Details for: ARSF

Gene ID: 416

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: ARSF

Ensembl ID: ENSG00000062096

Description: arylsulfatase F

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • epithelial cell of proximal tubule CL0002306
    CSI 3.91
    rCSI 9.55%
    PRS 94.87
  • sncg GABAergic cortical interneuron CL4023015
    CSI 3.69
    rCSI 5.93%
    PRS 93.84
  • VIP GABAergic cortical interneuron CL4023016
    CSI 3.54
    rCSI 4.23%
    PRS 93.76
  • suprabasal keratinocyte CL4033013
    CSI 2.53
    rCSI 4.13%
    PRS 82.44
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 2.48
    rCSI 3.01%
    PRS 86.06
  • basal cell of epidermis CL0002187
    CSI 1.7
    rCSI 3.01%
    PRS 80.71
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.45
    rCSI 3.26%
    PRS 93.81
  • melanocyte of skin CL1000458
    CSI 1.25
    rCSI 1.71%
    PRS 81.73

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [ARSF](/details-gene/416) (arylsulfatase F) is a protein-coding gene located on the X chromosome that encodes a member of the sulfatase family of enzymes. These enzymes are critical for the hydrolysis of sulfate esters from a variety of substrates, including steroids, glycosaminoglycans, and glycolipids. Functionally, [ARSF](/details-gene/416) exhibits [Arylsulfatase activity](/details-ontology/GO:0004065) and is localized to the [Endoplasmic reticulum lumen](/details-ontology/GO:0005788). Its expression profile is notably diverse, with high significance in renal [epithelial cell of proximal tubule](/details-cell/CL0002306), distinct neuronal subtypes such as [sncg GABAergic cortical interneuron](/details-cell/CL4023015), and various skin cells including [suprabasal keratinocyte](/details-cell/CL4033013). The gene is part of a cluster of sulfatase genes on chromosome Xp22.3, and mutations in this region are associated with X-linked chondrodysplasia punctata ([OMIM [300003](https://omim.org/entry/300003)]), a disorder of cartilage and bone development ([Link](https://doi.org/10.1016/0092-8674(95)90367-4)). ## Cellular Roles and Expression Landscape The expression pattern of [ARSF](/details-gene/416) suggests specialized roles across multiple, distinct tissue types. - **Overall**, the gene shows its highest significance in the [epithelial cell of proximal tubule](/details-cell/CL0002306) (CSI: 3.91), indicating a potentially crucial role in metabolic or reabsorptive processes within the kidney. - A second major site of expression is the central nervous system, specifically within certain inhibitory interneuron populations, including [sncg GABAergic cortical interneuron](/details-cell/CL4023015) (CSI: 3.69) and [VIP GABAergic cortical interneuron](/details-cell/CL4023016) (CSI: 3.54). This points towards a specific function in neuronal biology, possibly related to the metabolism of sulfated lipids that are abundant in neural membranes. - The gene is also a significant marker in the skin, with high CSI scores in [suprabasal keratinocyte](/details-cell/CL4033013) (CSI: 2.53), [basal cell of epidermis](/details-cell/CL0002187) (CSI: 1.70), and [melanocyte of skin](/details-cell/CL1000458) (CSI: 1.25). This pattern suggests an involvement in epidermal differentiation, barrier formation, or pigmentation. - Finally, a notable level of significance is observed in [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203) (CSI: 2.48), hinting at a role in the long-term maintenance or function of this adaptive immune cell subset. The broad but specific expression across renal, neural, epidermal, and immune cells highlights [ARSF](/details-gene/416) as a multifunctional enzyme whose role is tailored to the metabolic needs of diverse cellular contexts. ## Pathways and Molecular Function The known molecular functions and pathway involvements of [ARSF](/details-gene/416) are consistent with its role as a sulfatase. Its primary molecular function is [Arylsulfatase activity](/details-ontology/GO:0004065), which requires [Metal ion binding](/details-ontology/GO:0046872) for catalysis. This activity is part of a broader biological process known as [The activation of arylsulfatases](/details-pathway/R-HSA-1663150), which itself is a form of [Post-translational protein modification](/details-pathway/R-HSA-597592). The substrates for [ARSF](/details-gene/416) are likely lipids, as suggested by its strong association with [Metabolism of lipids](/details-pathway/R-HSA-556833) pathways. More specifically, it is implicated in [Sphingolipid metabolism](/details-pathway/R-HSA-428157) and [Glycosphingolipid catabolism](/details-pathway/R-HSA-9840310). This functional annotation aligns well with its high expression in cell types that rely on complex lipid structures for their function, such as neurons for myelination and signaling, and keratinocytes for building the waterproof skin barrier. ## Research Directions The diverse expression pattern of [ARSF](/details-gene/416) and its link to a developmental disorder offer several avenues for future research. The gene is part of a cluster on chromosome Xp22.3, and its deficiency is implicated in X-linked chondrodysplasia punctata, highlighting its non-redundant role in development despite the presence of other arylsulfatases ([Link](https://doi.org/10.1006/geno.1997.4716)). ### Testable Hypotheses 1. **Renal Function:** Given its top-ranking significance in [epithelial cell of proximal tubule](/details-cell/CL0002306), [ARSF](/details-gene/416) is hypothesized to be essential for the catabolism and reabsorption of sulfated steroids or lipids from the glomerular filtrate. Its dysfunction may lead to a specific form of renal tubular acidosis or lipiduria not currently associated with the gene. 2. **Epidermal Barrier Integrity:** The high significance of [ARSF](/details-gene/416) in both [basal cell of epidermis](/details-cell/CL0002187) and [suprabasal keratinocyte](/details-cell/CL4033013), combined with its role in [Sphingolipid metabolism](/details-pathway/R-HSA-428157), suggests it is critical for synthesizing the lipid lamellae that form the skin's waterproof barrier. Reduced [ARSF](/details-gene/416) activity could lead to increased transepidermal water loss and a phenotype resembling ichthyosis. 3. **Neuronal Homeostasis:** The specific expression in GABAergic interneurons suggests [ARSF](/details-gene/416) is involved in degrading sulfated glycosphingolipids to maintain neuronal membrane health or regulate signaling pathways in these inhibitory circuits. A loss of function could result in substrate accumulation, leading to neuronal dysfunction and contributing to neurological symptoms. ### Proposed Experiment To test hypothesis #2 regarding skin barrier function, a conditional knockout of [ARSF](/details-gene/416) in mice using a keratinocyte-specific Cre-Lox system (e.g., KRT14-Cre) would be highly informative. The resulting mouse model could be assessed for skin abnormalities, with transepidermal water loss (TEWL) measurements quantifying barrier integrity. Furthermore, lipidomic analysis of the epidermis from these mice compared to wild-type controls would directly reveal the specific sulfated lipid substrates that accumulate in the absence of [ARSF](/details-gene/416) function. ### Therapeutic Potential As [ARSF](/details-gene/416) is an enzyme, its primary clinical relevance lies in loss-of-function disorders like chondrodysplasia punctata ([OMIM [300003](https://omim.org/entry/300003)]). This makes it a potential candidate for enzyme replacement therapy (ERT), where a recombinant form of the enzyme could be administered to supplement the deficient protein. However, the diverse tissues affected and the enzyme's intracellular location in the endoplasmic reticulum present significant drug delivery challenges. Targeting the gene for inhibition is unlikely to be a therapeutic strategy, as its function appears to be homeostatic.

Genular Protein ID: 1337108659

Symbol: ARSF_HUMAN

Name: Arylsulfatase F

UniProtKB Accession Codes:

P54793 Q8TCC5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 11 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 3 Ensembl 2 GO 4 Gene3D 3 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 2 RefSeq 3 Rhea 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9192838

Title: Identification by shotgun sequencing, genomic organization, and functional analysis of a fourth arylsulfatase gene (ARSF) from the Xp22.3 region.

PubMed ID: 9192838

DOI: 10.1006/geno.1997.4716

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 7720070

Title: A cluster of sulfatase genes on Xp22.3: mutations in chondrodysplasia punctata (CDPX) and implications for warfarin embryopathy.

PubMed ID: 7720070

DOI: 10.1016/0092-8674(95)90367-4

Sequence Information:

  • Length: 590
  • Mass: 65940
  • Checksum: EA9B7289040AE79A
  • Sequence:
    • MRPRRPLVFM SLVCALLNTC QAHRVHDDKP NIVLIMVDDL GIGDLGCYGN DTMRTPHIDR 
LAREGVRLTQ HISAASLCSP SRSAFLTGRY PIRSGMVSSG NRRVIQNLAV PAGLPLNETT 
LAALLKKQGY STGLIGKWHQ GLNCDSRSDQ CHHPYNYGFD YYYGMPFTLV DSCWPDPSRN 
TELAFESQLW LCVQLVAIAI LTLTFGKLSG WVSVPWLLIF SMILFIFLLG YAWFSSHTSP 
LYWDCLLMRG HEITEQPMKA ERAGSIMVKE AISFLERHSK ETFLLFFSFL HVHTPLPTTD 
DFTGTSKHGL YGDNVEEMDS MVGKILDAID DFGLRNNTLV YFTSDHGGHL EARRGHAQLG 
GWNGIYKGGK GMGGWEGGIR VPGIVRWPGK VPAGRLIKEP TSLMDILPTV ASVSGGSLPQ 
DRVIDGRDLM PLLQGNVRHS EHEFLFHYCG SYLHAVRWIP KDDSGSVWKA HYVTPVFQPP 
ASGGCYVTSL CRCFGEQVTY HNPPLLFDLS RDPSESTPLT PATEPLHDFV IKKVANALKE 
HQETIVPVTY QLSELNQGRT WLKPCCGVFP FCLCDKEEEV SQPRGPNEKR