ST8SIA1

Summary

ST8SIA1 (ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1, HGNC:10869) is a protein-coding gene on chromosome 12p12.1, encoding Alpha-N-acetylneuraminide alpha-2,8-sialyltransferase (Q92185). Catalyzes the addition of sialic acid in alpha 2,8-linkage to the sialic acid moiety of the ganglioside GM3 to form ganglioside GD3; gangliosides are a subfamily of complex glycosphingolipds that contain one or more residues of sialic acid.

Gangliosides are membrane-bound glycosphingolipids containing sialic acid. Ganglioside GD3 is known to be important for cell adhesion and growth of cultured malignant cells. The protein encoded by this gene is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to GM3 to produce gangliosides GD3 and GT3. The encoded protein may be found in the Golgi apparatus and is a member of glycosyltransferase family 29. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 6489 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_003034

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10869
Approved symbol	ST8SIA1
Name	ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1
Location	12p12.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000111728
Ensembl biotype	protein_coding
OMIM	601123
Entrez	6489

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 8 protein_coding_CDS_not_defined, 7 protein_coding, 1 nonsense_mediated_decay

ENST00000261197, ENST00000381424, ENST00000396037, ENST00000404299, ENST00000508924, ENST00000536535, ENST00000536558, ENST00000537795, ENST00000538256, ENST00000540824, ENST00000541868, ENST00000544732, ENST00000545185, ENST00000545494, ENST00000545524, ENST00000859896

RefSeq mRNA: 2 — MANE Select: NM_003034 NM_001304450, NM_003034

CCDS: CCDS8697

Canonical transcript exons

ENST00000396037 — 5 exons

Exon	Start	End
ENSE00003530324	22255280	22255389
ENSE00003536557	22193391	22202038
ENSE00003686359	22249006	22249098
ENSE00003687762	22287149	22287293
ENSE00003910700	22333997	22334707

Expression profiles

Bgee: expression breadth ubiquitous, 224 present calls, max score 94.79.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2435 / max 108.0910, expressed in 434 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130068	0.3526	201
130067	0.3402	182
130069	0.2283	134
130066	0.2079	116
130065	0.1146	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	94.79	gold quality
ganglionic eminence	UBERON:0004023	93.38	gold quality
cortical plate	UBERON:0005343	87.96	gold quality
calcaneal tendon	UBERON:0003701	86.99	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.07	gold quality
cerebellar hemisphere	UBERON:0002245	85.03	gold quality
cerebellar cortex	UBERON:0002129	84.91	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.01	gold quality
cerebellum	UBERON:0002037	83.88	gold quality
adrenal tissue	UBERON:0018303	82.55	gold quality
muscle layer of sigmoid colon	UBERON:0035805	81.70	gold quality
prefrontal cortex	UBERON:0000451	81.52	gold quality
right adrenal gland cortex	UBERON:0035827	81.33	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.88	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.86	gold quality
right adrenal gland	UBERON:0001233	80.60	gold quality
right frontal lobe	UBERON:0002810	80.55	gold quality
cingulate cortex	UBERON:0003027	80.45	gold quality
left adrenal gland cortex	UBERON:0035825	80.35	gold quality
embryo	UBERON:0000922	80.34	gold quality
left adrenal gland	UBERON:0001234	80.31	gold quality
anterior cingulate cortex	UBERON:0009835	80.28	gold quality
hypothalamus	UBERON:0001898	80.04	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	79.79	gold quality
amygdala	UBERON:0001876	79.65	gold quality
ectocervix	UBERON:0012249	79.61	gold quality
adrenal gland	UBERON:0002369	79.34	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	79.30	gold quality
spinal cord	UBERON:0002240	79.26	gold quality
neocortex	UBERON:0001950	79.22	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.77

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, NFKB, RELA, SP1

miRNA regulators (miRDB)

276 targeting ST8SIA1, 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-8485	100.00	77.57	4731
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-520D-5P	99.98	73.34	4883

Literature-anchored findings (GeneRIF, showing 39)

• down regulation of GD3 synthase is associated with reduction in GD3 ganglioside expression affecting tumorigenesis and metastasis in F-11 cells. (PMID:11849746)
• Human GD3 synthase gene consisted of five exons and span about 135 kilobases. The 5’-flanking region lacked canonical TATA and CAAT boxes, but contained SP1 binding site(s) as in rat and mouse (PMID:12818424)
• findings suggest that the disialoganglioside(GD3) synthase gene represents a physiological modulator of vascular smooth muscle cell responses that may contribute to plaque instability in atherosclerosis (PMID:15175338)
• has an apoptotic effect on ECV304 cells through downregulation of Bcl-2 expression via dephosphorylation of AKT and CREB (PMID:15196944)
• calnexin controls the biological outcome of GD3 accumulation and reveals a novel role in the stress response (PMID:15319364)
• The cloning and characterization of ST8SIA1 in humans is reported. (PMID:16120058)
• Transcriptional regulation of GD3S expression in Fas-induced Jurkat T-cells shows a critical role of NF-kappa B in regulated expression. (PMID:16481330)
• effects of small interfering (si) RNAs against GD3 synthase gene on the expression of ganglioside GD2 and biological phenotypes of human lung cancer cells expressing GD2. (PMID:16862187)
• These results indicate that NF-kappaB plays an essential role in the transcriptional activity of human GD3 synthase gene essential for GD3 synthesis (PMID:17913261)
• This work advances the hypothesis that GD3 induces a post-translational modification of histone H1 thus influencing the apoptosis process through transcriptional activation/repression of specific genes. (PMID:18261989)
• The functions of four conserved residues between the L and S sialylmotifs in human GD3-synthase were investigated, and it was found that these sites are involved in determining the alpha2,8-linkage specificity of GD3-synthase. (PMID:18348864)
• Two independent studies support an allelic association of multiple sclerosis with polymorphisms in the ST8SIA1 gene. (PMID:18612409)
• Data propose that the recruitment of TG2 into membranes by GD3 might play an important role in the erythroid differentiation in K562 cells. (PMID:18690648)
• Ganglioside GD3-Synthase was associated with poor pathohistological grading in breast cancer (PMID:19125296)
• Isolation and functional characterization of the human glioblastoma-specific promoter region of the human GD3 synthase (hST8Sia1) gene are reported. (PMID:19280063)
• G(D3) synthase overexpression may contribute to increasing the malignant properties of breast cancer cells. (PMID:19335207)
• Variants in ST8SIA1 do not play a major role in susceptibility to multiple sclerosis in Canadian families. (PMID:19428123)
• GD3 has a role in hypoxia susceptibility by disabling the c-Src/NF-kappaB survival pathway resulting in lower Mn-SOD expression (PMID:19956670)
• Results show that G(D3) synthase expression is sufficient to enhance the tumorigenicity of MDA-MB-231 breast cancer cells through a ganglioside-dependent activation of the c-Met receptor. (PMID:20889649)
• This indicates that ST8Sia I is able to act as an oligosialyltransferase in a cellular context. (PMID:22885356)
• TNF-alpha and IL-6 secreted from keratinocytes enhanced ST8SIA1 expression in melanocytes. (PMID:24548412)
• our study provides support for the GD3-induced cell cycle arrest, disruption of integrin-b1-mediated anchorage, inhibition of angiogenesis and thereby induced apoptosis in pancreatic cancer cells. (PMID:24842107)
• Results show that GD3S regulates stem cell function via c-Met and the expression of GD3S is regulated by FOXC2, a transcription factor functioning downstream of several epithelial-mesenchymal transition signaling pathways. (PMID:25109336)
• Though results are limited by the small sample size, variants in BDNF and ST8SIA may slow down the early response to antidepressants in subjects non-exposed to stressors at the illness onset, with a remarkable gene-environment interaction (PMID:25163442)
• GD3 and GD3S are highly expressed in glioblastoma multiforme (GBM) stem cell, play a key role in glioblastoma tumorigenicity, and are potential therapeutic targets against GBM. (PMID:27143722)
• Data suggest that ganglioside glycosyltransferases ST3GAL5, ST8SIA1, and B4GALNT1 are S-acylated at conserved cysteine residues located close to cytoplasmic border of their transmembrane domains; ST3Gal-II is acylated at conserved cysteine residue in N-terminal cytoplasmic tail; for B4GALNT1 and ST3Gal-II, dimer formation controls their S-acylation status. (PMID:28698248)
• altered expression of miR-33a/let-7e was correlated with ST8SIA1 level, which might contribute to CRC progression (PMID:28751193)
• These results from genotype-phenotype analysis might suggest a possible link between the ST8SIA1 functional promoter haplotype and the clinical severity of TAO [thyroid-associated ophthalmopathy]. (PMID:29047240)
• These results suggest that curcumin controls hST8Sia I gene expression via AMPK signal pathway in A549 cells. (PMID:30004453)
• these data demonstrate the mechanism by which ST8SIA1 regulates tumor growth and metastasis in triple-negative breast cancer. (PMID:30237308)
• genetic variants at the genes SSH1 and ST8SIA1 were related to the genetic predisposition to early-onset periodontitis that is in part triggered by smoking (PMID:31537151)
• TNFalpha-signal and cAMP-mediated signals oppositely regulate melanoma- associated ganglioside GD3 synthase gene in human melanocytes. (PMID:31611597)
• ST8SIA1 inhibition sensitizes triple negative breast cancer to chemotherapy via suppressing Wnt/beta-catenin and FAK/Akt/mTOR. (PMID:32939659)
• Comprehensive Transcriptomic Analysis Identifies ST8SIA1 as a Survival-Related Sialyltransferase Gene in Breast Cancer. (PMID:33260650)
• Knockdown of lncRNA MIR44352HG and ST8SIA1 expression inhibits the proliferation, invasion and migration of prostate cancer cells in vitro and in vivo by blocking the activation of the FAK/AKT/betacatenin signaling pathway. (PMID:33846784)
• BACH1 Binding Links the Genetic Risk for Severe Periodontitis with ST8SIA1. (PMID:34160287)
• Long noncoding RNA NR2F1-AS1 plays a carcinogenic role in gastric cancer by recruiting transcriptional factor SPI1 to upregulate ST8SIA1 expression. (PMID:34738863)
• Possible regulation of ganglioside GD3 synthase gene expression with DNA methylation in human glioma cells. (PMID:36897478)
• The yes-associated protein (YAP) is associated with resistance to anti-GD2 immunotherapy in neuroblastoma through downregulation of ST8SIA1. (PMID:37554309)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	st8sia1	ENSDARG00000098221
mus_musculus	St8sia1	ENSMUSG00000030283
rattus_norvegicus	St8sia1	ENSRNOG00000014018

Paralogs (5): ST8SIA5 (ENSG00000101638), ST8SIA4 (ENSG00000113532), ST8SIA2 (ENSG00000140557), ST8SIA6 (ENSG00000148488), ST8SIA3 (ENSG00000177511)

Protein

Protein identifiers

Alpha-N-acetylneuraminide alpha-2,8-sialyltransferase — Q92185 (reviewed: Q92185)

Alternative names: Alpha-2,8-sialyltransferase 8A, Ganglioside GD3 synthase, Ganglioside GT3 synthase, Sialyltransferase 8A, Sialyltransferase St8Sia I

All UniProt accessions (6): Q92185, F8WCS8, H0YFU1, H0YG41, H0YGV9, Q86X71

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the addition of sialic acid in alpha 2,8-linkage to the sialic acid moiety of the ganglioside GM3 to form ganglioside GD3; gangliosides are a subfamily of complex glycosphingolipds that contain one or more residues of sialic acid. Can catalyze the addition of a second alpha-2,8-sialic acid to GD3 to form GT3. Can use GM1b, GD1a and GT1b as acceptor substrates to synthesize GD1c, GT1a and GQ1b respectively. Can synthesize unusual tetra- and pentasialylated lactosylceramide derivatives identified as GQ3 (II3Neu5Ac4-Gg2Cer) and GP3 (II3Neu5Ac5-Gg2Cer) in breast cancer cells.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Strongly expressed in melanoma cell lines, adult and fetal brain and to a lesser extent in adult and fetal lung.

Pathway. Protein modification; protein glycosylation. Lipid metabolism; sphingolipid metabolism.

Similarity. Belongs to the glycosyltransferase 29 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q92185-1	1	yes
Q92185-2	2, Sat-2

RefSeq proteins (2): NP_001291379, NP_003025* (*=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), 8 shown:

• an N-acetyl-alpha-neuraminyl-(2->3)-beta-D-galactosyl derivative + CMP-N-acetyl-beta-neuraminate = an N-acetyl-alpha-neuraminyl-(2->8)-N-acetyl-alpha-neuraminyl-(2->3)-beta-D-galactosyl derivative + CMP + H(+) (RHEA:19313)
• a ganglioside GM3 (d18:1(4E)) + CMP-N-acetyl-beta-neuraminate = a ganglioside GD3 (d18:1(4E)) + CMP + H(+) (RHEA:41760)
• 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 GD3 + CMP-N-acetyl-beta-neuraminate = a ganglioside GT3 + CMP + H(+) (RHEA:77295)
• alpha-N-acetylneuraminyl-(2->8)-alpha-N-acetylneuraminyl-(2->8)-alpha-N-acetylneuraminyl-(2->3)-beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide + CMP-N-acetyl-beta-neuraminate = alpha-N-acetylneuraminyl-(2->8)-alpha-N-acetylneuraminyl-(2->8)-alpha-N-acetylneuraminyl-(2->3)-beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide + CMP + H(+) (RHEA:77371)

UniProt features (26 total): binding site 7, mutagenesis site 6, glycosylation site 4, topological domain 2, disulfide bond 2, splice variant 2, chain 1, transmembrane region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92185-F1	88.71	0.75

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): 322 (proton donor/acceptor)

Ligand- & substrate-binding residues (7): 296; 310; 143; 166; 274; 275; 276

Disulfide bonds (2): 138–287, 152–347

Glycosylation sites (4): 71, 119, 214, 245

Mutagenesis-validated functional residues (6):

Position	Phenotype
188	enzyme activity is 42% of the wild-type. a 2.5-fold increase in km value for cmp-n-acetyl-beta-neuraminate. a 2.3-fold d
189	enzyme activity is 91% of the wild-type.
190	enzyme activity is 33% of the wild-type. a 2-fold increase in km value for ganglioside gm3 and 1.25 fold increase in km
272	enzyme activity is 20% of the wild-type. a 10-fold increase in km value for ganglioside gm3. a 5-fold decrease in vmax f
272	enzyme activity is 19% of the wild-type.
272	enzyme activity is 98% of the wild-type.

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: 293 (showing top): MORF_ITGA2, GOBP_OLIGOSACCHARIDE_METABOLIC_PROCESS, GOBP_N_GLYCAN_PROCESSING, GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, TGACCTY_ERR1_Q2, GGGTGGRR_PAX4_03, MORF_RAD51L3, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, NFKB_Q6, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, MCLACHLAN_DENTAL_CARIES_DN, MORF_CTSB

GO Biological Process (11): carbohydrate metabolic process (GO:0005975), N-glycan processing (GO:0006491), glycosphingolipid biosynthetic process (GO:0006688), oligosaccharide metabolic process (GO:0009311), cellular response to heat (GO:0034605), epithelial cell proliferation (GO:0050673), positive regulation of epithelial cell proliferation (GO:0050679), obsolete protein glycosylation (GO:0006486), lipid metabolic process (GO:0006629), sphingolipid metabolic process (GO:0006665), cell population proliferation (GO:0008283)

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), membrane (GO:0016020), Golgi apparatus (GO:0005794)

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
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
response to heat	1
cellular response to stress	1
cell population proliferation	1
positive regulation of cell population proliferation	1
epithelial cell proliferation	1
regulation of epithelial cell proliferation	1
lipid metabolic process	1
cellular process	1
sialyltransferase activity	1
glycosyltransferase activity	1
binding	1
catalytic activity	1
transferase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

718 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ST8SIA1	B4GALNT1	Q00973	857
ST8SIA1	ST3GAL5	Q9UNP4	824
ST8SIA1	GDAP1	Q8TB36	769
ST8SIA1	CFAP126	Q5VTH2	670
ST8SIA1	CASD1	Q96PB1	597
ST8SIA1	B3GALT4	O96024	574
ST8SIA1	ST6GALNAC6	Q969X2	564
ST8SIA1	ST6GALNAC3	Q8NDV1	551
ST8SIA1	ST3GAL6	Q9Y274	546
ST8SIA1	ST6GAL2	Q96JF0	536
ST8SIA1	NEU4	Q8WWR8	513
ST8SIA1	NEU2	Q9Y3R4	509
ST8SIA1	UGCG	Q16739	499
ST8SIA1	B4GALT6	Q9UBX8	493
ST8SIA1	MAG	P20916	472

IntAct

7 interactions, top by confidence:

A	B	Type	Score
ST8SIA1	OPTN	psi-mi:“MI:0915”(physical association)	0.560
ST8SIA1	POTEF	psi-mi:“MI:0914”(association)	0.530
ST8SIA1	ALOX12B	psi-mi:“MI:0914”(association)	0.350

BioGRID (31): POTEF (Affinity Capture-MS), RPIA (Affinity Capture-MS), BRAT1 (Affinity Capture-MS), INTS12 (Affinity Capture-MS), NMD3 (Affinity Capture-MS), IPO13 (Affinity Capture-MS), HOOK2 (Affinity Capture-MS), INTS1 (Affinity Capture-MS), RUFY1 (Affinity Capture-MS), ZMYM2 (Affinity Capture-MS), RPIA (Affinity Capture-MS), NMD3 (Affinity Capture-MS), HOOK2 (Affinity Capture-MS), RUFY1 (Affinity Capture-MS), IPO13 (Affinity Capture-MS)

ESM2 similar proteins: A0A0D3QS98, A0A0D3QS99, A4D0V7, C5H5C4, F6Q1T7, O70309, O75354, P17405, P18084, P18424, P22413, P50747, P52850, P58242, P61642, P80747, Q04519, Q0VBD0, Q0VD19, Q13219, Q52KP5, Q58CQ9, Q5QQ51, Q5STE3, Q64687, Q6DFZ6, Q6KFX9, Q6MZW2, Q6P988, Q6UWX4, Q6YGZ1, Q6ZXD2, Q71RP1, Q812F8, Q8BJQ9, Q8C1F4, Q8C419, Q8N5D6, Q8N6G5, Q8R116

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2068 predictions. Top by Δscore:

Variant	Effect	Δscore
12:22287144:CTAA:C	donor_loss	1.0000
12:22287145:TAAC:T	donor_loss	1.0000
12:22287146:AACCT:A	donor_loss	1.0000
12:22287147:A:AT	donor_loss	1.0000
12:22287202:C:CA	donor_gain	1.0000
12:22287203:C:A	donor_gain	1.0000
12:22287212:C:CT	donor_gain	1.0000
12:22287307:C:CT	acceptor_gain	1.0000
12:22309730:T:A	donor_gain	1.0000
12:22331002:T:TA	donor_gain	1.0000
12:22331025:CAG:C	donor_gain	1.0000
12:22202036:AACCT:A	acceptor_gain	0.9900
12:22202037:ACC:A	acceptor_gain	0.9900
12:22202038:CC:C	acceptor_loss	0.9900
12:22202038:CCT:C	acceptor_gain	0.9900
12:22202038:CCTAT:C	acceptor_gain	0.9900
12:22202039:C:CC	acceptor_gain	0.9900
12:22202039:CTATT:C	acceptor_gain	0.9900
12:22249099:C:CC	acceptor_gain	0.9900
12:22255278:A:AC	donor_gain	0.9900
12:22255279:C:CC	donor_gain	0.9900
12:22255279:CCG:C	donor_gain	0.9900
12:22287289:GTTTC:G	acceptor_gain	0.9900
12:22287291:TTC:T	acceptor_gain	0.9900
12:22287292:TC:T	acceptor_gain	0.9900
12:22287293:CC:C	acceptor_gain	0.9900
12:22287294:C:CC	acceptor_gain	0.9900
12:22287294:C:CG	acceptor_loss	0.9900
12:22287295:T:A	acceptor_loss	0.9900
12:22287308:A:T	acceptor_gain	0.9900

AlphaMissense

2348 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:22201659:G:C	H322D	1.000
12:22201738:G:C	F295L	1.000
12:22201738:G:T	F295L	1.000
12:22201740:A:G	F295L	1.000
12:22201799:G:A	T275I	1.000
12:22201802:G:A	S274F	1.000
12:22249092:A:C	N166K	1.000
12:22249092:A:T	N166K	1.000
12:22255358:C:G	C138S	1.000
12:22255359:A:G	C138R	1.000
12:22255359:A:T	C138S	1.000
12:22201639:A:C	F328L	0.999
12:22201639:A:T	F328L	0.999
12:22201641:A:G	F328L	0.999
12:22201643:T:A	E327V	0.999
12:22201657:A:C	H322Q	0.999
12:22201657:A:T	H322Q	0.999
12:22201659:G:T	H322N	0.999
12:22201692:A:C	Y311D	0.999
12:22201693:G:C	H310Q	0.999
12:22201693:G:T	H310Q	0.999
12:22201695:G:C	H310D	0.999
12:22201729:G:C	F298L	0.999
12:22201729:G:T	F298L	0.999
12:22201731:A:G	F298L	0.999
12:22201733:G:T	P297H	0.999
12:22201735:C:A	W296C	0.999
12:22201735:C:G	W296C	0.999
12:22201737:A:G	W296R	0.999
12:22201737:A:T	W296R	0.999

dbSNP variants (sampled 300 via entrez): RS1000023645 (12:22195271 C>G,T), RS1000040919 (12:22324748 C>T), RS1000059726 (12:22282560 G>T), RS1000101399 (12:22317108 T>C), RS1000117589 (12:22218420 C>A,G,T), RS1000118835 (12:22241587 C>T), RS1000127560 (12:22227256 C>CTTTAAGTCACATT), RS1000134816 (12:22282340 G>A,C), RS1000162036 (12:22193783 T>C), RS1000179354 (12:22201124 A>G), RS1000255889 (12:22292752 G>T), RS1000258049 (12:22288329 T>C), RS1000263971 (12:22318505 G>A), RS1000304197 (12:22202443 A>G), RS1000305014 (12:22312890 A>C)

Disease associations

OMIM: gene MIM:601123 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000766_1	Non-alcoholic fatty liver disease histology (lobular)	4.000000e-06
GCST002058_7	DNA methylation (variation)	5.000000e-06
GCST003264_123	Post bronchodilator FEV1/FVC ratio	2.000000e-06
GCST003264_489	Post bronchodilator FEV1/FVC ratio	3.000000e-06
GCST006291_83	Spherical equivalent or myopia (age of diagnosis)	1.000000e-09
GCST010002_211	Refractive error	9.000000e-26

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0022599	DNA methylation
EFO:0004713	FEV/FVC ratio
EFO:0004847	age at onset

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	4
afuresertib	increases expression	1
trichostatin A	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Benzo(a)pyrene	increases methylation	1
Calcitriol	increases expression	1
Carmustine	increases expression	1
Cycloheximide	increases expression, affects cotreatment	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Emodin	increases expression	1
Methapyrilene	increases methylation	1
Nickel	increases expression	1
Progesterone	decreases expression	1
Silicon Dioxide	decreases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Zearalenone	decreases expression	1
Aflatoxin B1	decreases methylation	1
Acrylamide	decreases expression	1
Particulate Matter	decreases expression	1

Clinical trials (associated diseases)

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