Arylsulfatase A (ARSA)

MLD; ASA; Metachromatic Leucodystrophy; Cerebroside-sulfatase

SPN	Q185
HGNC	713
MGI	88077
PubMed	2562955
RGD	1310381
UniProt	P15289
Wiki	ARSA

Arylsulfatase A hydrolyzes cerebroside sulfate to cerebroside and sulfate. Defects in this gene lead to metachromatic leucodystrophy (MLD), a progressive demyelination disease which results in a variety of neurological symptoms and ultimately death. Multiple alternatively spliced transcript variants, one of which encodes a distinct protein, have been described for this gene

The predicted amino acid sequence comprised 507 residues, including a putative signal peptide of 18 residues. The sequence contains 3 potential N-glycosylation sites. The cDNA hybridized to 2.0- and 3.9-kb species in RNA from human fibroblasts and human liver.

Reference

"Cloning and expression of human arylsulfatase A."
J. Biol. Chem. 264:1252-1259(1989) [PubMed] [Europe PMC] [Abstract]

"Structure of the arylsulfatase A gene."
Eur. J. Biochem. 191:627-631(1990) [PubMed] [Europe PMC] [Abstract]

"Characterization of the arylsulfatase I (ARSI) gene preferentially expressed in the human retinal pigment epithelium cell line ARPE-19."
Mol. Vis. 15:482-494(2009) [PubMed] [Europe PMC] [Abstract]

"A genome annotation-driven approach to cloning the human ORFeome."
Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence of human chromosome 22."
Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Proteolytic processing of human lysosomal arylsulfatase A."
Biochim. Biophys. Acta 1122:93-98(1992) [PubMed] [Europe PMC] [Abstract]

"A novel amino acid modification in sulfatases that is defective in multiple sulfatase deficiency."
Cell 82:271-278(1995) [PubMed] [Europe PMC] [Abstract]

"Molecular and functional analysis of SUMF1 mutations in multiple sulfatase deficiency."
Hum. Mutat. 23:576-581(2004) [PubMed] [Europe PMC] [Abstract]

"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]

"Crystal structure of human arylsulfatase A: the aldehyde function and the metal ion at the active site suggest a novel mechanism for sulfate ester hydrolysis."
Biochemistry 37:3654-3664(1998) [PubMed] [Europe PMC] [Abstract]

"Crystal structure of an enzyme-substrate complex provides insight into the interaction between human arylsulfatase A and its substrates during catalysis."
J. Mol. Biol. 305:269-277(2001) [PubMed] [Europe PMC] [Abstract]

"Crystal structure of a covalent intermediate of endogenous human arylsulfatase A."
J. Inorg. Biochem. 96:386-392(2003) [PubMed] [Europe PMC] [Abstract]

"A general binding mechanism for all human sulfatases by the formylglycine-generating enzyme."
Proc. Natl. Acad. Sci. U.S.A. 103:81-86(2006) [PubMed] [Europe PMC] [Abstract]

"Molecular genetics of metachromatic leukodystrophy."
Hum. Mutat. 4:233-242(1994) [PubMed] [Europe PMC] [Abstract]

"Arylsulfatase A pseudodeficiency: loss of a polyadenylylation signal and N-glycosylation site."
Proc. Natl. Acad. Sci. U.S.A. 86:9436-9440(1989) [PubMed] [Europe PMC] [Abstract]

"Identification of a mutation in the arylsulfatase A gene of a patient with adult-type metachromatic leukodystrophy."
Am. J. Hum. Genet. 48:971-978(1991) [PubMed] [Europe PMC] [Abstract]

"Mutations in the arylsulfatase A pseudodeficiency allele causing metachromatic leukodystrophy."
Am. J. Hum. Genet. 49:407-413(1991) [PubMed] [Europe PMC] [Abstract]

"Molecular basis of different forms of metachromatic leukodystrophy."
N. Engl. J. Med. 324:18-22(1991) [PubMed] [Europe PMC] [Abstract]

"Late-onset metachromatic leukodystrophy: molecular pathology in two siblings."
Ann. Neurol. 31:256-261(1992) [PubMed] [Europe PMC] [Abstract]

"High residual arylsulfatase A (ARSA) activity in a patient with late-infantile metachromatic leukodystrophy."
Am. J. Hum. Genet. 53:339-346(1993) [PubMed] [Europe PMC] [Abstract]

"Mutations in the arylsulfatase A gene of Japanese patients with metachromatic leukodystrophy."
DNA Cell Biol. 12:493-498(1993) [PubMed] [Europe PMC] [Abstract]

"Prevalence of common mutations in the arylsulphatase A gene in metachromatic leukodystrophy patients diagnosed in Britain."
Hum. Genet. 91:73-77(1993) [PubMed] [Europe PMC] [Abstract]

"An adult-type metachromatic leukodystrophy caused by substitution of serine for glycine-122 in arylsulfatase A."
Hum. Genet. 92:451-456(1993) [PubMed] [Europe PMC] [Abstract]

"Missense mutations in the arylsulphatase A genes of metachromatic leukodystrophy patients."
Hum. Mol. Genet. 2:2117-2121(1993) [PubMed] [Europe PMC] [Abstract]

"An arylsulfatase A (ARSA) missense mutation (T274M) causing late-infantile metachromatic leukodystrophy."
Hum. Mutat. 2:261-267(1993) [PubMed] [Europe PMC] [Abstract]

"Single exon mutation in arylsulfatase A gene has two effects: loss of enzyme activity and aberrant splicing."
Hum. Genet. 93:415-420(1994) [PubMed] [Europe PMC] [Abstract]

"Multiple mutations are responsible for the high frequency of metachromatic leukodystrophy in a small geographic area."
Am. J. Hum. Genet. 56:51-57(1995) [PubMed] [Europe PMC] [Abstract]

"A missense mutation P136L in the arylsulfatase A gene causes instability and loss of activity of the mutant enzyme."
Hum. Genet. 95:201-204(1995) [PubMed] [Europe PMC] [Abstract]

"Identification of seven novel mutations associated with metachromatic leukodystrophy."
Hum. Mutat. 6:170-176(1995) [PubMed] [Europe PMC] [Abstract]

"Two novel mutations in a Japanese patient with the late-infantile form of metachromatic leukodystrophy."
Brain Dev. 18:400-403(1996) [PubMed] [Europe PMC] [Abstract]

"Characterization of two arylsulfatase A missense mutations D335V and T274M causing late infantile metachromatic leukodystrophy."
Hum. Mutat. 7:311-317(1996) [PubMed] [Europe PMC] [Abstract]

"A T > C transition causing a Leu > Pro substitution in a conserved region of the arylsulfatase A gene in a late infantile metachromatic leukodystrophy patient."
Clin. Genet. 52:65-67(1997) [PubMed] [Europe PMC] [Abstract]

"Metachromatic leukodystrophy: identification of the first deletion in exon 1 and of nine novel point mutations in the arylsulfatase A gene."
Hum. Mutat. 9:234-242(1997) [PubMed] [Europe PMC] [Abstract]

"A 9-bp deletion (2320del9) on the background of the arylsulfatase A pseudodeficiency allele in a metachromatic leukodystrophy patient and in a patient with nonprogressive neurological symptoms."
Hum. Genet. 102:50-53(1998) [PubMed] [Europe PMC] [Abstract]

"Molecular genetic characterization of two metachromatic leukodystrophy patients who carry the T799G mutation and show different phenotypes; description of a novel null-type mutation."
Hum. Genet. 102:459-463(1998) [PubMed] [Europe PMC] [Abstract]

Erratum
Hum. Genet. 102:602-602(1998)

"The R496H mutation of arylsulfatase A does not cause metachromatic leukodystrophy."
Hum. Mutat. 12:238-239(1998) [PubMed] [Europe PMC] [Abstract]

"Two novel mutations in the arylsulfatase A gene associated with juvenile (R390Q) and adult onset (H397Y) metachromatic leukodystrophy."
Hum. Mutat. Suppl. 1:S254-S256(1998) [PubMed] [Europe PMC] [Abstract]

"Prevalence of arylsulphatase A mutations in 11 Japanese patients with metachromatic leukodystrophy: identification of two novel mutations."
J. Inherit. Metab. Dis. 21:781-782(1998) [PubMed] [Europe PMC] [Abstract]

"Coincidence of two novel arylsulfatase A alleles and mutation 459+1G>A within a family with metachromatic leukodystrophy: molecular basis of phenotypic heterogeneity."
Hum. Mutat. 13:61-68(1999) [PubMed] [Europe PMC] [Abstract]

"Metachromatic leucodystrophy in Portugal-finding of four new molecular lesions: C300F, P425T, g.1190-1191insC, and g.2408delC."
Hum. Mutat. 13:337-338(1999) [PubMed] [Europe PMC] [Abstract]

"Identification of 12 novel mutations and two new polymorphisms in the arylsulfatase A gene: haplotype and genotype-phenotype correlation studies in Spanish metachromatic leukodystrophy patients."
Hum. Mutat. 14:240-248(1999) [PubMed] [Europe PMC] [Abstract]

"Metachromatic leucodystrophy: a newly identified mutation in arylsulphatase A, D281Y, found as a compound heterozygote with I179L in an adult onset case."
Hum. Mutat. 14:447-447(1999) [PubMed] [Europe PMC] [Abstract]

"Metachromatic leukodystrophy: subtype genotype/phenotype correlations and identification of novel missense mutations (P148L and P191T) causing the juvenile-onset disease."
Mol. Genet. Metab. 67:206-212(1999) [PubMed] [Europe PMC] [Abstract]

"Characterization of four arylsulfatase A missense mutations G86D, Y201C, D255H, and E312D causing metachromatic leukodystrophy."
Am. J. Med. Genet. 91:68-73(2000) [PubMed] [Europe PMC] [Abstract]

"Adult-onset MLD: a gene mutation with isolated polyneuropathy."
Neurology 55:1036-1039(2000) [PubMed] [Europe PMC] [Abstract]

"Variable onset of metachromatic leukodystrophy in a Vietnamese family."
Pediatr. Neurol. 23:173-176(2000) [PubMed] [Europe PMC] [Abstract]

"Late-onset metachromatic leukodystrophy clinically presenting as isolated peripheral neuropathy: compound heterozygosity for the IVS2+1G-->A mutation and a newly identified missense mutation (Thr408Ile) in a Spanish family."
Ann. Neurol. 50:108-112(2001) [PubMed] [Europe PMC] [Abstract]

"Contribution of arylsulfatase A mutations located on the same allele to enzyme activity reduction and metachromatic leukodystrophy severity."
Hum. Genet. 110:351-355(2002) [PubMed] [Europe PMC] [Abstract]

"Biochemical characterization of two (C300F, P425T) arylsulfatase A missense mutations."
Am. J. Med. Genet. A 116:238-242(2003) [PubMed] [Europe PMC] [Abstract]

"Oligomerization capacity of two arylsulfatase A mutants: C300F and P425T."
Biochem. Biophys. Res. Commun. 306:293-297(2003) [PubMed] [Europe PMC] [Abstract]

"Identification of nine novel arylsulfatase A (ARSA) gene mutations in patients with metachromatic leukodystrophy (MLD)."
Hum. Mutat. 22:418-419(2003) [PubMed] [Europe PMC] [Abstract]

"Novel mutations in arylsulfatase A gene in three Ukrainian families with metachromatic leukodystrophy."
Mol. Genet. Metab. 80:360-363(2003) [PubMed] [Europe PMC] [Abstract]

"Novel mutations associated with metachromatic leukodystrophy: phenotype and expression studies in nine Czech and Slovak patients."
Am. J. Med. Genet. A 129:277-281(2004) [PubMed] [Europe PMC] [Abstract]

"Late onset MLD with normal nerve conduction associated with two novel missense mutations in the ASA gene."
J. Neurol. Neurosurg. Psych. 75:655-657(2004) [PubMed] [Europe PMC] [Abstract]

"Adult onset metachromatic leukodystrophy without electroclinical peripheral nervous system involvement: a new mutation in the ARSA gene."
Arch. Neurol. 62:309-313(2005) [PubMed] [Europe PMC] [Abstract]

"Molecular analysis of ARSA and PSAP genes in twenty-one Italian patients with metachromatic leukodystrophy: identification and functional characterization of 11 novel ARSA alleles."
Hum. Mutat. 29:E220-E230(2008) [PubMed] [Europe PMC] [Abstract]

"Characterization of new arylsulfatase A gene mutations reinforces genotype-phenotype correlation in metachromatic leukodystrophy."
Hum. Mutat. 30:E936-E945(2009) [PubMed] [Europe PMC] [Abstract]

"Molecular bases of metachromatic leukodystrophy in Polish patients."
J. Hum. Genet. 55:394-396(2010) [PubMed] [Europe PMC] [Abstract]

"Adult-type metachromatic leukodystrophy with compound heterozygous ARSA mutations: a case report and phenotypic comparison with a previously reported case."
Psychiatry Clin. Neurosci. 65:105-108(2011) [PubMed] [Europe PMC] [Abstract]