ARSL

Chr XXLR

arylsulfatase L

Also known as: ARSE, ASE, CDPX, CDPX1, CDPXR

NCBI Gene: 415ENSG00000157399UniProt: P51690OMIM: 300180

Arylsulfatase E localizes to the Golgi apparatus and exhibits arylsulfatase activity essential for correct cartilage and bone matrix composition during development. Mutations cause X-linked recessive chondrodysplasia punctata, characterized by abnormalities in cartilage and bone development. The pathogenic mechanism involves loss of function leading to defective sulfatase activity required for proper skeletal matrix formation.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismXLRLOEUF 0.491 OMIM phenotype
Clinical Summary— ARSL
🧬
Gene-Disease Validity (ClinGen)
X-linked chondrodysplasia punctata 1 · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.59) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
152 unique Pathogenic / Likely Pathogenic· 94 VUS of 500 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — ARSL
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.49LOEUF
pLI 0.590
Z-score 2.98
OE 0.19 (0.09–0.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.95Z-score
OE missense 0.66 (0.58–0.75)
173 obs / 262.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.19 (0.09–0.49)
0≤0.351.4
Missense OE0.66 (0.58–0.75)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 3 / 15.8Missense obs/exp: 173 / 262.0Syn Z: 0.61
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveARSL-related chondrodysplasia punctataLOFXLR
DN
0.6356th %ile
GOF
0.5563th %ile
LOF
0.3358th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic134
Likely Pathogenic18
VUS94
Likely Benign149
Benign32
Conflicting20
134
Pathogenic
18
Likely Pathogenic
94
VUS
149
Likely Benign
32
Benign
20
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
4
122
0
134
Likely Pathogenic
9
5
4
0
18
VUS
1
66
27
0
94
Likely Benign
1
13
42
93
149
Benign
2
9
11
10
32
Conflicting
—20
Total2197206103447

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

View in ClinVar →

Protein Context — Lollipop Plot

ARSL · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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
A novel frameshift deletion variant of ARSL associated with X-linked recessive chondrodysplasia punctata 1: a case report and literature review of prenatal, confirmed cases.
Zhou L et al.·BMC Med Genomics
2024Review
Prenatal Ultrasonographic Features Associated With ARSL and X-Linked Chondrodysplasia Punctata 1 (CDPX1): Literature Review and Case Series.
Broeren E et al.·Prenat Diagn
2024Review
[Molecular mechanism study of fetal nasal bone aplasia due to a frameshift variant of ARSL gene].
Zhu Y et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2026Case report
Binder Phenotype: Evaluating the Utility and Influence of Genetic Results on Parental Decision Making in Antenatally Diagnosed Cases.
Gupta S et al.·Am J Med Genet A
2026Cohort
Uniparental disomy as a mechanism for X-linked chondrodysplasia punctata.
Woods E et al.·Clin Dysmorphol
2022Functional
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