ARSL

Chr XXLR

arylsulfatase L

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

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.

Summary from RefSeq, OMIM, UniProt, Mechanism

Primary Disease Associations & Inheritance

Chondrodysplasia punctata, X-linked recessiveMIM #302950
XLR
0
Active trials
10
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.49
LOEUF
LOF*
Mechanism· G2P
Clinical SummaryARSL
🧬
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.
📖
GeneReview available — ARSL
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.49LOEUF
pLI 0.590
Z-score 2.98
OE 0.19 (0.090.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.95Z-score
OE missense 0.66 (0.580.75)
173 obs / 262.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.19 (0.090.49)
00.351.4
Missense OE0.66 (0.580.75)
00.61.4
Synonymous OE0.93
01.21.6
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

0 submitted variants 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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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