ARSL (arylsulfatase L)

Gene

• Entrez ID: 415
• Gene name: Arylsulfatase L
• Gene symbol: ARSL
• Synonyms (NCBI Gene): ARSE, ASE, CDPX, CDPX1, CDPXR
• Chromosome: X
• Chromosome location: Xp22.33
• Summary: Arylsulfatase E is a member of the sulfatase family. It is glycosylated postranslationally and localized to the golgi apparatus. Sulfatases are essential for the correct composition of bone and cartilage matrix. X-linked chondrodysplasia punctata, a disea

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs28935474	G>A	Pathogenic	Coding sequence variant, missense variant
rs80338710	A>C	Pathogenic	Coding sequence variant, intron variant, missense variant
rs80338711	C>A,G	Pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs80338713	G>A	Pathogenic	Coding sequence variant, missense variant
rs80338714	C>T	Pathogenic	Coding sequence variant, stop gained
rs122460152	C>T	Pathogenic	Coding sequence variant, missense variant
rs122460153	C>G,T	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs122460154	C>G	Pathogenic	Coding sequence variant, intron variant, missense variant
rs122460155	C>T	Pathogenic	Coding sequence variant, missense variant
rs143383382	G>A,T	Likely-pathogenic	Coding sequence variant, synonymous variant, intron variant, stop gained
rs144630754	C>T	Conflicting-interpretations-of-pathogenicity	Intron variant, missense variant, coding sequence variant
rs145946864	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs201424543	C>G,T	Benign, likely-pathogenic	Missense variant, coding sequence variant
rs886041134	C>T	Pathogenic	Missense variant, coding sequence variant
rs886041135	G>A	Pathogenic	Stop gained, coding sequence variant
rs1085307895	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs1131691809	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs1555909466	A>G	Likely-pathogenic	Intron variant, missense variant, coding sequence variant
rs1555910687	AAG>-	Pathogenic	Intron variant, inframe deletion, coding sequence variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001501	Process	Skeletal system development	TAS	7720070
GO:0004065	Function	Arylsulfatase activity	IBA
GO:0004065	Function	Arylsulfatase activity	IDA	9497243
GO:0004065	Function	Arylsulfatase activity	IEA
GO:0004065	Function	Arylsulfatase activity	TAS	9192838
GO:0005788	Component	Endoplasmic reticulum lumen	IEA
GO:0005788	Component	Endoplasmic reticulum lumen	TAS
GO:0005794	Component	Golgi apparatus	IDA	9497243
GO:0005794	Component	Golgi apparatus	IEA
GO:0005795	Component	Golgi stack	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0070062	Component	Extracellular exosome	HDA	19056867

Other IDs

• MIM: 300180
• HGNC: 719
• e!Ensembl: ENSG00000157399

Protein

• UniProt ID: P51690
• Protein name: Arylsulfatase L (EC 3.1.6.1) (Arylsulfatase E) (ASE)
• Protein function: Exhibits arylsulfatase activity towards the artificial substrate 4-methylumbelliferyl sulfate (PubMed:7720070, PubMed:9497243). May be essential for the correct composition of cartilage and bone matrix during development (PubMed:7720070). Has no
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00884	Sulfatase	38 → 424	Sulfatase	Family
  PF14707	Sulfatase_C	448 → 582		Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in the pancreas, liver and kidney. {ECO:0000269|PubMed:7720070}.
• Sequence:

  MLHLHHSCLCFRSWLPAMLAVLLSLAPSASSDISASRPNILLLMADDLGIGDIGCYGNNT
  MRTPNIDRLAEDGVKLTQHISAASLCTPSRAAFLTGRYPVRSGMVSSIGYRVLQWTGASG
  GLPTNETTFAKILKEKGYATGLIGKWHLGLNCESASDHCHHPLHHGFDHFYGMPFSLMGD
  CARWELSEKRVNLEQKLNFLFQVLALVALTLVAGKLTHLIPVSWMPVIWSALSAVLLLAS
  SYFVGALIVHADCFLMRNHTITEQPMCFQRTTPLILQEVASFLKRNKHGPFLLFVSFLHV
  HIPLITMENFLGKSLHGLYGDNVEEMDWMVGRILDTLDVEGLSNSTLIYFTSDHGGSLEN
  QLGNTQYGGWNGIYKGGKGMGGWEGGIRVPGIFRWPGVLPAGRVIGEPTSLMDVFPTVVR
  LAGGEVPQDRVIDGQDLLPLLLGTAQHSDHEFLMHYCERFLHAARWHQRDRGTMWKVHFV
  TPVFQPEGAGACYGRKVCPCFGEKVVHHDPPLLFDLSRDPSETHILTPASEPVFYQVMER
  VQQAVWEHQRTLSPVPLQLDRLGNIWRPWLQPCCGPFPLCWCLREDDPQ

• Sequence length: 589

Pathways

Reactome:

Glycosphingolipid metabolism
The activation of arylsulfatases

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Chondrodysplasia punctata, brachytelephalangic, autosomal	Likely pathogenic; Pathogenic	rs2147394157, rs2147401174, rs2147401694, rs1335931206, rs2518385575, rs2518385011, rs372316277, rs2089231699	RCV002242769 RCV002238542 RCV002238544 RCV003064667 RCV003596277 RCV003596386 RCV003596457 RCV002240261	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Nonpapillary renal cell carcinoma	Likely pathogenic; Pathogenic	rs2147349066	RCV005930026	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
X-linked chondrodysplasia punctata 1	Likely pathogenic; Pathogenic	rs2147394157, rs2147349066, rs1272438892, rs2518346615, rs2518369116, rs122460152, rs122460153, rs80338711, rs122460154, rs122460155, rs28935474, rs2518346073, rs80338710	RCV001376980 RCV002238739 RCV002272711 RCV002306434 RCV002472154 RCV000012279 RCV000012280 RCV000012281 RCV000012282 RCV000012283 RCV000012284 RCV003486302 RCV000020090	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ARSL-related disorder	Benign; Likely benign; Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BRACHYTELEPHALANGIC CHONDRODYSPLASIA PUNCTATA	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHONDRODYSPLASIA PUNCTATA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHONDRODYSPLASIA PUNCTATA 1, X-LINKED RECESSIVE	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Coffin-Siris syndrome 1	Conflicting classifications of pathogenicity	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Colon adenocarcinoma	Conflicting classifications of pathogenicity; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONNECTIVE TISSUE DISEASES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Connective tissue disorder	Conflicting classifications of pathogenicity; Benign; Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DESBUQUOIS SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Epilepsy	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intellectual disability	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Conflicting classifications of pathogenicity; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adrenoleukodystrophy	Adrenoleukodystrophy	Pubtator	2339111	Associate	★☆☆☆☆ Found in Text Mining only
Arteriosclerosis	Arteriosclerosis	BEFREE	31094087		★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	BEFREE	31094087		★☆☆☆☆ Found in Text Mining only
Autoimmune Diseases	Autoimmune Diseases	BEFREE	23470839		★☆☆☆☆ Found in Text Mining only
Brachytelephalangic Chondrodysplasia Punctata	Brachytelephalangic Chondrodysplasia Punctata	GENOMICS_ENGLAND_DG	12567415, 7720070		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Brachytelephalangic Chondrodysplasia Punctata	Brachytelephalangic Chondrodysplasia Punctata	UNIPROT_DG	12567415, 7720070, 9409863		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Brachytelephalangic Chondrodysplasia Punctata	Brachytelephalangic Chondrodysplasia Punctata	BEFREE	18348268, 19839041, 23470839		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Brachytelephalangic chondrodysplasia punctata	Brachytelephalangic Chondrodysplasia Punctata	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Brachytelephalangic Chondrodysplasia Punctata	Brachytelephalangic Chondrodysplasia Punctata	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cartilage Diseases	Cartilage Diseases	BEFREE	9229115		★☆☆☆☆ Found in Text Mining only
Cataract	Cataract	HPO_DG			★☆☆☆☆ Found in Text Mining only
Chondrodysplasia Punctata	Chondrodysplasia Punctata	BEFREE	10607480, 11186896, 11260213, 12567415, 15246527, 15309625, 16470742, 18348268, 19839041, 20523025, 24458983, 28799855, 9229115, 9409863, 9497243		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Chondrodysplasia Punctata	Chondrodysplasia Punctata	GENOMICS_ENGLAND_DG	7720070		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Chondrodysplasia Punctata	Chondrodysplasia	Pubtator	7720070	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congestive heart failure	Congestive Heart Failure	BEFREE	31155469		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	31155469		★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	BEFREE	11260213		★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Growth Disorders	Growth disorder	Pubtator	36026611	Associate	★☆☆☆☆ Found in Text Mining only
Heart Diseases	Heart Diseases	BEFREE	28165130		★☆☆☆☆ Found in Text Mining only
Heart failure	Heart Failure	BEFREE	31155469		★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	BEFREE	24903240		★☆☆☆☆ Found in Text Mining only
Hypogonadism	Hypogonadism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ichthyoses	Ichthyosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Keutel syndrome	Keutel Syndrome	BEFREE	24458983		★☆☆☆☆ Found in Text Mining only
Kidney Diseases	Kidney Disease	BEFREE	24903240		★☆☆☆☆ Found in Text Mining only
Kidney Failure	Kidney Failure	BEFREE	24903240		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	25889339		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of testis	Malignant Neoplasm Of Testis	BEFREE	15885892		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	25315065		★☆☆☆☆ Found in Text Mining only
Malignant Testicular Germ Cell Tumor	Malignant testicular germ cell tumor	BEFREE	15885892		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	25889339		★☆☆☆☆ Found in Text Mining only
Respiratory Failure	Respiratory Failure	BEFREE	28799855		★☆☆☆☆ Found in Text Mining only
Testicular Diseases	Testicular disease	Pubtator	36026611	Associate	★☆☆☆☆ Found in Text Mining only
Turner Syndrome	Turner Syndrome	BEFREE	20422505, 25366798		★☆☆☆☆ Found in Text Mining only
Turner Syndrome	Turner syndrome	Pubtator	25366798	Associate	★☆☆☆☆ Found in Text Mining only
Uterine Cervical Neoplasms	Uterine neoplasm	Pubtator	32306508	Associate	★☆☆☆☆ Found in Text Mining only
X-Linked Chondrodysplasia Punctata 1	Chondrodysplasia Punctata X-Linked	BEFREE	18348268		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
X-Linked Chondrodysplasia Punctata 1	Chondrodysplasia Punctata X-Linked	CTD_human_DG	7720070		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
X-Linked Chondrodysplasia Punctata 1	Chondrodysplasia Punctata X-Linked	GENOMICS_ENGLAND_DG	7720070		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)