Desbuquois dysplasia 1

Summary

Desbuquois dysplasia 1 (MONDO:0009629) is a disease caused by CANT1 (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: CANT1 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 617

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Desbuquois dysplasia 1
Mondo ID	MONDO:0009629
OMIM	251450
UMLS	C4012146
MedGen	860583
GARD	0016451
Is cancer (heuristic)	no

Also known as: CANT1 Desbuquois dysplasia · DBQD1 · Desbuquois dysplasia 1 · Desbuquois dysplasia caused by mutation in CANT1 · Desbuquois dysplasia type 1

Data availability: 617 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 1

Related subtypes (1): Desbuquois dysplasia 2

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

600 retrieved; paginated sample, class counts are floors:

257 uncertain significance, 223 likely benign, 49 benign, 23 conflicting classifications of pathogenicity, 21 pathogenic, 11 benign/likely benign, 9 pathogenic/likely pathogenic, 7 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2426738	NC_000016.9:g.(?15758636)(17564653_?)del	ABCC1	Pathogenic	criteria provided, single submitter
1324008	NM_001159773.2(CANT1):c.71dup (p.Leu25fs)	CANT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
197369	NM_001159773.2(CANT1):c.836-9G>A	CANT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
277	5’UTR-exon 1 deletion (2703 bp)	CANT1	Pathogenic	no assertion criteria provided
278	NM_001159773.2(CANT1):c.734del (p.Pro245fs)	CANT1	Pathogenic	no assertion criteria provided
2780153	NM_001159773.2(CANT1):c.347_348del (p.Glu116fs)	CANT1	Pathogenic	criteria provided, multiple submitters, no conflicts
279	NM_001159773.2(CANT1):c.898C>T (p.Arg300Cys)	CANT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
281	NM_001159773.2(CANT1):c.909_910insGCCGC (p.Gln304fs)	CANT1	Pathogenic	no assertion criteria provided
2838791	NM_001159773.2(CANT1):c.188del (p.Arg63fs)	CANT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31013	NM_001159773.2(CANT1):c.902_906dup (p.Ser303fs)	CANT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31014	NM_001159773.2(CANT1):c.228dup (p.Trp77fs)	CANT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31015	NM_001159773.2(CANT1):c.277_278del (p.Leu93fs)	CANT1	Pathogenic	criteria provided, multiple submitters, no conflicts
31017	NM_001159773.2(CANT1):c.375G>C (p.Trp125Cys)	CANT1	Pathogenic	no assertion criteria provided
31018	NM_001159773.2(CANT1):c.676G>A (p.Val226Met)	CANT1	Pathogenic	criteria provided, multiple submitters, no conflicts
31019	NM_001159773.2(CANT1):c.1079C>A (p.Ala360Asp)	CANT1	Pathogenic	no assertion criteria provided
3366599	NM_001159773.2(CANT1):c.467C>T (p.Ser156Phe)	CANT1	Pathogenic	criteria provided, single submitter
41426	NM_001159773.2(CANT1):c.-147+1G>A	CANT1	Pathogenic	no assertion criteria provided
452497	NM_001159773.2(CANT1):c.734C>T (p.Pro245Leu)	CANT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
808323	NM_001159773.2(CANT1):c.643G>A (p.Glu215Lys)	CANT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3657470	NM_022166.4(XYLT1):c.1629del (p.Asp543fs)	LOC102723692	Pathogenic	criteria provided, single submitter
541800	NC_000016.10:g.(?17108675)(17470816_?)del	LOC130058564	Pathogenic	criteria provided, single submitter
127236	NM_022166.4(XYLT1):c.439C>T (p.Arg147Ter)	LOC130058566	Pathogenic	criteria provided, single submitter
1073304	NC_000016.9:g.(?17564281)(17564653_?)del	XYLT1	Pathogenic	criteria provided, single submitter
1977942	NM_022166.4(XYLT1):c.2462G>A (p.Trp821Ter)	XYLT1	Pathogenic	criteria provided, single submitter
2137795	NM_022166.4(XYLT1):c.2026C>T (p.Arg676Ter)	XYLT1	Pathogenic	criteria provided, single submitter
2734363	NM_022166.4(XYLT1):c.-110_280del (p.Met1_Gln94del)	XYLT1	Pathogenic	criteria provided, single submitter
2794457	NM_022166.4(XYLT1):c.1510G>T (p.Glu504Ter)	XYLT1	Pathogenic	criteria provided, single submitter
3243529	NC_000016.9:g.(?17292049)(17451927_?)del	XYLT1	Pathogenic	criteria provided, single submitter
452883	NM_022166.4(XYLT1):c.2122_2123del (p.Ala708fs)	XYLT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4715309	NM_022166.4(XYLT1):c.1245del (p.Trp416fs)	XYLT1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 5 · 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
CANT1	Definitive	Autosomal recessive	Desbuquois dysplasia 1	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CANT1	Orphanet:1425	Desbuquois syndrome
CANT1	Orphanet:647676	Multiple epiphyseal dysplasia type 7
XYLT1	Orphanet:1425	Desbuquois syndrome
XYLT1	Orphanet:370930	XYLT1-CDG
ABCC1	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CANT1	HGNC:19721	ENSG00000171302	Q8WVQ1	Soluble calcium-activated nucleotidase 1	gencc,clinvar
XYLT1	HGNC:15516	ENSG00000103489	Q86Y38	Xylosyltransferase 1	clinvar
ABCC1	HGNC:51	ENSG00000103222	P33527	Multidrug resistance-associated protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CANT1	Soluble calcium-activated nucleotidase 1	Calcium-dependent nucleotidase with a preference for UDP.
XYLT1	Xylosyltransferase 1	Catalyzes the first step in the biosynthesis of chondroitin sulfate and dermatan sulfate proteoglycans, such as DCN.
ABCC1	Multidrug resistance-associated protein 1	Mediates export of organic anions and drugs from the cytoplasm.

Protein-family classification

Druggable: 3 · 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
Transporter	1	25.9×	0.038
Enzyme (other)	2	8.0×	0.038

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CANT1	Enzyme (other)	yes	3.6.1.5	Apyrase, Apyrase_sf
XYLT1	Enzyme (other)	yes	2.4.2.26	Glyco_trans_14, XylT_C, XYLT
ABCC1	Transporter	yes	7.6.2.2	ABC_transporter-like_ATP-bd, AAA+_ATPase, MRP

Expression context

Cohort genes with no expression data: 0.

3 cohort genes 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
colonic mucosa	1
mucosa of transverse colon	1
pancreatic ductal cell	1
cartilage tissue	1
hair follicle	1
tibia	1
lower esophagus	1
lower esophagus mucosa	1
lower esophagus muscularis layer	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CANT1	280	ubiquitous	marker	pancreatic ductal cell, mucosa of transverse colon, colonic mucosa
XYLT1	272	broad	marker	tibia, cartilage tissue, hair follicle
ABCC1	134	ubiquitous	marker	lower esophagus mucosa, lower esophagus, lower esophagus muscularis layer

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ABCC1	3,018
CANT1	1,231
XYLT1	704

Intra-cohort edges

A	B	Sources
CANT1	XYLT1	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
XYLT1	Q86Y38	9
ABCC1	P33527	5
CANT1	Q8WVQ1	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 28. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Metabolism of porphyrins	1	475.8×	0.020	ABCC1
Transport of RCbl within the body	1	475.8×	0.020	ABCC1
NFE2L2 regulating MDR associated enzymes	1	475.8×	0.020	ABCC1
Heme degradation	1	271.9×	0.021	ABCC1
Cobalamin (Cbl, vitamin B12) transport and metabolism	1	211.5×	0.021	ABCC1
Synthesis of Leukotrienes (LT) and Eoxins (EX)	1	190.3×	0.021	ABCC1
Arachidonate metabolism	1	190.3×	0.021	ABCC1
Paracetamol ADME	1	141.0×	0.024	ABCC1
Glycosaminoglycan-protein linkage region biosynthesis	1	131.3×	0.024	XYLT1
Nuclear events mediated by NFE2L2	1	112.0×	0.025	ABCC1
Sphingolipid de novo biosynthesis	1	95.2×	0.027	ABCC1
Drug ADME	1	76.1×	0.031	ABCC1
Cytoprotection by HMOX1	1	61.4×	0.033	ABCC1
Metabolism of water-soluble vitamins and cofactors	1	60.4×	0.033	ABCC1
Sphingolipid metabolism	1	56.0×	0.033	ABCC1
Cellular response to chemical stress	1	47.6×	0.036	ABCC1
Fatty acid metabolism	1	43.8×	0.036	ABCC1
ABC-family protein mediated transport	1	40.5×	0.036	ABCC1
KEAP1-NFE2L2 pathway	1	40.1×	0.036	ABCC1
Metabolism of vitamins and cofactors	1	38.8×	0.036	ABCC1
Cellular responses to stress	1	12.3×	0.106	ABCC1
Metabolism of lipids	1	10.5×	0.112	ABCC1
Cellular responses to stimuli	1	10.5×	0.112	ABCC1
Innate Immune System	1	8.5×	0.128	CANT1
Transport of small molecules	1	8.4×	0.128	ABCC1
Neutrophil degranulation	1	7.7×	0.134	CANT1
Immune System	1	4.3×	0.222	CANT1
Metabolism	1	3.9×	0.237	ABCC1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
proteoglycan biosynthetic process	2	561.7×	3e-04	CANT1, XYLT1
antigen processing and presentation of lipid antigen via MHC class Ib	1	5617.3×	0.002	ABCC1
cyclic nucleotide transport	1	5617.3×	0.002	ABCC1
sphingolipid translocation	1	5617.3×	0.002	ABCC1
intracellular nitrogen homeostasis	1	5617.3×	0.002	ABCC1
pigment accumulation	1	2808.7×	0.004	ABCC1
granuloma formation	1	1872.4×	0.005	ABCC1
glutathione transmembrane transport	1	1404.3×	0.005	ABCC1
neural tissue regeneration	1	1404.3×	0.005	ABCC1
glycosaminoglycan-protein linkage region biosynthetic process	1	1404.3×	0.005	XYLT1
glucocorticoid metabolic process	1	936.2×	0.005	ABCC1
amygdala development	1	936.2×	0.005	ABCC1
NK T cell activation	1	936.2×	0.005	ABCC1
carboxylic acid transmembrane transport	1	936.2×	0.005	ABCC1
xenobiotic transport across blood-brain barrier	1	936.2×	0.005	ABCC1
leukotriene transport	1	802.5×	0.005	ABCC1
lymphocyte migration	1	802.5×	0.005	ABCC1
cobalamin transport	1	624.1×	0.005	ABCC1
response to fluid shear stress	1	624.1×	0.005	ABCC1
export across plasma membrane	1	561.7×	0.005	ABCC1
heme catabolic process	1	510.7×	0.005	ABCC1
amyloid-beta metabolic process	1	510.7×	0.005	ABCC1
ossification involved in bone maturation	1	468.1×	0.005	XYLT1
hydrogen peroxide biosynthetic process	1	468.1×	0.005	ABCC1
endothelium development	1	432.1×	0.005	ABCC1
leukotriene metabolic process	1	432.1×	0.005	ABCC1
leukotriene biosynthetic process	1	432.1×	0.005	ABCC1
endothelial cell apoptotic process	1	432.1×	0.005	ABCC1
transepithelial transport	1	401.2×	0.006	ABCC1
inflammatory response to antigenic stimulus	1	312.1×	0.007	ABCC1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ABCC1	RIMONABANT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ABCC1	23	4
CANT1	0	0
XYLT1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RIMONABANT	4	ABCC1
VINBLASTINE	4	ABCC1
CYCLOSPORINE	4	ABCC1
DAUNORUBICIN	4	ABCC1
ETRAVIRINE	4	ABCC1
BENZBROMARONE	4	ABCC1
ESTRONE SULFURIC ACID	4	ABCC1
DOXORUBICIN	4	ABCC1
MITOXANTRONE	4	ABCC1
INDOMETHACIN	4	ABCC1
IVERMECTIN	4	ABCC1
VERAPAMIL	4	ABCC1
VINCRISTINE	4	ABCC1
VALSPODAR	3	ABCC1
TARIQUIDAR	3	ABCC1
QUERCETIN	3	ABCC1
DEXVERAPAMIL	2	ABCC1
VEDROPREVIR	2	ABCC1
VERLUKAST	2	ABCC1
BIRICODAR	2	ABCC1
CLESACOSTAT	2	ABCC1
BMS-754807	2	ABCC1
KAEMPFEROL	1	ABCC1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ABCC1	459	Binding:270, Functional:166, ADMET:23

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CANT1	3.6.1.5	apyrase
XYLT1	2.4.2.26	protein xylosyltransferase
ABCC1	7.6.2.2, 7.6.2.3	ABC-type xenobiotic transporter, ABC-type glutathione-S-conjugate transporter

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
ABCC1	459

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

23 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.

Compound	Max phase	Cohort target (bioactivity)
RIMONABANT	4	ABCC1
VINBLASTINE	4	ABCC1
CYCLOSPORINE	4	ABCC1
DAUNORUBICIN	4	ABCC1
ETRAVIRINE	4	ABCC1
BENZBROMARONE	4	ABCC1
ESTRONE SULFURIC ACID	4	ABCC1
DOXORUBICIN	4	ABCC1
MITOXANTRONE	4	ABCC1
INDOMETHACIN	4	ABCC1
IVERMECTIN	4	ABCC1
VERAPAMIL	4	ABCC1
VINCRISTINE	4	ABCC1
VALSPODAR	3	ABCC1
TARIQUIDAR	3	ABCC1
QUERCETIN	3	ABCC1
DEXVERAPAMIL	2	ABCC1
VEDROPREVIR	2	ABCC1
VERLUKAST	2	ABCC1
BIRICODAR	2	ABCC1
CLESACOSTAT	2	ABCC1
BMS-754807	2	ABCC1
KAEMPFEROL	1	ABCC1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ABCC1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	CANT1, XYLT1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CANT1	0	—
XYLT1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.