Desbuquois dysplasia 2

Summary

Desbuquois dysplasia 2 (MONDO:0014343) is a disease caused by XYLT1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: XYLT1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 37

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Desbuquois dysplasia 2
Mondo ID	MONDO:0014343
OMIM	615777
UMLS	C4014294
MedGen	862731
GARD	0016466
Is cancer (heuristic)	no

Also known as: Baratela-Scott syndrome · DBQD2 · Desbuquois dysplasia 2 · Desbuquois dysplasia caused by mutation in XYLT1 · Desbuquois dysplasia type 2 · XYLT1 Desbuquois dysplasia

Data availability: 37 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone development disease › osteochondrodysplasia › Desbuquois dysplasia › Desbuquois dysplasia 2

Related subtypes (1): Desbuquois dysplasia 1

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

37 retrieved; paginated sample, class counts are floors:

13 benign, 11 pathogenic, 7 uncertain significance, 2 benign/likely benign, 2 likely pathogenic, 1 likely benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1224360	NM_022166.4(XYLT1):c.1651C>T (p.Arg551Cys)	LOC102723692	Pathogenic	criteria provided, multiple submitters, no conflicts
426319	NM_022166.4(XYLT1):c.1730_1733dup (p.Asp578delinsGluTer)	LOC102723692	Pathogenic	criteria provided, single submitter
127236	NM_022166.4(XYLT1):c.439C>T (p.Arg147Ter)	LOC130058566	Pathogenic	criteria provided, single submitter
127234	NM_022166.4(XYLT1):c.1441C>T (p.Arg481Trp)	XYLT1	Pathogenic	no assertion criteria provided
127237	NM_022166.4(XYLT1):c.276dup (p.Pro93fs)	XYLT1	Pathogenic	no assertion criteria provided
127239	NM_022166.4(XYLT1):c.1290-2A>C	XYLT1	Pathogenic	no assertion criteria provided
3339666	NM_022166.4(XYLT1):c.1108C>T (p.Gln370Ter)	XYLT1	Pathogenic	criteria provided, single submitter
619181	NM_022166.4(XYLT1):c.319G>T (p.Gly107Ter)	XYLT1	Pathogenic	no assertion criteria provided
619182	NW_019805500.1:g.472169CCG[(100-833)]	XYLT1	Pathogenic	no assertion criteria provided
619183	NM_022166.4(XYLT1):c.281_306del (p.Gln94fs)	XYLT1	Pathogenic	no assertion criteria provided
619184	NM_022166.4(XYLT1):c.1290-1G>A	XYLT1	Pathogenic	no assertion criteria provided
3237504	NM_022166.4(XYLT1):c.578del (p.Leu192_Leu193insTer)	LOC130058566	Likely pathogenic	criteria provided, single submitter
3384002	NM_022166.4(XYLT1):c.2169dup (p.Val724fs)	XYLT1	Likely pathogenic	criteria provided, single submitter
2053799	NM_022166.4(XYLT1):c.2768G>A (p.Gly923Asp)	XYLT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
127235	NM_022166.4(XYLT1):c.1792C>T (p.Arg598Cys)	LOC102723692	Uncertain significance	criteria provided, single submitter
4292607	NM_022166.4(XYLT1):c.1764+1555G>C	LOC102723692	Uncertain significance	criteria provided, single submitter
573227	NM_022166.4(XYLT1):c.1756C>T (p.Arg586Cys)	LOC102723692	Uncertain significance	criteria provided, multiple submitters, no conflicts
2438630	NM_022166.4(XYLT1):c.962T>G (p.Met321Arg)	XYLT1	Uncertain significance	criteria provided, single submitter
2584952	NM_022166.4(XYLT1):c.2267T>G (p.Phe756Cys)	XYLT1	Uncertain significance	criteria provided, single submitter
3578690	NM_022166.4(XYLT1):c.380C>T (p.Pro127Leu)	XYLT1	Uncertain significance	criteria provided, single submitter
808014	NM_022166.4(XYLT1):c.1216C>T (p.Arg406Trp)	XYLT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1168621	NM_022166.4(XYLT1):c.1989C>T (p.Ala663=)	LOC102723692	Benign	criteria provided, multiple submitters, no conflicts
1170431	NM_022166.4(XYLT1):c.1994C>T (p.Thr665Met)	LOC102723692	Benign	criteria provided, multiple submitters, no conflicts
127238	NM_022166.4(XYLT1):c.1588-3C>T	LOC102723692	Likely benign	criteria provided, multiple submitters, no conflicts
1164905	NM_022166.4(XYLT1):c.1077C>T (p.His359=)	XYLT1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1166614	NM_022166.4(XYLT1):c.913+9C>T	XYLT1	Benign	criteria provided, multiple submitters, no conflicts
1167692	NM_022166.4(XYLT1):c.2631C>T (p.Pro877=)	XYLT1	Benign	criteria provided, multiple submitters, no conflicts
1168620	NM_022166.4(XYLT1):c.2675G>A (p.Arg892Gln)	XYLT1	Benign	criteria provided, multiple submitters, no conflicts
1168622	NM_022166.4(XYLT1):c.668C>G (p.Ala223Gly)	XYLT1	Benign	criteria provided, multiple submitters, no conflicts
1169572	NM_022166.4(XYLT1):c.2515G>A (p.Val839Ile)	XYLT1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
XYLT1	Strong	Autosomal recessive	Desbuquois dysplasia 2	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
XYLT1	Orphanet:1425	Desbuquois syndrome
XYLT1	Orphanet:370930	XYLT1-CDG

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
XYLT1	HGNC:15516	ENSG00000103489	Q86Y38	Xylosyltransferase 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
XYLT1	Xylosyltransferase 1	Catalyzes the first step in the biosynthesis of chondroitin sulfate and dermatan sulfate proteoglycans, such as DCN.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
XYLT1	Enzyme (other)	yes	2.4.2.26	Glyco_trans_14, XylT_C, XYLT

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cartilage tissue	1
hair follicle	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
XYLT1	272	broad	marker	tibia, cartilage tissue, hair follicle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
XYLT1	704

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
XYLT1	Q86Y38	9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Glycosaminoglycan-protein linkage region biosynthesis	1	393.8×	0.003	XYLT1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
glycosaminoglycan-protein linkage region biosynthetic process	1	4213.0×	0.002	XYLT1
ossification involved in bone maturation	1	1404.3×	0.002	XYLT1
glycosaminoglycan biosynthetic process	1	842.6×	0.002	XYLT1
proteoglycan biosynthetic process	1	842.6×	0.002	XYLT1
chondroitin sulfate proteoglycan biosynthetic process	1	624.1×	0.002	XYLT1
heparan sulfate proteoglycan biosynthetic process	1	561.7×	0.002	XYLT1
embryonic skeletal system development	1	391.9×	0.003	XYLT1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
XYLT1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
XYLT1	2.4.2.26	protein xylosyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	XYLT1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
XYLT1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.