ARSA

Chr 22AR

arylsulfatase A

Also known as: ASA, MLD

NCBI Gene: 410ENSG00000100299UniProt: O43681OMIM: 607574

The protein hydrolyzes cerebroside sulfate to cerebroside and sulfate, functioning as a lysosomal enzyme essential for sulfatide metabolism. Mutations cause metachromatic leukodystrophy, a progressive demyelinating disease that presents with neurological deterioration and is ultimately fatal. This condition follows autosomal recessive inheritance.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.341 OMIM phenotype
Clinical Summary— ARSA
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Gene-Disease Validity (ClinGen)
metachromatic leukodystrophy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
92 unique Pathogenic / Likely Pathogenic· 89 VUS of 300 total submissions
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.34LOEUF
pLI 0.000
Z-score 0.40
OE 0.90 (0.62–1.34)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.38Z-score
OE missense 0.94 (0.85–1.03)
298 obs / 317.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.90 (0.62–1.34)
0≤0.351.4
Missense OE0.94 (0.85–1.03)
0≤0.61.4
Synonymous OE1.02
0≤1.21.6
LoF obs/exp: 18 / 19.9Missense obs/exp: 298 / 317.0Syn Z: -0.16
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveARSA-related arylsulfatase A deficiencyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6356th %ile
GOF
0.6051th %ile
LOF
0.3164th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

300 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic41
Likely Pathogenic51
VUS89
Likely Benign101
Conflicting2
41
Pathogenic
51
Likely Pathogenic
89
VUS
101
Likely Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
5
20
0
41
Likely Pathogenic
15
34
2
0
51
VUS
0
74
8
7
89
Likely Benign
0
1
50
50
101
Benign
0
0
0
0
0
Conflicting
—2
Total311148057284

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

View in ClinVar →

Protein Context — Lollipop Plot

ARSA · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
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
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Fetal Aberrant Subclavian Artery (ARSA): flow dynamics and its impact on fetal development assessed by doppler ultrasonography.
Bestel M et al.·Rev Bras Ginecol Obstet
2026Open Access
Aberrant right subclavian artery (ARSA) presenting with esophageal pseudo-neoplastic symptoms, dyspepsia, and hemodynamic findings.
Mirzaei S et al.·Radiol Case Rep
2026Open Access
ARSA Variants Associated With Cognitive Decline and Long-Term Preservation of Motor Function in Metachromatic Leukodystrophy.
Beerepoot S et al.·J Inherit Metab Dis
2025Open Access
Nucleotide- and metalloid-driven conformational changes in the arsenite efflux ATPase ArsA.
Mahajan S et al.·Proc Natl Acad Sci U S A
2025Open Access
Cross-species efficacy of AAV-mediated ARSA replacement for metachromatic leukodystrophy.
Ramachandran S et al.·J Clin Invest
2025Open Access
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