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Set Analyses:

VarElect

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ARSA Gene

protein-coding GIFtS: 70
GCID: GC22M051063

Arylsulfatase A

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
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Aliases
Arylsulfatase A¹ ²		cerebroside-sulfatase²
ASA² ³		Cerebroside-sulfatase³
Metachromatic Leucodystrophy¹		EC 3.1.6.8³
MLD²		EC 3.1.6⁸

External Ids:	HGNC: 713¹	Entrez Gene: 410²	Ensembl: ENSG00000100299⁷	OMIM: 607574⁵	UniProtKB: P15289³

Export aliases for ARSA gene to outside databases

Previous GC identifers: GC22M047567 GC22M049195 GC22M049353 GC22M049410 GC22M033953

(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for ARSA Gene:

The protein encoded by this gene 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. Alternatively spliced transcript variants have been described for

this gene. (provided by RefSeq, Dec 2010)

GeneCards Summary for ARSA Gene:

ARSA (arylsulfatase A) is a protein-coding gene. Diseases associated with ARSA include cerebral lipidosis, and nervous system cancer. GO annotations related to this gene include sulfuric ester hydrolase activity and calcium ion binding. An important paralog of this gene is ARSF.

UniProtKB/Swiss-Prot: ARSA_HUMAN, P15289

Function: Hydrolyzes cerebroside sulfate

Gene Wiki entry for ARSA (Arylsulfatase A) Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:

NC_000022.11 NT_011526.8 NC_018933.2

Regulatory elements:

Regulatory transcription factor binding sites in the ARSA gene promoter:
GR ER-alpha AML1a RelA Nkx2-5 E4BP4 NF-kappaB COMP1 GR-alpha NF-kappaB1
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: ARSA promoter sequence

Search Chromatin IP Primers for ARSA

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat ARSA

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 22q13.33 Ensembl cytogenetic band: 22q13.33 HGNC cytogenetic band: 22q13.33

ARSA Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
ARSA gene location

GeneLoc information about chromosome 22 GeneLoc Exon Structure

GeneLoc location for GC22M051063: view genomic region (about GC identifiers)

Start:	51,061,182 bp from pter	End:	51,066,607 bp from pter
Size:	5,426 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: ARSA_HUMAN, P15289 (See protein sequence)

Recommended Name: Arylsulfatase A precursor

Size: 507 amino acids; 53588 Da

Cofactor: Binds 1 calcium ion per subunit

Subunit: Homodimer at neutral pH and homooctamer at acidic pH. Exists both as a single chain of 58 kDa (component

A) or as a chain of 50 kDa (component B) linked by disulfide bond(s) to a 7 kDa chain (component C). Interacts

with SUMF1

Miscellaneous: The metal cofactor was first identified as magnesium ion, based on the structure of the recombinant

protein, but when purified from human placenta, the protein contains 1 calcium ion per subunit

Sequence caution: Sequence=AAB03341.1; Type=Erroneous initiation; Sequence=BAH11167.1; Type=Erroneous initiation;

Selected PDB 3D structures from and Proteopedia for ARSA (see all 9):

1AUK (3D)

1E1Z (3D)

1E2S (3D)

1E33 (3D)

1E3C (3D)

1N2K (3D)

Secondary accessions: B2RCA6 B7XD04 F8WCC8 Q6ICI5 Q96CJ0

Alternative splicing: 2 isoforms: P15289-1 P15289-2 (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for ARSA: NX_P15289

Explore proteomics data for ARSA at MOPED

Post-translational modifications:

The conversion to 3-oxoalanine (also known as C-formylglycine, FGly), of a serine or cysteine residue in

prokaryotes and of a cysteine residue in eukaryotes, is critical for catalytic activity. This post-translational

modification is severely defective in multiple sulfatase deficiency (MSD)¹

Glycosylation² at Asn158, Asn184, Asn350

2 DME Specific Peptides for ARSA (P15289)

GKYKAHF

PSRAALLTGRLP

See ARSA Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins (5 alternative transcripts):

NP_000478.3 NP_001078894.2 NP_001078895.2 NP_001078896.2 NP_001078897.1

ENSEMBL proteins:

ENSP00000477013 ENSP00000348406 ENSP00000216124 ENSP00000378983 ENSP00000412542

ENSP00000378981 ENSP00000448440 ENSP00000448932

Reactome Protein details: P15289

ARSA Human Recombinant Protein Products:

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	Novus Biologicals ARSA Proteins Novus Biologicals ARSA Lysates
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	Cloud-Clone Corp. Proteins for ARSA

ARSA Antibody Products:

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	Novus Biologicals ARSA Antibodies
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	ThermoFisher Antibody for ARSA
	LSBio Antibodies in human, mouse, rat for ARSA

ARSA Assay Products:

	Browse Kits and Assays available from EMD Millipore
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	Cloud-Clone Corp. ELISAs for ARSA Cloud-Clone Corp. CLIAs for ARSA

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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HGNC Gene Families:

ARS: Arylsulfatase family

4 InterPro protein domains:

IPR017849 Alkaline_Pase-like_a/b/a

IPR000917 Sulfatase

IPR024607 Sulfatase_CS

IPR017850 Alkaline_phosphatase_core

Graphical View of Domain Structure for InterPro Entry P15289

ProtoNet protein and cluster: P15289

1 Blocks protein domain: IPB000917 Sulfatase

UniProtKB/Swiss-Prot: ARSA_HUMAN, P15289

Similarity: Belongs to the sulfatase family

ARSA for domains About GeneDecksing

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

UniProtKB/Swiss-Prot Summary: ARSA_HUMAN, P15289

Function: Hydrolyzes cerebroside sulfate

Catalytic activity: A cerebroside 3-sulfate + H(2)O = a cerebroside + sulfate

Enzyme regulation: Inhibited by phosphate. The phosphate forms a covalent bond with the active site 3-oxoalanine

Genatlas biochemistry entry for ARSA:

arylsulfatase A,lysosomal,hydrolyzing esters bonds in cerebrosides,sulfation of most sulfolipids

Enzyme Numbers (IUBMB): EC 3.1.6.8¹ EC 3.1.6²

Gene Ontology (GO): 5 molecular function terms: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0003824	catalytic activity	--	--
GO:0004065	arylsulfatase activity	IEA	--
GO:0004098	cerebroside-sulfatase activity	TAS	--
GO:0005509	calcium ion binding	IDA	12888274
GO:0008484	sulfuric ester hydrolase activity	IDA	15962010

ARSA for ontologies About GeneDecksing

Phenotypes:
2 GenomeRNAi human phenotypes for ARSA:

Cell cycle / mitosis defect

Decreased viability of wild-ty

6 MGI mutant phenotypes (inferred from 1 allele) (MGI details for Arsa):

behavior/neurological	hearing/vestibular/ear	hematopoietic system	homeostasis/metabolism	immune system
nervous system

ARSA for phenotypes About GeneDecksing

Animal Models:
MGI mouse knock-out Arsa^tm1Gie for ARSA

inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for ARSA

inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for ARSA

genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for ARSA

genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for ARSA

miRNA Products:		miRTarBase miRNAs that target ARSA: hsa-mir-335-5p (MIRT018147)

		Block miRNA regulation of human, mouse, rat ARSA using miScript Target Protectors
		Selected qRT-PCR Assays for microRNAs that regulate ARSA (see all 9):
		hsa-miR-374b* hsa-miR-485-5p hsa-miR-892b hsa-miR-3918 hsa-miR-619 hsa-miR-646 hsa-miR-221* hsa-miR-24

		Browse SwitchGear 3'UTR luciferase reporter plasmids

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for ARSA
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Gene Editing
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		GenScript: all cDNA clones in your preferred vector (see all 5): ARSA (NM_001085428)
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		Browse ESI BIO Cell Lines and PureStem Progenitors for ARSA

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for ARSA

(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot

ARSA_HUMAN, P15289: Lysosome

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
lysosome	5
vacuole	5
endoplasmic reticulum	4
cytosol	2
endosome	2
golgi apparatus	2
extracellular	1
plasma membrane	1

About this image

Gene Ontology (GO): Selected cellular component terms (see all 10): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001669	acrosomal vesicle	IEA	--
GO:0005615	extracellular space	IEA	--
GO:0005737	cytoplasm	--	--
GO:0005764	lysosome	TAS	2562955
GO:0005768	endosome	IEA	--

ARSA for ontologies About GeneDecksing

(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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SuperPaths for ARSA About

See pathways by source

SuperPath

Contained pathways About

Sphingolipid metabolism

	Sphingolipid metabolism	0.61			Glycosphingolipid metabolism	0.56
	Sphingolipid metabolism	0.61

Metabolism

Metabolism

0.38

Metabolism of lipids and lipoproteins

0.37

PTM- gamma carboxylation, hypusine formation and arylsulfatase activation

PTM- gamma carboxylation, hypusine formation and arylsulfatase activation

0.31

The activation of arylsulfatases

0.00

Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein

Post-translational protein modification

0.43

Metabolism of proteins

0.30

Lysosome

Lysosome

Pathways by source See SuperPaths
Show all pathways

2 Reactome Pathways for ARSA

	Glycosphingolipid metabolism
	The activation of arylsulfatases

2 Kegg Pathways (Kegg details for ARSA):

	Sphingolipid metabolism
	Lysosome

ARSA for pathways About GeneDecksing

Custom Pathway & Disease-focused RT² Profiler PCR Arrays for ARSA
Interactions:

Search GeneGlobe Interaction Network for ARSA

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

Selected Interacting proteins for ARSA (P15289³ ENSP00000216124⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 26)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
CLEC4G	Q6UXB4³, ENSP00000327599⁴	I2D: score=2 STRING: ENSP00000327599
CTSL	P07711³, ENSP00000345344⁴	I2D: score=1 STRING: ENSP00000345344
TRIP13	Q15645³	I2D: score=1
ARSB	ENSP00000264914⁴	STRING: ENSP00000264914
ARSD	ENSP00000370546⁴	STRING: ENSP00000370546

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Gene Ontology (GO): Selected biological process terms (see all 14): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006665	sphingolipid metabolic process	TAS	--
GO:0006687	glycosphingolipid metabolic process	TAS	--
GO:0006914	autophagy	IEA	--
GO:0007339	binding of sperm to zona pellucida	IEA	--
GO:0007417	central nervous system development	IEA	--

ARSA for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse compounds at ApexBio

Browse Tocris compounds for ARSA

Selected HMDB Compounds for ARSA (see all 11) About this table

Compound	Synonyms	CAS #	PubMed Ids
3-O-Sulfogalactosylceramide (d18:1/24:0)	Sulfatide (d18:1/24:0) (see all 16)	151122-71-3	--
Galactosylceramide (d18:1/16:0)	Galactocerebroside (see all 15)	--	--
Galactosylceramide (d18:1/18:0)	Galactocerebroside (see all 15)	--	--
Galactosylceramide (d18:1/18:1(9Z))	Galactocerebroside (see all 15)	--	--
Galactosylceramide (d18:1/20:0)	Galactocerebroside (see all 15)	--	--
Galactosylceramide (d18:1/22:0)	Galactocerebroside (see all 15)	--	--
Galactosylceramide (d18:1/24:1(15Z))	Galactocerebroside (see all 15)	--	--
Galactosylceramide (d18:1/26:1(17Z))	Galactocerebroside (see all 15)	--	--
Magnesium	Magnesium (see all 2)	7439-95-4	--
Sulfate	Sulfate (ion 2-) (see all 9)	14808-79-8	--

4 DrugBank Compounds for ARSA About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Micafungin	--	235114-32-6	enzyme	substrate	15882123 17516879
N,4-Dihydroxy-N-Oxo-3-(Sulfooxy)Benzenaminium	--	--	target	--	10592235
Suramin	Bayer 205 (see all 6)	145-63-1	enzyme	inhibitor	7291729
2-Amino-3-Hydroxy-3-Phosphonooxy-Propionic Acid	--	--	target	--	--
2-Amino-3-Hydroxy-3-Phosphonooxy-Propionic Acid	--	--	enzyme	--	--

Selected Novoseek inferred chemical compound relationships for ARSA gene (see all 42) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
sulfatide	95.1	72	1359786 (6), 10894127 (3), 15322834 (2), 17204333 (2) (see all 37)
formylglycine	90.1	3	10212197 (1), 9497327 (1), 9760228 (1)
p-nitrocatechol sulfate	89.9	14	10464659 (2), 1687673 (2), 16613739 (2), 11870284 (1) (see all 7)
cerebroside	77.4	9	10082381 (1), 11746679 (1), 1687673 (1), 15275696 (1) (see all 6)
n-acetylgalactosamine 6-sulfate	72.1	2	1755850 (1), 1875023 (1)
mannose 6-phosphate	70.3	12	12296771 (3), 1352293 (1), 8106525 (1), 15709909 (1) (see all 7)
sulf	66.4	5	16311251 (2), 17093507 (2)
galactosylceramide	65.7	3	9024105 (1), 18097285 (1)
mucopolysaccharide	40.9	3	9336808 (2), 11315200 (1)
mannose	35.5	3	1352293 (1), 7890120 (1), 9202426 (1)

ARSA for compounds About GeneDecksing

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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REFSEQ mRNAs for ARSA gene (5 alternative transcripts):

NM_000487.5 NM_001085425.2 NM_001085426.2 NM_001085427.2 NM_001085428.2

Unigene Cluster for ARSA:

Arylsulfatase A

Hs.88251 [show with all ESTs]

Unigene Representative Sequence: NM_000487

10 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000610191 ENST00000608497 ENST00000356098 ENST00000216124(uc003bna.4 uc021wsd.1 uc021wse.1 uc021wsf.1 uc003bmz.4)

ENST00000395621 ENST00000453344 ENST00000395619 ENST00000551731(uc010hbf.3)

ENST00000547307 ENST00000547805

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		Selected qRT-PCR Assays for microRNAs that regulate ARSA (see all 9):
		hsa-miR-374b* hsa-miR-485-5p hsa-miR-892b hsa-miR-3918 hsa-miR-619 hsa-miR-646 hsa-miR-221* hsa-miR-24

		Browse SwitchGear 3'UTR luciferase reporter plasmids

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		GenScript: all cDNA clones in your preferred vector (see all 5): ARSA (NM_001085428)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for ARSA
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat ARSA

Primer Products:		OriGene qPCR primer pairs and template standards for ARSA OriGene qSTAR qPCR primer pairs in human, mouse for ARSA
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat ARSA
		QuantiTect SYBR Green Assays in human, mouse, rat ARSA
		QuantiFast Probe-based Assays in human, mouse, rat ARSA

Additional mRNA sequence:

AB448736.1 AK092752.1 AK098659.1 AK315011.1 BC014210.2 BX648618.1 CR456383.1 X52151.1

15 DOTS entries:

DT.100877746 DT.453952 DT.100731419 DT.65287834 DT.95337986 DT.100028446 DT.100644967 DT.100877740

DT.100877741 DT.100877744 DT.120644762 DT.40230542 DT.91745500 DT.95337982 DT.97844860

Selected AceView cDNA sequences (see all 228):

CR607373 C01652 BP367614 BG035223 CB124424 CR598173 CB126238 AI459538

BX365605 BQ184813 BQ917626 CB151533 CR590422 BM763358 CB306644 BM547797

BU632246 CR600807 R96096 CA423492 T28370 BQ109579 CB125745 BE465784

GeneLoc Exon Structure

Selected Alternative Splicing Database (ASD) splice patterns (SP) for ARSA (see all 8) About this scheme

ExUns:	1a	·	1b	·	1c	·	1d	·	1e	^	2a	·	2b	^	3a	·	3b	·	3c	·	3d	^	4a	·	4b	·	4c	^	5a	·	5b	^	6a	·	6b	·	6c	^	7	^	8a	·	8b	^	9
SP1:																																	-
SP2:																													-				-
SP3:							-		-				-		-		-		-		-		-		-								-
SP4:																							-		-		-						-
SP5:									-

ECgene alternative splicing isoforms for ARSA

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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ARSA expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: TACCCTGGCG

About this image

ARSA expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database
selected tissues (see all 7) fully expand


Brain (Nervous System) fully expand to see all 4 entries
Cerebral Cortex

Trophoblast (Extraembryonic Tissues)
Trophoblast Cells Trophoblast

Ovary (Reproductive System)
Oviduct

Pancreas (Endocrine System)
Islets of Langerhans

Testis (Reproductive System)
Leydig Cells Testis Interstitium

ARSA Protein expression data from MOPED¹, PaxDb² and MaxQB³:

About this image

ARSA Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.88251

Custom PCR Arrays for ARSA

Primer Products:		OriGene qPCR primer pairs and template standards for ARSA OriGene qSTAR qPCR primer pairs in human, mouse for ARSA
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat ARSA
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		QuantiFast Probe-based Assays in human, mouse, rat ARSA

In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for ARSA

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of animals.

Orthologs for ARSA gene from Selected species (see all 13) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Arsa^{1 , 5}	arylsulfatase A^{1, 5}	83.68(n)¹ 87.6(a)¹		15 (44.94 cM)⁵ 11883¹ NM_009713.4¹ NP_033843.2¹ 89472476⁵
chicken (Gallus gallus)	Aves	ARSA¹	arylsulfatase A	67.43(n) 66.32(a)		426863 XM_424471.4 XP_424471.3
lizard (Anolis carolinensis)	Reptilia	ARSA⁶	arylsulfatase A	67(a)	1 ↔ 1	GL343765.1(209941-216295)
tropical clawed frog (Xenopus tropicalis)	Amphibia	arsa¹	arylsulfatase A	58.75(n) 57.71(a)		100486429 XM_002938291.2 XP_002938337.2
zebrafish (Danio rerio)	Actinopterygii	arsa¹	arylsulfatase A	59.82(n) 58.28(a)		541416 NM_001013543.2 NP_001013561.2
worm (Caenorhabditis elegans)	Secernentea	D1014.1³	arylsulfatase	36(a)		V(8160224-8161279) --

ENSEMBL Gene Tree for ARSA (if available)
TreeFam Gene Tree for ARSA (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for ARSA gene

ARSF² ARSI² ARSJ² ARSG² STS² ARSH² ARSB² GALNS²

ARSE² ARSD²

3 SIMAP similar genes for ARSA using alignment to 2 protein entries: ARSA_HUMAN (see all proteins):

DKFZp686G12235 GALNS ARSG

ARSA for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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SNP ID	Valid	Clinical significance	Chr 22 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs28940893^1,2,,4	C	Leukodystrophy metachromatic (MLD)⁴ pathogenic¹	35006735(-)	`GCCCCC/TGCTGC`	10	P L	mis¹ ese³		1		NA	3842
rs74315485^1,2,,4	C	Leukodystrophy metachromatic (MLD)⁴ pathogenic¹	35006739(-)	`ATGAGA/CCCCCG`	10	T P	mis¹		0	--	--	--	--
rs74315481^1,2,,4	C	Leukodystrophy metachromatic (MLD)⁴ pathogenic¹	35006786(-)	`TACCAC/TTGCAG`	10	T I	mis¹		0	--	--	--	--
rs28940895^1,2,,4	C	Leukodystrophy metachromatic (MLD)⁴ pathogenic¹	35006789(-)	`TGATAC/TCACTG`	10	T I	mis¹ ese³		0	--	--	--	--
rs199476391^1,2,,4	C	Leukodystrophy metachromatic (MLD)⁴ untested¹	35006957(-)	`TGTGCG/AGACTG`	10	/Q /R	mis¹		1		EU	1315
rs74315480^1,2,,4	C	Leukodystrophy metachromatic (MLD)⁴ pathogenic¹	35006958(-)	`CTGTGC/TGGACT`	10	R W	mis¹		0	--	--	--	--
rs199476370^1,2,,4	C	Leukodystrophy metachromatic (MLD)⁴ untested¹	35006976(-)	`AGGTCC/TGTGGG`	10	R C	mis¹		0	--	--	--	--
rs74315479^1,2,,4	C	Leukodystrophy metachromatic (MLD)⁴ pathogenic¹	35006982(-)	`CAGACA/GAGGTC`	10	K E	mis¹		0	--	--	--	--
rs6151425^1,2,,4	C,F,H	Leukodystrophy metachromatic (MLD)⁴ untested¹	35006983(-)	`CCAGAC/G/TGAGGT`	10	D E	mis¹ ese³		22		NS NA EU	8383
rs74315478^1,2,,4	C	Leukodystrophy metachromatic (MLD)⁴ pathogenic¹	35006996(-)	`CTACCA/C/TGTCCT`	10	P L	mis¹		1		NA	4486

HapMap Linkage Disequilibrium report for ARSA (51061182 - 51066607 bp)

Structural Variations
Database of Genomic Variants (DGV) 9 variations for ARSA: About this table

Variant ID	Type	Subtype	PubMed ID
dgv5069n71	CNV	Loss	21882294
nsv915495	CNV	Loss	21882294
dgv5068n71	CNV	Loss	21882294
nsv914543	CNV	Loss	21882294
nsv834239	CNV	Loss	17160897
dgv5066n71	CNV	Loss	21882294
dgv5067n71	CNV	Loss	21882294
nsv914542	CNV	Loss	21882294
nsv519694	CNV	Gain+Loss	19592680

Human Gene Mutation Database (HGMD): ARSA

Site Specific Mutation Identification with PCR Assays

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DNA2.0 Custom Variant and Variant Library Synthesis for ARSA

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 607574
OMIM disorders: 250100
UniProtKB/Swiss-Prot: ARSA_HUMAN, P15289

Leukodystrophy metachromatic (MLD) [MIM:250100]: A leukodystrophy due to a lysosomal storage defect.

Characterized by intralysosomal storage of cerebroside-3-sulfate in neural and non-neural tissues, with a diffuse

loss of myelin in the central nervous system. Progressive demyelination causes a variety of neurological

symptoms, including gait disturbances, ataxias, optical atrophy, dementia, seizures, and spastic tetraparesis.

Three forms of the disease can be distinguished according to the age at onset: late-infantile, juvenile and

adult. Note=The disease is caused by mutations affecting the gene represented in this entry

Multiple sulfatase deficiency (MSD) [MIM:272200]: A clinically and biochemically heterogeneous disorder

caused by the simultaneous impairment of all sulfatases, due to defective post-translational modification and

activation. It combines features of individual sulfatase deficiencies such as metachromatic leukodystrophy,

mucopolysaccharidosis, chondrodysplasia punctata, hydrocephalus, ichthyosis, neurologic deterioration and

developmental delay. Note=The protein represented in this entry is involved in disease pathogenesis.

Arylsulfatase A activity is impaired in multiple sulfatase deficiency due to mutations in SUMF1. SUMF1 mutations

result in defective post-translational modification of ARSA at residue Cys-69 that is not converted to

3-oxoalanine

Selected diseases for ARSA (see all 59):
About MalaCards

cerebral lipidosis nervous system cancer metachromatic leukodystrophy central nervous system cancer

metachromatic leukodystrophy, late infantile form metachromatic leukodystrophy, adult form metachromatic leukodystrophy, juvenile form fabry disease

sneddon syndrome gangliosidosis gm1 sandhoff disease wilson disease

mucosulfatidosis krabbe disease tay-sachs disease choroideremia

leukodystrophy gangliosidosis pervasive developmental disorder essential tremor

6 diseases from the University of Copenhagen DISEASES database for ARSA:

Metachromatic leukodystrophy Mucosulfatidosis Mucopolysaccharidosis Krabbe disease

Mucolipidosis Cerebral lipidosis

ARSA for disorders About GeneDecksing

Congresses - knowledge worth sharing:
Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

Selected Novoseek inferred disease relationships for ARSA gene (see all 37) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
leukodystrophy metachromatic	99	308	1687673 (4), 1670590 (3), 12427515 (3), 1357970 (3) (see all 99)
leukodystrophy metachromatic late infantile	95.6	8	8723680 (1), 14571263 (1), 9272717 (1), 9888390 (1) (see all 6)
leukodystrophy metachromatic adult	93.3	2	7710377 (2)
multiple sulfatase deficiency	90.5	6	9336808 (2), 12809637 (1), 15446395 (1), 1687673 (1)
leukodystrophy metachromatic juvenile	89.2	3	8707308 (1), 1684088 (1)
lysosomal storage diseases	87.2	43	1348043 (1), 7860068 (1), 8542433 (1), 9090526 (1) (see all 27)
demyelination	75	16	7904733 (2), 7866401 (1), 10822308 (1), 15322834 (1) (see all 11)
sphingolipidoses	67.3	1	18360747 (1)
krabbe disease	64.2	4	7755846 (1), 10713632 (1), 15275696 (1)
enzyme deficiency	59.1	4	18797988 (1), 17980709 (1), 1968615 (1)

GeneTests: ARSA
GeneReviews: ARSA
Genetic Association Database (GAD): ARSA
Human Genome Epidemiology (HuGE) Navigator: ARSA (5 documents)

Export disorders for ARSA gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for ARSA gene, integrated from 10 sources (see all 334):
(articles sorted by number of sources associating them with ARSA)

Utopia: connect your pdf to the dynamic
world of online information

Late onset MLD with normal nerve conduction associated with two novel missense mutations in the ASA gene. (PubMed id 15026521)^{1, 2, 4} Gallo S.... Pandolfo M. (J. Neurol. Neurosurg. Psych. 2004)
Oligomerization capacity of two arylsulfatase A mutants: C300F and P425T. (PubMed id 12788103)^{1, 2, 9} Marcao A.... Sa Miranda M.C. (Biochem. Biophys. Res. Commun. 2003)
High residual arylsulfatase A (ARSA) activity in a patient with late- infantile metachromatic leukodystrophy. (PubMed id 8101038)^{1, 2, 9} Kreysing J.... Gieselmann V. (Am. J. Hum. Genet. 1993)
Molecular analysis of ARSA and PSAP genes in twenty-one Italian patients with metachromatic leukodystrophy: identification and functional characterization of 11 novel ARSA alleles. (PubMed id 18693274)^{1, 2, 9} Grossi S....Filocamo M. (Hum. Mutat. 2008)
Croatian population data for arylsulfatase a pseudodeficiency-associated mutations in healthy subjects, and in patients with Alzheimer-type dementia and Down syndrome. (PubMed id 12459318)^{1, 4, 9} Bognar S.K....Demarin V. (Arch. Med. Res. 2002)
Crystal structure of an enzyme-substrate complex provides insight into the interaction between human arylsulfatase A and its substrates during catalysis. (PubMed id 11124905)^{1, 2, 9} von Buelow R.... Uson I. (J. Mol. Biol. 2001)
Coincidence of two novel arylsulfatase A alleles and mutation 459+1G>A within a family with metachromatic leukodystrophy: molecular basis of phenotypic heterogeneity. (PubMed id 9888390)^{1, 2, 9} Berger J.... Bernheimer H. (Hum. Mutat. 1999)
An arylsulfatase A (ARSA) missense mutation (T274M) causing late- infantile metachromatic leukodystrophy. (PubMed id 8104633)^{1, 2, 9} Harvey J.S.... Morris C.P. (Hum. Mutat. 1993)
Adult onset metachromatic leukodystrophy without electroclinical peripheral nervous system involvement: a new mutation in the ARSA gene. (PubMed id 15710861)^{1, 2, 9} Marcao A.M.... Gieselmann V. (Arch. Neurol. 2005)
The R496H mutation of arylsulfatase A does not cause metachromatic leukodystrophy. (PubMed id 9744473)^{1, 2, 9} Ricketts M.H.... Manowitz P. (Hum. Mutat. 1998)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 410	HGNC: 713	AceView: ARSA	Ensembl:ENSG00000100299	euGenes: HUgn410
ECgene: ARSA	Kegg: 410	H-InvDB: ARSA

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for ARSA	Pharmacogenomics, SNPs, Pathways
GeneReviews	http://www.ncbi.nlm.nih.gov/books/NBK1116/?term=ARSA[genesymbol]
NIEHS-SNPs	http://egp.gs.washington.edu/data/arsa/
Wikipedia	http://en.wikipedia.org/wiki/Arylsulfatase_A

Intellectual Property for ARSA gene
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Patent Information for ARSA gene:
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GeneCards and IP:
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Arylsulfatase A

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ENZYME DEFICIENCY
major depression
WILSON DISEASE
Neurodegenerative Diseases
Dementia
Down Syndrome
Neurological Disorders
Demyelination
Lysosomal Storage Diseases
Dysostosis
Polyneuropathy
Breast Cancer
Leukodystrophy Metachromatic Adult
neurodegeneration
MULTIPLE SULFATASE DEFICIENCY
Leukodystrophy Metachromatic
Schizophrenia
Alcoholism
disability
Cancer
Gangliosidosis GM1
Gaucher Disease
KRABBE DISEASE
Fabry Disease
Maroteaux-Lamy Syndrome
Sphingolipidoses
Sandhoff Disease
Demyelinating Diseases
central nervous system cancer
Leukodystrophy Metachromatic Juvenile
Leukodystrophy Metachromatic Late Infantile
psychiatric disorder
Tumors
Arylsulfatase A Deficiency
metabolic disorder
Tay-Sachs Disease
Psychotic
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Arylsulfatase A

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