GXYLT2

Summary

GXYLT2 (glucoside xylosyltransferase 2, HGNC:33383) is a protein-coding gene on chromosome 3p13, encoding Glucoside xylosyltransferase 2 (A0PJZ3). Glycosyltransferase which elongates the O-linked glucose attached to EGF-like repeats in the extracellular domain of Notch proteins by catalyzing the addition of xylose.

The protein encoded by this gene is a xylosyltransferase that elongates O-linked glucose bound to epidermal growth factor (EGF) repeats. The encoded protein catalyzes the addition of xylose to the O-glucose-modified residues of EGF repeats of Notch proteins.

Source: NCBI Gene 727936 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 94 total
• MANE Select transcript: NM_001080393

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33383
Approved symbol	GXYLT2
Name	glucoside xylosyltransferase 2
Location	3p13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000172986
Ensembl biotype	protein_coding
OMIM	613322
Entrez	727936

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000389617, ENST00000491839, ENST00000498315

RefSeq mRNA: 1 — MANE Select: NM_001080393 NM_001080393

CCDS: CCDS46870

Canonical transcript exons

ENST00000389617 — 7 exons

Exon	Start	End
ENSE00001293556	72957229	72957352
ENSE00001405448	72967547	72967719
ENSE00001506372	72974977	72976915
ENSE00001506373	72955098	72955349
ENSE00001506374	72922204	72922335
ENSE00001506375	72908367	72908559
ENSE00001506376	72888046	72888508

Expression profiles

Bgee: expression breadth ubiquitous, 226 present calls, max score 95.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.5587 / max 180.4658, expressed in 1361 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37319	9.5684	1355
37321	0.7476	400
37320	0.2427	123

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of paranasal sinus	UBERON:0005030	95.91	gold quality
pericardium	UBERON:0002407	94.82	gold quality
caput epididymis	UBERON:0004358	94.29	gold quality
buccal mucosa cell	CL:0002336	93.87	gold quality
tibia	UBERON:0000979	93.09	gold quality
cardiac muscle of right atrium	UBERON:0003379	92.96	silver quality
corpus epididymis	UBERON:0004359	92.13	gold quality
vena cava	UBERON:0004087	91.34	gold quality
cauda epididymis	UBERON:0004360	91.32	gold quality
saphenous vein	UBERON:0007318	91.29	gold quality
skin of hip	UBERON:0001554	90.74	gold quality
parietal pleura	UBERON:0002400	90.73	gold quality
myocardium	UBERON:0002349	90.68	silver quality
mammary duct	UBERON:0001765	90.43	gold quality
epithelium of mammary gland	UBERON:0003244	90.14	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.60	gold quality
oviduct epithelium	UBERON:0004804	89.34	gold quality
trachea	UBERON:0003126	87.88	gold quality
germinal epithelium of ovary	UBERON:0001304	87.84	gold quality
cartilage tissue	UBERON:0002418	86.66	gold quality
trigeminal ganglion	UBERON:0001675	86.47	gold quality
heart right ventricle	UBERON:0002080	85.73	gold quality
adult organism	UBERON:0007023	85.72	gold quality
superficial temporal artery	UBERON:0001614	85.68	gold quality
visceral pleura	UBERON:0002401	85.14	gold quality
cardiac atrium	UBERON:0002081	83.98	gold quality
trabecular bone tissue	UBERON:0002483	83.71	gold quality
ovary	UBERON:0000992	83.42	gold quality
right atrium auricular region	UBERON:0006631	83.29	gold quality
endometrium	UBERON:0001295	83.18	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.23
E-GEOD-124858	no	778.81
E-MTAB-6058	no	212.88

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting GXYLT2, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-6512-5P	98.76	69.29	1195
HSA-MIR-3938	98.72	66.07	834
HSA-MIR-4709-5P	98.51	67.25	1335

Literature-anchored findings (GeneRIF, showing 5)

• We have identified two enzymes of the human glycosyltransferase 8 family, now named GXYLT1 and GXYLT2 (glucoside xylosyltransferase), as UDP-d-xylose:beta-d-glucoside alpha1,3-d-xylosyltransferases adding the first xylose. (PMID:19940119)
• our findings indicated that GXYLT2 plays an important role in cell activities via regulation of the Notch signaling (PMID:30716301)
• Glucoside xylosyltransferase 2 as a diagnostic and prognostic marker in gastric cancer via comprehensive analysis. (PMID:34506251)
• MicroRNA-204-5p Hampers the Malignant Progression of Clear Cell Renal Cell Carcinoma through GXYLT2 Downregulation. (PMID:36063796)
• Pan-cancer analysis of the prognostic significance and oncogenic role of GXYLT2. (PMID:37986328)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	gxylt2	ENSDARG00000044191
mus_musculus	Gxylt2	ENSMUSG00000030074
rattus_norvegicus	Gxylt2	ENSRNOG00000005621
drosophila_melanogaster	CG11149	FBGN0031732
drosophila_melanogaster	CG9171	FBGN0031738
drosophila_melanogaster	CG15483	FBGN0032457
caenorhabditis_elegans	bgnt-1.8	WBGENE00008290
caenorhabditis_elegans		WBGENE00009032
caenorhabditis_elegans	bgnt-1.6	WBGENE00010167
caenorhabditis_elegans		WBGENE00010694
caenorhabditis_elegans		WBGENE00010716
caenorhabditis_elegans	bgnt-1.7	WBGENE00011779
caenorhabditis_elegans		WBGENE00015982
caenorhabditis_elegans		WBGENE00017723

Paralogs (5): LARGE1 (ENSG00000133424), GXYLT1 (ENSG00000151233), LARGE2 (ENSG00000165905), XXYLT1 (ENSG00000173950), B4GAT1 (ENSG00000174684)

Protein

Protein identifiers

Glucoside xylosyltransferase 2 — A0PJZ3 (reviewed: A0PJZ3)

Alternative names: Glycosyltransferase 8 domain-containing protein 4

All UniProt accessions (3): A0PJZ3, C9J3Q6, C9JND4

UniProt curated annotations — full annotation on UniProt →

Function. Glycosyltransferase which elongates the O-linked glucose attached to EGF-like repeats in the extracellular domain of Notch proteins by catalyzing the addition of xylose.

Subcellular location. Membrane.

Similarity. Belongs to the glycosyltransferase 8 family.

RefSeq proteins (1): NP_001073862* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002495	Glyco_trans_8	Family
IPR029044	Nucleotide-diphossugar_trans	Homologous_superfamily
IPR051993	Glycosyltransferase_8	Family

Pfam: PF01501

Catalyzed reactions (Rhea), 1 shown:

• 3-O-(beta-D-glucosyl)-L-seryl-[EGF-like domain protein] + UDP-alpha-D-xylose = 3-O-[alpha-D-xylosyl-(1->3)-beta-D-glucosyl]-L-seryl-[EGF-like domain protein] + UDP + H(+) (RHEA:56064)

UniProt features (10 total): compositionally biased region 3, topological domain 2, glycosylation site 2, chain 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0PJZ3-F1	83.89	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.

Glycosylation sites (2): 233, 274

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9926550	Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition

MSigDB gene sets: 86 (showing top): GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, chr3p13, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, RIGGI_EWING_SARCOMA_PROGENITOR_DN, LIAO_METASTASIS, HOOI_ST7_TARGETS_DN, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, GOBP_PROTEIN_O_LINKED_GLYCOSYLATION_VIA_N_ACETYL_GALACTOSAMINE, CUI_TCF21_TARGETS_2_UP, GOBP_PROTEIN_O_LINKED_GLYCOSYLATION, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS, VECCHI_GASTRIC_CANCER_ADVANCED_VS_EARLY_UP, GOMF_GLYCOSYLTRANSFERASE_ACTIVITY

GO Biological Process (2): protein O-linked glycosylation via N-acetylgalactosamine (GO:0016266), protein O-linked glycosylation via glucose (GO:0180059)

GO Molecular Function (4): UDP-xylosyltransferase activity (GO:0035252), UDP-D-xylose:beta-D-glucoside alpha-1,3-D-xylosyltransferase activity (GO:0140563), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
MITF-M-dependent gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein O-linked glycosylation	2
UDP-glycosyltransferase activity	1
xylosyltransferase activity	1
UDP-xylosyltransferase activity	1
catalytic activity	1
transferase activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

534 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GXYLT2	UGGT1	Q9NYU2	895
GXYLT2	XXYLT1	Q8NBI6	787
GXYLT2	F7	P08709	766
GXYLT2	POGLUT1	Q8NBL1	723
GXYLT2	POGLUT2	Q6UW63	607
GXYLT2	NOTCH1	P46531	590
GXYLT2	SHQ1	Q6PI26	530
GXYLT2	EGF	P01133	516
GXYLT2	POGLUT3	Q7Z4H8	479
GXYLT2	POFUT1	Q9H488	457
GXYLT2	ARL15	Q9NXU5	453
GXYLT2	OSBP2	Q969R2	450
GXYLT2	PPP4R2	Q9NY27	441
GXYLT2	EIF4E3	Q8N5X7	434
GXYLT2	MGAT4C	Q9UBM8	386

IntAct

24 interactions, top by confidence:

A	B	Type	Score
NEUROG3	GXYLT2	psi-mi:“MI:0914”(association)	0.640
KLRG2	GXYLT2	psi-mi:“MI:0914”(association)	0.530
MGAT4C	GXYLT2	psi-mi:“MI:0914”(association)	0.530
HLA-DPA1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
FBL	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CD70	GXYLT2	psi-mi:“MI:0914”(association)	0.350
KCNC4	GXYLT2	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
LDLRAD1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
BST1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
AVPR2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
OS9	GXYLT2	psi-mi:“MI:0914”(association)	0.350
RAMP2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
GXYLT2	HSPA8	psi-mi:“MI:0914”(association)	0.350
VSIG4	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC15A3	GXYLT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (30): GXYLT2 (Affinity Capture-MS), GXYLT2 (Biochemical Activity), GXYLT2 (Affinity Capture-MS), GXYLT2 (Affinity Capture-MS), GXYLT2 (Affinity Capture-MS), GXYLT2 (Affinity Capture-MS), GXYLT2 (Affinity Capture-MS), GXYLT2 (Affinity Capture-MS), GXYLT2 (Affinity Capture-MS), GXYLT2 (Affinity Capture-MS), GXYLT2 (Affinity Capture-RNA), GXYLT2 (Affinity Capture-MS), GXYLT2 (Affinity Capture-MS), GXYLT2 (Affinity Capture-MS), GXYLT2 (Affinity Capture-MS)

ESM2 similar proteins: A0PJZ3, A2XFP3, A2XFT5, A2XFT6, B8AIZ4, C7J0P3, O04536, O48684, O88829, P08037, P15291, P15535, Q02527, Q09327, Q0V7R1, Q0WV13, Q10470, Q10MK2, Q10MQ0, Q16842, Q3UHH8, Q4G148, Q5CAZ6, Q5K027, Q5MJS3, Q5SP46, Q5ZKI6, Q68G12, Q6DE37, Q6GX83, Q6H765, Q6KB58, Q701R2, Q70D51, Q810K9, Q8CID3, Q8GWT1, Q8IXL6, Q8RXE1, Q92184

Diamond homologs: A0PJZ3, Q3UHH8, Q4G148, Q5SP46, Q5ZKI6, Q6DE37, Q6GX83, Q810K9, Q3U4G3

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
GXYLT2	up-regulates	NOTCH1	binding
GXYLT2	up-regulates	NOTCH2	binding
GXYLT2	up-regulates	NOTCH	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	80
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1826 predictions. Top by Δscore:

Variant	Effect	Δscore
3:72908362:TCTA:T	acceptor_loss	1.0000
3:72908364:TAG:T	acceptor_loss	1.0000
3:72908365:A:AG	acceptor_gain	1.0000
3:72908365:A:T	acceptor_loss	1.0000
3:72908365:AG:A	acceptor_gain	1.0000
3:72908365:AGGAG:A	acceptor_gain	1.0000
3:72908366:G:GG	acceptor_gain	1.0000
3:72908366:G:T	acceptor_loss	1.0000
3:72908366:GG:G	acceptor_gain	1.0000
3:72908366:GGA:G	acceptor_gain	1.0000
3:72908366:GGAGG:G	acceptor_gain	1.0000
3:72908556:GCAG:G	donor_gain	1.0000
3:72908556:GCAGG:G	donor_loss	1.0000
3:72908558:AGGT:A	donor_loss	1.0000
3:72908560:G:GA	donor_loss	1.0000
3:72908561:T:A	donor_loss	1.0000
3:72908592:C:CG	donor_gain	1.0000
3:72955076:C:G	acceptor_gain	1.0000
3:72957227:A:AG	acceptor_gain	1.0000
3:72957228:G:GG	acceptor_gain	1.0000
3:72957319:GATT:G	donor_gain	1.0000
3:72965555:G:GT	donor_gain	1.0000
3:72965559:C:G	donor_gain	1.0000
3:72965563:G:GT	donor_gain	1.0000
3:72967539:A:AG	acceptor_gain	1.0000
3:72967540:C:G	acceptor_gain	1.0000
3:72967545:A:AG	acceptor_gain	1.0000
3:72967546:G:GG	acceptor_gain	1.0000
3:72967546:GA:G	acceptor_gain	1.0000
3:72967546:GAGT:G	acceptor_gain	1.0000

AlphaMissense

2884 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:72908441:G:A	C117Y	1.000
3:72922288:T:A	W185R	1.000
3:72922288:T:C	W185R	1.000
3:72922300:T:A	F189I	1.000
3:72922300:T:C	F189L	1.000
3:72922300:T:G	F189V	1.000
3:72922301:T:G	F189C	1.000
3:72922302:C:A	F189L	1.000
3:72922302:C:G	F189L	1.000
3:72922309:T:C	C192R	1.000
3:72922311:T:G	C192W	1.000
3:72922313:C:A	A193D	1.000
3:72922322:G:C	R196T	1.000
3:72922323:A:C	R196S	1.000
3:72922323:A:T	R196S	1.000
3:72955135:A:C	D213A	1.000
3:72955135:A:T	D213V	1.000
3:72955140:G:C	D215H	1.000
3:72955140:G:T	D215Y	1.000
3:72955141:A:C	D215A	1.000
3:72955141:A:G	D215G	1.000
3:72955141:A:T	D215V	1.000
3:72955248:T:A	W251R	1.000
3:72955248:T:C	W251R	1.000
3:72955250:G:C	W251C	1.000
3:72955250:G:T	W251C	1.000
3:72955260:T:C	F255L	1.000
3:72955262:T:A	F255L	1.000
3:72955262:T:G	F255L	1.000
3:72955298:T:A	N267K	1.000

dbSNP variants (sampled 300 via entrez): RS1000003926 (3:72943737 A>G), RS1000015965 (3:72971398 C>A,G), RS1000062831 (3:72898104 G>T), RS1000096912 (3:72905791 A>G), RS1000193283 (3:72922063 G>A), RS1000300704 (3:72949622 C>T), RS1000328237 (3:72973928 C>A,G,T), RS1000330700 (3:72973620 G>A), RS1000338419 (3:72940165 T>C), RS1000389767 (3:72971078 A>C), RS1000410415 (3:72904222 G>C), RS1000415464 (3:72961965 G>A), RS1000429017 (3:72886659 C>A,T), RS1000440135 (3:72934242 G>A), RS1000458813 (3:72886840 C>T)

Disease associations

OMIM: gene MIM:613322 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002759_34	Motion sickness	3.000000e-08
GCST012490_252	Femur bone mineral density x serum urate levels interaction	9.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006928	motion sickness
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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	7
trichostatin A	affects cotreatment, increases expression	2
sulforaphane	decreases expression	2
sodium arsenite	increases abundance, decreases expression, affects cotreatment	2
Benzo(a)pyrene	decreases expression	2
Estradiol	affects expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Tretinoin	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	increases methylation, decreases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	increases expression	1
bisphenol A	affects cotreatment, affects methylation, decreases methylation	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
hydroxyhydroquinone	decreases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	decreases expression	1
mercuric bromide	increases expression, affects cotreatment	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
bisphenol S	affects cotreatment, decreases methylation	1
jinfukang	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects methylation, decreases methylation, affects cotreatment	1
Air Pollutants	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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