Details for: AAAS

Gene ID: 8086

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: AAAS

Ensembl ID: ENSG00000094914

Description: aladin WD repeat nucleoporin

Cell Significance Landscape

Associated with

Significant Cells

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

  • sst GABAergic cortical interneuron CL4023017
    CSI 6.07
    rCSI 7.83%
    PRS 65.89
  • mesodermal cell CL0000222
    CSI 4.85
    rCSI 5.82%
    PRS 80.19
  • interneuron CL0000099
    CSI 3.83
    rCSI 7.7%
    PRS 72.93
  • lung macrophage CL1001603
    CSI 3.43
    rCSI 7.66%
    PRS 88.69
  • neural crest cell CL0011012
    CSI 3.25
    rCSI 2.57%
    PRS 71.62
  • rod bipolar cell CL0000751
    CSI 3.07
    rCSI 5.51%
    PRS 75.68
  • plasmacytoid dendritic cell, human CL0001058
    CSI 3.07
    rCSI 2.14%
    PRS 85.53
  • epithelial cell of lung CL0000082
    CSI 2.93
    rCSI 2.43%
    PRS 83.04
  • CD16-positive, CD56-dim natural killer cell, human CL0000939
    CSI 2.9
    rCSI 1.93%
    PRS 92.38
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.71
    rCSI 2.09%
    PRS 85.02
  • interstitial cell of Cajal CL0002088
    CSI 2.65
    rCSI 3.38%
    PRS 86.91
  • primitive red blood cell CL0002355
    CSI 2.64
    rCSI 14.22%
    PRS 87.46
  • mature B cell CL0000785
    CSI 2.61
    rCSI 2.27%
    PRS 90.45
  • pulmonary ionocyte CL0017000
    CSI 2.6
    rCSI 3.17%
    PRS 87.98
  • early lymphoid progenitor CL0000936
    CSI 2.59
    rCSI 2.27%
    PRS 86.91
  • intestinal epithelial cell CL0002563
    CSI 2.44
    rCSI 2.55%
    PRS 79.76
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.38
    rCSI 2.96%
    PRS 62.59
  • hematopoietic stem cell CL0000037
    CSI 2.37
    rCSI 1.58%
    PRS 84.57
  • stem cell CL0000034
    CSI 2.36
    rCSI 2.28%
    PRS 75.98
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 2.23
    rCSI 2.58%
    PRS 74.43
  • extravillous trophoblast CL0008036
    CSI 2.21
    rCSI 2.74%
    PRS 80.36
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 2.2
    rCSI 6.51%
    PRS 82.9
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.11
    rCSI 1.91%
    PRS 80.32
  • ciliated epithelial cell CL0000067
    CSI 2.1
    rCSI 1.85%
    PRS 71.68
  • erythrocyte CL0000232
    CSI 2.1
    rCSI 4.76%
    PRS 82.31
  • intestinal tuft cell CL0019032
    CSI 2.05
    rCSI 3.14%
    PRS 85.45
  • lung ciliated cell CL1000271
    CSI 2.01
    rCSI 2.32%
    PRS 74.69
  • radial glial cell CL0000681
    CSI 1.98
    rCSI 2.76%
    PRS 80.57
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 1.94
    rCSI 2.49%
    PRS 78.29
  • chondrocyte CL0000138
    CSI 1.91
    rCSI 3.04%
    PRS 75.46
  • keratinocyte CL0000312
    CSI 1.86
    rCSI 1.56%
    PRS 84.4
  • club cell CL0000158
    CSI 1.77
    rCSI 2.59%
    PRS 76.85
  • peripheral nervous system neuron CL2000032
    CSI 1.76
    rCSI 2.4%
    PRS 74.07
  • glioblast CL0000030
    CSI 1.75
    rCSI 2.79%
    PRS 73.8
  • retina horizontal cell CL0000745
    CSI 1.71
    rCSI 2.6%
    PRS 78.89
  • regular ventricular cardiac myocyte CL0002131
    CSI 1.7
    rCSI 10.61%
    PRS 74.05
  • placental villous trophoblast CL2000060
    CSI 1.66
    rCSI 2.57%
    PRS 81.25
  • erythroid progenitor cell CL0000038
    CSI 1.57
    rCSI 9.01%
    PRS 86.69
  • common myeloid progenitor CL0000049
    CSI 1.57
    rCSI 1.27%
    PRS 84.18
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.53
    rCSI 3.43%
    PRS 65.58
  • mesenchymal cell CL0008019
    CSI 1.41
    rCSI 3.59%
    PRS 75.9
  • retinal cone cell CL0000573
    CSI 1.13
    rCSI 1.81%
    PRS 72.53
  • large pre-B-II cell CL0000957
    CSI 1.04
    rCSI 2.98%
    PRS 86.55
  • forebrain radial glial cell CL0013000
    CSI 1.01
    rCSI 3.23%
    PRS 83.51
  • microcirculation associated smooth muscle cell CL0008035
    CSI 0.89
    rCSI 2.57%
    PRS 81.55

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 [AAAS](/details-gene/8086), also known as aladin WD repeat nucleoporin, encodes a core component of the nuclear pore complex (NPC). This protein, Aladin, plays a fundamental role in [nucleocytoplasmic transport](/details-ontology/GO:0006913), the regulated movement of molecules between the nucleus and the cytoplasm. Its function is critical for various cellular processes, including [mrna transport](/details-ontology/GO:0051028), cell division ([mitotic spindle assembly](/details-ontology/GO:0090307)), and cellular responses to stress. Expression data indicates that while [AAAS](/details-gene/8086) is broadly important, it shows particular significance in diverse cell types, including neuronal subtypes like [sst GABAergic cortical interneuron](/details-cell/CL4023017) and cells of the immune system such as [lung macrophage](/details-cell/CL1001603). Clinically, mutations in [AAAS](/details-gene/8086) are the cause of Triple-A syndrome (Allgrove syndrome), a rare autosomal recessive disorder ([OMIM: 231550](https://omim.org/entry/231550)), characterized by adrenal insufficiency, achalasia, and alacrima [Link](https://doi.org/10.1038/81642). ## Cellular Roles and Expression Landscape The expression profile of [AAAS](/details-gene/8086) highlights its essential role in the fundamental machinery of a wide array of cell types. **Overall**, the gene exhibits high significance scores across distinct lineages, suggesting it is a crucial 'workhorse' protein rather than a specific lineage marker. Its highest significance is observed in neuronal populations, particularly the [sst GABAergic cortical interneuron](/details-cell/CL4023017) (CSI: 6.07) and other [interneuron](/details-cell/CL0000099) subtypes. This is consistent with the neurological deficits observed in Triple-A syndrome and suggests a critical role for precise nucleocytoplasmic transport in maintaining the function and integrity of these specific neural circuits. [AAAS](/details-gene/8086) is also highly significant in various cells of the immune system. This includes both innate immune cells, such as the [lung macrophage](/details-cell/CL1001603), [plasmacytoid dendritic cell, human](/details-cell/CL0001058), and [CD14-low, CD16-positive monocyte](/details-cell/CL0002396), as well as adaptive immune cells like the [mature B cell](/details-cell/CL0000785) and [CD16-positive, CD56-dim natural killer cell, human](/details-cell/CL0000939). This broad pattern of significance within the immune compartment points towards a central role in processes like immune cell development, activation, and response to pathogens. Furthermore, the gene is significant in various progenitor and specialized cells, including [mesodermal cell](/details-cell/CL0000222), [neural crest cell](/details-cell/CL0011012), and [epithelial cell of lung](/details-cell/CL0000082), reinforcing its widespread importance in cellular homeostasis and development. ## Pathways and Molecular Function Functionally, [AAAS](/details-gene/8086) is integral to the [nuclear pore](/details-ontology/GO:0005643), where it facilitates the transport of proteins and RNA. Its involvement is central to [gene expression (transcription)](/details-ontology/R-HSA-74160) through its role in the [transport of mature mRNA to cytoplasm](/details-ontology/R-HSA-72202). Beyond this canonical function, [AAAS](/details-gene/8086) is critically involved in the [cell cycle, mitotic](/details-ontology/R-HSA-69278). It regulates the localization of the Aurora A kinase to ensure robust [mitotic spindle assembly](/details-ontology/GO:0090307), a process essential for correct chromosome segregation during cell division [Link](https://doi.org/10.1091/mbc.e15-02-0113). This is supported by its annotation to cellular components like the [centrosome](/details-ontology/GO:0005813) and [mitotic spindle](/details-ontology/GO:0072686). The extensive annotation of [AAAS](/details-gene/8086) in pathways related to the [immune system](/details-ontology/R-HSA-168256) and [infectious disease](/details-ontology/R-HSA-5663205) aligns with its expression in immune cells. It is implicated in [cytokine signaling in immune system](/details-ontology/R-HSA-1280215), [interferon signaling](/details-ontology/R-HSA-913531), and numerous host-pathogen interaction pathways, including those for [HIV infection](/details-ontology/R-HSA-162906), [influenza infection](/details-ontology/R-HSA-168255), and [SARS-CoV-2 infection](/details-ontology/R-HSA-9694516). This suggests that Aladin may mediate the transport of key factors involved in antiviral responses, such as transcription factors or viral components. Furthermore, its role in [cellular responses to stress](/details-ontology/R-HSA-2262752) underscores its importance in maintaining cellular homeostasis under adverse conditions. ## Research Directions The widespread yet cell-type-specific significance of [AAAS](/details-gene/8086) provides a basis for several testable hypotheses regarding its precise roles in health and disease. 1. **Hypothesis 1:** Given its high significance in [sst GABAergic cortical interneuron](/details-cell/CL4023017), [AAAS](/details-gene/8086) may be responsible for the selective nuclear transport of a specific subset of mRNAs or proteins that are essential for the unique metabolic or signaling functions of these inhibitory neurons. Disruption of this selective transport could be a primary driver of the neurodegenerative aspects of Triple-A syndrome. 2. **Hypothesis 2:** Based on its significance in [lung macrophage](/details-cell/CL1001603) and its deep integration into antiviral signaling pathways, [AAAS](/details-gene/8086) may function as a crucial gatekeeper for the nuclear import of transcription factors (e.g., STAT1/2, IRFs) or the nuclear export of antiviral gene transcripts following pathogen recognition. Its dysfunction could lead to an impaired or delayed interferon response, increasing susceptibility to infection. To investigate the second hypothesis, a key experiment could be proposed: * **Experimental Approach:** Utilize CRISPR-Cas9 to generate an [AAAS](/details-gene/8086) knockout in a human monocytic cell line (e.g., THP-1). Differentiate both wild-type and knockout cells into macrophages and challenge them with a viral mimic, such as poly(I:C) or a replication-deficient influenza virus. The cellular response can be assessed by measuring the expression and secretion of type I interferons (IFN-β) and pro-inflammatory cytokines (TNF-α, IL-6) via qRT-PCR and ELISA. To probe the mechanism, subcellular fractionation followed by Western blotting or quantitative proteomics could be used to determine if key signaling proteins (e.g., phosphorylated STAT1) fail to properly accumulate in the nucleus in the absence of [AAAS](/details-gene/8086). **Therapeutic Potential:** As [AAAS](/details-gene/8086) encodes a core component of the essential nuclear pore machinery, it is likely a poor candidate for direct therapeutic inhibition or activation due to the high probability of inducing widespread cellular toxicity. Therapeutic strategies for diseases linked to [AAAS](/details-gene/8086) mutations, such as Triple-A syndrome, are more likely to focus on downstream consequences or gene-replacement therapies rather than pharmacological modulation of the Aladin protein itself.

Genular Protein ID: 1359976088

Symbol: AAAS_HUMAN

Name: Aladin

UniProtKB Accession Codes:

Q9NRG9 Q5JB47 Q9NWI6 Q9UG19

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 ChiTaRS 1 ComplexPortal 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 25 EMDB 2 Ensembl 4 ExpressionAtlas 1 GO 18 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 29 RefSeq 2 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11062474

Title: Mutant WD-repeat protein in triple-A syndrome.

PubMed ID: 11062474

DOI: 10.1038/81642

PubMed ID: 11159947

Title: Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene.

PubMed ID: 11159947

DOI: 10.1093/hmg/10.3.283

PubMed ID: 16022285

Title: Molecular cloning and characterization of AAAS-V2, a novel splice variant of human AAAS.

PubMed ID: 16022285

DOI: 10.1007/s11033-004-6939-9

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16541075

Title: The finished DNA sequence of human chromosome 12.

PubMed ID: 16541075

DOI: 10.1038/nature04569

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: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19782045

Title: The nuclear pore complex protein ALADIN is anchored via NDC1 but not via POM121 and GP210 in the nuclear envelope.

PubMed ID: 19782045

DOI: 10.1016/j.bbrc.2009.09.080

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 22223895

Title: Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features.

PubMed ID: 22223895

DOI: 10.1074/mcp.m111.015131

PubMed ID: 22814378

Title: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.

PubMed ID: 22814378

DOI: 10.1073/pnas.1210303109

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 26246606

Title: The nucleoporin ALADIN regulates Aurora A localization to ensure robust mitotic spindle formation.

PubMed ID: 26246606

DOI: 10.1091/mbc.e15-02-0113

PubMed ID: 25944712

Title: N-terminome analysis of the human mitochondrial proteome.

PubMed ID: 25944712

DOI: 10.1002/pmic.201400617

PubMed ID: 27754849

Title: Identification of a novel putative interaction partner of the nucleoporin ALADIN.

PubMed ID: 27754849

DOI: 10.1242/bio.021162

Sequence Information:

  • Length: 546
  • Mass: 59574
  • Checksum: E0F4E7145D8C192E
  • Sequence:
    • MCSLGLFPPP PPRGQVTLYE HNNELVTGSS YESPPPDFRG QWINLPVLQL TKDPLKTPGR 
LDHGTRTAFI HHREQVWKRC INIWRDVGLF GVLNEIANSE EEVFEWVKTA SGWALALCRW 
ASSLHGSLFP HLSLRSEDLI AEFAQVTNWS SCCLRVFAWH PHTNKFAVAL LDDSVRVYNA 
SSTIVPSLKH RLQRNVASLA WKPLSASVLA VACQSCILIW TLDPTSLSTR PSSGCAQVLS 
HPGHTPVTSL AWAPSGGRLL SASPVDAAIR VWDVSTETCV PLPWFRGGGV TNLLWSPDGS 
KILATTPSAV FRVWEAQMWT CERWPTLSGR CQTGCWSPDG SRLLFTVLGE PLIYSLSFPE 
RCGEGKGCVG GAKSATIVAD LSETTIQTPD GEERLGGEAH SMVWDPSGER LAVLMKGKPR 
VQDGKPVILL FRTRNSPVFE LLPCGIIQGE PGAQPQLITF HPSFNKGALL SVGWSTGRIA 
HIPLYFVNAQ FPRFSPVLGR AQEPPAGGGG SIHDLPLFTE TSPTSAPWDP LPGPPPVLPH 
SPHSHL