ST6GAL2

Summary

ST6GAL2 (ST6 beta-galactoside alpha-2,6-sialyltransferase 2, HGNC:10861) is a protein-coding gene on chromosome 2q12.3, encoding Beta-galactoside alpha-2,6-sialyltransferase 2 (Q96JF0). Transfers sialic acid from the donor of substrate CMP-sialic acid to galactose containing acceptor substrates.

This locus encodes a sialyltransferase. The encoded type II transmembrane protein catalyzes the transfer of sialic acid from CMP to an oligosaccharide substrate. Polymorphisms at this locus may be associated with variations in risperidone response in schizophrenic patients. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 84620 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 84 total
• MANE Select transcript: NM_001142351

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10861
Approved symbol	ST6GAL2
Name	ST6 beta-galactoside alpha-2,6-sialyltransferase 2
Location	2q12.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1877, St6GalII
Ensembl gene	ENSG00000144057
Ensembl biotype	protein_coding
OMIM	608472
Entrez	84620

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000361686, ENST00000361803, ENST00000409087, ENST00000409382, ENST00000419159, ENST00000868339, ENST00000868340, ENST00000964517

RefSeq mRNA: 4 — MANE Select: NM_001142351 NM_001142351, NM_001142352, NM_001322362, NM_032528

CCDS: CCDS2073, CCDS46380

Canonical transcript exons

ENST00000409382 — 6 exons

Exon	Start	End
ENSE00000963473	106834049	106834146
ENSE00000963474	106832565	106832666
ENSE00000963475	106830066	106830240
ENSE00001321244	106843035	106844034
ENSE00001723505	106886093	106886167
ENSE00001932534	106801600	106806949

Expression profiles

Bgee: expression breadth ubiquitous, 180 present calls, max score 93.15.

FANTOM5 (CAGE): breadth broad, TPM avg 2.7458 / max 275.2641, expressed in 512 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
30065	0.6125	288
30062	0.5899	184
30066	0.3526	180
30061	0.2570	111
30069	0.2284	94
30067	0.2276	127
30060	0.1665	81
30068	0.1224	38
30064	0.0847	49
30063	0.0626	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	93.15	gold quality
right coronary artery	UBERON:0001625	91.30	gold quality
ganglionic eminence	UBERON:0004023	91.00	gold quality
descending thoracic aorta	UBERON:0002345	89.06	gold quality
thoracic aorta	UBERON:0001515	88.71	gold quality
ascending aorta	UBERON:0001496	88.57	gold quality
coronary artery	UBERON:0001621	83.88	gold quality
left coronary artery	UBERON:0001626	83.79	gold quality
aorta	UBERON:0000947	82.92	gold quality
germinal epithelium of ovary	UBERON:0001304	81.90	gold quality
thyroid gland	UBERON:0002046	81.11	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.97	gold quality
right lobe of thyroid gland	UBERON:0001119	80.96	gold quality
left lobe of thyroid gland	UBERON:0001120	79.76	gold quality
ventricular zone	UBERON:0003053	78.93	gold quality
amygdala	UBERON:0001876	78.62	gold quality
popliteal artery	UBERON:0002250	78.56	gold quality
tibial artery	UBERON:0007610	78.52	gold quality
Brodmann (1909) area 46	UBERON:0006483	77.59	gold quality
mucosa of sigmoid colon	UBERON:0004993	77.27	gold quality
prefrontal cortex	UBERON:0000451	76.60	gold quality
primary visual cortex	UBERON:0002436	76.11	gold quality
gall bladder	UBERON:0002110	75.50	gold quality
temporal lobe	UBERON:0001871	75.25	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	74.84	gold quality
anterior cingulate cortex	UBERON:0009835	74.52	gold quality
occipital lobe	UBERON:0002021	74.41	gold quality
neocortex	UBERON:0001950	74.40	gold quality
mucosa of paranasal sinus	UBERON:0005030	74.36	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.78	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.96

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EBF1, PURA, SOX5

miRNA regulators (miRDB)

199 targeting ST6GAL2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819

Literature-anchored findings (GeneRIF, showing 3)

• identification and expression and localization in brain (PMID:12603328)
• This suggests that ST6GAL2 transcription could be potentially activated for specific neuronal functions. (PMID:19768537)
• Role of ST6GAL1 and ST6GAL2 in subversion of cellular signaling during enteroaggregative Escherichia coli infection of human intestinal epithelial cell lines. (PMID:36646912)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	st6gal2a	ENSDARG00000039335
danio_rerio	st6gal2b	ENSDARG00000088515
mus_musculus	St6gal2	ENSMUSG00000024172
rattus_norvegicus	St6gal2	ENSRNOG00000046515

Paralogs (14): ST3GAL1 (ENSG00000008513), ST3GAL6 (ENSG00000064225), ST6GALNAC1 (ENSG00000070526), ST6GALNAC2 (ENSG00000070731), ST6GAL1 (ENSG00000073849), ST3GAL4 (ENSG00000110080), ST3GAL5 (ENSG00000115525), ST6GALNAC5 (ENSG00000117069), C20orf173 (ENSG00000125975), ST3GAL3 (ENSG00000126091), ST6GALNAC4 (ENSG00000136840), ST3GAL2 (ENSG00000157350), ST6GALNAC6 (ENSG00000160408), ST6GALNAC3 (ENSG00000184005)

Protein

Protein identifiers

Beta-galactoside alpha-2,6-sialyltransferase 2 — Q96JF0 (reviewed: Q96JF0)

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

All UniProt accessions (3): Q96JF0, C9JIK2, H7BY52

UniProt curated annotations — full annotation on UniProt →

Function. Transfers sialic acid from the donor of substrate CMP-sialic acid to galactose containing acceptor substrates. Has alpha-2,6-sialyltransferase activity toward oligosaccharides that have the Gal-beta-1,4-GlcNAc sequence at the non-reducing end of their carbohydrate groups, but it has weak or no activities toward glycoproteins and glycolipids.

Subcellular location. Golgi apparatus. Golgi stack membrane.

Tissue specificity. Weakly expressed in some tissues, such as small intestine, colon and fetal brain.

Post-translational modifications. O-glycosylated.

Induction. By IL6/interleukin-6 and IL8//interleukin-8.

Similarity. Belongs to the glycosyltransferase 29 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96JF0-1	1	yes
Q96JF0-2	2

RefSeq proteins (4): NP_001135823, NP_001135824, NP_001309291, NP_115917 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001675	Glyco_trans_29	Family
IPR011330	Glyco_hydro/deAcase_b/a-brl	Homologous_superfamily
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), 1 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)

UniProt features (12 total): disulfide bond 3, topological domain 2, sequence variant 2, glycosylation site 2, chain 1, transmembrane region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96JF0-F1	75.56	0.61

Functional residue map

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

Disulfide bonds (3): 253–519, 296–448, 466–477

Glycosylation sites (2): 69, 211

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-4085001	Sialic acid metabolism
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-597592	Post-translational protein modification

MSigDB gene sets: 112 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GSE45365_NK_CELL_VS_CD8_TCELL_DN, GOBP_OLIGOSACCHARIDE_METABOLIC_PROCESS, chr2q12, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, GOBP_SIALYLATION, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, GOCC_GOLGI_STACK, NUYTTEN_EZH2_TARGETS_DN, GRYDER_PAX3FOXO1_TOP_ENHANCERS, GOCC_GOLGI_CISTERNA, GOCC_GOLGI_CISTERNA_MEMBRANE, GOCC_ORGANELLE_SUBCOMPARTMENT, ZHENG_GLIOBLASTOMA_PLASTICITY_UP

GO Biological Process (4): oligosaccharide metabolic process (GO:0009311), sialylation (GO:0097503), carbohydrate metabolic process (GO:0005975), obsolete protein glycosylation (GO:0006486)

GO Molecular Function (5): beta-galactoside alpha-2,6-sialyltransferase activity (GO:0003835), protein binding (GO:0005515), sialyltransferase activity (GO:0008373), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (4): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), Golgi cisterna membrane (GO:0032580), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Synthesis of substrates in N-glycan biosythesis	1
Asparagine N-linked glycosylation	1
Post-translational protein modification	1
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
carbohydrate metabolic process	1
macromolecule modification	1
primary metabolic process	1
sialyltransferase activity	1
binding	1
glycosyltransferase activity	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
cellular anatomical structure	1

Protein interactions and networks

STRING

698 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ST6GAL2	B4GALT2	O60909	606
ST6GAL2	ST8SIA1	Q92185	536
ST6GAL2	B4GALT1	P15291	530
ST6GAL2	NEU2	Q9Y3R4	514
ST6GAL2	ZNF614	Q8N883	507
ST6GAL2	NEU4	Q8WWR8	495
ST6GAL2	SLC5A7	Q9GZV3	489
ST6GAL2	WDR64	B1ANS9	481
ST6GAL2	KPRP	Q5T749	444
ST6GAL2	SLC37A3	Q8NCC5	438
ST6GAL2	FUT8	Q9BYC5	435
ST6GAL2	B3GNT2	Q9NY97	431
ST6GAL2	SETD4	Q9NVD3	416
ST6GAL2	TP53	P04637	411
ST6GAL2	EGFR	P00533	397

IntAct

2 interactions, top by confidence:

A	B	Type	Score
MCM7		psi-mi:“MI:0914”(association)	0.350

BioGRID (17): ST6GAL2 (Two-hybrid), ST6GAL2 (Two-hybrid), ST6GAL2 (Two-hybrid), ST6GAL2 (Two-hybrid), ST6GAL2 (Two-hybrid), ST6GAL2 (Two-hybrid), ST6GAL2 (Two-hybrid), SLC26A1 (Two-hybrid), TMEM237 (Two-hybrid), PGRMC2 (Two-hybrid), GPX8 (Two-hybrid), SLC39A2 (Two-hybrid), PSCA (Two-hybrid), HSD17B13 (Two-hybrid), FNDC9 (Two-hybrid)

ESM2 similar proteins: A2A699, A2BD09, A4IIT5, A5D7T4, A6QLD2, A8MVW0, O35764, O43278, O70624, O95502, O95897, P35054, P51693, Q03157, Q2PT31, Q3UPI1, Q3UZZ4, Q3V1G4, Q568Y7, Q594P2, Q5QQ37, Q66H86, Q68BL7, Q68BL8, Q6AYE5, Q6P7B4, Q6UWH4, Q6UWY5, Q6ZMI3, Q701R2, Q701R3, Q701R4, Q766D5, Q76KP1, Q80WL1, Q863A3, Q866N2, Q86VZ4, Q8BHP7, Q8BM13

Diamond homologs: A2WX64, A2XVC2, A2ZI41, A5D7T4, O35696, O43173, P61132, P61643, P61644, P61645, P97325, Q02734, Q07977, Q11203, Q2QXM3, Q5K027, Q5QQ37, Q64689, Q64690, Q64692, Q6ZXC9, Q701R0, Q701R1, Q701R2, Q701R3, Q701R4, Q76K27, Q7FA29, Q92183, Q92186, Q92187, Q94DD4, Q96JF0, Q9SGD2, Q9UJ37, Q16842, Q2R2B1, Q6KB58, Q6ZH45, Q8VZJ0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1468 predictions. Top by Δscore:

Variant	Effect	Δscore
2:106830238:CCA:C	acceptor_gain	1.0000
2:106830239:CAC:C	acceptor_gain	1.0000
2:106830241:C:CC	acceptor_gain	1.0000
2:106832561:TTAC:T	donor_loss	1.0000
2:106832562:T:TG	donor_loss	1.0000
2:106832563:A:AC	donor_gain	1.0000
2:106832563:ACCAG:A	donor_loss	1.0000
2:106832564:C:A	donor_loss	1.0000
2:106832564:C:CC	donor_gain	1.0000
2:106832564:CCA:C	donor_gain	1.0000
2:106832564:CCAG:C	donor_gain	1.0000
2:106832564:CCAGG:C	donor_gain	1.0000
2:106832662:AGAAT:A	acceptor_gain	1.0000
2:106832663:GAAT:G	acceptor_gain	1.0000
2:106832665:AT:A	acceptor_gain	1.0000
2:106832666:TC:T	acceptor_loss	1.0000
2:106832667:C:CC	acceptor_gain	1.0000
2:106832667:CTGC:C	acceptor_loss	1.0000
2:106832668:T:A	acceptor_loss	1.0000
2:106844030:TGAAC:T	acceptor_gain	1.0000
2:106806747:G:A	donor_gain	0.9900
2:106830236:TACCA:T	acceptor_gain	0.9900
2:106830239:CA:C	acceptor_gain	0.9900
2:106832563:AC:A	donor_gain	0.9900
2:106832564:CC:C	donor_gain	0.9900
2:106832664:AAT:A	acceptor_gain	0.9900
2:106832674:C:CT	acceptor_gain	0.9900
2:106834043:TCTTA:T	donor_loss	0.9900
2:106834044:CTTA:C	donor_loss	0.9900
2:106834045:TTAC:T	donor_loss	0.9900

AlphaMissense

3471 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:106806805:T:A	E488V	1.000
2:106806819:G:C	H483Q	1.000
2:106806819:G:T	H483Q	1.000
2:106806821:G:C	H483D	1.000
2:106806821:G:T	H483N	1.000
2:106806837:G:C	C477W	1.000
2:106806838:C:G	C477S	1.000
2:106806838:C:T	C477Y	1.000
2:106806839:A:G	C477R	1.000
2:106806839:A:T	C477S	1.000
2:106806870:G:C	C466W	1.000
2:106806871:C:G	C466S	1.000
2:106806871:C:T	C466Y	1.000
2:106806872:A:G	C466R	1.000
2:106806872:A:T	C466S	1.000
2:106832598:C:A	W370C	1.000
2:106832598:C:G	W370C	1.000
2:106832600:A:G	W370R	1.000
2:106832600:A:T	W370R	1.000
2:106834055:A:C	N345K	1.000
2:106834055:A:T	N345K	1.000
2:106834083:C:A	G336V	1.000
2:106834118:G:C	N324K	1.000
2:106834118:G:T	N324K	1.000
2:106806804:C:A	E488D	0.999
2:106806804:C:G	E488D	0.999
2:106806814:A:G	L485P	0.999
2:106806817:G:T	P484Q	0.999
2:106806820:T:C	H483R	0.999
2:106806823:T:C	Y482C	0.999

dbSNP variants (sampled 300 via entrez): RS1000001500 (2:106824741 T>C), RS1000061092 (2:106808161 A>C), RS1000084355 (2:106850311 C>T), RS1000134604 (2:106861162 A>G), RS1000238362 (2:106874851 G>A), RS1000256991 (2:106883601 G>C), RS1000296197 (2:106868313 C>T), RS1000327935 (2:106868552 A>T), RS1000339442 (2:106828737 A>G), RS1000351293 (2:106854465 C>A), RS1000438661 (2:106848627 T>C), RS1000439106 (2:106821214 A>G), RS1000444350 (2:106807073 T>C), RS1000458019 (2:106850076 A>G), RS1000510038 (2:106824843 C>G)

Disease associations

OMIM: gene MIM:608472 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010146_1	Serum immune biomarker levels	2.000000e-10
GCST010146_40	Serum immune biomarker levels	6.000000e-09
GCST010396_273	Gut microbiota (bacterial taxa, hurdle binary method)	4.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004869	YKL40 measurement
EFO:0004872	inflammatory biomarker measurement
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	3
Valproic Acid	decreases expression, increases expression	3
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
Nickel	decreases expression	2
methylmercuric chloride	decreases expression	1
bisphenol A	affects cotreatment, increases methylation	1
terbufos	increases methylation	1
trichostatin A	increases expression	1
butyraldehyde	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases methylation	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Malathion	increases expression	1
Parathion	increases methylation	1
Progesterone	decreases expression	1
Silicon Dioxide	decreases expression	1
Aflatoxin B1	decreases methylation	1
Palmitic Acid	increases expression	1
Okadaic Acid	increases expression	1
Acrylamide	decreases expression	1
p-Chloromercuribenzoic Acid	decreases expression	1

Clinical trials (associated diseases)

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