ARSG

protein-coding

arylsulfatase G, the group of Sulfatases

Gene summary

The protein encoded by this gene belongs to the sulfatase enzyme family. Sulfatases hydrolyze sulfate esters from sulfated steroids, carbohydrates, proteoglycans, and glycolipids. They are involved in hormone biosynthesis, modulation of cell signaling, and degradation of macromolecules. This protein displays arylsulfatase activity at acidic pH, as is typical of lysosomal sulfatases, and has been shown to localize in the lysosomes. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2012]

MANE transcript

NM_001267727.2

Inheritance

ClinVar variants

P:52U:201B:135

Top phenotype

Usher syndrome, type IV

gnomAD constraint

pLI —, LoF o/e 0.76

Max pathogenic AF

—

Genomic locus

chr17:68,259,182-68,422,731

External References & Databases

Ensembl (ENSG00000141337)

Transcript & Mutation Effects

hg38 • Region Span ~163.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Usher syndrome, type 4LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0029141

Submitter: Ambry Genetics

Usher syndrome type 3SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0016485

Submitter: Orphanet

Usher syndrome, type 4STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0029141

Submitter: PanelApp Australia

Usher syndrome, type 4STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0029141

Submitter: Labcorp Genetics (formerly Invitae)

Usher syndrome, type 4MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0029141

Submitter: Genomics England PanelApp

Usher syndrome, type 4LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0029141

Submitter: G2P

Clinical Genomic Database (CGD)

Usher syndrome, type IVAR

Manifestation: Audiologic/Otolaryngologic; Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Comments: The onset of hearing loss has been described as postlingual

Refs: 29300381; 32455177; 33300174; 33629623

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ARSG variants in ClinVar

7 Conditions Cataloged

not providedTotal: 402

not specifiedTotal: 129

ARSG-related disorderTotal: 45

Usher syndrome, type 4Total: 18

Retinal dystrophyTotal: 2

Retinal disorderTotal: 1

Usher syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001267727.2. 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			3 clinvar	116 clinvar	3 clinvar	122
missense	2 clinvar	6 clinvar	191 clinvar	14 clinvar	2 clinvar	215
nonsense	8 clinvar	4 clinvar				12
start loss						0
frameshift	8 clinvar	5 clinvar	6 clinvar			19
splice donor/acceptor (+/-2bp)	6 clinvar	13 clinvar	1 clinvar			20
Total	24	28	201	130	5	388

Highest pathogenic variant AF is 0.00017781093

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 55 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001267727.2	RefSeq	NP_001254656.1	11	MANE Select
ENST00000621439.5	Ensembl	ENSP00000480910.1	11	MANE Select
NM_001352899.2	RefSeq	NP_001339828.1	11	Standard
NM_001352900.2	RefSeq	NP_001339829.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Lysosome - Homo sapiens (human)
Metabolism of lipids
Post-translational protein modification
Metabolism of proteins
The activation of arylsulfatases

Biological Process

sulfur compound metabolic process

Molecular Function

arylsulfatase activity
metal ion binding

Cellular Component

extracellular space
lysosome
endoplasmic reticulum
endoplasmic reticulum lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000448504
Coding exons: 11
Length: 163550
Individuals with no LoFs: 125658
Homozygous LoFs: 0
Heterozygous LoFs: 90
Defined: 125748
p: 0.000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.893	274	319	0.859	0.0000185	3399
Missense (PolyPhen)		96	121.71	0.78873		1236
Synonymous	0.786	115	126	0.911	0.00000809	1069
Loss of Function	1.03	17	22.2	0.765	9.43e-7	258

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00049	0.00049	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00071	0.00071	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00040	0.00040	rare
South Asian	0.00046	0.00046	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Displays arylsulfatase activity at acidic pH with pseudosubstrates, such as p-nitrocatechol sulfate and also, but with lower activity, p-nitrophenyl sulfate and 4- methylumbelliferyl sulfate. {ECO:0000269|PubMed:18283100}.;

Recessive Scores

pRec: 0.126

Intolerance Scores

LoFtool: 0.171
RVIS EVS: 0.31
RVIS percentile EVS: 72.75

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.443

Gene Damage Prediction

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