ARSI

protein-coding

arylsulfatase family member I, the group of Sulfatases

Gene summary

This gene encodes a protein that belongs to a large family of sulfatases that hydrolyze sulfate esters and sulfamates. Members of this family play a role in several cellular processes, including hormone synthesis, cell signaling in development and degradation of macromolecules. The protein encoded by this gene is thought to be secreted, and to function in extracellular space. [provided by RefSeq, Jul 2016]

MANE transcript

NM_001012301.4

Inheritance

ClinVar variants

U:140B:51

Top phenotype

autosomal recessive spastic paraplegia type 66

gnomAD constraint

pLI —, LoF o/e 0.99

Max pathogenic AF

—

Genomic locus

chr5:150,296,343-150,339,307

External References & Databases

Ensembl (ENSG00000183876)

Transcript & Mutation Effects

hg38 • Region Span ~43.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal recessive spastic paraplegia type 66SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018418

Submitter: Orphanet

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ARSI variants in ClinVar

5 Conditions Cataloged

Spastic paraplegiaTotal: 131

not specifiedTotal: 89

ARSI-related disorderTotal: 12

not providedTotal: 11

Hereditary spastic paraplegiaTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001012301.4. 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				37 clinvar	7 clinvar	44
missense			130 clinvar	6 clinvar	1 clinvar	137
nonsense			8 clinvar			8
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)						0
Total	0	0	140	43	8	191

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001012301.4	RefSeq	NP_001012301.1	2	MANE Select
ENST00000328668.8	Ensembl	ENSP00000333395.7	2	MANE Select
ENST00000509146.1	Ensembl	ENSP00000420955.1	1	Standard
ENST00000515301.2	Ensembl	ENSP00000426879.2	1	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
protein binding
metal ion binding

Cellular Component

extracellular region
endoplasmic reticulum lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000328668
Coding exons: 2
Length: 42965
Individuals with no LoFs: 125662
Homozygous LoFs: 0
Heterozygous LoFs: 86
Defined: 125748
p: 0.000342

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.853	339	386	0.878	0.0000262	3667
Missense (PolyPhen)		136	166.02	0.81915		1655
Synonymous	0.210	154	157	0.979	0.0000102	1202
Loss of Function	0.0423	22	22.2	0.990	0.00000129	196

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00060	0.00060	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00029	0.00028	rare
South Asian	0.00099	0.00098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Displays arylsulfatase activity at neutral pH, when co- expressed with SUMF1; arylsulfatase activity is measured in the secretion medium of retinal cell line, but no activity is recorded when measured in cell extracts. {ECO:0000269|PubMed:16500042, ECO:0000269|PubMed:19262745}.;

Recessive Scores

pRec: 0.158

Intolerance Scores

LoFtool: 0.136
RVIS EVS: -1.04
RVIS percentile EVS: 7.8

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.352

Gene Damage Prediction

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