B3GAT1

Summary

B3GAT1 (beta-1,3-glucuronyltransferase 1, HGNC:921) is a protein-coding gene on chromosome 11q25, encoding Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1 (Q9P2W7). Involved in the biosynthesis of L2/HNK-1 carbohydrate epitope on glycoproteins.

The protein encoded by this gene is a member of the glucuronyltransferase gene family. These enzymes exhibit strict acceptor specificity, recognizing nonreducing terminal sugars and their anomeric linkages. This gene product functions as the key enzyme in a glucuronyl transfer reaction during the biosynthesis of the carbohydrate epitope HNK-1 (human natural killer-1, also known as CD57 and LEU7). Alternate transcriptional splice variants have been characterized.

Source: NCBI Gene 27087 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 39 total
• MANE Select transcript: NM_054025

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:921
Approved symbol	B3GAT1
Name	beta-1,3-glucuronyltransferase 1
Location	11q25
Locus type	gene with protein product
Status	Approved
Aliases	GlcAT-P
Ensembl gene	ENSG00000109956
Ensembl biotype	protein_coding
OMIM	151290
Entrez	27087

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000312527, ENST00000392580, ENST00000524765, ENST00000531510, ENST00000531778, ENST00000869329, ENST00000869330, ENST00000869331, ENST00000869332, ENST00000869333

RefSeq mRNA: 3 — MANE Select: NM_054025 NM_001367973, NM_018644, NM_054025

CCDS: CCDS8500

Canonical transcript exons

ENST00000312527 — 6 exons

Exon	Start	End
ENSE00000749062	134383680	134384188
ENSE00002199935	134378508	134380747
ENSE00003540822	134382710	134383006
ENSE00003548842	134387548	134387940
ENSE00003639408	134381924	134382024
ENSE00003843089	134411807	134412242

Expression profiles

Bgee: expression breadth ubiquitous, 191 present calls, max score 98.76.

FANTOM5 (CAGE): breadth broad, TPM avg 8.3574 / max 516.2704, expressed in 497 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123271	4.5135	433
123270	2.7694	314
123269	0.3550	110
123277	0.1341	62
123276	0.1208	54
123272	0.1066	52
123267	0.1060	68
123273	0.0947	40
123275	0.0799	42
123274	0.0414	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	98.76	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.54	gold quality
spinal cord	UBERON:0002240	98.14	gold quality
right frontal lobe	UBERON:0002810	98.02	gold quality
amygdala	UBERON:0001876	97.75	gold quality
anterior cingulate cortex	UBERON:0009835	97.72	gold quality
cingulate cortex	UBERON:0003027	97.69	gold quality
prefrontal cortex	UBERON:0000451	97.67	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.31	gold quality
Ammon’s horn	UBERON:0001954	97.23	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.04	gold quality
frontal cortex	UBERON:0001870	96.92	gold quality
frontal lobe	UBERON:0016525	96.92	gold quality
neocortex	UBERON:0001950	96.91	gold quality
cerebral cortex	UBERON:0000956	96.72	gold quality
temporal lobe	UBERON:0001871	96.65	gold quality
telencephalon	UBERON:0001893	96.46	gold quality
putamen	UBERON:0001874	96.40	gold quality
nucleus accumbens	UBERON:0001882	96.32	gold quality
CA1 field of hippocampus	UBERON:0003881	96.02	gold quality
caudate nucleus	UBERON:0001873	95.99	gold quality
endothelial cell	CL:0000115	95.97	gold quality
substantia nigra	UBERON:0002038	95.83	gold quality
inferior olivary complex	UBERON:0002127	95.79	gold quality
midbrain	UBERON:0001891	95.29	gold quality
hypothalamus	UBERON:0001898	95.04	gold quality
entorhinal cortex	UBERON:0002728	95.02	gold quality
middle temporal gyrus	UBERON:0002771	95.02	gold quality
ganglionic eminence	UBERON:0004023	94.93	gold quality
inferior vagus X ganglion	UBERON:0005363	94.93	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.70

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TBX21

miRNA regulators (miRDB)

127 targeting B3GAT1, 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-4713-3P	100.00	65.92	505
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-6785-5P	99.82	68.68	4428

Literature-anchored findings (GeneRIF, showing 40)

• substrate specificity toward UDP-glucuronic acid determined by two crucial histidine and arginine residues (PMID:11986319)
• Expression of CD57 defines replicative senescence and HIV antigen-induced apoptotic death of CD8+ T cells, and CD57 may be involved in apoptosis and lack of proliferation. (PMID:12433688)
• differences in CgA and CD57 expression in human neuroendocrine tumors are related to the degree of differentiation of the neoplasms and probably reflect the degree of maturation (functional state) of neuroendocrine granules within the neoplastic cells. (PMID:12687271)
• Polymorphic or other variation of the 11q telomere may affect the activity of B3GAT1 and be a risk factor for schizophrenia and related psychoses in the general population. (PMID:12874601)
• CD57 has a role in antitumor immunity which is impaired in gastric cancer (PMID:12883721)
• GlcAT-P is an enzyme critical in the biosynthesis of the carbohydrate epitope HNK-1 (PMID:14993226)
• first pediatric case describing coexpression of CD57 on B-lineage acute lymphoblastic leukemia (PMID:15626024)
• CD8-positive T cells expressing CD57, a marker of replicative senescence, also express killer cell lectin-like receptor G1 (KLRG1); however, a population of CD57-negative KLRG1+ cells is also identified. This population may represent a “memory” phenotype. (PMID:15879103)
• It was found that collagen type IX and HNK-1 epitope were present in tears, the amount of the former being increased 2.7 times compared to normal. (PMID:16257185)
• study identifies GlcAT-I as a target of calcium-dependent signaling pathway and evidences the critical role of Sp1 transcription factor in the activation of GlcAT-I expression (PMID:16807373)
• CD8+CD57+ T cells are a subset of effector cells that could be helpful to evaluate the cell-mediated immune response to Mycobacterium tuberculosis (PMID:17035093)
• A comparison of substrate specificity of beta1,3-glucuronosyltransferases revealed that GlcAT-I was selective toward Galbeta1,3Gal, whereas GlcAT-P presented a broader profile. (PMID:17567734)
• data suggest that the expression of CD30 and CD57 cell markers on T cells could reflect circulating effector T cell early activation in the allergic airway disease. (PMID:18201430)
• ability of CD8hi CD57+ T cells to further differentiate is highlighted by a distinct cytokine profile late after activation that includes the unexpected release of high levels of interleukin (PMID:18383036)
• Overexpression of HNK-1 is associated with metastasis in melanoma. (PMID:18802400)
• CD57 was linked to higher apoptosis resistance in CD8(+) T cells in HIV infection. (PMID:19564339)
• The donor HNK1 haplotype is associated with better clinical outcome among recipients, with standard-risk disease, of bone marrow transplants from HLA-matched unrelated donors. (PMID:19794085)
• Protein-bound polysaccharide K improves overall survival of stage III gastric cancer patients partly by inhibiting CD57(+) T cells. (PMID:20229169)
• The density of CD57+ cells within lymphoid follicles of chronic obstructive pulmonary disease patients was significantly increased compared to that of nonsmokers and smokers without chronic obstructive pulmonary disease. (PMID:20525712)
• CD56(dim) NK cells continue to differentiate. During this process, they lose expression of NKG2A, sequentially acquire inhibitory killer cell inhibitory immunoglobulin-like receptors and CD57. (PMID:20696944)
• assessed the transcriptional, phenotypic, and functional differences between CD57(+) and CD57(-) NK cells within the CD56(dim) mature NK subset (PMID:20733159)
• Lung biopsies from idiopathic pulmonary fibrosis showed upregulation of GlcAT-I, a rate-limiting enzyme in GAG synthesis. (PMID:21056957)
• an increase in CD4+CD57+ T cells controls the capability of PB to produce the anti-tumor cytokine IFN-gamma and PB-IFN-gamma production is impaired with HCC tumor progression (PMID:21491089)
• 33 directly measured and 13 derived glycosylation traits in 3533 individuals were identified and three novel gene association (MGAT5, B3GAT1 and SLC9A9) were identified using an additional European cohort. (PMID:21908519)
• CD57+ cells may be involved in chronic obstructive pulmonary disease pathogenesis, especially in the most severe stages of the disease. (PMID:22127595)
• HIV infected subjects had higher percentage of T cell subsets expressing CD57. (PMID:22310831)
• Strong expression of CD57 correlates with aggressive attributes of U-NB1 and SK-N-BE(2)-C neuroblastoma cells and is linked with undifferentiated neuroblastoma cells in patients. (PMID:22900004)
• Analysis identified CD57(bright) expression as a reliable phenotype of granule marker-containing cytotoxic T-lymphocytes. (PMID:23287865)
• T cells in unaffected skin from psoriasis patients exhibit a phenotype compatible with replicative inability. As they have a lower replicative capacity, CD57+ T cells are less frequent in lesional tissue due to the high cellular turnover. (PMID:23468834)
• NKG2Chi CD57hi natural killer cells are highly responsive to human cytomegalovirus-infected macrophages only in the presence of HCMV-specific antibodies, whereas they are functionally poor effectors of natural cytotoxicity. (PMID:23637420)
• polyfunctional CD57+ cell expansion has a role in CD8+ T cell response to Staphylococcal Enterotoxin B during CMV latent infection (PMID:24533103)
• Abnormally low proportions of CD28(-)CD8(+) T cells expressing CD57 predict increased mortality during treated HIV infection and may be reversed with early ART initiation. (PMID:24585893)
• NKG2C(hi)CD57+ NK cells respond specifically to acute infection with cytomegalovirus and not Epstein-Barr virus. (PMID:24740502)
• CD56dim CD57int NK cells represent an intermediate functional phenotype in response to vaccine-induced and receptor-mediated stimuli. (PMID:24843874)
• analysis of CD57 in prostate neoplasms and benign prostatic tissue (PMID:24977150)
• Our results suggest that an increase in the population of CD57(+) T-cells is a potent prognostic marker and may also influence the systemic immunity of patients with OSCC. (PMID:25275081)
• glioblastoma stem cells are killed by CD133-specific CAR T cells but induce the T cell aging marker CD57 (PMID:25426558)
• The frequency of CD57-expressing antigen specific CD4+ T cells was higher in active compared to latent tuberculosis. (PMID:25931385)
• Case Report: chronic lymphocytic leukemia with aberrant CD56 and CD57 expression. (PMID:26013700)
• Among CD8+ T-lymphocytes, CD28+CD57+ cells represent a subset with some senescent features that are distinct from the CD28-CD57+ cells. (PMID:26277688)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	b3gat1a	ENSDARG00000040547
danio_rerio	B3GAT1	ENSDARG00000113928
mus_musculus	B3gat1	ENSMUSG00000045994
rattus_norvegicus	B3gat1	ENSRNOG00000007142
caenorhabditis_elegans	glct-4	WBGENE00008160
caenorhabditis_elegans	glct-5	WBGENE00008293
caenorhabditis_elegans	glct-2	WBGENE00008479
caenorhabditis_elegans	glct-1	WBGENE00011650
caenorhabditis_elegans	glct-3	WBGENE00011781
caenorhabditis_elegans		WBGENE00019546

Paralogs (2): B3GAT2 (ENSG00000112309), B3GAT3 (ENSG00000149541)

Protein

Protein identifiers

Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1 — Q9P2W7 (reviewed: Q9P2W7)

Alternative names: Beta-1,3-glucuronyltransferase 1, Glucuronosyltransferase P, UDP-GlcUA:glycoprotein beta-1,3-glucuronyltransferase

All UniProt accessions (1): Q9P2W7

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the biosynthesis of L2/HNK-1 carbohydrate epitope on glycoproteins. Can also play a role in glycosaminoglycan biosynthesis. Substrates include asialo-orosomucoid (ASOR), asialo-fetuin, and asialo-neural cell adhesion molecule. Requires sphingomyelin for activity: stearoyl-sphingomyelin was the most effective, followed by palmitoyl-sphingomyelin and lignoceroyl-sphingomyelin. Activity was demonstrated only for sphingomyelin with a saturated fatty acid and not for that with an unsaturated fatty acid, regardless of the length of the acyl group.

Subunit / interactions. Homodimer. Interacts with SAR1A.

Subcellular location. Golgi apparatus membrane. Secreted Golgi apparatus membrane. Endoplasmic reticulum membrane. Secreted.

Tissue specificity. Mainly expressed in the brain.

Post-translational modifications. The soluble form derives from the membrane form by proteolytic processing.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the glycosyltransferase 43 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9P2W7-1	1, sGlcAT-P	yes
Q9P2W7-2	2, lGlcAT-P

RefSeq proteins (3): NP_001354902, NP_061114, NP_473366* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005027	Glyco_trans_43	Family
IPR029044	Nucleotide-diphossugar_trans	Homologous_superfamily

Pfam: PF03360

Enzyme classification (BRENDA):

• EC 2.4.1.135 — galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase (BRENDA: 8 organisms, 54 substrates, 4 inhibitors, 31 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

17 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
UDP-GLUCURONATE	0.04–1.27	10
UDPGLUCURONATE	0.0003–0.287	4
UDP-GLCA	0.0499–0.059	2
3-BETA-GALACTOSYL-GALACTOSE	0.0091	1
GALBETA(1-3)GAL(6-O-SULFATE)BETA(1-4)XYL(2-O-PHO	0.035	1
GALBETA(1-3)GAL(6-O-SULFATE)BETA(1-4)XYLBETA1-O-	0.049	1
GALBETA(1-3)GALBETA(1-4)XYL	0.0804	1
GALBETA(1-3)GALBETA(1-4)XYL(2-O-PHOSPHATE)BETA1-	0.025	1
GALBETA(1-3)GALBETA(1-4)XYLBETA1-O-SER	0.046	1
GALBETA1,3GALBETA-O-NAPHTHALENEMETHANOL	0.67	1
GALBETA1,3GALNACBETA-O-NAPHTHALENEMETHANOL	3.2	1
GALBETA1,3GLCNACBETA-O-NAPHTHALENEMETHANOL	2.9	1
GALBETA1,4GLCNACBETA-O-NAPHTHALENEMETHANOL	1.8	1
GALBETA1-3GAL	4.48	1
UDP-GLCNAC	0.108	1

Catalyzed reactions (Rhea), 1 shown:

• 3-O-(beta-D-galactosyl-(1->3)-beta-D-galactosyl-(1->4)-beta-D-xylosyl)-L-seryl-[protein] + UDP-alpha-D-glucuronate = 3-O-(beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-seryl-[protein] + UDP + H(+) (RHEA:24168)

UniProt features (53 total): strand 14, helix 11, binding site 7, glycosylation site 3, sequence conflict 3, region of interest 3, topological domain 2, site 2, modified residue 2, chain 1, transmembrane region 1, splice variant 1, sequence variant 1, turn 1, active site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
1V84	X-RAY DIFFRACTION	1.82
1V82	X-RAY DIFFRACTION	1.85
1V83	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P2W7-F1	86.91	0.68

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 (3): 228 (interaction with galactose moiety of substrate glycoprotein); 321 (interaction with galactose moiety of substrate glycoprotein); 284 (proton donor/acceptor)

Ligand- & substrate-binding residues (7): 165; 170; 195–197; 197; 311–313; 91–93; 122

Post-translational modifications (2): 103, 108

Glycosylation sites (3): 140, 184, 303

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-1971475	Glycosaminoglycan-protein linkage region biosynthesis
R-HSA-1430728	Metabolism
R-HSA-1630316	Glycosaminoglycan metabolism
R-HSA-1638091	Heparan sulfate/heparin (HS-GAG) metabolism
R-HSA-1793185	Chondroitin sulfate/dermatan sulfate metabolism
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives

MSigDB gene sets: 136 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_AMINOGLYCAN_BIOSYNTHETIC_PROCESS, STARK_HYPPOCAMPUS_22Q11_DELETION_UP, GOBP_CHONDROITIN_SULFATE_PROTEOGLYCAN_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_AMINOGLYCAN_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, DOUGLAS_BMI1_TARGETS_UP, GOBP_CHONDROITIN_SULFATE_PROTEOGLYCAN_METABOLIC_PROCESS, chr11q25, GOBP_PROTEIN_O_LINKED_GLYCOSYLATION, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS, REACTOME_METABOLISM_OF_CARBOHYDRATES_AND_CARBOHYDRATE_DERIVATIVES

GO Biological Process (5): carbohydrate metabolic process (GO:0005975), glycosaminoglycan biosynthetic process (GO:0006024), visual learning (GO:0008542), chondroitin sulfate proteoglycan biosynthetic process (GO:0050650), obsolete protein glycosylation (GO:0006486)

GO Molecular Function (4): galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase activity (GO:0015018), metal ion binding (GO:0046872), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (6): Golgi membrane (GO:0000139), extracellular region (GO:0005576), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Glycosaminoglycan metabolism	3
Metabolism of carbohydrates and carbohydrate derivatives	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
primary metabolic process	1
aminoglycan biosynthetic process	1
glycosaminoglycan metabolic process	1
visual behavior	1
associative learning	1
proteoglycan biosynthetic process	1
chondroitin sulfate proteoglycan metabolic process	1
protein O-linked glycosylation via xylose	1
glucuronosyltransferase activity	1
cation binding	1
binding	1
catalytic activity	1
Golgi apparatus	1
bounding membrane of organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1

Protein interactions and networks

STRING

1848 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
B3GAT1	NCAM1	P13591	915
B3GAT1	CD28	P10747	867
B3GAT1	CD27	P26842	861
B3GAT1	CD8A	P01732	842
B3GAT1	CXCR5	P32302	829
B3GAT1	FCGR3A	P08637	803
B3GAT1	KLRC2	P26717	799
B3GAT1	CHST10	O43529	798
B3GAT1	CD4	P01730	796
B3GAT1	FCGR3B	O75015	794
B3GAT1	KLRC1	P26715	773
B3GAT1	LILRB1	Q8NHL6	749
B3GAT1	CCR7	P32248	722
B3GAT1	CD38	P28907	720
B3GAT1	KLRD1	Q13241	720
B3GAT1	PRF1	P14222	720

IntAct

7 interactions, top by confidence:

A	B	Type	Score
CMTM7	B3GAT1	psi-mi:“MI:0915”(physical association)	0.560
DMA	B3GAT1	psi-mi:“MI:0915”(physical association)	0.370
SH3GL1	B3GAT1	psi-mi:“MI:0915”(physical association)	0.370
B3GAT1	RTL8C	psi-mi:“MI:0914”(association)	0.350
CMTM7	B3GAT1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (377): CMTM7 (Two-hybrid), ABCA3 (Proximity Label-MS), ACBD3 (Proximity Label-MS), ACSL3 (Proximity Label-MS), ADCY9 (Proximity Label-MS), AGPAT1 (Proximity Label-MS), ALDH3A2 (Proximity Label-MS), ANKLE2 (Proximity Label-MS), AP1AR (Proximity Label-MS), APBB1 (Proximity Label-MS), APBB2 (Proximity Label-MS), APC (Proximity Label-MS), APLP2 (Proximity Label-MS), APP (Proximity Label-MS), ARCN1 (Proximity Label-MS)

ESM2 similar proteins: A1CPP3, A2QR20, A2X933, A2XFP3, A2XFT5, A2XFT6, A2XVC2, A2ZF66, A2ZI32, A2ZI41, A4VCL2, B8AIZ4, B9FCV3, C7J0P3, O22775, O35789, O81007, P45895, P59270, Q09327, Q10MK2, Q10MQ0, Q2QNS6, Q2QXM3, Q2QXP0, Q2R224, Q2R2W8, Q3UHH8, Q53JI9, Q564G7, Q5CAZ6, Q5CB03, Q5CB04, Q653F4, Q6GX83, Q6H765, Q6JHU7, Q6Z5M3, Q75BD5, Q7FA29

Diamond homologs: O35789, O94766, O97422, P58158, P59270, Q09363, Q10N05, Q5CAZ6, Q5CB03, Q5CB04, Q5QM25, Q5ZCC5, Q653F4, Q6AT32, Q7XTB2, Q8L707, Q8S626, Q9CW73, Q9NPZ5, Q9P2W7, Q9SXC4, Q9VLA1, Q9VTG7, Q9WU47, Q9Z137, Q9FH90, B9FCV3, Q6Z3Y6, Q75L84, Q9ZQC6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1659 predictions. Top by Δscore:

Variant	Effect	Δscore
11:134411802:CTGA:C	donor_loss	1.0000
11:134411803:TGACC:T	donor_loss	1.0000
11:134411804:GAC:G	donor_loss	1.0000
11:134411806:C:CT	donor_loss	1.0000
11:134382704:TCTCA:T	donor_loss	0.9900
11:134382705:CTCA:C	donor_loss	0.9900
11:134382706:TCA:T	donor_loss	0.9900
11:134382707:CA:C	donor_loss	0.9900
11:134382708:ACCT:A	donor_loss	0.9900
11:134382709:CCTT:C	donor_loss	0.9900
11:134383002:CGCAT:C	acceptor_gain	0.9900
11:134383004:CAT:C	acceptor_gain	0.9900
11:134383677:CACCT:C	donor_loss	0.9900
11:134383679:CCT:C	donor_gain	0.9900
11:134387546:AC:A	donor_gain	0.9900
11:134387547:CC:C	donor_gain	0.9900
11:134382034:C:CT	acceptor_gain	0.9800
11:134382871:T:TC	acceptor_gain	0.9800
11:134383005:AT:A	acceptor_gain	0.9800
11:134383005:ATCTA:A	acceptor_loss	0.9800
11:134383006:TC:T	acceptor_loss	0.9800
11:134383007:C:CC	acceptor_gain	0.9800
11:134383007:C:G	acceptor_loss	0.9800
11:134384207:G:T	acceptor_gain	0.9800
11:134411805:A:AC	donor_gain	0.9800
11:134411806:C:CC	donor_gain	0.9800
11:134411806:CCTG:C	donor_gain	0.9800
11:134383675:CTCA:C	donor_gain	0.9700
11:134383676:TCA:T	donor_gain	0.9700
11:134383677:CACC:C	donor_gain	0.9700

AlphaMissense

2141 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:134382012:G:C	H311D	1.000
11:134382013:C:A	W310C	1.000
11:134382013:C:G	W310C	1.000
11:134382015:A:G	W310R	1.000
11:134382015:A:T	W310R	1.000
11:134382716:G:C	C304W	1.000
11:134382717:C:T	C304Y	1.000
11:134382765:A:T	L288H	1.000
11:134382854:A:C	F258L	1.000
11:134382854:A:T	F258L	1.000
11:134382855:A:G	F258S	1.000
11:134382856:A:G	F258L	1.000
11:134382867:T:A	D254V	1.000
11:134382867:T:G	D254A	1.000
11:134382875:A:C	F251L	1.000
11:134382875:A:T	F251L	1.000
11:134382877:A:G	F251L	1.000
11:134382893:A:C	F245L	1.000
11:134382893:A:T	F245L	1.000
11:134382894:A:C	F245C	1.000
11:134382895:A:G	F245L	1.000
11:134382905:C:A	W241C	1.000
11:134382905:C:G	W241C	1.000
11:134382907:A:G	W241R	1.000
11:134382907:A:T	W241R	1.000
11:134382979:A:G	W217R	1.000
11:134382979:A:T	W217R	1.000
11:134383707:G:C	N198K	1.000
11:134383707:G:T	N198K	1.000
11:134383711:T:A	D197V	1.000

dbSNP variants (sampled 300 via entrez): RS1000027795 (11:134409158 T>A,C), RS1000056457 (11:134409420 G>A,C), RS1000298256 (11:134398933 G>A), RS1000481313 (11:134405959 G>C), RS1000617463 (11:134402349 C>T), RS1000782088 (11:134395228 G>A,C), RS1000837313 (11:134380747 C>A,T), RS1000854304 (11:134394034 C>T), RS1000876579 (11:134388090 G>A), RS1000897486 (11:134393116 C>G), RS1000957846 (11:134390081 C>A,T), RS1001017781 (11:134383099 A>G), RS1001170365 (11:134382705 C>A), RS1001201324 (11:134382486 G>A), RS1001246642 (11:134387864 G>A)

Disease associations

OMIM: gene MIM:151290 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002701_28	Verbal declarative memory	5.000000e-06
GCST005046_21	N-glycan levels	2.000000e-08
GCST006085_53	Prostate cancer	5.000000e-08
GCST011768_9	Schizophrenia	3.000000e-09
GCST011769_22	Schizophrenia	2.000000e-08
GCST011780_5	Neonatal white matter microstructure	1.000000e-06
GCST90011900_63	Serum alkaline phosphatase levels	8.000000e-19
GCST90013406_245	Liver enzyme levels (alkaline phosphatase)	1.000000e-26

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004874	memory performance
EFO:0006805	word list delayed recall measurement
EFO:0004999	N-glycan measurement
EFO:0005674	white matter microstructure measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, affects methylation, increases methylation	1
trichostatin A	decreases expression	1
benzo(e)pyrene	increases methylation	1
nickel sulfate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
deguelin	decreases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
pyrachlostrobin	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases methylation	1
(+)-JQ1 compound	decreases expression	1
Decitabine	affects expression	1
Fulvestrant	affects cotreatment, affects methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cisplatin	affects expression	1
Diethylhexyl Phthalate	decreases expression	1
Methapyrilene	increases methylation	1
Tretinoin	decreases expression	1
Valproic Acid	increases methylation	1
Zinc	increases expression	1
Aflatoxin B1	decreases expression	1

Clinical trials (associated diseases)

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