ARSK

protein-coding

arylsulfatase family member K, the group of Sulfatases

Gene summary

Sulfatases (EC 3.1.5.6), such as ARSK, hydrolyze sulfate esters from sulfated steroids, carbohydrates, proteoglycans, and glycolipids. They are involved in hormone biosynthesis, modulation of cell signaling, and degradation of macromolecules (Sardiello et al., 2005 [PubMed 16174644]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_198150.3

Inheritance

ClinVar variants

P:5U:75B:12

Top phenotype

Mucopolysaccharidosis, type X

gnomAD constraint

pLI —, LoF o/e 0.73

Max pathogenic AF

—

Genomic locus

chr5:95,555,101-95,605,102

External References & Databases

Ensembl (ENSG00000164291)

Transcript & Mutation Effects

hg38 • Region Span ~50.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

mucopolysaccharidosis, type 10STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030524

Submitter: Labcorp Genetics (formerly Invitae)

mucopolysaccharidosisSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0019249

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Mucopolysaccharidosis, type XAR

Manifestation: Biochemical; Cardiovascular;Craniofacial; Musculoskeletal

Intervention: Cardiovascular

Rationale: The condition can include cardiovascular manifestations, and awareness may allow surveillance and early detection, which may lead to improved management

Refs: 34916232

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ARSK variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 80

Mucopolysaccharidosis, type 10Total: 7

not providedTotal: 3

ARSK-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_198150.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				6 clinvar	2 clinvar	8
missense	1 clinvar		72 clinvar	4 clinvar		77
nonsense	2 clinvar		2 clinvar			4
start loss						0
frameshift		2 clinvar				2
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	3	2	75	10	2	92

Highest pathogenic variant AF is 0.000025416364

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_198150.3	RefSeq	NP_937793.1	8	MANE Select
ENST00000380009.9	Ensembl	ENSP00000369346.4	8	MANE Select
ENST00000504763.1	Ensembl	ENSP00000422126.1	2	Standard
ENST00000504763.2	Ensembl	ENSP00000422126.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of lipids
Post-translational protein modification
Metabolism of proteins
The activation of arylsulfatases
Gamma carboxylation, hypusine formation and arylsulfatase activation

Molecular Function

arylsulfatase activity
metal ion binding

Cellular Component

extracellular region
endoplasmic reticulum lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000380009
Coding exons: 8
Length: 49991
Individuals with no LoFs: 125692
Homozygous LoFs: 0
Heterozygous LoFs: 56
Defined: 125748
p: 0.000223

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.250	291	279	1.04	0.0000136	3513
Missense (PolyPhen)		116	119.05	0.97437		1518
Synonymous	-0.0500	100	99.4	1.01	0.00000498	1012
Loss of Function	1.24	18	24.6	0.731	0.00000128	304

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.00030	0.00026	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00054	0.00054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00023	0.00023	rare
South Asian	0.00025	0.00023	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.218
RVIS EVS: -0.27
RVIS percentile EVS: 34.82

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.574

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium