XYLT2

Summary

XYLT2 (xylosyltransferase 2, HGNC:15517) is a protein-coding gene on chromosome 17q21.33, encoding Xylosyltransferase 2 (Q9H1B5). Catalyzes the first step in the biosynthesis of chondroitin sulfate, heparan sulfate and dermatan sulfate proteoglycans, such as DCN. It is a selective cancer dependency (DepMap: 20.5% of cell lines).

The protein encoded by this gene is an isoform of xylosyltransferase, which belongs to a family of glycosyltransferases. This enzyme transfers xylose from UDP-xylose to specific serine residues of the core protein and initiates the biosynthesis of glycosaminoglycan chains in proteoglycans including chondroitin sulfate, heparan sulfate, heparin and dermatan sulfate. The enzyme activity, which is increased in scleroderma patients, is a diagnostic marker for the determination of sclerotic activity in systemic sclerosis. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 64132 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spondylo-ocular syndrome (Strong, GenCC)
• Clinical variants (ClinVar): 478 total — 9 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 83
• Cancer dependency (DepMap): dependent in 20.5% of screened cell lines
• MANE Select transcript: NM_022167

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15517
Approved symbol	XYLT2
Name	xylosyltransferase 2
Location	17q21.33
Locus type	gene with protein product
Status	Approved
Aliases	XT-II, PXYLT2
Ensembl gene	ENSG00000015532
Ensembl biotype	protein_coding
OMIM	608125
Entrez	64132

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000017003, ENST00000376550, ENST00000507602, ENST00000509778, ENST00000511654, ENST00000571021, ENST00000574840, ENST00000854775

RefSeq mRNA: 1 — MANE Select: NM_022167 NM_022167

CCDS: CCDS11563

Canonical transcript exons

ENST00000017003 — 11 exons

Exon	Start	End
ENSE00000418885	50354408	50354583
ENSE00000418886	50354854	50355056
ENSE00000418888	50355781	50355997
ENSE00000418890	50356511	50356773
ENSE00000736911	50353630	50354122
ENSE00000736917	50355501	50355581
ENSE00000736929	50357057	50357252
ENSE00001292962	50346126	50346275
ENSE00001764711	50356085	50356261
ENSE00003577394	50358207	50358540
ENSE00003580740	50359969	50361185

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 94.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.9700 / max 113.2051, expressed in 1773 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161652	13.9700	1773

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of stomach	UBERON:0001161	94.22	gold quality
stomach	UBERON:0000945	92.32	gold quality
fundus of stomach	UBERON:0001160	91.34	gold quality
cervix squamous epithelium	UBERON:0006922	90.35	gold quality
stromal cell of endometrium	CL:0002255	90.22	gold quality
left testis	UBERON:0004533	87.74	gold quality
apex of heart	UBERON:0002098	87.54	gold quality
right testis	UBERON:0004534	87.37	gold quality
testis	UBERON:0000473	86.04	gold quality
right uterine tube	UBERON:0001302	85.74	gold quality
right ovary	UBERON:0002118	85.26	gold quality
granulocyte	CL:0000094	84.99	gold quality
prostate gland	UBERON:0002367	84.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.97	gold quality
left ovary	UBERON:0002119	83.91	gold quality
cerebellar hemisphere	UBERON:0002245	83.72	gold quality
endocervix	UBERON:0000458	83.71	gold quality
parotid gland	UBERON:0001831	83.71	silver quality
cerebellar cortex	UBERON:0002129	83.60	gold quality
skin of abdomen	UBERON:0001416	83.33	gold quality
vagina	UBERON:0000996	83.30	gold quality
right coronary artery	UBERON:0001625	83.22	gold quality
lower esophagus mucosa	UBERON:0035834	83.10	gold quality
right adrenal gland	UBERON:0001233	83.08	gold quality
skin of leg	UBERON:0001511	83.08	gold quality
ectocervix	UBERON:0012249	83.02	gold quality
right adrenal gland cortex	UBERON:0035827	82.96	gold quality
left uterine tube	UBERON:0001303	82.85	gold quality
ovary	UBERON:0000992	82.82	gold quality
body of uterus	UBERON:0009853	82.78	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.57

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1, SPI1

miRNA regulators (miRDB)

53 targeting XYLT2, 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-4455	100.00	65.48	1587
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-889-5P	99.41	68.75	1025
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-18A-5P	99.29	71.05	806
HSA-MIR-18B-5P	99.29	71.05	806
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-6734-3P	99.15	66.27	1627

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 20.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 20)

• xylotransferase genes might be potential candidate genes predisposing to diabetic nephropathy in type 1 diabetic patients (PMID:16164625)
• recombinant expression and cloning of active full-length xylosyltransferase I (XT-I) and characterization of subcellular localization of XT-I and XT-II (PMID:16569644)
• demonstrate that a soluble form of human XT-II expressed in the xylosyltransferase-deficient pgsA-745 (S745) Chinese hamster ovary cell line is indeed capable of catalyzing the transfer of xylose to a variety of peptide substrates (PMID:17194707)
• Our data show for the first time that XT-I and XT-II are xylosyltransferases with similar but not identical properties, pointing to their potential role in modulating the cellular proteoglycan pool. (PMID:18023272)
• These results point to skeletal growth and tissue remodeling as a cause of the high XT activity in children (PMID:18763033)
• Our data show that a XYLT2 haplotype is associated with nephropathy in type 1 diabetic patients (PMID:18789912)
• The deviation from Hardy-Weinberg equilibrium of two XYLT2 variants might be due to gene-phenotype associations which remain to be explored, as well as the possibility of gene-gene interactions. (PMID:19197251)
• A protein sequence alignment and polarity plot of XylT-I and XylT-II revealed several Cardin-Weintraub motifs and charged surface clusters, which might be involved in electrostatic-mediated heparin-binding. (PMID:19289103)
• serum XylT levels may be an informative biomarker in patients who suffer from diseases affecting platelet and/or liver homeostasis. (PMID:19389916)
• The study identified and characterized for the first time the XYLT2 gene promoter region and transcription factors involved in its regulation. (PMID:22886070)
• Seven XYLT2 promoter single nucleotide variants (SNVs) were identified and genotyped. (PMID:25704086)
• Demonstrate that XT-II is the predominant isoenzyme responsible for XT activity in serum. The proof was performed using UDP-xylose as the xylose donor, as well as the compound UDP-4-azido-4-deoxyxylose, which is a selective xylose donor for XT-I. (PMID:25748573)
• Homozygosity for frameshift mutations in XYLT2 result in a spondylo-ocular syndrome with bone fragility, cataracts, and hearing defects. (PMID:26027496)
• mutations in the XYLT2 gene result in a variable phenotype dominated by spinal osteoporosis, cataract, and hearing loss. (PMID:26987875)
• XYLT2 mutations cause a relatively distinct phenotype, the so-called spondyloocular syndrome. (PMID:27871115)
• Using DNA from affected members of the same 2 families, we performed whole exome sequencing, which revealed 2 novel homozygous missense variants (c.1159C > T, p.Arg387Trp) and (c.2548G > C, p.Asp850His). Our findings extend the body of evidence that SOS is caused by homozygous variants in the XYLT2 gene (PMID:29136277)
• We report on two siblings with spondyloocular syndrome who presented with varying clinical severity. A novel XYLT2 missense mutation was detected in a region evolutionary conserved across the species (PMID:30496831)
• HEK293 cells lacking both XT-isoforms are not viable (PMID:31677793)
• Expression of xylosyltransferases I and II and their role in the pathogenesis of arthrofibrosis. (PMID:31973761)
• Development of a xylosyltransferase-I-selective UPLC MS/MS activity assay using a specific acceptor peptide. (PMID:33609631)

Cross-species orthologs

22 orthologs

Organism	Symbol	Gene ID
danio_rerio	xylt2	ENSDARG00000059557
mus_musculus	Xylt2	ENSMUSG00000020868
rattus_norvegicus	Xylt2	ENSRNOG00000003728
drosophila_melanogaster	oxt	FBGN0015360
drosophila_melanogaster	CG9164	FBGN0030634
caenorhabditis_elegans	gly-15	WBGENE00001640
caenorhabditis_elegans	gly-16	WBGENE00001641
caenorhabditis_elegans	gly-17	WBGENE00001642
caenorhabditis_elegans	gly-18	WBGENE00001643
caenorhabditis_elegans	gly-19	WBGENE00001644
caenorhabditis_elegans		WBGENE00005024
caenorhabditis_elegans		WBGENE00009148
caenorhabditis_elegans	F30A10.4	WBGENE00009263
caenorhabditis_elegans		WBGENE00011090
caenorhabditis_elegans	T09E11.6	WBGENE00011655
caenorhabditis_elegans	T09E11.9	WBGENE00011658
caenorhabditis_elegans	T27F6.1	WBGENE00012102
caenorhabditis_elegans		WBGENE00012135
caenorhabditis_elegans		WBGENE00013119
caenorhabditis_elegans	ZK1225.2	WBGENE00014236
caenorhabditis_elegans		WBGENE00019270
caenorhabditis_elegans		WBGENE00019919

Paralogs (8): WSCD2 (ENSG00000075035), XYLT1 (ENSG00000103489), GCNT2 (ENSG00000111846), GCNT7 (ENSG00000124091), GCNT3 (ENSG00000140297), GCNT4 (ENSG00000176928), WSCD1 (ENSG00000179314), GCNT1 (ENSG00000187210)

Protein

Protein identifiers

Xylosyltransferase 2 — Q9H1B5 (reviewed: Q9H1B5)

Alternative names: Peptide O-xylosyltransferase 1, Xylosyltransferase II

All UniProt accessions (6): Q9H1B5, A0A0C4DFW8, B4DT06, D6RCT0, H0YB00, I3L3K2

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the first step in the biosynthesis of chondroitin sulfate, heparan sulfate and dermatan sulfate proteoglycans, such as DCN. Transfers D-xylose from UDP-D-xylose to specific serine residues of the core protein.

Subunit / interactions. Monomer.

Subcellular location. Golgi apparatus membrane. Secreted.

Tissue specificity. Widely expressed. Expressed at higher level in kidney and pancreas.

Post-translational modifications. Contains disulfide bonds.

Disease relevance. Spondyloocular syndrome (SOS) [MIM:605822] A syndrome characterized by cataract, loss of vision due to retinal detachment, facial dysmorphism, facial hypotonia, normal height with disproportional short trunk, osteoporosis, immobile spine with thoracic kyphosis and reduced lumbal lordosis. The disease is caused by variants affecting the gene represented in this entry. Pseudoxanthoma elasticum (PXE) [MIM:264800] A multisystem disorder characterized by accumulation of mineralized and fragmented elastic fibers in the skin, vascular walls, and Burch membrane in the eye. Clinically, patients exhibit characteristic lesions of the posterior segment of the eye including peau d’orange, angioid streaks, and choroidal neovascularizations, of the skin including soft, ivory colored papules in a reticular pattern that predominantly affect the neck and large flexor surfaces, and of the cardiovascular system with peripheral and coronary arterial occlusive disease as well as gastrointestinal bleedings. The gene represented in this entry acts as a disease modifier. PXE patients carrying causative ABCC6 mutations, manifest a more severe disease course characterized by earlier onset, frequent skin lesions and higher organ involvement, in the presence of XYLT2 variants.

Cofactor. Active with either Mg(2+) or Mn(2+), but activity is highest when both are present.

Pathway. Glycan metabolism; chondroitin sulfate biosynthesis. Glycan metabolism; heparan sulfate biosynthesis.

Similarity. Belongs to the glycosyltransferase 14 family. XylT subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H1B5-1	1	yes
Q9H1B5-2	2

RefSeq proteins (1): NP_071450* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003406	Glyco_trans_14	Family
IPR024448	XylT_C	Domain
IPR043538	XYLT	Family

Pfam: PF02485, PF12529

Enzyme classification (BRENDA):

• EC 2.4.2.26 — protein xylosyltransferase (BRENDA: 8 organisms, 138 substrates, 27 inhibitors, 180 Km, 8 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
BIKUNIN	0.0006–0.0656	70
UDP-D-XYLOSE	0.0065–0.25	7
BIOTIN-NH-QEEEGSGGGQKK(5-FLUORESCEIN)-CONH2	0.0025–0.0061	3
CARTILAGE CHONDROITIN SULFATE PROTEOGLYCAN	0.11–0.19	3
HF-DEGRADED CHONDROITIN SULFATE PROTEOGLYCAN	0.0001–1.02	3
QEEEGSGGGQKK	0.0117–0.093	3
SILK FIBROIN	0.545–0.677	3
TENEGSGLTNIK	0.02–0.3905	3
BAMCAN	0.0179–0.0222	2
BFGF-PEPTIDE	0.0093–0.0137	2
FRAGMENT(1-24) OF HUMAN BASIC FIBROBLAST GROWTH	0.0208–0.0223	2
GLYPICAN-1	0.0109–0.0171	2
L-APLP2	0.0104–0.0134	2
NEUROGLYCAN C	0.0032–0.0236	2
PERLECAN-2	0.0102–0.0145	2

Catalyzed reactions (Rhea), 1 shown:

• UDP-alpha-D-xylose + L-seryl-[protein] = 3-O-(beta-D-xylosyl)-L-seryl-[protein] + UDP + H(+) (RHEA:50192)

UniProt features (32 total): binding site 6, disulfide bond 6, sequence variant 6, glycosylation site 3, compositionally biased region 3, topological domain 2, splice variant 2, region of interest 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H1B5-F1	84.79	0.71

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (6): 267; 296–298; 400–401; 481; 504–505; 239

Disulfide bonds (6): 162–190, 206–448, 467–480, 469–478, 581–833, 826–839

Glycosylation sites (3): 122, 327, 683

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1971475	Glycosaminoglycan-protein linkage region biosynthesis

MSigDB gene sets: 371 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GCACCTT_MIR18A_MIR18B, GCM_GSPT1, TGACCTY_ERR1_Q2, LHX3_01, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_AMINOGLYCAN_BIOSYNTHETIC_PROCESS, EVI1_05, GOBP_CHONDROITIN_SULFATE_PROTEOGLYCAN_BIOSYNTHETIC_PROCESS, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM2, GOBP_HEPARAN_SULFATE_PROTEOGLYCAN_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_AMINOGLYCAN_METABOLIC_PROCESS, OCT1_07, LYF1_01

GO Biological Process (8): glycosaminoglycan biosynthetic process (GO:0006024), heparan sulfate proteoglycan biosynthetic process (GO:0015012), chondroitin sulfate proteoglycan biosynthetic process (GO:0050650), glycosaminoglycan-protein linkage region biosynthetic process (GO:0120532), glycoprotein biosynthetic process (GO:0009101), proteoglycan biosynthetic process (GO:0030166), glycosaminoglycan metabolic process (GO:0030203), heparin proteoglycan biosynthetic process (GO:0030210)

GO Molecular Function (7): magnesium ion binding (GO:0000287), manganese ion binding (GO:0030145), protein xylosyltransferase activity (GO:0030158), UDP-glycosyltransferase activity (GO:0008194), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), metal ion binding (GO:0046872)

GO Cellular Component (5): Golgi membrane (GO:0000139), obsolete extracellular space (GO:0005615), Golgi apparatus (GO:0005794), extracellular region (GO:0005576), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glycosaminoglycan metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein O-linked glycosylation via xylose	4
proteoglycan biosynthetic process	2
cellular anatomical structure	2
aminoglycan biosynthetic process	1
glycosaminoglycan metabolic process	1
heparan sulfate proteoglycan metabolic process	1
chondroitin sulfate proteoglycan metabolic process	1
heparan sulfate proteoglycan biosynthetic process	1
heparin proteoglycan biosynthetic process	1
chondroitin sulfate proteoglycan biosynthetic process	1
dermatan sulfate proteoglycan biosynthetic process	1
macromolecule biosynthetic process	1
glycoprotein metabolic process	1
carbohydrate derivative biosynthetic process	1
proteoglycan metabolic process	1
glycoprotein biosynthetic process	1
aminoglycan metabolic process	1
heparin proteoglycan metabolic process	1
metal ion binding	1
transition metal ion binding	1
UDP-xylosyltransferase activity	1
catalytic activity, acting on a protein	1
glycosyltransferase activity	1
catalytic activity	1
transferase activity	1
cation binding	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

704 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
XYLT2	SLC6A20	Q9NP91	919
XYLT2	GRB2	P29354	918
XYLT2	B4GALT7	Q9UBV7	797
XYLT2	B3GALT6	Q96L58	788
XYLT2	B3GAT3	O94766	745
XYLT2	EXTL3	O43909	721
XYLT2	ABCC6	P78420	702
XYLT2	FAM20B	O75063	657
XYLT2	EXTL2	Q9UBQ6	653
XYLT2	EXT2	Q93063	593
XYLT2	UXS1	Q8NBZ7	587
XYLT2	SLC35B2	Q8TB61	584
XYLT2	NDST1	P52848	574
XYLT2	EXT1	Q16394	568
XYLT2	HAND1	O96004	567

IntAct

71 interactions, top by confidence:

A	B	Type	Score
FOXJ1	RFX3	psi-mi:“MI:0914”(association)	0.730
RETREG3	PLSCR1	psi-mi:“MI:0914”(association)	0.640
B3GAT3	GOLIM4	psi-mi:“MI:0914”(association)	0.640
POMK	LRP5	psi-mi:“MI:0914”(association)	0.640
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
POMK	TMEM120B	psi-mi:“MI:0914”(association)	0.530
B4GALT3	SLC19A2	psi-mi:“MI:0914”(association)	0.530
UST	GOLIM4	psi-mi:“MI:0914”(association)	0.530
PBXIP1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
GPC3	CLGN	psi-mi:“MI:0914”(association)	0.530
B4GALT3	ATP5MC1	psi-mi:“MI:0914”(association)	0.530
GPC3	CANX	psi-mi:“MI:0914”(association)	0.530
FLVCR1	TNFRSF10B	psi-mi:“MI:0914”(association)	0.530
UNC93B1	GPR89A	psi-mi:“MI:0914”(association)	0.530
SCGB2A2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLEC2D	TMEM120B	psi-mi:“MI:0914”(association)	0.350
TAZ	MANBA	psi-mi:“MI:0914”(association)	0.350
LYPD4	DPYSL4	psi-mi:“MI:0914”(association)	0.350
RETREG3		psi-mi:“MI:0914”(association)	0.350
IDS	COCH	psi-mi:“MI:0914”(association)	0.350
CAMK1D		psi-mi:“MI:0914”(association)	0.350
GPC1	ATP2B4	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
POMK	ESYT2	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (75): XYLT2 (Affinity Capture-MS), XYLT2 (Affinity Capture-MS), XYLT2 (Affinity Capture-MS), XYLT2 (Affinity Capture-MS), XYLT2 (Affinity Capture-MS), XYLT2 (Affinity Capture-MS), XYLT2 (Affinity Capture-MS), XYLT2 (Affinity Capture-MS), XYLT2 (Affinity Capture-MS), XYLT2 (Affinity Capture-MS), XYLT2 (Affinity Capture-MS), XYLT2 (Affinity Capture-MS), XYLT2 (Affinity Capture-MS), XYLT2 (Affinity Capture-MS), XYLT2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0D3QS98, A0A0D3QS99, C5H5C4, O70309, O97583, P05106, P17405, P18084, P18424, P50747, P52849, P52850, P58242, P61642, P70207, P80747, Q04519, Q0V8G3, Q0VBD0, Q0VD19, Q13219, Q5NDF2, Q5QQ51, Q5STE3, Q64687, Q6DFZ6, Q6KFX9, Q6MZW2, Q6P988, Q6PCX7, Q6UWX4, Q6YGZ1, Q6ZXD2, Q71RP1, Q7TQ33, Q812F8, Q8BJQ9, Q8C1F4, Q8N6G5, Q8R116

Diamond homologs: Q5QQ49, Q5QQ50, Q5QQ51, Q5QQ52, Q5QQ53, Q5QQ54, Q5QQ55, Q5QQ56, Q5QQ57, Q7KVA1, Q811B1, Q86Y38, Q965Q8, Q9EPI0, Q9EPI1, Q9EPL0, Q9H1B5, A2BGL3, Q0IIY2, Q2TBF2, Q505J3, Q658N2, Q80XH4, D4AUF4, D4PHA7, E9Q649, P54867, P84675, Q8NCW0, Q8S8P3, Q9P109, Q1M0V6, Q7YQE1, Q80RC7, Q866Z4, Q866Z5, A0A1U9VX91, D4AUF1, P83097, Q8N0V5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 86 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Formation of ATP by chemiosmotic coupling	5	51.0×	1e-05
Cristae formation	5	30.9×	8e-05
Mitochondrial biogenesis	5	15.0×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
proton motive force-driven ATP synthesis	5	54.2×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	5
Uncertain significance	217
Likely benign	184
Benign	36

Top pathogenic / likely-pathogenic (14)

Variant ID	HGVS	Classification
207977	NM_022167.4(XYLT2):c.692dup (p.Val232fs)	Pathogenic
207978	NM_022167.4(XYLT2):c.520del (p.Ala174fs)	Pathogenic
2108028	NM_022167.4(XYLT2):c.1454del (p.Phe485fs)	Pathogenic
2755688	NM_022167.4(XYLT2):c.2478_2479del (p.Ala827fs)	Pathogenic
2776265	NM_022167.4(XYLT2):c.1980del (p.Asn661fs)	Pathogenic
3654325	NM_022167.4(XYLT2):c.1500del (p.Phe501fs)	Pathogenic
3702192	NM_022167.4(XYLT2):c.577C>T (p.Gln193Ter)	Pathogenic
546804	NM_022167.4(XYLT2):c.1159C>T (p.Arg387Trp)	Pathogenic
863214	NM_022167.4(XYLT2):c.1446del (p.Asn483fs)	Pathogenic
3340122	NM_022167.4(XYLT2):c.1736del (p.Pro579fs)	Likely pathogenic
521122	NM_022167.4(XYLT2):c.1687C>T (p.Arg563Cys)	Likely pathogenic
548446	NM_022167.4(XYLT2):c.2548G>A (p.Asp850Asn)	Likely pathogenic
804420	NM_022167.4(XYLT2):c.1584dup (p.Gly529fs)	Likely pathogenic
974777	NM_022167.4(XYLT2):c.1552del (p.Leu518fs)	Likely pathogenic

SpliceAI

1677 predictions. Top by Δscore:

Variant	Effect	Δscore
17:50346258:G:GT	donor_gain	1.0000
17:50346261:G:GT	donor_gain	1.0000
17:50354580:CAAG:C	donor_loss	1.0000
17:50354582:AGG:A	donor_loss	1.0000
17:50354583:GGTAC:G	donor_loss	1.0000
17:50354851:CAG:C	acceptor_loss	1.0000
17:50354852:A:AG	acceptor_gain	1.0000
17:50354852:AGC:A	acceptor_gain	1.0000
17:50354853:G:GT	acceptor_gain	1.0000
17:50354853:GC:G	acceptor_gain	1.0000
17:50354853:GCG:G	acceptor_gain	1.0000
17:50354853:GCGTT:G	acceptor_gain	1.0000
17:50355053:CCAG:C	donor_loss	1.0000
17:50355054:CAG:C	donor_loss	1.0000
17:50355055:AG:A	donor_loss	1.0000
17:50355056:GGTGT:G	donor_loss	1.0000
17:50355057:G:T	donor_loss	1.0000
17:50355058:T:A	donor_loss	1.0000
17:50355496:A:AG	acceptor_gain	1.0000
17:50355496:ACCAG:A	acceptor_gain	1.0000
17:50355499:A:AG	acceptor_gain	1.0000
17:50355500:G:GA	acceptor_gain	1.0000
17:50355500:GGACC:G	acceptor_gain	1.0000
17:50355579:CAGG:C	donor_loss	1.0000
17:50355582:GT:G	donor_loss	1.0000
17:50355583:T:G	donor_loss	1.0000
17:50355772:T:A	acceptor_gain	1.0000
17:50355776:CACAG:C	acceptor_loss	1.0000
17:50355778:CA:C	acceptor_loss	1.0000
17:50355779:A:AG	acceptor_gain	1.0000

AlphaMissense

5610 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:50354941:T:A	W298R	1.000
17:50354941:T:C	W298R	1.000
17:50354943:G:C	W298C	1.000
17:50354943:G:T	W298C	1.000
17:50354944:G:C	G299R	1.000
17:50354944:G:T	G299C	1.000
17:50354945:G:A	G299D	1.000
17:50355562:C:G	H357D	1.000
17:50355782:T:C	F364L	1.000
17:50355783:T:C	F364S	1.000
17:50355783:T:G	F364C	1.000
17:50355784:C:A	F364L	1.000
17:50355784:C:G	F364L	1.000
17:50355791:A:G	K367E	1.000
17:50355792:A:T	K367I	1.000
17:50355793:A:C	K367N	1.000
17:50355793:A:T	K367N	1.000
17:50355796:G:C	Q368H	1.000
17:50355796:G:T	Q368H	1.000
17:50355801:T:C	L370P	1.000
17:50355807:G:C	R372P	1.000
17:50355812:T:C	F374L	1.000
17:50355813:T:C	F374S	1.000
17:50355813:T:G	F374C	1.000
17:50355814:C:A	F374L	1.000
17:50355814:C:G	F374L	1.000
17:50355836:T:A	W382R	1.000
17:50355836:T:C	W382R	1.000
17:50355838:G:C	W382C	1.000
17:50355838:G:T	W382C	1.000

dbSNP variants (sampled 300 via entrez): RS1000089130 (17:50359276 G>A), RS1000282121 (17:50346513 G>A), RS1000399959 (17:50347028 G>A), RS1000624922 (17:50345805 A>C), RS1000770177 (17:50351728 G>C), RS1000842613 (17:50352996 C>G), RS1000853968 (17:50347247 C>T), RS1000858332 (17:50351783 C>A,T), RS1000971138 (17:50351418 C>T), RS1001055462 (17:50356900 G>A,T), RS1001565220 (17:50357722 C>T), RS1001567894 (17:50345707 C>T), RS1001570434 (17:50346659 G>C), RS1001741522 (17:50352771 G>A), RS1002084327 (17:50350631 A>G)

Disease associations

OMIM: gene MIM:608125 | disease phenotypes: MIM:605822, MIM:166200, MIM:264800

GenCC curated gene-disease

Disease	Classification	Inheritance
spondylo-ocular syndrome	Strong	Autosomal recessive

Mondo (3): spondylo-ocular syndrome (MONDO:0011604), osteogenesis imperfecta (MONDO:0019019), autosomal recessive inherited pseudoxanthoma elasticum (MONDO:0009925)

Orphanet (3): Spondylo-ocular syndrome (Orphanet:85194), Osteogenesis imperfecta (Orphanet:666), Pseudoxanthoma elasticum (Orphanet:758)

HPO phenotypes

83 total (30 of 83 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000164	Abnormality of the dentition
HP:0000233	Thin vermilion border
HP:0000297	Facial hypotonia
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000391	Thickened helices
HP:0000407	Sensorineural hearing impairment
HP:0000465	Webbed neck
HP:0000470	Short neck
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000534	Abnormal eyebrow morphology
HP:0000541	Retinal detachment
HP:0000545	Myopia
HP:0000568	Microphthalmia
HP:0000572	Visual loss
HP:0000573	Retinal hemorrhage
HP:0000591	Abnormal sclera morphology
HP:0000608	Macular degeneration
HP:0000639	Nystagmus
HP:0000646	Amblyopia
HP:0000768	Pectus carinatum
HP:0000822	Hypertension
HP:0000914	Shield chest
HP:0000926	Platyspondyly
HP:0000938	Osteopenia
HP:0000939	Osteoporosis

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D010013	Osteogenesis Imperfecta	C05.116.099.708.685; C16.320.737; C17.300.200.540
D011561	Pseudoxanthoma Elasticum	C14.907.454.530; C15.378.463.515.530; C16.131.831.766; C16.320.850.750; C17.300.766; C17.800.804.766; C17.800.827.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs6504649	Toxicity	3	carboplatin;gemcitabine	Non-Small Cell Lung Carcinoma;Thrombocytopenia

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6504649	XYLT2	3	2.50	1	carboplatin;gemcitabine

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	3
Arsenic	affects methylation, increases abundance, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Cyclosporine	decreases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Copper	affects binding, increases expression	1
Disulfiram	affects binding, increases expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects expression	1
Lead	affects expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Plant Oils	decreases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Aflatoxin B1	increases methylation	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_DX58	HAP1 SLC35B2 (-) XYLT2 (-)	Cancer cell line	Male
CVCL_XV17	HAP1 XYLT2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00131469	PHASE4	COMPLETED	Study of Teriparatide (FORTEO) to Treat Adults With Osteogenesis Imperfecta
NCT00159419	PHASE4	COMPLETED	Bisphosphonate Therapy for Osteogenesis Imperfecta
NCT01713231	PHASE4	COMPLETED	Effect of High-Dose Vitamin D on Bone Density in Osteogenesis Imperfecta
NCT02303873	PHASE4	COMPLETED	Efficacy and Safety of Alendronate in Chinese Children or Adolescents With Osteogenesis Imperfecta
NCT03735537	PHASE4	COMPLETED	Treatment of Osteogenesis Imperfecta With Parathyroid Hormone and Zoledronic Acid
NCT04152551	PHASE4	RECRUITING	Effects of Bisphosphonates on OI-Related Hearing Loss
NCT00001305	PHASE3	COMPLETED	Growth Hormone Therapy in Osteogenesis Imperfecta
NCT00005901	PHASE3	COMPLETED	Pamidronate to Treat Osteogenesis Imperfecta in Children
NCT00106028	PHASE3	COMPLETED	Safety and Efficacy of Risedronate in the Treatment of Osteogenesis Imperfecta in Children
NCT00982124	PHASE3	COMPLETED	An Efficacy and Safety Trial of Intravenous Zoledronic Acid in Infants Less Than One Year of Age, With Severe Osteogenesis Imperfecta
NCT02352753	PHASE3	TERMINATED	Multicenter,Single-arm Study to Evaluate Efficacy, Safety, & Pharmacokinetics of Denosumab in Children w/ OI
NCT03638128	PHASE3	TERMINATED	Open-label Extension of Study 20130173 of Denosumab in Children and Young Adults With Osteogenesis Imperfecta
NCT05768854	PHASE3	ACTIVE_NOT_RECRUITING	Setrusumab vs Bisphosphonates in Pediatric Subjects With Osteogenesis Imperfecta
NCT05972551	PHASE3	ACTIVE_NOT_RECRUITING	Study to Evaluate Efficacy and Safety of Romosozumab Compared With Bisphosphonates in Children and Adolescents With Osteogenesis Imperfecta
NCT06636071	PHASE3	ACTIVE_NOT_RECRUITING	Setrusumab in Pediatric Japanese Subjects With Osteogenesis Imperfecta
NCT07366086	PHASE3	RECRUITING	Pediatric Safety Follow-up Study of Prior Treatment With Romosozumab for Osteogenesis Imperfecta
NCT05832580	PHASE3	RECRUITING	The Prevention of Systemic Ectopic Mineralization in Pseudoxanthoma Elasticum
NCT00063479	PHASE2	COMPLETED	Bisphosphonate Treatment of Osteogenesis Imperfecta
NCT00131118	PHASE2	COMPLETED	Zoledronic Acid in Children (1 -17 Years) With Severe Osteogenesis Imperfecta
NCT01417091	PHASE2	COMPLETED	Safety, Pharmacokinetics and Pharmacodynamics of BPS804 in Osteogenesis Imperfecta
NCT01679080	PHASE2	TERMINATED	The Effect of Treatment With Teriparatide and Zoledronic Acid in Patients With Osteogenesis Imperfecta
NCT01799798	PHASE2	COMPLETED	Translational Therapy in Patients With Osteogenesis Imperfecta - A Pilot Trial on Treatment With the Rankl-Antibody Denosumab
NCT03208582	PHASE2	COMPLETED	Do Bisphosphonates Alter the Skeletal Response to Mechanical Stimulation in Children With Osteogenesis Imperfecta?
NCT03216486	PHASE2	WITHDRAWN	An Exploratory Study of BPS804 Treatment in Adult Patients With Type I, III or IV Osteogenesis Imperfecta
NCT05312697	PHASE2	TERMINATED	Long-term Extension Study of Setrusumab in Adults With Type I, III, or IV Osteogenesis Imperfecta
NCT07062588	PHASE2	RECRUITING	Osteogenesis Imperfecta Trial of AGA2115 for ADUlts With COL1A1 and/or COL1A2 GeNetic Variations (IDUN)
NCT07557446	PHASE2	NOT_YET_RECRUITING	A Dose REgimen-Finding Study of AGA2115 in Chinese Patients With Osteogenesis ImpeRfecta (EIR)
NCT01525875	PHASE2	COMPLETED	Magnesium Supplements In The Treatment Of Pseudoxanthoma Elasticum (PXE)
NCT02537054	PHASE2	COMPLETED	Intravitreal Aflibercept for Therapy of Patients With Pseudoxanthoma Elasticum (PXE)
NCT04441671	PHASE2	WITHDRAWN	Oral Pyrophosphate Absorption in PXE Disease
NCT05569252	PHASE2	COMPLETED	A Study of DS-1211b in Individuals With PseudoXanthoma Elasticum
NCT06462547	PHASE2	RECRUITING	ADAPT Study: Long-term Safety Study of INZ-701 in Patients With ENPP1 Deficiency and ABCC6 Deficiency
NCT00705120	PHASE1	COMPLETED	Treatment of Severe Osteogenesis Imperfecta by Allogeneic Bone Marrow Transplantation
NCT02172885	PHASE1	COMPLETED	Mesenchymal Stem Cell Based Therapy for the Treatment of Osteogenesis Imperfecta
NCT03064074	PHASE1	COMPLETED	Safety of Fresolimumab in the Treatment of Osteogenesis Imperfecta
NCT04545554	PHASE1	COMPLETED	Study to Evaluate Romosozumab in Children and Adolescents With Osteogenesis Imperfecta
NCT05231668	PHASE1	TERMINATED	Single Ascending Dose Study of SAR439459 in Adults With Osteogenesis Imperfecta (OI)
NCT06086613	PHASE1	COMPLETED	A First-in-Human Study Evaluating AGA2115 in Adult Healthy Volunteers
NCT05734196	PHASE1	RECRUITING	The ENERGY Study: Evaluation of Safety and Tolerability of INZ-701 in Infants With ENPP1 Deficiency or ABCC6 Deficiency
NCT05125809	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Setrusumab vs Placebo for Osteogenesis Imperfecta