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ARSA

arylsulfatase A

The ARSA gene provides instructions for producing the arylsulfatase A enzyme, which plays a critical role in the breakdown of specific fats called sulfatides within cellular lysosomes. The ARSA gene is responsible for creating the arylsulfatase A enzyme.

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 encodes the enzyme arylsulfatase A, a key component of cellular lysosomes. Lysosomes are often referred to as the 'recycling centres' of the cell, where they break down waste products and cellular debris.

Arylsulfatase A is particularly important for the metabolism of sulfatides, a type of fat molecule critical for nerve cell membranes. Inherited changes in the ARSA gene can impair this enzymatic activity, leading to the accumulation of sulfatides.

What the gene does

The arylsulfatase A enzyme, encoded by the ARSA gene, functions within lysosomes to break down sulfatides. Sulfatides are a subgroup of sphingolipids, which are fatty molecules integral to cell membranes, especially abundant in the white matter of the nervous system. White matter consists of nerve fibres insulated and protected by myelin, a multi-layered membrane rich in these lipids.

Normal functioning of arylsulfatase A ensures that sulfatides are properly processed and recycled. When the enzyme's activity is significantly reduced due to genetic changes, sulfatides can accumulate to toxic levels within cells. This build-up primarily affects the nervous system, leading to its deterioration.

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Chromosome location

The ARSA gene is situated on chromosome 22, specifically at position 22q13.33. This indicates its location on the long (q) arm of chromosome 22, in region 1, band 3, sub-band 3. The ARSA gene encodes a protein that is 507 amino acids in length.

Protein structure

Domain architecture has not been experimentally characterised in detail for this protein.

Key variants

Variants within the ARSA gene can impact the production or function of the arylsulfatase A enzyme. Over 110 different genetic changes in ARSA have been identified that are associated with a reduced activity of this enzyme. These variants typically result in a substantial decrease in the enzyme's ability to process sulfatides.

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.264del
Deletion
 p.Met89fs 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.585G>A
single nucleotide variant
 p.Trp195Ter 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

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 condition is inherited in an autosomal recessive pattern, meaning an individual must inherit two affected copies of the ARSA gene (one from each parent) to develop the disorder. Metachromatic Leukodystrophy is characterised by the progressive deterioration of nervous system functions due to the toxic accumulation of sulfatides.

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 UK NHS national genomic testing panels. It is listed as 'green' on PanelApp UK for various conditions, indicating strong evidence for its association with these disorders. These panels include 'Ataxia and cerebellar anomalies - childhood onset', 'Inherited white matter disorders', 'Leukodystrophy, adult onset', and 'Lysosomal storage disorder', among others, reflecting its importance in neurodevelopmental and metabolic health.

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, which is crucial for breaking down sulfatides, a type of fat, within the cell's lysosomes. This process is vital for the proper function of the nervous system.

What happens if the ARSA gene is not working correctly?

If the ARSA gene has pathogenic variants, the arylsulfatase A enzyme may not function properly or may be deficient. This leads to the accumulation of sulfatides, primarily affecting the nervous system and causing conditions such as Metachromatic Leukodystrophy.

How is Metachromatic Leukodystrophy inherited?

Metachromatic Leukodystrophy, associated with the ARSA gene, is inherited in an autosomal recessive manner. This means that an individual must inherit two copies of the altered gene, 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 4 October 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .