XYLT1

Chr 16AR

xylosyltransferase 1

Also known as: DBQD2, PXYLT1, XT-I, XT1, XTI, XYLTI, xylT-I

NCBI Gene: 64131ENSG00000103489UniProt: Q86Y38

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]

Primary Disease Associations & Inheritance

{Pseudoxanthoma elasticum, modifier of severity of}MIM #264800
AR
Desbuquois dysplasia 2MIM #615777
AR
683
ClinVar variants
59
Pathogenic / LP
0.92
pLI score· haploinsufficient
0
Active trials
Clinical Summary— XYLT1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.92). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
59 Pathogenic / Likely Pathogenic· 319 VUS of 683 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.34LOEUF
pLI 0.924
Z-score 4.76
OE 0.18 (0.10–0.34)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.59Z-score
OE missense 0.93 (0.86–1.00)
508 obs / 546.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.18 (0.10–0.34)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.86–1.00)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.14
0≤1.21.6
LoF obs/exp: 7 / 39.1Missense obs/exp: 508 / 546.5Syn Z: -1.62

ClinVar Variant Classifications

683 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic41
Likely Pathogenic18
VUS319
Likely Benign236
Benign62
Conflicting7
41
Pathogenic
18
Likely Pathogenic
319
VUS
236
Likely Benign
62
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
1
36
0
41
Likely Pathogenic
3
0
15
0
18
VUS
1
289
29
0
319
Likely Benign
0
9
67
160
236
Benign
0
7
39
16
62
Conflicting
—7
Total8306186176683

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

XYLT1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

XYLT1-related Desbuquois dysplasia

strong
ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. DisordersSkeletal
G2P ↗
splice donor variantframeshift variantstop gainedmissense variantregulatory region variantshort tandem repeat change

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

{Pseudoxanthoma elasticum, modifier of severity of}

MIM #264800

Molecular basis of disorder known

Autosomal recessive

Desbuquois dysplasia 2

MIM #615777

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — XYLT1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
GGC Repeat Expansion and Exon 1 Methylation of XYLT1 Is a Common Pathogenic Variant in Baratela-Scott Syndrome.
LaCroix AJ et al.·Am J Hum Genet
2019
Complete and partial XYLT1 deletion in a patient with neonatal short limb skeletal dysplasia.
van Koningsbruggen S et al.·Am J Med Genet A
2016
Clinical and Genetic Insights into Desbuquois Dysplasia: Review of 111 Case Reports.
Piwar H et al.·Int J Mol Sci
2024Review
Novel compound heterozygous variants in XYLT1 gene caused Desbuquois dysplasia type 2 in an aborted fetus: a case report.
Rajabi F et al.·BMC Pediatr
2022Case report
Prenatal Diagnosis, Ultrasound Findings, and Follow-Up Evaluation of 16p13.11 Deletion and Duplication Syndromes: Preliminary Assessment of Fetal Genotype-Phenotype.
Luo X et al.·J Clin Lab Anal
2025Natural history
Abnormal Proteoglycan Synthesis Due to Gene Defects Causes Skeletal Diseases with Overlapping Phenotypes.
Taylan F et al.·Horm Metab Res
2016Review
The missing "link": an autosomal recessive short stature syndrome caused by a hypofunctional XYLT1 mutation.
Schreml J et al.·Hum Genet
2014Functional
Further Defining the Phenotypic Spectrum of B3GAT3 Mutations and Literature Review on Linkeropathy Syndromes.
Ritelli M et al.·Genes (Basel)
2019Review
Genetic diagnosis of acute aortic dissection in South China Han population using next-generation sequencing.
Zheng J et al.·Int J Legal Med
2018
A novel gene (FAM20B encoding glycosaminoglycan xylosylkinase) for neonatal short limb dysplasia resembling Desbuquois dysplasia.
Kuroda Y et al.·Clin Genet
2019Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools