Chondrodysplasia punctata, brachytelephalangic, autosomal

Summary

Chondrodysplasia punctata, brachytelephalangic, autosomal (MONDO:0011238) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 318

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	chondrodysplasia punctata, brachytelephalangic, autosomal
Mondo ID	MONDO:0011238
OMIM	602497
UMLS	C1844853
MedGen	337102
GARD	0015347
Is cancer (heuristic)	no

Also known as: chondrodysplasia punctata, brachytelephalangic, autosomal

Data availability: 318 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › autosomal dominant chondrodysplasia punctata › chondrodysplasia punctata, brachytelephalangic, autosomal

Related subtypes (1): chondrodysplasia punctata, tibial-metacarpal type

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

318 retrieved; paginated sample, class counts are floors:

182 likely benign, 61 uncertain significance, 27 conflicting classifications of pathogenicity, 21 benign, 13 benign/likely benign, 9 pathogenic, 5 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2422194	NC_000023.10:g.(?2835825)(2878441_?)del	ARSD	Pathogenic	criteria provided, single submitter
1683207	NM_000047.3(ARSL):c.74del (p.Leu25fs)	ARSL	Pathogenic	criteria provided, single submitter
2138468	NM_000047.3(ARSL):c.1618C>T (p.Arg540Ter)	ARSL	Pathogenic	criteria provided, single submitter
2709852	NM_000047.3(ARSL):c.131_140del (p.Met44fs)	ARSL	Pathogenic	criteria provided, single submitter
3244441	NC_000023.10:g.(?2852873)(2878441_?)del	ARSL	Pathogenic	criteria provided, single submitter
3721569	NM_000047.3(ARSL):c.30T>A (p.Cys10Ter)	ARSL	Pathogenic	criteria provided, single submitter
4847304	NM_000047.3(ARSL):c.983G>A (p.Trp328Ter)	ARSL	Pathogenic	criteria provided, single submitter
832204	NC_000023.11:g.(?2934812)(2958455_?)del	ARSL	Pathogenic	criteria provided, single submitter
851645	NM_000047.3(ARSL):c.1158del (p.Ile387fs)	ARSL	Pathogenic	criteria provided, single submitter
1066074	NM_000047.3(ARSL):c.217G>A (p.Gly73Ser)	ARSL	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1683205	NM_000047.3(ARSL):c.185+1G>A	ARSL	Likely pathogenic	criteria provided, single submitter
2694715	NM_000047.3(ARSL):c.24-2A>G	ARSL	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2717967	NM_000047.3(ARSL):c.23+1G>C	ARSL	Likely pathogenic	criteria provided, single submitter
3244452	NC_000023.10:g.(?2873437)(2876496_?)dup	ARSL	Likely pathogenic	criteria provided, single submitter
11529	NM_000047.3(ARSL):c.1743G>A (p.Trp581Ter)	ARSL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1224384	NM_000047.3(ARSL):c.1163G>A (p.Arg388His)	ARSL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1683178	NM_000047.3(ARSL):c.1597G>A (p.Val533Met)	ARSL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1683181	NM_000047.3(ARSL):c.1405C>T (p.Arg469Trp)	ARSL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1683184	NM_000047.3(ARSL):c.1199C>T (p.Pro400Leu)	ARSL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1683189	NM_000047.3(ARSL):c.1015G>A (p.Val339Met)	ARSL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1683191	NM_000047.3(ARSL):c.987G>A (p.Met329Ile)	ARSL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1683192	NM_000047.3(ARSL):c.949G>A (p.Gly317Arg)	ARSL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1683193	NM_000047.3(ARSL):c.934G>A (p.Gly312Arg)	ARSL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1683197	NM_000047.3(ARSL):c.728T>C (p.Phe243Ser)	ARSL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1683203	NM_000047.3(ARSL):c.280C>T (p.Leu94Phe)	ARSL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1683209	NM_000047.3(ARSL):c.58G>A (p.Ala20Thr)	ARSL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1683210	NM_000047.3(ARSL):c.24-1G>A	ARSL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1702419	NM_000047.3(ARSL):c.1419A>G (p.Thr473=)	ARSL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1702461	NM_000047.3(ARSL):c.1629G>A (p.Gln543=)	ARSL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2056469	NM_000047.3(ARSL):c.1468G>A (p.Gly490Ser)	ARSL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ARSL	Orphanet:79345	Brachytelephalangic chondrodysplasia punctata

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ARSD	HGNC:717	ENSG00000006756	P51689	Arylsulfatase D	clinvar
ARSL	HGNC:719	ENSG00000157399	P51690	Arylsulfatase L	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ARSL	Arylsulfatase L	Exhibits arylsulfatase activity towards the artificial substrate 4-methylumbelliferyl sulfate.

Protein-family classification

Druggable: 2 · 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
Phosphatase	2	83.9×	1e-04

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ARSD	Phosphatase	yes		Sulfatase_N, Alkaline_phosphatase_core_sf, Sulfatase_CS
ARSL	Phosphatase	yes		Sulfatase_N, Alkaline_phosphatase_core_sf, Sulfatase_CS

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cardia of stomach	1
pylorus	1
renal medulla	1
body of pancreas	1
liver	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ARSD	263	ubiquitous	marker	renal medulla, cardia of stomach, pylorus
ARSL	174	broad	marker	body of pancreas, liver, right lobe of liver

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ARSL	1,114
ARSD	956

Intra-cohort edges

A	B	Sources
ARSD	ARSL	biogrid_interaction, intact

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ARSD	P51689	92.71
ARSL	P51690	92.57

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
The activation of arylsulfatases	2	878.5×	1e-05	ARSD, ARSL
Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	2	423.0×	2e-05	ARSD, ARSL
Glycosphingolipid metabolism	2	300.5×	3e-05	ARSD, ARSL
Glycosphingolipid catabolism	2	292.8×	3e-05	ARSD, ARSL
Sphingolipid metabolism	2	167.9×	6e-05	ARSD, ARSL
Metabolism of lipids	2	31.6×	0.002	ARSD, ARSL
Post-translational protein modification	2	19.2×	0.003	ARSD, ARSL
Metabolism of proteins	2	12.4×	0.007	ARSD, ARSL
Metabolism	2	11.6×	0.007	ARSD, ARSL

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
skeletal system development	1	125.8×	0.008	ARSL

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
ARSD	0	0
ARSL	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	0
D	Druggable family + AlphaFold only, no drug	2	ARSD, ARSL
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)
ARSD	0	—
ARSL	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.