XYLT2

xylosyltransferase 2, the group of Glucosaminyl (N-acetyl) transferases/xylosyltransferases

Basic information

Region (hg38): 17:50346125-50363138

Links

ENSG00000015532 ∙ NCBI:64132 ∙ OMIM:608125 ∙ HGNC:15517 ∙ Uniprot:Q9H1B5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spondylo-ocular syndrome (Strong), mode of inheritance: AR
• spondylo-ocular syndrome (Supportive), mode of inheritance: AR
• spondylo-ocular syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spondyloocular syndrome	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Musculoskeletal; Ophthalmologic; Renal	26027496

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the XYLT2 gene.

• not provided (276 variants)
• Inborn genetic diseases (40 variants)
• Osteogenesis imperfecta (33 variants)
• Spondylo-ocular syndrome (13 variants)
• XYLT2-related condition (2 variants)
• Autosomal recessive inherited pseudoxanthoma elasticum (1 variants)
• not specified (1 variants)
• Pseudoxanthoma elasticum, modifier of severity of (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the XYLT2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	85	11	97
missense	1	1	136	9	3	150
nonsense			1			1
start loss						0
frameshift	4	3				7
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region			4	6	1	11
non coding				18	21	39
Total	5	4	140	112	35

Highest pathogenic variant AF is 0.0000198

Variants in XYLT2

This is a list of pathogenic ClinVar variants found in the XYLT2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-50346145-T-G			Uncertain significance (Jul 06, 2022)
17-50346148-C-T		Inborn genetic diseases	Uncertain significance (Feb 10, 2022)
17-50346155-G-A			Likely benign (Jan 25, 2024)
17-50346169-T-A			Uncertain significance (Apr 25, 2022)
17-50346170-G-T		Spondylo-ocular syndrome • Osteogenesis imperfecta	Benign (Jan 25, 2024)
17-50346172-T-G			Uncertain significance (Sep 10, 2021)
17-50346174-C-T		Inborn genetic diseases	Uncertain significance (Aug 04, 2023)
17-50346178-G-T		Osteogenesis imperfecta	Uncertain significance (Aug 01, 2018)
17-50346186-C-T			Likely benign (Nov 14, 2023)
17-50346202-C-T			Uncertain significance (Jul 06, 2022)
17-50346209-C-T			Likely benign (Dec 16, 2023)
17-50346269-G-C			Likely benign (Jul 19, 2022)
17-50346284-A-C			Likely benign (Dec 07, 2022)
17-50346285-C-A			Benign (Dec 15, 2023)
17-50346289-C-T			Likely benign (Dec 20, 2023)
17-50346373-G-C			Benign (May 19, 2021)
17-50353603-A-C			Benign (May 23, 2021)
17-50353614-T-C			Likely benign (Sep 19, 2023)
17-50353638-G-T		XYLT2-related disorder	Uncertain significance (Feb 02, 2024)
17-50353650-A-G			Likely benign (Nov 15, 2022)
17-50353652-G-A		Inborn genetic diseases	Uncertain significance (Feb 15, 2023)
17-50353660-G-A		not specified • Osteogenesis imperfecta • XYLT2-related disorder	Benign/Likely benign (Jan 31, 2024)
17-50353668-C-T		XYLT2-related disorder	Likely benign (Nov 12, 2023)
17-50353671-G-A		Spondylo-ocular syndrome	Benign (Jan 31, 2024)
17-50353687-G-A			Uncertain significance (Nov 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
XYLT2	protein_coding	protein_coding	ENST00000017003	11	17047

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.926	0.0742	125733	0	14	125747	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.09	400	536	0.746	0.0000356	5524
Missense in Polyphen		136	229.36	0.59294		2230
Synonymous	-0.266	239	234	1.02	0.0000159	1829
Loss of Function	4.52	6	34.8	0.173	0.00000172	368

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000579	0.0000579
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000625	0.0000615
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000269|PubMed:17189265, ECO:0000269|PubMed:26027496}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:26027496}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:16571645}. Note=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. {ECO:0000269|PubMed:16571645}.
• Pathway: Glycosaminoglycan biosynthesis - chondroitin sulfate / dermatan sulfate - Homo sapiens (human);Glycosaminoglycan biosynthesis - heparan sulfate / heparin - Homo sapiens (human);Metabolism of carbohydrates;A tetrasaccharide linker sequence is required for GAG synthesis;Heparan sulfate/heparin (HS-GAG) metabolism;Chondroitin sulfate/dermatan sulfate metabolism;Glycosaminoglycan metabolism;Proteoglycan biosynthesis;glycoaminoglycan-protein linkage region biosynthesis;chondroitin sulfate biosynthesis;heparan sulfate biosynthesis;dermatan sulfate biosynthesis;Metabolism (Consensus)

Recessive Scores

• pRec: 0.131

Intolerance Scores

• loftool: 0.495
• rvis_EVS: -0.48
• rvis_percentile_EVS: 22.8

Haploinsufficiency Scores

• pHI: 0.272
• hipred: Y
• hipred_score: 0.575
• ghis: 0.407

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0742

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Xylt2
• Phenotype: renal/urinary system phenotype; liver/biliary system phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: glycosaminoglycan biosynthetic process;heparan sulfate proteoglycan biosynthetic process;glycosaminoglycan metabolic process;chondroitin sulfate biosynthetic process;heparin biosynthetic process;chondroitin sulfate proteoglycan biosynthetic process
• Cellular component: Golgi membrane;extracellular space;integral component of membrane
• Molecular function: magnesium ion binding;acetylglucosaminyltransferase activity;manganese ion binding;protein xylosyltransferase activity