XYLT2

Chr 17AR

xylosyltransferase 2

Also known as: PXYLT2, SOS, XT-II, XT2, xylT-II

NCBI Gene: 64132ENSG00000015532UniProt: Q9H1B5

The protein catalyzes the first step in proteoglycan biosynthesis by transferring xylose from UDP-xylose to serine residues on core proteins, initiating the synthesis of chondroitin sulfate, heparan sulfate, and dermatan sulfate chains. Autosomal recessive mutations cause spondyloocular syndrome and act as modifiers of pseudoxanthoma elasticum severity. The pathogenic mechanism involves disrupted proteoglycan synthesis due to deficient xylosyltransferase activity.

Summary from RefSeq, OMIM, UniProt

Primary Disease Associations & Inheritance

{Pseudoxanthoma elasticum, modifier of severity of}MIM #264800
AR
Spondyloocular syndromeMIM #605822
AR
0
Active trials
3
Pubs (1 yr)
14
P/LP submissions
0%
P/LP missense
0.34
LOEUF· LoF intol.
LOF
Mechanism· G2P
Clinical Summary— XYLT2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.93). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
13 unique Pathogenic / Likely Pathogenic· 193 VUS of 403 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.34LOEUF
pLI 0.926
Z-score 4.52
OE 0.17 (0.09–0.34)
Highly constrained

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

Missense Constraint
2.09Z-score
OE missense 0.75 (0.69–0.81)
400 obs / 536.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.17 (0.09–0.34)
0≤0.351.4
Missense OE0.75 (0.69–0.81)
0≤0.61.4
Synonymous OE1.02
0≤1.21.6
LoF obs/exp: 6 / 34.8Missense obs/exp: 400 / 536.3Syn Z: -0.27

ClinVar Variant Classifications

403 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic2
VUS193
Likely Benign171
Benign10
Conflicting8
11
Pathogenic
2
Likely Pathogenic
193
VUS
171
Likely Benign
10
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
7
0
11
Likely Pathogenic
2
0
0
0
2
VUS
0
184
8
1
193
Likely Benign
0
1
39
131
171
Benign
0
1
6
3
10
Conflicting
—8
Total618660135395

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

View in ClinVar →

Protein Context — Lollipop Plot

XYLT2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients