ST8SIA5

Summary

ST8SIA5 (ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 5, HGNC:17827) is a protein-coding gene on chromosome 18q21.1, encoding Alpha-2,8-sialyltransferase 8E (O15466). Involved in the synthesis of gangliosides GD1c, GT1a, GQ1b, GP1c and GT3 from GD1a, GT1b, GM1b and GD3 respectively.

The protein encoded by this gene is a type II membrane protein that may be present in the Golgi apparatus. The encoded protein, which is a member of glycosyltransferase family 29, may be involved in the synthesis of gangliosides GD1c, GT1a, GQ1b, and GT3 from GD1a, GT1b, GM1b, and GD3, respectively.

Source: NCBI Gene 29906 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 58 total
• MANE Select transcript: NM_013305

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17827
Approved symbol	ST8SIA5
Name	ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 5
Location	18q21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000101638
Ensembl biotype	protein_coding
OMIM	607162
Entrez	29906

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 8 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000315087, ENST00000536490, ENST00000538168, ENST00000587428, ENST00000588155, ENST00000589088, ENST00000590488, ENST00000590497, ENST00000591375, ENST00000906001, ENST00000906002, ENST00000906003, ENST00000911623, ENST00000951068

RefSeq mRNA: 3 — MANE Select: NM_013305 NM_001307986, NM_001307987, NM_013305

CCDS: CCDS11930, CCDS77183, CCDS77184

Canonical transcript exons

ENST00000315087 — 7 exons

Exon	Start	End
ENSE00000668965	46688775	46688919
ENSE00001297372	46756378	46757053
ENSE00002268389	46667821	46680510
ENSE00003495248	46704572	46704664
ENSE00003558592	46686174	46686286
ENSE00003558862	46692169	46692255
ENSE00003599672	46681972	46682064

Expression profiles

Bgee: expression breadth ubiquitous, 179 present calls, max score 92.45.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3016 / max 148.1763, expressed in 192 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171822	0.5753	121
171826	0.3865	102
171825	0.1374	59
171824	0.1223	54
171823	0.0801	48

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	92.45	gold quality
postcentral gyrus	UBERON:0002581	91.27	gold quality
parietal lobe	UBERON:0001872	90.27	gold quality
cerebellar cortex	UBERON:0002129	89.82	gold quality
cerebellar hemisphere	UBERON:0002245	89.79	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.71	gold quality
cerebellum	UBERON:0002037	89.45	gold quality
cerebellar vermis	UBERON:0004720	89.32	gold quality
superior frontal gyrus	UBERON:0002661	88.67	gold quality
right adrenal gland cortex	UBERON:0035827	88.55	gold quality
Brodmann (1909) area 23	UBERON:0013554	88.47	gold quality
right adrenal gland	UBERON:0001233	88.34	gold quality
left adrenal gland	UBERON:0001234	87.35	gold quality
left adrenal gland cortex	UBERON:0035825	87.14	gold quality
adrenal cortex	UBERON:0001235	86.96	gold quality
middle temporal gyrus	UBERON:0002771	86.64	gold quality
adrenal tissue	UBERON:0018303	86.28	gold quality
entorhinal cortex	UBERON:0002728	85.71	gold quality
adrenal gland	UBERON:0002369	85.61	gold quality
primary visual cortex	UBERON:0002436	84.94	gold quality
occipital lobe	UBERON:0002021	83.87	gold quality
prefrontal cortex	UBERON:0000451	82.51	gold quality
frontal cortex	UBERON:0001870	82.32	gold quality
frontal lobe	UBERON:0016525	82.31	gold quality
right frontal lobe	UBERON:0002810	82.23	gold quality
triceps brachii	UBERON:0001509	82.13	gold quality
gluteal muscle	UBERON:0002000	81.44	gold quality
neocortex	UBERON:0001950	81.42	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	81.40	gold quality
apex of heart	UBERON:0002098	81.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.86

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

65 targeting ST8SIA5, 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-6867-5P	100.00	82.21	3464
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-3125	99.14	68.49	2269

Literature-anchored findings (GeneRIF, showing 2)

• Chol-1alpha antigens (cholinergic neuron-specific gangliosides), such as GT1aalpha and GQ1balpha, which are minor species in the brain, are increased in the double-transgenic mouse brain. (PMID:20930939)
• Upregulated lncHRK2:1 prompts nucleus pulposus cell senescence in intervertebral disc degeneration. (PMID:33174041)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	st8sia5	ENSDARG00000036584
mus_musculus	St8sia5	ENSMUSG00000025425
rattus_norvegicus	St8sia5	ENSRNOG00000022691

Paralogs (5): ST8SIA1 (ENSG00000111728), ST8SIA4 (ENSG00000113532), ST8SIA2 (ENSG00000140557), ST8SIA6 (ENSG00000148488), ST8SIA3 (ENSG00000177511)

Protein

Protein identifiers

Alpha-2,8-sialyltransferase 8E — O15466 (reviewed: O15466)

Alternative names: Sialyltransferase 8E, Sialyltransferase St8Sia V

All UniProt accessions (4): O15466, F5H8D1, K7EN49, K7ER54

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the synthesis of gangliosides GD1c, GT1a, GQ1b, GP1c and GT3 from GD1a, GT1b, GM1b and GD3 respectively.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Expressed in fetal and adult brain, adult heart and skeletal muscle. Expressed in fetal and adult brain, not detected in adult heart and skeletal muscle.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the glycosyltransferase 29 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O15466-1	1	yes
O15466-2	2

RefSeq proteins (3): NP_001294915, NP_001294916, NP_037437* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001675	Glyco_trans_29	Family
IPR012163	Sialyl_trans	Family
IPR038578	GT29-like_sf	Homologous_superfamily
IPR050943	Glycosyltr_29_Sialyltrsf	Family

Pfam: PF00777

Enzyme classification (BRENDA):

• EC 2.4.99.8 — alpha-N-acetylneuraminate alpha-2,8-sialyltransferase (BRENDA: 0 organisms, 0 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 5 shown:

• a ganglioside GD3 (d18:1(4E)) + CMP-N-acetyl-beta-neuraminate = a ganglioside GT3 (d18:1(4E)) + CMP + H(+) (RHEA:41764)
• a ganglioside GD1a (d18:1(4E)) + CMP-N-acetyl-beta-neuraminate = a ganglioside GT1a (d18:1(4E)) + CMP + H(+) (RHEA:41768)
• a ganglioside GT1b (d18:1(4E)) + CMP-N-acetyl-beta-neuraminate = a ganglioside GQ1b (d18:1(4E)) + CMP + H(+) (RHEA:41772)
• a ganglioside GM1b (d18:1(4E)) + CMP-N-acetyl-beta-neuraminate = a ganglioside GD1c (d18:1(4E)) + CMP + H(+) (RHEA:47576)
• a ganglioside GQ1c (d18:1(4E)) + CMP-N-acetyl-beta-neuraminate = a ganglioside GP1c (d18:1(4E)) + CMP + H(+) (RHEA:47592)

UniProt features (17 total): glycosylation site 4, binding site 3, topological domain 2, disulfide bond 2, sequence conflict 2, chain 1, splice variant 1, transmembrane region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15466-F1	90.67	0.82

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): 348 (proton donor/acceptor)

Ligand- & substrate-binding residues (3): 192; 214–216; 300–302

Disulfide bonds (2): 164–313, 178–373

Glycosylation sites (4): 241, 284, 56, 96

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-4085001	Sialic acid metabolism
R-HSA-9840309	Glycosphingolipid biosynthesis
R-HSA-1430728	Metabolism
R-HSA-1660662	Glycosphingolipid metabolism
R-HSA-392499	Metabolism of proteins
R-HSA-428157	Sphingolipid metabolism
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-556833	Metabolism of lipids
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 103 (showing top): GOBP_OLIGOSACCHARIDE_METABOLIC_PROCESS, GOBP_N_GLYCAN_PROCESSING, BENPORATH_ES_WITH_H3K27ME3, GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, TGACCTY_ERR1_Q2, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, KOYAMA_SEMA3B_TARGETS_UP, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_GLYCOSPHINGOLIPID_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, ATF4_Q2, GOBP_LIPID_BIOSYNTHETIC_PROCESS

GO Biological Process (6): carbohydrate metabolic process (GO:0005975), N-glycan processing (GO:0006491), glycosphingolipid biosynthetic process (GO:0006688), oligosaccharide metabolic process (GO:0009311), obsolete protein glycosylation (GO:0006486), lipid metabolic process (GO:0006629)

GO Molecular Function (5): alpha-N-acetylneuraminate alpha-2,8-sialyltransferase activity (GO:0003828), sialyltransferase activity (GO:0008373), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

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

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Synthesis of substrates in N-glycan biosythesis	1
Glycosphingolipid metabolism	1
Sphingolipid metabolism	1
Metabolism of lipids	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	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
primary metabolic process	2
protein N-linked glycosylation	1
glycoprotein biosynthetic process	1
glycosphingolipid metabolic process	1
glycolipid biosynthetic process	1
sphingolipid biosynthetic process	1
carbohydrate metabolic process	1
sialyltransferase activity	1
glycosyltransferase 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
cellular anatomical structure	1

Protein interactions and networks

STRING

768 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ST8SIA5	ST3GAL5	Q9UNP4	684
ST8SIA5	B3GALT4	O96024	645
ST8SIA5	ST6GALNAC6	Q969X2	618
ST8SIA5	B4GALT6	Q9UBX8	551
ST8SIA5	TATDN3	Q17R31	549
ST8SIA5	KATNAL2	Q8IYT4	546
ST8SIA5	NANP	Q8TBE9	529
ST8SIA5	ST6GALNAC5	Q9BVH7	528
ST8SIA5	BEND7	Q8N7W2	508
ST8SIA5	CSGALNACT1	Q8TDX6	492
ST8SIA5	OTOL1	A6NHN0	490
ST8SIA5	ANGEL2	Q5VTE6	487
ST8SIA5	TMEM62	Q0P6H9	484
ST8SIA5	ST6GALNAC3	Q8NDV1	476
ST8SIA5	CMAS	Q8NFW8	463

IntAct

8 interactions, top by confidence:

A	B	Type	Score
APPBP2	ST8SIA5	psi-mi:“MI:0915”(physical association)	0.560
ST8SIA5	APPBP2	psi-mi:“MI:0915”(physical association)	0.560
ST8SIA5	SELENON	psi-mi:“MI:0915”(physical association)	0.500
ST8SIA5	SELENON	psi-mi:“MI:0915”(physical association)	0.400
ST8SIA5	CLGN	psi-mi:“MI:0914”(association)	0.350
FECH	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (51): ST8SIA5 (Two-hybrid), SEPN1 (Affinity Capture-MS), SEPN1 (Affinity Capture-MS), SEPN1 (Affinity Capture-MS), SIL1 (Affinity Capture-MS), PON2 (Affinity Capture-MS), ADAM15 (Affinity Capture-MS), ITPRIP (Affinity Capture-MS), CLGN (Affinity Capture-MS), GPX8 (Affinity Capture-MS), KIAA2013 (Affinity Capture-MS), MR1 (Affinity Capture-MS), NMU (Affinity Capture-MS), NLGN2 (Affinity Capture-MS), CHST12 (Affinity Capture-MS)

ESM2 similar proteins: A2AJQ3, A2AUQ7, A5GFW8, A6NG13, A7RX69, D3ZNQ3, E1BPQ3, E9PU17, E9PX95, E9Q649, G3V9Q9, O15466, P0DN25, P23336, P27473, P38566, P38567, P48794, P61646, P97402, Q02742, Q09324, Q21389, Q2NKH9, Q2YDM8, Q3L7M0, Q3SX46, Q499P3, Q4R5T7, Q4V8F8, Q53G44, Q5U258, Q5ZLK4, Q6ZNI0, Q6ZXC8, Q71SG7, Q7Z388, Q7Z4J2, Q812F3, Q8BV66

Diamond homologs: O15466, O35696, O43173, P61642, P61643, P61644, P61645, P61646, P61647, P61648, P70126, Q07977, Q11200, Q64687, Q64689, Q64690, Q64692, Q6DNG6, Q6H8M7, Q6ZXA0, Q6ZXC8, Q6ZXC9, Q6ZXD2, Q8K4T1, Q92185, Q92186, Q92187, A2WX64, A2XVC2, A2ZI41, Q2QXM3, Q2R2B1, Q5K027, Q6ZH45, Q701R1, Q7FA29, Q8RY00, Q94DD4, Q9BVH7, Q9H4F1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	0
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1917 predictions. Top by Δscore:

Variant	Effect	Δscore
18:46680509:AC:A	acceptor_gain	1.0000
18:46680510:CC:C	acceptor_gain	1.0000
18:46680511:C:CA	acceptor_loss	1.0000
18:46680511:C:CC	acceptor_gain	1.0000
18:46680514:C:CT	acceptor_gain	1.0000
18:46681968:TGACC:T	donor_loss	1.0000
18:46681969:GACCT:G	donor_loss	1.0000
18:46681971:CCT:C	donor_gain	1.0000
18:46681971:CCTCT:C	donor_gain	1.0000
18:46682908:C:CA	donor_gain	1.0000
18:46686168:TTTTA:T	donor_loss	1.0000
18:46686169:TTTA:T	donor_loss	1.0000
18:46686170:TTACC:T	donor_loss	1.0000
18:46686171:TA:T	donor_loss	1.0000
18:46686173:C:A	donor_loss	1.0000
18:46686283:TGTC:T	acceptor_gain	1.0000
18:46686286:CCTGG:C	acceptor_loss	1.0000
18:46686287:CTGGG:C	acceptor_loss	1.0000
18:46688797:T:TA	donor_gain	1.0000
18:46692167:A:AC	donor_gain	1.0000
18:46692168:C:CC	donor_gain	1.0000
18:46704570:A:AC	donor_gain	1.0000
18:46704571:C:CC	donor_gain	1.0000
18:46680506:GGAAC:G	acceptor_gain	0.9900
18:46680507:GAAC:G	acceptor_gain	0.9900
18:46680508:AAC:A	acceptor_gain	0.9900
18:46681970:A:AC	donor_gain	0.9900
18:46681971:C:CC	donor_gain	0.9900
18:46682060:TGCAC:T	acceptor_gain	0.9900
18:46682061:GCAC:G	acceptor_gain	0.9900

AlphaMissense

2489 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:46680131:G:C	H348D	1.000
18:46680273:G:C	S300R	1.000
18:46680273:G:T	S300R	1.000
18:46680275:T:G	S300R	1.000
18:46682058:G:C	N192K	1.000
18:46682058:G:T	N192K	1.000
18:46692201:C:A	W93C	1.000
18:46692201:C:G	W93C	1.000
18:46680124:A:G	M350T	0.999
18:46680129:G:C	H348Q	0.999
18:46680129:G:T	H348Q	0.999
18:46680131:G:T	H348N	0.999
18:46680132:G:C	F347L	0.999
18:46680132:G:T	F347L	0.999
18:46680134:A:G	F347L	0.999
18:46680157:T:A	D339V	0.999
18:46680158:C:G	D339H	0.999
18:46680164:A:C	Y337D	0.999
18:46680165:G:C	H336Q	0.999
18:46680165:G:T	H336Q	0.999
18:46680167:G:C	H336D	0.999
18:46680207:C:A	W322C	0.999
18:46680207:C:G	W322C	0.999
18:46680209:A:G	W322R	0.999
18:46680209:A:T	W322R	0.999
18:46680210:G:C	F321L	0.999
18:46680210:G:T	F321L	0.999
18:46680212:A:G	F321L	0.999
18:46680235:C:T	C313Y	0.999
18:46680268:C:T	G302D	0.999

dbSNP variants (sampled 300 via entrez): RS1000000329 (18:46694971 C>G), RS1000001131 (18:46734632 G>A), RS1000003879 (18:46710403 CTTTCTTTCTTTCTTTT>C), RS1000033780 (18:46734373 C>A), RS1000036476 (18:46710147 C>T), RS1000042251 (18:46692983 G>A,C), RS1000057044 (18:46743549 G>A,C), RS1000111874 (18:46688552 C>T), RS1000127402 (18:46756263 C>A,G,T), RS1000176851 (18:46746298 G>A), RS1000210214 (18:46704056 G>A), RS1000215087 (18:46740528 A>T), RS1000268909 (18:46700946 T>C), RS1000316115 (18:46745970 T>A), RS1000359316 (18:46706350 A>G)

Disease associations

OMIM: gene MIM:607162 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010136_31	Fruit consumption	2.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Valproic Acid	affects expression, increases expression	2
alpha phellandrene	decreases expression	1
propionaldehyde	increases expression	1
arsenite	increases methylation	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Arsenic	affects methylation	1
Doxorubicin	decreases expression	1
Lead	affects methylation	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Plant Extracts	affects cotreatment, decreases expression	1
Dronabinol	increases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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