, increases expression	3
Tobacco Smoke Pollution	decreases expression, increases expression	3
Valproic Acid	affects expression, affects methylation, decreases expression	3
Cyclosporine	decreases expression	3
Aflatoxin B1	affects expression, decreases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
bisphenol A	affects expression, increases expression	2
Acetaminophen	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Silicon Dioxide	decreases expression	2
aristolochic acid I	decreases expression	1
tremortin	increases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	decreases expression	1
terbufos	decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
nickel chloride	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
cupric chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	increases reaction, affects binding	1
perfluoro-n-nonanoic acid	decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
abrine	decreases expression	1

ChEMBL screening assays

27 unique, capped per target: 27 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3598441	Binding	Inhibition of ST6Gal 1 (unknown origin)	Beyond substrate analogues: new inhibitor chemotypes for glycosyltransferases — Medchemcomm

Cellosaurus cell lines

8 cell lines: 4 transformed cell line, 3 spontaneously immortalized cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8WA	Ubigene HCT 116 ST6GAL1 KO	Cancer cell line	Male
CVCL_RQ73	BHK-21A EPO40-ST6NI	Spontaneously immortalized cell line	Male
CVCL_WL43	hCK	Spontaneously immortalized cell line	Female
CVCL_YY02	CHOmt17-0	Transformed cell line	Female
CVCL_YY03	CHOmt17-100	Transformed cell line	Female
CVCL_YY04	CHOmt17-200	Transformed cell line	Female
CVCL_YY05	CHOmt17-300	Transformed cell line	Female
CVCL_Z936	MDCK-SIAT1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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