XYLT1

xylosyltransferase 1, the group of Glucosaminyl (N-acetyl) transferases/xylosyltransferases

Basic information

Region (hg38): 16:17101769-17470960

Links

ENSG00000103489 ∙ NCBI:64131 ∙ OMIM:608124 ∙ HGNC:15516 ∙ Uniprot:Q86Y38 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Desbuquois dysplasia 2 (Strong), mode of inheritance: AR
• Desbuquois dysplasia (Supportive), mode of inheritance: AR
• XYLT1-congenital disorder of glycosylation (Supportive), mode of inheritance: AR
• Desbuquois dysplasia 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Desbuquois dysplasia 2	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	23982343; 24581741

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the XYLT1 gene.

• Desbuquois_dysplasia_1 (445 variants)
• Inborn_genetic_diseases (143 variants)
• not_provided (72 variants)
• Desbuquois_dysplasia_2 (27 variants)
• XYLT1-related_disorder (20 variants)
• not_specified (4 variants)
• Autosomal_recessive_inherited_pseudoxanthoma_elasticum (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the XYLT1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000022166.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				145	13	158
missense	2		268	16	6	292
nonsense	8	1	1			10
start loss	1					1
frameshift	5	3				8
splice donor/acceptor (+/-2bp)	2					2
Total	18	4	269	161	19

Highest pathogenic variant AF is 0.00000752456

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
XYLT1	protein_coding	protein_coding	ENST00000261381	12	369113

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.924	0.0758	125732	0	16	125748	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.586	508	547	0.929	0.0000353	6214
Missense in Polyphen		215	268.4	0.80104		2728
Synonymous	-1.62	258	227	1.14	0.0000157	1961
Loss of Function	4.76	7	39.1	0.179	0.00000210	424

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000793	0.0000791
Middle Eastern	0.000109	0.000109
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the first step in the biosynthesis of chondroitin sulfate and dermatan sulfate proteoglycans, such as DCN. Transfers D-xylose from UDP-D-xylose to specific serine residues of the core protein (PubMed:15461586, PubMed:17189265, PubMed:24581741, PubMed:23982343). Required for normal embryonic and postnatal skeleton development, especially of the long bones (PubMed:24581741, PubMed:23982343). Required for normal maturation of chondrocytes during bone development, and normal onset of ossification (By similarity). {ECO:0000250|UniProtKB:Q811B1, ECO:0000269|PubMed:15461586, ECO:0000269|PubMed:17189265, ECO:0000269|PubMed:23982343, ECO:0000269|PubMed:24581741}.
• Disease: DISEASE: Desbuquois dysplasia 2 (DBQD2) [MIM:615777]: A chondrodysplasia characterized by severe prenatal and postnatal growth retardation (less than -5 SD), joint laxity, short extremities, progressive scoliosis, round face, midface hypoplasia, prominent bulging eyes. The main radiologic features are short long bones with metaphyseal splay, a 'Swedish key' appearance of the proximal femur (exaggerated trochanter), and advance carpal and tarsal bone age. Two forms of Desbuquois dysplasia are distinguished on the basis of the presence or absence of characteristic hand anomalies: an extra ossification center distal to the second metacarpal, delta phalanx, bifid distal thumb phalanx, and phalangeal dislocations. {ECO:0000269|PubMed:23982343, ECO:0000269|PubMed:24581741, ECO:0000269|PubMed:28462984}. 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.
• Pathway: Glycosaminoglycan biosynthesis - chondroitin sulfate / dermatan sulfate - Homo sapiens (human);Glycosaminoglycan biosynthesis - heparan sulfate / heparin - Homo sapiens (human);Spinal Cord Injury;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: 0.130

Intolerance Scores

• loftool: 0.202
• rvis_EVS: -1.08
• rvis_percentile_EVS: 7.28

Haploinsufficiency Scores

• pHI: 0.418
• hipred: Y
• hipred_score: 0.595
• ghis: 0.521

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.290

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Xylt1
• Phenotype: cellular phenotype; craniofacial phenotype; growth/size/body region phenotype; skeleton phenotype; immune system phenotype; limbs/digits/tail phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Zebrafish Information Network

• Gene name: xylt1
• Affected structure: hypertrophic chondrocyte
• Phenotype tag: abnormal
• Phenotype quality: increased amount

Gene ontology

• Biological process: glycosaminoglycan biosynthetic process;heparan sulfate proteoglycan biosynthetic process;proteoglycan biosynthetic process;glycosaminoglycan metabolic process;chondroitin sulfate biosynthetic process;ossification involved in bone maturation;embryonic skeletal system development;chondroitin sulfate proteoglycan biosynthetic process
• Cellular component: Golgi cis cisterna;Golgi membrane;extracellular space;integral component of membrane
• Molecular function: acetylglucosaminyltransferase activity;protein xylosyltransferase activity;metal ion binding