XYLT1

Chr 16AR

xylosyltransferase 1

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

NCBI Gene: 64131 ENSG00000103489 UniProt: Q86Y38 OMIM: 608124

This gene encodes xylosyltransferase 1, which catalyzes the first step in chondroitin sulfate and dermatan sulfate proteoglycan biosynthesis by transferring xylose to serine residues of core proteins. Biallelic mutations cause Desbuquois dysplasia 2, an autosomal recessive skeletal dysplasia, and can modify the severity of pseudoxanthoma elasticum. The gene is highly constrained against loss-of-function variants (pLI 0.92, LOEUF 0.34), reflecting its essential role in skeletal development and proteoglycan synthesis.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.342 OMIM phenotypes

Clinical Summary— XYLT1

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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.

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ClinVar Variants

27 unique Pathogenic / Likely Pathogenic· 311 VUS of 661 total submissions

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GeneReview available — XYLT1

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

0.59Z-score

OE missense 0.93 (0.86–1.00)

508 obs / 546.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.18 (0.10–0.34)

0≤0.351.4

Missense OE?0.93 (0.86–1.00)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 7 / 39.1Missense obs/exp: 508 / 546.5Syn Z: -1.62

ClinVar Variant Classifications

661 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21

Likely Pathogenic6

VUS311

Likely Benign238

Benign62

Conflicting8

Pathogenic

Likely Pathogenic

311

VUS

238

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	15	3	3	0	21
Likely Pathogenic	6	0	0	0	6
VUS	2	300	9	0	311
Likely Benign	0	11	65	162	238
Benign	0	7	39	16	62
Conflicting	—				8
Total	23	321	116	178	646

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

View in ClinVar →

58 pathogenic / likely-pathogenic (of 112) ClinVar copy-number / structural variants overlap XYLT1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →