Details for: ARSD

Gene ID: 414

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: ARSD

Ensembl ID: ENSG00000006756

Description: arylsulfatase D

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • lung neuroendocrine cell CL1000223
    CSI 6.85
    rCSI 10.14%
    PRS 87.04
  • colon epithelial cell CL0011108
    CSI 5.95
    rCSI 6.23%
    PRS 81.57
  • astrocyte of the cerebral cortex CL0002605
    CSI 4.15
    rCSI 9.29%
    PRS 68.4
  • midzonal region hepatocyte CL0019028
    CSI 3.1
    rCSI 7.27%
    PRS 83.11
  • epithelial cell of lung CL0000082
    CSI 2.98
    rCSI 2.47%
    PRS 85.14
  • epithelial cell of lower respiratory tract CL0002632
    CSI 2.93
    rCSI 2.27%
    PRS 87.47
  • secretory cell CL0000151
    CSI 2.79
    rCSI 2.91%
    PRS 83.37
  • goblet cell CL0000160
    CSI 2.79
    rCSI 2.63%
    PRS 82.36
  • alternatively activated macrophage CL0000890
    CSI 2.78
    rCSI 3.49%
    PRS 91.81
  • intrahepatic cholangiocyte CL0002538
    CSI 2.74
    rCSI 6.58%
    PRS 86.56
  • nasal mucosa goblet cell CL0002480
    CSI 2.65
    rCSI 3.07%
    PRS 86.77
  • pulmonary ionocyte CL0017000
    CSI 2.6
    rCSI 3.16%
    PRS 89.66
  • stem cell CL0000034
    CSI 2.59
    rCSI 2.5%
    PRS 78.52
  • brush cell of tracheobronchial tree CL0002075
    CSI 2.57
    rCSI 7.63%
    PRS 91.23
  • squamous epithelial cell CL0000076
    CSI 2.49
    rCSI 5.92%
    PRS 83.21
  • ionocyte CL0005006
    CSI 2.45
    rCSI 2.62%
    PRS 85.93
  • fallopian tube secretory epithelial cell CL4030006
    CSI 2.43
    rCSI 2.34%
    PRS 83.42
  • hematopoietic stem cell CL0000037
    CSI 2.42
    rCSI 1.61%
    PRS 86.33
  • enteroendocrine cell CL0000164
    CSI 2.37
    rCSI 3.24%
    PRS 83.34
  • BEST4+ enteroycte CL4030026
    CSI 2.34
    rCSI 2.9%
    PRS 84.71
  • intestine goblet cell CL0019031
    CSI 2.33
    rCSI 2.07%
    PRS 81.86
  • plasmacytoid dendritic cell, human CL0001058
    CSI 2.29
    rCSI 1.6%
    PRS 87.47
  • ciliated cell CL0000064
    CSI 2.29
    rCSI 3.71%
    PRS 79.08
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.29
    rCSI 2.07%
    PRS 82.71
  • parietal epithelial cell CL1000452
    CSI 2.26
    rCSI 6.04%
    PRS 76.77
  • respiratory basal cell CL0002633
    CSI 2.26
    rCSI 2.34%
    PRS 87.19
  • intestinal epithelial cell CL0002563
    CSI 2.25
    rCSI 2.36%
    PRS 81.69
  • ciliated epithelial cell CL0000067
    CSI 2.19
    rCSI 1.92%
    PRS 74.07
  • multi-ciliated epithelial cell CL0005012
    CSI 2.18
    rCSI 2.18%
    PRS 78.27
  • lung secretory cell CL1000272
    CSI 2.17
    rCSI 5.38%
    PRS 84.32
  • renal principal cell CL0005009
    CSI 2.15
    rCSI 5.58%
    PRS 83.92
  • renal alpha-intercalated cell CL0005011
    CSI 2.13
    rCSI 2.85%
    PRS 89.21
  • duct epithelial cell CL0000068
    CSI 2.13
    rCSI 3.11%
    PRS 88.48
  • mucus secreting cell CL0000319
    CSI 2.11
    rCSI 3.35%
    PRS 90.95
  • tuft cell of colon CL0009041
    CSI 2.06
    rCSI 4.79%
    PRS 88.37
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.02
    rCSI 2.86%
    PRS 81.3
  • promyelocyte CL0000836
    CSI 1.99
    rCSI 2.87%
    PRS 88.55
  • acinar cell CL0000622
    CSI 1.9
    rCSI 2.79%
    PRS 91.85
  • mucous neck cell CL0000651
    CSI 1.87
    rCSI 2.7%
    PRS 89.4
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.86
    rCSI 2.23%
    PRS 67.56
  • foveolar cell of stomach CL0002179
    CSI 1.83
    rCSI 3.89%
    PRS 88.75
  • extravillous trophoblast CL0008036
    CSI 1.78
    rCSI 2.21%
    PRS 82.27
  • type L enteroendocrine cell CL0002279
    CSI 1.76
    rCSI 3.31%
    PRS 88.9
  • glandular epithelial cell CL0000150
    CSI 1.74
    rCSI 4.58%
    PRS 93.18
  • pancreatic acinar cell CL0002064
    CSI 1.7
    rCSI 2.27%
    PRS 88.71
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 1.68
    rCSI 4.35%
    PRS 80.11
  • brush cell CL0002204
    CSI 1.66
    rCSI 3.29%
    PRS 90.22
  • periportal region hepatocyte CL0019026
    CSI 1.64
    rCSI 6.37%
    PRS 82.52
  • transit amplifying cell of colon CL0009011
    CSI 1.62
    rCSI 1.91%
    PRS 85.48
  • club cell CL0000158
    CSI 1.58
    rCSI 2.31%
    PRS 79.03
  • epithelial cell of proximal tubule CL0002306
    CSI 1.54
    rCSI 3.77%
    PRS 76.68
  • paneth cell of epithelium of small intestine CL1000343
    CSI 1.54
    rCSI 4.32%
    PRS 89.43
  • hepatocyte CL0000182
    CSI 1.52
    rCSI 2.72%
    PRS 83.31
  • colonocyte CL1000347
    CSI 1.51
    rCSI 2.17%
    PRS 83.85
  • lung ciliated cell CL1000271
    CSI 1.5
    rCSI 1.73%
    PRS 77.22
  • luminal epithelial cell of mammary gland CL0002326
    CSI 1.35
    rCSI 2.46%
    PRS 91.92
  • pancreatic ductal cell CL0002079
    CSI 1.35
    rCSI 2.62%
    PRS 86.97
  • peripheral nervous system neuron CL2000032
    CSI 1.25
    rCSI 1.71%
    PRS 76.32
  • intestinal tuft cell CL0019032
    CSI 1.22
    rCSI 1.87%
    PRS 87.27
  • colon goblet cell CL0009039
    CSI 1.22
    rCSI 2.9%
    PRS 88
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.19
    rCSI 3.01%
    PRS 75.55
  • enteroendocrine cell of colon CL0009042
    CSI 1.08
    rCSI 5.06%
    PRS 89.67
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 1.03
    rCSI 2.77%
    PRS 87.75
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 0.97
    rCSI 2.22%
    PRS 77.65
  • bronchial goblet cell CL1000312
    CSI 0.88
    rCSI 3.51%
    PRS 89.95
  • enterocyte of epithelium of large intestine CL0002071
    CSI 0.85
    rCSI 4.47%
    PRS 88.08
  • dopaminergic neuron CL0000700
    CSI 0.71
    rCSI 4%
    PRS 70.84
  • type EC enteroendocrine cell CL0000577
    CSI 0.7
    rCSI 2.48%
    PRS 86.71
  • podocyte CL0000653
    CSI 0.68
    rCSI 3%
    PRS 84.84
  • intestinal crypt stem cell of colon CL0009043
    CSI 0.52
    rCSI 3.9%
    PRS 91.57
  • respiratory goblet cell CL0002370
    CSI 0.51
    rCSI 5.51%
    PRS 89.98
  • P/D1 enteroendocrine cell CL0002268
    CSI 0.49
    rCSI 2.68%
    PRS 89.76
  • peptic cell CL0000155
    CSI 0.44
    rCSI 4.35%
    PRS 91.84
  • medium spiny neuron CL1001474
    CSI 0.35
    rCSI 3.01%
    PRS 73.06
  • acinar cell of salivary gland CL0002623
    CSI 0.16
    rCSI 3.71%
    PRS 92.59

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.

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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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 [ARSD](/details-gene/414) (Arylsulfatase D) is a protein-coding gene located on the X chromosome that encodes a sulfatase enzyme. Functionally, [ARSD](/details-gene/414) is localized to the [lysosome](/details-go/GO:0005764) and the [endoplasmic reticulum lumen](/details-go/GO:0005788), where it participates in the catabolism of glycosphingolipids and the post-translational activation of other sulfatases. Its expression profile is characterized by high significance in a diverse array of secretory, epithelial, and metabolically active cell types, most notably [lung neuroendocrine cells](/details-cell/CL1000223), [colon epithelial cells](/details-cell/CL0011108), and [astrocytes of the cerebral cortex](/details-cell/CL0002605). Mutations in [ARSD](/details-gene/414) have been linked to X-linked chondrodysplasia punctata 1 ([300002](https://omim.org/entry/300002)), 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 [ARSD](/details-gene/414) suggests a crucial role in specialized metabolic and secretory functions across multiple tissues. **Overall**, the gene shows the highest significance in [lung neuroendocrine cells](/details-cell/CL1000223) (CSI: 6.85) and various epithelial populations, including [colon epithelial cells](/details-cell/CL0011108) (CSI: 5.95), [epithelial cells of the lung](/details-cell/CL0000082) (CSI: 2.98), and [goblet cells](/details-cell/CL0000160) (CSI: 2.79). This enrichment in cells responsible for secretion and forming barrier surfaces points towards a function in processing complex molecules, such as lipids and proteins, destined for export or for maintaining cellular integrity. Beyond epithelial tissues, [ARSD](/details-gene/414) is also a significant marker in cell types with high metabolic loads, including [astrocytes of the cerebral cortex](/details-cell/CL0002605) (CSI: 4.15) and [midzonal region hepatocytes](/details-cell/CL0019028) (CSI: 3.10). Its presence in these cells is consistent with its known role in lipid metabolism. Notably, [ARSD](/details-gene/414) is also significant in [alternatively activated macrophages](/details-cell/CL0000890) (CSI: 2.78), suggesting a potential role in the metabolic processes that support the specific functions of these immune cells, such as tissue repair and resolution of inflammation. The collective expression data paints a picture of [ARSD](/details-gene/414) as a key enzymatic player in cellular homeostasis and specialized metabolic pathways rather than a broad housekeeping gene. ## Pathways and Molecular Function The functional annotations for [ARSD](/details-gene/414) firmly place it within the family of sulfatases, with a primary molecular function of '[Arylsulfatase activity](/details-go/GO:0004065)'. It is an integral component of several major metabolic pathways, particularly those involving lipid processing. Reactome pathway analysis highlights its involvement in '[Sphingolipid metabolism](/details-reactome/R-HSA-428157)', including the specific process of '[Glycosphingolipid catabolism](/details-reactome/R-HSA-9840310)'. This function is consistent with its high expression in secretory cells like [goblet cells](/details-cell/CL0000160), which produce lipid-rich mucins, and in [astrocytes](/details-cell/CL0002605), which are critical for lipid homeostasis in the central nervous system. Furthermore, [ARSD](/details-gene/414) is implicated in the broader pathway of '[Post-translational protein modification](/details-reactome/R-HSA-597592)', specifically in '[The activation of arylsulfatases](/details-reactome/R-HSA-1663150)'. This suggests that [ARSD](/details-gene/414) may not only act directly on its own substrates but could also regulate the activity of other sulfatase enzymes, thereby exerting a wider influence on cellular metabolism. Its co-localization to the '[endoplasmic reticulum lumen](/details-go/GO:0005788)' and '[lysosome](/details-go/GO:0005764)' aligns perfectly with its roles in both protein processing and the degradation of complex macromolecules. ## Research Directions The expression profile and functional annotation of [ARSD](/details-gene/414) provide a foundation for several testable hypotheses regarding its physiological and pathological roles. 1. **Hypothesis 1:** Given its high significance in [colon epithelial cells](/details-cell/CL0011108) and [goblet cells](/details-cell/CL0000160), coupled with its role in glycosphingolipid catabolism, [ARSD](/details-gene/414) may be essential for maintaining the integrity and composition of the colonic mucus barrier. Its dysfunction could lead to altered mucus properties and increased susceptibility to inflammatory bowel disease. 2. **Hypothesis 2:** The prominent expression of [ARSD](/details-gene/414) in [lung neuroendocrine cells](/details-cell/CL1000223) suggests a role in the processing of sulfated neuropeptides or signaling molecules secreted by these cells, thereby modulating neuroendocrine signaling in the lung. 3. **Hypothesis 3:** In [alternatively activated macrophages](/details-cell/CL0000890), [ARSD](/details-gene/414) activity could be critical for the metabolic reprogramming required for M2 polarization, potentially by catabolizing specific sulfated lipids that act as signaling intermediates in pathways governing immune cell function. To investigate the role of [ARSD](/details-gene/414) in maintaining the gut barrier (Hypothesis 1), a key experimental approach would be to utilize human colon organoids. CRISPR-Cas9-mediated knockout of [ARSD](/details-gene/414) in these organoids would allow for direct assessment of its function. Subsequent analysis would involve evaluating the thickness and composition of the mucus layer via histological staining and performing glycolipidomics using mass spectrometry to identify specific substrate alterations. Barrier integrity could be functionally tested using permeability assays (e.g., FITC-dextran flux), and the organoid response to inflammatory stimuli could be measured by quantifying cytokine secretion. As a therapeutic target, [ARSD](/details-gene/414) is primarily relevant in the context of its associated loss-of-function monogenic disease, chondrodysplasia punctata ([300002](https://omim.org/entry/300002)). For this condition, therapeutic strategies would focus on restoration of function, such as through enzyme replacement therapy or gene therapy. Given that it is an intracellular enzyme, developing small molecule chaperones or activators could also be a viable approach. Its potential as a target for inhibition in other diseases, such as cancer or inflammation, remains underexplored but would depend on evidence of pathological overexpression or hyperactivity in those specific contexts.

Genular Protein ID: 2418391087

Symbol: ARSD_HUMAN

Name: Arylsulfatase D

UniProtKB Accession Codes:

P51689 Q9UHJ8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 6 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 4 Ensembl 1 ExpressionAtlas 1 GO 4 Gene3D 3 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyConnect 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 3 RNAct 1 Reactome 2 RefSeq 2 SMR 1 STRING 1 SUPFAM 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

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

PubMed ID: 11177574

Title: Arylsulfatase D gene in Xp22.3 encodes two protein isoforms.

PubMed ID: 11177574

DOI: 10.1089/104454900750058125

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: 19159218

Title: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.

PubMed ID: 19159218

DOI: 10.1021/pr8008012

Sequence Information:

  • Length: 593
  • Mass: 64860
  • Checksum: 982B29D0FCEF9D34
  • Sequence:
    • MRSAARRGRA APAARDSLPV LLFLCLLLKT CEPKTANAFK PNILLIMADD LGTGDLGCYG 
NNTLRTPNID QLAEEGVRLT QHLAAAPLCT PSRAAFLTGR HSFRSGMDAS NGYRALQWNA 
GSGGLPENET TFARILQQHG YATGLIGKWH QGVNCASRGD HCHHPLNHGF DYFYGMPFTL 
TNDCDPGRPP EVDAALRAQL WGYTQFLALG ILTLAAGQTC GFFSVSARAV TGMAGVGCLF 
FISWYSSFGF VRRWNCILMR NHDVTEQPMV LEKTASLMLK EAVSYIERHK HGPFLLFLSL 
LHVHIPLVTT SAFLGKSQHG LYGDNVEEMD WLIGKVLNAI EDNGLKNSTF TYFTSDHGGH 
LEARDGHSQL GGWNGIYKGG KGMGGWEGGI RVPGIFHWPG VLPAGRVIGE PTSLMDVFPT 
VVQLVGGEVP QDRVIDGHSL VPLLQGAEAR SAHEFLFHYC GQHLHAARWH QKDSGSVWKV 
HYTTPQFHPE GAGACYGRGV CPCSGEGVTH HRPPLLFDLS RDPSEARPLT PDSEPLYHAV 
IARVGAAVSE HRQTLSPVPQ QFSMSNILWK PWLQPCCGHF PFCSCHEDGD GTP