GeneBe

XYLT2

protein-coding

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

Gene summary

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. [provided by RefSeq, Dec 2013]

MANE transcript

NM_022167.4

Inheritance

AR

ClinVar variants

P:17U:218B:183

Top phenotype

Spondyloocular syndrome

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr17:50,346,126-50,363,138

External References & Databases

Ensembl (ENSG00000015532)NCBI Gene (64132)OMIM (608125)HGNC:15517GenCCUniProt (Q9H1B5)AlphaFoldClinVar (XYLT2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~17.0 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spondylo-ocular syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011604

Submitter: PanelApp Australia

spondylo-ocular syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011604

Submitter: G2P

spondylo-ocular syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011604

Submitter: Labcorp Genetics (formerly Invitae)

spondylo-ocular syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011604

Submitter: Orphanet

Clinical Genomic Database (CGD)

Spondyloocular syndromeAR

Manifestation: Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Musculoskeletal; Ophthalmologic; Renal

Intervention: Cardiovascular

Rationale: The condition can involve congenital cardiac anomalies, and awareness may allow early management

Refs: 26027496Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to XYLT2 variants in ClinVar

7 Conditions Cataloged
not providedTotal: 377
Inborn genetic diseasesTotal: 127
XYLT2-related disorderTotal: 66
not specifiedTotal: 51
Osteogenesis imperfectaTotal: 31
Spondylo-ocular syndromeTotal: 15
Autosomal recessive inherited pseudoxanthoma elasticumTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022167.4. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
163
clinvar
4
clinvar
 168
missense
1
clinvar
3
clinvar
212
clinvar
15
clinvar
1
clinvar
 232
nonsense
1
clinvar
4
clinvar
 5
start loss
0
frameshift
7
clinvar
5
clinvar
 12
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total982181785418

Highest pathogenic variant AF is 0.00001487955

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_022167.4RefSeqNP_071450.211MANE Select
ENST00000017003.7EnsemblENSP00000017003.211MANE Select
ENST00000376550.7EnsemblENSP00000365733.39Standard
ENST00000507602.5EnsemblENSP00000426501.110Standard

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)
  • Metabolism of carbohydrates
  • A tetrasaccharide linker sequence is required for GAG synthesis
  • Heparan sulfate/heparin (HS-GAG) metabolism

Biological Process

  • glycosaminoglycan biosynthetic process
  • heparan sulfate proteoglycan biosynthetic process
  • glycosaminoglycan metabolic process
  • chondroitin sulfate biosynthetic process
  • heparin biosynthetic process

Molecular Function

  • magnesium ion binding
  • acetylglucosaminyltransferase activity
  • manganese ion binding
  • protein xylosyltransferase activity

Cellular Component

  • Golgi membrane
  • extracellular space
  • integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000017003
Coding exons
11
Length
17047
Individuals with no LoFs
125733
Homozygous LoFs
0
Heterozygous LoFs
14
Defined
125747
p
0.0000557
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.094005360.7460.00003565524
Missense (PolyPhen)136229.360.592942230
Synonymous-0.2662392341.020.00001591829
Loss of Function4.52634.80.1730.00000172368

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000580.000058rare
Ashkenazi Jewish0.000200.00020rare
East Asian0.0000540.000054rare
Finnish00.0absent
European (Non-Finnish)0.0000620.000062rare
South Asian0.0000650.000065rare
Other00.0absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec
0.131

Intolerance Scores

LoFtool
0.495
RVIS EVS
-0.48
RVIS percentile EVS
22.8

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
E
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.0742

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.