STS

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

Basic information

Region (hg38): X:7147237-7804358

Previous symbols: [ "ARSC1" ]

Links

ENSG00000101846 ∙ NCBI:412 ∙ OMIM:300747 ∙ HGNC:11425 ∙ Uniprot:P08842 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• recessive X-linked ichthyosis (Definitive), mode of inheritance: XLR
• recessive X-linked ichthyosis (Strong), mode of inheritance: XL
• recessive X-linked ichthyosis (Strong), mode of inheritance: XL
• recessive X-linked ichthyosis (Supportive), mode of inheritance: XL
• recessive X-linked ichthyosis (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Steroid sulfatase deficiency	XL	Obstetric; Oncologic; Genitourinary	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	Biochemical; Dermatologic; Obstetric; Oncologic; Ophthalmologic; Genitourinary	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; 23442483

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the STS gene.

• X-linked ichthyosis with steryl-sulfatase deficiency (2 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the STS gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				7	3	10
missense	1	4	36	10	6	57
nonsense	2					2
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	4	1	6
non coding			3	7	12	22
Total	3	5	39	24	21

Variants in STS

This is a list of pathogenic ClinVar variants found in the STS region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-7148071-T-C		not specified	Uncertain significance (Apr 25, 2022)
X-7148092-C-A		not specified	Uncertain significance (Jan 31, 2024)
X-7219197-C-T			Benign (Mar 26, 2020)
X-7252884-C-G			Benign (Aug 20, 2019)
X-7253206-A-T			Benign (Sep 01, 2022)
X-7253251-G-A		STS-related disorder	Benign/Likely benign (Feb 01, 2023)
X-7253264-C-T			Uncertain significance (Oct 12, 2020)
X-7253296-G-A		Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 18, 2022)
X-7253334-C-G		Inborn genetic diseases	Uncertain significance (Nov 17, 2023)
X-7257233-T-G			Likely benign (Dec 31, 2019)
X-7257242-G-A		STS-related disorder	Benign (Jun 26, 2018)
X-7257252-A-C		Inborn genetic diseases	Uncertain significance (Jan 23, 2023)
X-7257258-C-T			Benign (Dec 31, 2019)
X-7257273-G-T			Pathogenic (Jan 15, 2020)
X-7257274-G-A			Uncertain significance (Jul 06, 2022)
X-7257307-C-T			Uncertain significance (Aug 15, 2023)
X-7257311-G-A			Likely benign (Jul 29, 2022)
X-7257323-C-G			Uncertain significance (Jan 20, 2024)
X-7257336-A-G			Likely benign (May 23, 2023)
X-7257345-C-T		X-linked ichthyosis with steryl-sulfatase deficiency	Uncertain significance (Jan 19, 2024)
X-7257354-G-A		Inborn genetic diseases	Uncertain significance (Apr 14, 2016)
X-7257367-ACCT-A		X-linked ichthyosis with steryl-sulfatase deficiency	Benign/Likely benign (Jan 02, 2024)
X-7257468-A-G		Inborn genetic diseases	Uncertain significance (Jun 12, 2023)
X-7257478-G-A		X-linked ichthyosis with steryl-sulfatase deficiency	Pathogenic (Apr 30, 2019)
X-7257483-C-T		Inborn genetic diseases	Uncertain significance (Oct 12, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
STS	protein_coding	protein_coding	ENST00000217961	10	135355

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.809	0.191	125693	0	2	125695	0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.09	194	242	0.803	0.0000198	3842
Missense in Polyphen		66	107.59	0.61344		1717
Synonymous	-0.827	114	103	1.10	0.00000939	1160
Loss of Function	3.00	2	14.2	0.141	9.75e-7	246

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000625	0.0000462
European (Non-Finnish)	0.0000122	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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.
• Pathway: Steroid hormone biosynthesis - Homo sapiens (human);Aromatase Inhibitor Pathway (Multiple Tissues), Pharmacodynamics;17-Beta Hydroxysteroid Dehydrogenase III Deficiency;Androgen and Estrogen Metabolism;Aromatase deficiency;Vitamin D Receptor Pathway;Estrogen metabolism;Metabolism of lipids;Post-translational protein modification;Metabolism of proteins;Tyrosine metabolism;The activation of arylsulfatases;Gamma carboxylation, hypusine formation and arylsulfatase activation;Androgen and estrogen biosynthesis and metabolism;Metabolism;C21-steroid hormone biosynthesis and metabolism;Glycosphingolipid metabolism;Sphingolipid metabolism (Consensus)

Recessive Scores

• pRec: 0.856

Intolerance Scores

• rvis_EVS: -0.18
• rvis_percentile_EVS: 40.45

Haploinsufficiency Scores

• pHI: 0.224
• hipred: N
• hipred_score: 0.478
• ghis: 0.496

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.836

Gene Damage Prediction

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

Gene ontology

• Biological process: glycosphingolipid metabolic process;steroid catabolic process;female pregnancy;epidermis development
• Cellular component: lysosome;endosome;endoplasmic reticulum;endoplasmic reticulum lumen;endoplasmic reticulum membrane;Golgi apparatus;plasma membrane;membrane;integral component of membrane;intracellular membrane-bounded organelle
• Molecular function: steryl-sulfatase activity;sulfuric ester hydrolase activity;metal ion binding