XYLT1
protein-codingxylosyltransferase 1, the group of Glucosaminyl (N-acetyl) transferases/xylosyltransferases
Gene summary
This locus encodes a xylosyltransferase enzyme. The encoded protein catalyzes transfer of UDP-xylose to serine residues of an acceptor protein substrate. This transfer reaction is necessary for biosynthesis of glycosaminoglycan chains. Mutations in this gene have been associated with increased severity of pseudoxanthoma elasticum.[provided by RefSeq, Nov 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~369.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0014343
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0014343
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0018273
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0015426
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0014343
Submitter: G2P
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Musculoskeletal; Neurologic
Intervention: General
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to XYLT1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_022166.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 169 | 9 | 179 | ||
| missense | 1 | 294 | 18 | 5 | 318 | |
| nonsense | 8 | 3 | 2 | 13 | ||
| start loss | 1 | 1 | 2 | |||
| frameshift | 6 | 4 | 10 | |||
| splice donor/acceptor (+/-2bp) | 2 | 1 | 1 | 4 | ||
| Total | 18 | 8 | 299 | 187 | 14 | 526 |
Highest pathogenic variant AF is 0.0000075245575
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_071449.1 | 12 | MANE Select | |
| Ensembl | ENSP00000261381.6 | 12 | MANE Select | |
| Ensembl | ENSP00000603816.1 | 12 | Standard | |
| Ensembl | ENSP00000603816.1 | 12 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| xylt1 | Danio rerio | Structure: hypertrophic chondrocyte Quality: increased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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
Biological Process
- glycosaminoglycan biosynthetic process
- heparan sulfate proteoglycan biosynthetic process
- proteoglycan biosynthetic process
- glycosaminoglycan metabolic process
- chondroitin sulfate biosynthetic process
Molecular Function
- acetylglucosaminyltransferase activity
- protein xylosyltransferase activity
- metal ion binding
Cellular Component
- Golgi cis cisterna
- Golgi membrane
- extracellular space
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000261381
- Coding exons
- 12
- Length
- 369113
- Individuals with no LoFs
- 125732
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 16
- Defined
- 125748
- p
- 0.0000636
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.586 | 508 | 547 | 0.929 | 0.0000353 | 6214 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000079 | 0.000079 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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.;
Recessive Scores
- pRec
- 0.130
Intolerance Scores
- LoFtool
- 0.202
- RVIS EVS
- -1.08
- RVIS percentile EVS
- 7.28
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.290
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |