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ARSA

arylsulfatase A

The ARSA gene provides instructions for making the arylsulfatase A enzyme, which plays a critical role in cellular waste processing within lysosomes. The ARSA gene encodes an enzyme essential for breaking down specific fatty substances called sulfatides, particularly abundant in the nervous system.

Chromosome 22q13.33 Autosomal recessive HGNC:713 Tier C
ARSA 22q13.33 p arm q arm 22

ARSA is located on the long (q) arm of chromosome 22, at band 22q13.33. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 22 in the library →

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Clinical tests that include this

Carrier Screening panel
ARSA is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions
Newborn Genetic Screening panel
ARSA is 1 of 258 genes on this panel
Genomic newborn screening for actionable paediatric conditions

Overview

The ARSA gene provides the genetic blueprint for an enzyme called arylsulfatase A. This enzyme is primarily active within lysosomes, which are cellular organelles responsible for breaking down and recycling waste products. Arylsulfatase A is vital for the proper processing of sulfatides, a type of fat molecule important for cell membranes, especially in the nervous system.

What the gene does

The arylsulfatase A enzyme, encoded by the ARSA gene, functions within lysosomes, acting as a crucial component of the cell's recycling machinery. Its primary role involves breaking down sulfatides, which are complex fatty substances (a subgroup of sphingolipids). Sulfatides are particularly concentrated in the myelin sheath, a fatty insulation that surrounds nerve fibres and is essential for rapid nerve signal transmission. By metabolising these sulfatides, arylsulfatase A prevents their accumulation. When ARSA activity is significantly reduced, sulfatides build up to toxic levels, especially in the white matter of the brain, leading to cellular dysfunction and neurological problems.

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Chromosome location

The ARSA gene is located on chromosome 22. Specifically, it can be found at position 22q13.33, which refers to the long (q) arm of chromosome 22, in region 13, band 33.

Protein structure

The ARSA gene codes for a protein that is 507 amino acids long. Domain architecture has not been experimentally characterised in detail for this protein.

Key variants

Variations within the ARSA gene can alter the function of the arylsulfatase A enzyme. Over 110 different genetic changes in the ARSA gene have been identified that are associated with a range of clinical presentations, primarily affecting enzyme activity.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for ARSA.
View all on ClinVar →

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.116G>A
single nucleotide variant
 p.Gly39Asp Pathogenic/Likely pathogenic ★★☆☆ Metachromatic leukodystrophy
c.1399C>T
single nucleotide variant
 p.Gln467Ter Pathogenic/Likely pathogenic ★★☆☆ Metachromatic leukodystrophy
c.427T>C
single nucleotide variant
 p.Phe143Leu Pathogenic/Likely pathogenic ★★☆☆ Metachromatic leukodystrophy
c.475C>T
single nucleotide variant
 p.Gln159Ter Pathogenic ★★☆☆ Metachromatic leukodystrophy
c.586del
Deletion
 p.Leu196fs Pathogenic/Likely pathogenic ★★☆☆ Metachromatic leukodystrophy
c.61del
Deletion
 p.Arg21fs Pathogenic/Likely pathogenic ★★☆☆ Metachromatic leukodystrophy
c.737_744dup
Duplication
 p.Phe249fs Pathogenic/Likely pathogenic ★★☆☆ Metachromatic leukodystrophy
c.868_873del
Deletion
 p.Arg290_Met291del Pathogenic/Likely pathogenic ★★☆☆ Lysosomal storage disease
c.907G>A
single nucleotide variant
 p.Gly303Arg Pathogenic/Likely pathogenic ★★☆☆ Metachromatic leukodystrophy
c.93C>G
single nucleotide variant
 p.Asp31Glu Pathogenic/Likely pathogenic ★★☆☆ Metachromatic leukodystrophy

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Pathogenic variants in the ARSA gene are primarily associated with Metachromatic leukodystrophy. This is an inherited metabolic disorder where the body cannot properly break down sulfatides, leading to their toxic accumulation and progressive damage to the nervous system.

Inheritance pattern

Conditions caused by pathogenic ARSA variants typically follow autosomal recessive inheritance.

♀ Carrier parent 1 altered copy ♂ Carrier parent 1 altered copy Affected Carrier Carrier Unaffected Affected Carrier Unaffected Circles = females · Squares = males

When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.

Carrier frequency by population How common is heterozygous ARSA carrier status across ancestry groups?

UK clinical status

The ARSA gene is included in several NHS England Genomic Medicine Service national genomic test directories, indicating its clinical significance in the UK. It is a 'green' gene on panels for conditions such as Inherited white matter disorders, Leukodystrophy, adult onset, Hereditary ataxia, and Lysosomal storage disorder, among others. This signifies there is strong evidence for a gene-disease association and it is routinely tested.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Dystonia, chorea or related movement disorder, childhood onset · R57 NHS GMS → Fetal anomalies · R21 NHS GMS → Hereditary neuropathy or pain disorder · R78 NHS GMS → Leukodystrophy, adult onset · R62 NHS GMS → Likely inborn error of metabolism · R98 NHS GMS → Lysosomal storage disorder · R276 NHS GMS → Ataxia and cerebellar anomalies - childhood onset NHS GMS → DDG2P NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the main function of the ARSA gene?

The ARSA gene provides instructions for making the arylsulfatase A enzyme. This enzyme works in lysosomes to break down fatty substances called sulfatides, which are important components of cell membranes, particularly in the nervous system.

What happens if the ARSA gene doesn't work correctly?

If the ARSA gene has pathogenic variants, the arylsulfatase A enzyme's activity can be significantly reduced. This leads to the accumulation of sulfatides, primarily in the brain's white matter, causing damage to nerve cells and leading to conditions like metachromatic leukodystrophy.

Is metachromatic leukodystrophy inherited?

Yes, metachromatic leukodystrophy, which is caused by pathogenic variants in the ARSA gene, is inherited in an autosomal recessive pattern. This means an individual must inherit two copies of the pathogenic variant (one from each parent) to develop the condition.

References

  1. Shukla P, Vasisht S, Srivastava R. Molecular and structural analysis of metachromatic leukodystrophy patients in Indian population. Journal of the neurological sciences. 2011. PMID: 21167507
  2. Lugowska A, Płoski R, Włodarski P. Molecular bases of metachromatic leukodystrophy in Polish patients. Journal of human genetics. 2010. PMID: 20339381
  3. Gieselmann V, Krägeloh-Mann I. Metachromatic leukodystrophy--an update. Neuropediatrics. 2010. PMID: 20571983
  4. Cesani M, Capotondo A, Plati T. Characterization of new arylsulfatase A gene mutations reinforces genotype-phenotype correlation in metachromatic leukodystrophy. Human mutation. 2009. PMID: 19606494
  5. Grossi S, Regis S, Rosano C. Molecular analysis of ARSA and PSAP genes in twenty-one Italian patients with metachromatic leukodystrophy: identification and functional characterization of 11 novel ARSA alleles. Human mutation. 2008. PMID: 18693274
  6. Rauschka H, Colsch B, Baumann N. Late-onset metachromatic leukodystrophy: genotype strongly influences phenotype. Neurology. 2006. PMID: 16966551
  7. Poeppel P, Habetha M, Marcão A. Missense mutations as a cause of metachromatic leukodystrophy. Degradation of arylsulfatase A in the endoplasmic reticulum. The FEBS journal. 2005. PMID: 15720392
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 13 September 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .