GeneBe

STS

protein-coding

steroid sulfatase, the group of Sulfatases|MicroRNA protein coding host genes

Gene summary

This gene encodes a multi-pass membrane protein that is localized to the endoplasmic reticulum. It belongs to the sulfatase family and hydrolyzes several 3-beta-hydroxysteroid sulfates, which serve as metabolic precursors for estrogens, androgens, and cholesterol. Mutations in this gene are associated with X-linked ichthyosis (XLI). Alternatively spliced transcript variants resulting from the use of different promoters have been described for this gene (PMID:17601726). [provided by RefSeq, Mar 2016]

Previous symbols:
  • ARSC1

MANE transcript

NM_001320752.2

Inheritance

XL

ClinVar variants

P:19U:152B:43

Top phenotype

Steroid sulfatase deficiency

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chrX:7,147,237-7,804,358

External References & Databases

Ensembl (ENSG00000101846)NCBI Gene (412)OMIM (300747)HGNC:11425GenCCUniProt (P08842)AlphaFoldClinVar (STS)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~657.1 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

recessive X-linked ichthyosisSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010622

Submitter: PanelApp Australia

recessive X-linked ichthyosisSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010622

Submitter: Labcorp Genetics (formerly Invitae)

recessive X-linked ichthyosisSUPPORTIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010622

Submitter: Orphanet

recessive X-linked ichthyosisSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010622

Submitter: Genomics England PanelApp

recessive X-linked ichthyosisDEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010622

Submitter: G2P

Clinical Genomic Database (CGD)

Steroid sulfatase deficiencyXL

Manifestation: Biochemical; Dermatologic; Obstetric; Oncologic; Ophthalmologic; Genitourinary

Intervention: Obstetric; Oncologic; Genitourinary

Rationale: In pregnancy, affected females may manifest with birth/delivery complications, such as failure to progress in labor, and awareness may allow improved planning and management of pregnancy and delivery; Individuals are at risk for testicular cancer, and awareness may allow preventive measures/early management, which may decrease morbidity and mortality

Refs: 3864397; 5303230; 5307231; 6135610; 6140547; 6234482; 6652948; 6135610; 6929654; 6482910; 2866054; 3480263; 3480541; 3032454; 1539590; 7546451; 9252398; 10583107; 10692123; 11477606; 16191859; 16403384; 18076704; 19200188; 20236202; 21530180; 22419362; 22486194; 23442483Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to STS variants in ClinVar

5 Conditions Cataloged
not providedTotal: 85
Inborn genetic diseasesTotal: 70
X-linked ichthyosis with steryl-sulfatase deficiencyTotal: 23
STS-related disorderTotal: 9
not specifiedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001320752.2. 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.

EffectPLPVUSLBBSum
synonymous
11
clinvar
9
clinvar
7
clinvar
 27
missense
3
clinvar
9
clinvar
123
clinvar
16
clinvar
11
clinvar
 162
nonsense
2
clinvar
6
clinvar
 8
start loss
0
frameshift
2
clinvar
 2
splice donor/acceptor (+/-2bp)
2
clinvar
1
clinvar
12
clinvar
 15
Total7121522518214

Highest pathogenic variant AF is 0.0000054727698

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001320752.2RefSeqNP_001307681.29MANE Select
ENST00000674429.1EnsemblENSP00000501534.19MANE Select
NM_000351.7RefSeqNP_000342.39Standard
NM_001320750.3RefSeqNP_001307679.110Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Steroid hormone biosynthesis - Homo sapiens (human)
  • Aromatase Inhibitor Pathway (Multiple Tissues), Pharmacodynamics
  • 17-Beta Hydroxysteroid Dehydrogenase III Deficiency
  • Androgen and Estrogen Metabolism
  • Aromatase deficiency

Biological Process

  • glycosphingolipid metabolic process
  • steroid catabolic process
  • female pregnancy
  • epidermis development

Molecular Function

  • steryl-sulfatase activity
  • sulfuric ester hydrolase activity
  • metal ion binding

Cellular Component

  • lysosome
  • endosome
  • endoplasmic reticulum
  • endoplasmic reticulum lumen
  • endoplasmic reticulum membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000217961
Coding exons
10
Length
135355
Individuals with no LoFs
125693
Homozygous LoFs
0
Heterozygous LoFs
2
Defined
125695
p
0.00000796
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.091942420.8030.00001983842
Missense (PolyPhen)66107.590.613441717
Synonymous-0.8271141031.100.000009391160
Loss of Function3.00214.20.1419.75e-7246

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish0.0000630.000046rare
European (Non-Finnish)0.0000120.0000088rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Conversion of sulfated steroid precursors to estrogens during pregnancy.;
Disease
DISEASE: Ichthyosis, X-linked (IXL) [MIM:308100]: A keratinization disorder manifesting with mild erythroderma and generalized exfoliation of the skin within a few weeks after birth. Affected boys later develop large, polygonal, dark brown scales, especially on the neck, extremities, trunk, and buttocks. {ECO:0000269|PubMed:10679952, ECO:0000269|PubMed:10844566, ECO:0000269|PubMed:1539590, ECO:0000269|PubMed:9252398}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.856

Intolerance Scores

RVIS EVS
-0.18
RVIS percentile EVS
40.45

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.836

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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