ST8SIA2

Summary

ST8SIA2 (ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2, HGNC:10870) is a protein-coding gene on chromosome 15q26.1, encoding Alpha-2,8-sialyltransferase 8B (Q92186). Catalyzes the transfer of a sialic acid from a CMP-linked sialic acid donor onto a terminal alpha-2,3-, alpha-2,6-, or alpha-2,8-linked sialic acid of an N-linked glycan acceptor through alpha-2,8-linkages.

The protein encoded by this gene is a type II membrane protein that is thought to catalyze the transfer of sialic acid from CMP-sialic acid to N-linked oligosaccharides and glycoproteins. The encoded protein may be found in the Golgi apparatus and may be involved in the production of polysialic acid, a modulator of the adhesive properties of neural cell adhesion molecule (NCAM1). This protein is a member of glycosyltransferase family 29.

Source: NCBI Gene 8128 — RefSeq curated summary.

At a glance

• Gene–disease (curated): schizophrenia (Limited, GenCC)
• GWAS associations: 10
• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_006011

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10870
Approved symbol	ST8SIA2
Name	ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2
Location	15q26.1
Locus type	gene with protein product
Status	Approved
Aliases	STX, ST8SIA-II, HsT19690
Ensembl gene	ENSG00000140557
Ensembl biotype	protein_coding
OMIM	602546
Entrez	8128

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000268164, ENST00000539113, ENST00000555434, ENST00000556382, ENST00000957924

RefSeq mRNA: 2 — MANE Select: NM_006011 NM_001330416, NM_006011

CCDS: CCDS10372, CCDS81919

Canonical transcript exons

ENST00000268164 — 6 exons

Exon	Start	End
ENSE00000943816	92430049	92430111
ENSE00000943817	92434247	92434375
ENSE00000943819	92444636	92444929
ENSE00000943820	92464100	92468728
ENSE00001179916	92393881	92394162
ENSE00003500567	92438353	92438610

Expression profiles

Bgee: expression breadth broad, 98 present calls, max score 96.72.

FANTOM5 (CAGE): breadth broad, TPM avg 1.9404 / max 221.8448, expressed in 359 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
148612	1.6787	341
148613	0.2617	106

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	96.72	gold quality
ganglionic eminence	UBERON:0004023	95.28	gold quality
ventricular zone	UBERON:0003053	85.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.06	gold quality
heart left ventricle	UBERON:0002084	63.51	gold quality
apex of heart	UBERON:0002098	63.49	gold quality
cardiac ventricle	UBERON:0002082	62.73	gold quality
tibialis anterior	UBERON:0001385	60.45	silver quality
ileal mucosa	UBERON:0000331	57.39	silver quality
deltoid	UBERON:0001476	57.16	gold quality
pancreatic ductal cell	CL:0002079	56.17	silver quality
prefrontal cortex	UBERON:0000451	54.84	gold quality
pigmented layer of retina	UBERON:0001782	54.55	gold quality
cerebellar vermis	UBERON:0004720	54.40	gold quality
buccal mucosa cell	CL:0002336	54.35	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
epithelial cell of pancreas	CL:0000083	54.19	gold quality
hypothalamus	UBERON:0001898	54.01	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
pons	UBERON:0000988	53.68	silver quality
upper arm skin	UBERON:0004263	53.52	gold quality
heart	UBERON:0000948	52.38	gold quality
parotid gland	UBERON:0001831	51.77	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	51.48	gold quality
anterior cingulate cortex	UBERON:0009835	51.03	gold quality
hindlimb stylopod muscle	UBERON:0004252	50.63	gold quality
gall bladder	UBERON:0002110	50.35	gold quality
myocardium	UBERON:0002349	50.25	gold quality
islet of Langerhans	UBERON:0000006	50.06	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-7	yes	205.83
E-ENAD-21	yes	195.68
E-ANND-3	yes	3.60

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PITX2, TFAP2D

miRNA regulators (miRDB)

169 targeting ST8SIA2, 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-5011-5P	100.00	83.46	5820
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-6753-3P	99.93	66.57	637

Literature-anchored findings (GeneRIF, showing 23)

• SIAT8B has a role in neural development and sialic acid synthesis on NCAM (PMID:12138100)
• The upregulation of ST8SIA4 and the donwregulation of ST8SIA2 by valproic acid in HUVEC and tumor cell lines are reported. (PMID:15710344)
• SIAT8B gene is involved in schizophrenia in the Japanese. (PMID:16229822)
• Amino acid substitutions in conserved sequences are critical for the protein-specific polysialylation of NCAM. (PMID:19336400)
• This study provided that ST8SIA2 are associated with Bipolar I in the Han Chinese population. (PMID:20386566)
• STX(G421A) shows a dramatic decrease in polySia synthetic activity on NCAM, whereas STX(C621G) does not; polySia shows a dopamine (DA) binding activity (PMID:21464126)
• ST8SIA2 is a target gene of the BACH1 transcription factor according to ChIP-seq analysis in HEK 293 cells. (PMID:21555518)
• NCAM and polySia are expressed and developmentally regulated in chick corneas. Both membrane-associated and soluble NCAM isoforms are expressed in chick corneas. (PMID:22281821)
• that variation the ST8SIA2 gene is associated with increased risk to mental illness (PMID:22693595)
• Expression of ST8SIA2 in omental fat at baseline was significantly associated with weight loss after Roux-en-Y gastric bypass. (PMID:23643386)
• translational modification of the neural cell adhesion molecule NCAM and the polysialyltransferase ST8SiaII in mammalian semen involves polysialic acid (PMID:23671285)
• Our study showed interesting sex-specific associations between ST8SIAII and schizophrenia. (PMID:24070986)
• the role of ST8SIA2 sequence variation affecting polysialic acid-NCAM formation in 48 Caucasian cases with bipolar disorder (PMID:24651862)
• Data indicate a possible role of STX polysialyltransferase (ST8SIA2) in the common susceptibility of schizophrenia and bipolar I disorder (BD-I). (PMID:26418860)
• the relationships between psychiatric disorders and polySia and/or ST8SIA2 (PMID:27105834)
• impairment of the regulated expression of ST8SIA2 and the resulting downstream effects on gene products by these two intronic single nucleotide polymorphism contribute to the development of these psychiatric disorders. (PMID:27565727)
• ST8SiaII role in the invasiveness and metastasis of small cell lung cancer cells (PMID:28004110)
• Different properties of polysialic acids synthesized by the polysialyltransferases ST8SIA2 and ST8SIA4 have been described. (PMID:28810663)
• 8 SNPs of ST8SIA2 and 2 SNPs of NCAM1 are associated with seasonality in mood changes and circadian preference (PMID:29215920)
• The ST8SIA2 risk haplotype copy number did not show any differential effects on white matter in schizophrenia. (PMID:29353880)
• High ST8SIA2 expression is associated with lung cancer Invasion. (PMID:30978569)
• A cancer-unique glycan: de-N-acetyl polysialic acid (dPSA) linked to cell surface nucleolin depends on re-expression of the fetal polysialyltransferase ST8SIA2 gene. (PMID:34544457)
• Identification of a buried beta-strand as a novel disease-related motif in the human polysialyltransferases. (PMID:38103644)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	st8sia2	ENSDARG00000018788
mus_musculus	St8sia2	ENSMUSG00000025789
rattus_norvegicus	St8sia2	ENSRNOG00000065528

Paralogs (5): ST8SIA5 (ENSG00000101638), ST8SIA1 (ENSG00000111728), ST8SIA4 (ENSG00000113532), ST8SIA6 (ENSG00000148488), ST8SIA3 (ENSG00000177511)

Protein

Protein identifiers

Alpha-2,8-sialyltransferase 8B — Q92186 (reviewed: Q92186)

Alternative names: Sialyltransferase 8B, Sialyltransferase St8Sia II, Sialyltransferase X

All UniProt accessions (4): B2R9U8, C6G488, Q92186, G3V2T1

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the transfer of a sialic acid from a CMP-linked sialic acid donor onto a terminal alpha-2,3-, alpha-2,6-, or alpha-2,8-linked sialic acid of an N-linked glycan acceptor through alpha-2,8-linkages. Therefore, participates in polysialic acid synthesis on various sialylated N-acetyllactosaminyl oligosaccharides (alpha-2,3-, alpha-2,6-, or alpha-2,8-linked sialic acid), including NCAM1, NCAM1 N-glycans, FETUB N-glycans, and to a lesser extent sialylparagloboside (SPG) and AHSG, which does not require the initial addition of an alpha 2,8-sialic acid. However, does not exhibit sialic acid-polymerase activity. Catalyzes polysialic acid synthesis in the hippocampal on NCAM1 and supports neurite outgrowth. ST8SIA2-mediated polysialylation influences on oligodendrocyte differentiation and may promote the integrity of myelin and axons.

Subcellular location. Golgi apparatus membrane. Secreted. Cell membrane.

Tissue specificity. Highly expressed in fetal brain, kidney and heart and to a much lesser extent in adult heart and thymus.

Post-translational modifications. Autopolysialylated. Autopolysialylation is not a prerequisite for the polysialylation acitity, but enhances the polysialylation acitity.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the glycosyltransferase 29 family.

RefSeq proteins (2): NP_001317345, NP_006002* (*=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), 1 shown:

• N-acetyl-alpha-D-neuraminosyl-(2->8) + CMP-N-acetyl-beta-neuraminate = N-acetyl-alpha-D-neuraminosyl-(2->8) + CMP + H(+) (RHEA:77367)

UniProt features (32 total): mutagenesis site 9, binding site 8, glycosylation site 6, topological domain 2, disulfide bond 2, sequence conflict 2, chain 1, transmembrane region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92186-F1	85.70	0.76

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): 346 (proton donor/acceptor)

Ligand- & substrate-binding residues (8): 316; 329; 330; 162; 185; 294; 295; 296

Disulfide bonds (2): 157–307, 171–371

Glycosylation sites (6): 60, 72, 89, 134, 219, 234

Mutagenesis-validated functional residues (9):

Position	Phenotype
60	does not affect autopolysialylation.
72	does not affect autopolysialylation.
89	loss of autopolysialylation; when associated with q-219 and q-234. loss of polysialylation activity; when associated wit
89	decreases autopolysialylation. does not affect localization at golgi apparatus. increases cell surface autopolysialylate
134	does not affect autopolysialylation.
219	loss of autopolysialylation; when associated with q-89 and s-234. loss of polysialylation activity; when associated with
219	decreases autopolysialylation. does not affect localization at golgi apparatus. increases cell surface autopolysialylate
234	loss of autopolysialylation; when associated with q-89 and q-219. loss of polysialylation activity; when associated with
234	decreases autopolysialylation. does not affect localization at golgi apparatus. loss of autopolysialylation; when associ

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-4085001	Sialic acid metabolism
R-HSA-419037	NCAM1 interactions
R-HSA-975577	N-Glycan antennae elongation
R-HSA-1266738	Developmental Biology
R-HSA-375165	NCAM signaling for neurite out-growth
R-HSA-392499	Metabolism of proteins
R-HSA-422475	Axon guidance
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
R-HSA-948021	Transport to the Golgi and subsequent modification
R-HSA-9675108	Nervous system development
R-HSA-975576	N-glycan antennae elongation in the medial/trans-Golgi

MSigDB gene sets: 218 (showing top): RNGTGGGC_UNKNOWN, GOBP_OLIGOSACCHARIDE_METABOLIC_PROCESS, GOBP_N_GLYCAN_PROCESSING, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BENPORATH_ES_WITH_H3K27ME3, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_RESPONSE_TO_COCAINE, GOBP_SYNAPSE_ASSEMBLY, GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, TGCACTT_MIR519C_MIR519B_MIR519A, PEREZ_TP63_TARGETS, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, GOBP_POSITIVE_REGULATION_OF_SYNAPSE_ASSEMBLY, GOBP_GROWTH, REACTOME_NCAM_SIGNALING_FOR_NEURITE_OUT_GROWTH

GO Biological Process (14): ganglioside biosynthetic process (GO:0001574), carbohydrate metabolic process (GO:0005975), N-glycan processing (GO:0006491), nervous system development (GO:0007399), glycoprotein biosynthetic process (GO:0009101), oligosaccharide metabolic process (GO:0009311), protein modification process (GO:0036211), response to cocaine (GO:0042220), positive regulation of neuron apoptotic process (GO:0043525), positive regulation of synapse assembly (GO:0051965), sialylation (GO:0097503), neuron projection extension (GO:1990138), obsolete protein glycosylation (GO:0006486), neuron differentiation (GO:0030182)

GO Molecular Function (6): nucleotide binding (GO:0000166), alpha-N-acetylneuraminate alpha-2,8-sialyltransferase activity (GO:0003828), sialic acid binding (GO:0033691), sialyltransferase activity (GO:0008373), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (10): Golgi membrane (GO:0000139), extracellular region (GO:0005576), nucleoplasm (GO:0005654), early endosome (GO:0005769), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), perinuclear region of cytoplasm (GO:0048471), recycling endosome (GO:0055037), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Asparagine N-linked glycosylation	2
Synthesis of substrates in N-glycan biosythesis	1
NCAM signaling for neurite out-growth	1
N-glycan antennae elongation in the medial/trans-Golgi	1
Axon guidance	1
Nervous system development	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
Developmental Biology	1
Transport to the Golgi and subsequent modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	3
macromolecule modification	2
endosome	2
ganglioside metabolic process	1
glycosphingolipid biosynthetic process	1
ceramide biosynthetic process	1
primary metabolic process	1
protein N-linked glycosylation	1
glycoprotein biosynthetic process	1
system development	1
macromolecule biosynthetic process	1
glycoprotein metabolic process	1
carbohydrate derivative biosynthetic process	1
carbohydrate metabolic process	1
protein metabolic process	1
response to alkaloid	1
response to oxygen-containing compound	1
positive regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
synapse assembly	1
positive regulation of nervous system development	1
regulation of synapse assembly	1
positive regulation of cell junction assembly	1
developmental cell growth	1
neuron projection morphogenesis	1
developmental growth involved in morphogenesis	1
cell differentiation	1
generation of neurons	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
sialyltransferase activity	1
carboxylic acid binding	1
carbohydrate derivative binding	1
glycosyltransferase activity	1
catalytic activity	1
transferase activity	1
Golgi apparatus	1
bounding membrane of organelle	1

Protein interactions and networks

STRING

1018 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ST8SIA2	STX2	P32856	960
ST8SIA2	STX1A	Q16623	940
ST8SIA2	NCAM1	P13591	849
ST8SIA2	DNAJB11	Q9UBS4	759
ST8SIA2	STX1B	P61266	663
ST8SIA2	ST6GALNAC4	Q9H4F1	644
ST8SIA2	SAA1	P02735	643
ST8SIA2	SAA1	P02735	622
ST8SIA2	VAMP2	P19065	609
ST8SIA2	A4GALT	Q9NPC4	609
ST8SIA2	NRP2	O60462	604
ST8SIA2	RNF112	Q9ULX5	583
ST8SIA2	SNAP25	P13795	526
ST8SIA2	FAM174B	Q3ZCQ3	523
ST8SIA2	ST6GALNAC3	Q8NDV1	512

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ST8SIA2	HS3ST1	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): GOLM1 (Affinity Capture-MS), IGF2R (Affinity Capture-MS), HS3ST1 (Affinity Capture-MS), PCDH1 (Affinity Capture-MS), HNRNPCL1 (Affinity Capture-MS), ST8SIA4 (Affinity Capture-MS), HSPA13 (Affinity Capture-MS), NMU (Affinity Capture-MS), TMEM59 (Affinity Capture-MS), ST8SIA2 (Affinity Capture-MS)

ESM2 similar proteins: A6NG13, A7RX69, A8E7N9, E7F9T0, F1QWZ4, F1S5L4, I1FQB6, O15466, O35696, O43173, O97827, P23613, P38566, P48794, P61643, P61644, P61645, P61646, P61647, P61648, P70126, P85857, P97564, Q07977, Q17678, Q1LYL8, Q26974, Q4V8F8, Q5GJ77, Q5RCN4, Q61089, Q61586, Q64689, Q64690, Q64692, Q66KL4, Q6ZXC8, Q6ZXC9, Q765H6, Q80TS3

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

1 interactions.

A	Effect	B	Mechanism
TFAP2D	“up-regulates quantity by expression”	ST8SIA2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1701 predictions. Top by Δscore:

Variant	Effect	Δscore
15:92394159:TCGGG:T	donor_loss	1.0000
15:92394160:CGGGT:C	donor_loss	1.0000
15:92394161:GGGTA:G	donor_loss	1.0000
15:92394164:T:A	donor_loss	1.0000
15:92434245:A:AG	acceptor_gain	1.0000
15:92434246:G:GG	acceptor_gain	1.0000
15:92434246:GA:G	acceptor_gain	1.0000
15:92394161:GG:G	donor_gain	0.9900
15:92394162:GG:G	donor_gain	0.9900
15:92394163:G:GG	donor_gain	0.9900
15:92434242:TCCA:T	acceptor_loss	0.9900
15:92434242:TCCAG:T	acceptor_gain	0.9900
15:92434243:CCAG:C	acceptor_gain	0.9900
15:92434244:CA:C	acceptor_loss	0.9900
15:92434244:CAG:C	acceptor_gain	0.9900
15:92434245:AGA:A	acceptor_gain	0.9900
15:92434246:GAG:G	acceptor_gain	0.9900
15:92434246:GAGCT:G	acceptor_gain	0.9900
15:92438606:ATCAG:A	donor_loss	0.9900
15:92438607:TCAGG:T	donor_loss	0.9900
15:92438608:CAGG:C	donor_loss	0.9900
15:92438609:AG:A	donor_loss	0.9900
15:92438610:GGT:G	donor_loss	0.9900
15:92438611:GTAA:G	donor_loss	0.9900
15:92438612:T:G	donor_loss	0.9900
15:92444634:A:AG	acceptor_gain	0.9900
15:92444635:G:GG	acceptor_gain	0.9900
15:92444953:G:GG	donor_gain	0.9900
15:92464237:TC:T	donor_gain	0.9900
15:92464265:G:GG	donor_gain	0.9900

AlphaMissense

2455 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:92438532:G:A	C157Y	1.000
15:92438533:T:G	C157W	1.000
15:92438543:G:C	G161R	1.000
15:92438544:G:A	G161D	1.000
15:92438544:G:T	G161V	1.000
15:92438548:C:A	N162K	1.000
15:92438548:C:G	N162K	1.000
15:92438610:G:T	R183M	1.000
15:92444642:C:A	N185K	1.000
15:92444642:C:G	N185K	1.000
15:92444676:G:T	G197W	1.000
15:92444677:G:A	G197E	1.000
15:92444677:G:T	G197V	1.000
15:92444692:T:C	L202P	1.000
15:92444705:C:A	N206K	1.000
15:92444705:C:G	N206K	1.000
15:92444802:T:A	W239R	1.000
15:92444802:T:C	W239R	1.000
15:92464104:T:A	W283R	1.000
15:92464104:T:C	W283R	1.000
15:92464106:G:C	W283C	1.000
15:92464106:G:T	W283C	1.000
15:92464135:C:A	P293H	1.000
15:92464138:C:T	T294I	1.000
15:92464144:G:A	G296D	1.000
15:92464147:T:C	L297P	1.000
15:92464177:G:A	C307Y	1.000
15:92464178:C:G	C307W	1.000
15:92464197:G:C	G314R	1.000
15:92464198:G:T	G314V	1.000

dbSNP variants (sampled 300 via entrez): RS1000012850 (15:92465905 G>A,C), RS1000057978 (15:92394901 G>A), RS1000088585 (15:92394630 G>A), RS1000144998 (15:92459835 G>A,C,T), RS1000185632 (15:92411658 C>G), RS1000217431 (15:92421734 A>G,T), RS1000252087 (15:92399507 G>C), RS1000366891 (15:92406171 G>A), RS1000375943 (15:92400391 A>G), RS1000481629 (15:92405928 G>A), RS1000541754 (15:92458279 G>A), RS1000613664 (15:92466961 C>G,T), RS1000645068 (15:92464076 T>TC), RS1000647180 (15:92417271 T>C), RS1000650697 (15:92438230 C>A,G,T)

Disease associations

OMIM: gene MIM:602546 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
schizophrenia	Limited	Autosomal dominant

Mondo (1): schizophrenia (MONDO:0005090)

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000654_1	Bipolar I disorder	6.000000e-06
GCST001621_18	Airflow obstruction	4.000000e-07
GCST001991_5	Weight loss (gastric bypass surgery)	7.000000e-08
GCST002396_27	Smoking initiation	9.000000e-08
GCST002415_10	Colorectal cancer (diet interaction)	8.000000e-07
GCST002550_19	Allergic rhinitis	7.000000e-07
GCST002550_20	Allergic rhinitis	1.000000e-07
GCST003542_96	Night sleep phenotypes	4.000000e-06
GCST009391_242	Metabolite levels	4.000000e-07
GCST012490_535	Femur bone mineral density x serum urate levels interaction	3.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0005245	body weight loss
EFO:0005670	smoking initiation
EFO:0008111	diet measurement
EFO:0010494	guanosine diphosphate measurement
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression, increases methylation	7
sodium arsenite	affects methylation, increases expression	3
entinostat	decreases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
bisphenol A	decreases methylation	1
trichostatin A	decreases expression	1
arsenite	increases methylation	1
afimoxifene	decreases reaction, decreases expression	1
benzo(e)pyrene	affects methylation	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
incobotulinumtoxinA	decreases expression	1
(+)-JQ1 compound	affects expression, increases reaction	1
Sunitinib	increases expression	1
Panobinostat	affects expression, increases reaction	1
Allergens	decreases expression	1
Azacitidine	decreases expression	1
Doxorubicin	decreases expression	1
Estrogens	decreases expression, decreases reaction	1
Hydralazine	affects cotreatment, increases expression	1
Lead	affects splicing	1
Methapyrilene	affects methylation	1
Methotrexate	increases expression	1
Tunicamycin	decreases expression	1
Antirheumatic Agents	increases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety