The protein encoded by this gene is a member of the WD-repeat family of regulatory proteins and may be involved in normal development of the peripheral and central nervous system. The encoded protein is part of the nuclear pore complex and is anchored there by NDC1. Defects in this gene are a cause of achalasia-addisonianism-alacrima syndrome (AAAS), also called triple-A syndro... See more...

Aliases for AAAS Gene

Aliases for AAAS Gene

  • Aladin WD Repeat Nucleoporin 2 3 5
  • Aladin 2 3 4
  • Achalasia, Adrenocortical Insufficiency, Alacrimia 2 3
  • Allgrove, Triple-A 2 3
  • Adracalin 2 4
  • ADRACALA 3 4
  • Achalasia, Adrenocortical Insufficiency, Alacrimia (Allgrove, Triple-A) 2
  • ADRACALIN 3
  • ALADIN 3
  • AAASb 3
  • GL003 3
  • AAAS 5
  • AAA 3

External Ids for AAAS Gene

Previous GeneCards Identifiers for AAAS Gene

  • GC12P053994
  • GC12P053789
  • GC12M053417
  • GC12M051987
  • GC12M053701
  • GC12M050742

Summaries for AAAS Gene

Entrez Gene Summary for AAAS Gene

  • The protein encoded by this gene is a member of the WD-repeat family of regulatory proteins and may be involved in normal development of the peripheral and central nervous system. The encoded protein is part of the nuclear pore complex and is anchored there by NDC1. Defects in this gene are a cause of achalasia-addisonianism-alacrima syndrome (AAAS), also called triple-A syndrome or Allgrove syndrome. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

GeneCards Summary for AAAS Gene

AAAS (Aladin WD Repeat Nucleoporin) is a Protein Coding gene. Diseases associated with AAAS include Achalasia-Addisonianism-Alacrima Syndrome and Spastic Paraparesis. Among its related pathways are Cell Cycle, Mitotic and Transport of the SLBP independent Mature mRNA.

UniProtKB/Swiss-Prot Summary for AAAS Gene

  • Plays a role in the normal development of the peripheral and central nervous system (PubMed:11062474, PubMed:11159947, PubMed:16022285). Required for the correct localization of aurora kinase AURKA and the microtubule minus end-binding protein NUMA1 as well as a subset of AURKA targets which ensures proper spindle formation and timely chromosome alignment (PubMed:26246606).

Gene Wiki entry for AAAS Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for AAAS Gene

Genomics for AAAS Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for AAAS Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around AAAS on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for AAAS

Top Transcription factor binding sites by QIAGEN in the AAAS gene promoter:
  • AP-1
  • AP-2alpha
  • AP-2alphaA
  • AP-2beta
  • ATF-2
  • c-Jun
  • MyoD
  • NF-kappaB1

Genomic Locations for AAAS Gene

Latest Assembly
chr12:53,307,456-53,324,864
(GRCh38/hg38)
Size:
17,409 bases
Orientation:
Minus strand

Previous Assembly
chr12:53,701,244-53,715,394
(GRCh37/hg19 by Entrez Gene)
Size:
14,151 bases
Orientation:
Minus strand

chr12:53,701,240-53,718,648
(GRCh37/hg19 by Ensembl)
Size:
17,409 bases
Orientation:
Minus strand

Genomic View for AAAS Gene

Genes around AAAS on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
AAAS Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for AAAS Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for AAAS Gene

Proteins for AAAS Gene

  • Protein details for AAAS Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NRG9-AAAS_HUMAN
    Recommended name:
    Aladin
    Protein Accession:
    Q9NRG9
    Secondary Accessions:
    • Q5JB47
    • Q9NWI6
    • Q9UG19

    Protein attributes for AAAS Gene

    Size:
    546 amino acids
    Molecular mass:
    59574 Da
    Quaternary structure:
    • Interacts with NDC1, the interaction is required for nuclear pore localization (PubMed:19782045). Interacts with the inactive form aurora kinase AURKA (PubMed:26246606). Interacts with PGRMC2 (PubMed:27754849).
    Miscellaneous:
    • [Isoform 2]: Ubiquitously expressed.

    Alternative splice isoforms for AAAS Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for AAAS Gene

Post-translational modifications for AAAS Gene

  • Ubiquitination at Lys52, Lys56, Lys301, Lys373, Lys416, Lys425, and Lys466
  • Modification sites at PhosphoSitePlus

Antibodies for research

No data available for DME Specific Peptides for AAAS Gene

Domains & Families for AAAS Gene

Gene Families for AAAS Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Potential drug targets
  • Predicted intracellular proteins
  • Transporters

Suggested Antigen Peptide Sequences for AAAS Gene

GenScript: Design optimal peptide antigens:
  • Adracalin (AAAS_HUMAN)
  • Mutant Allgrove syndrome protein (D9DBS9_HUMAN)
  • Mutant Allgrove syndrome protein (D9DBT0_HUMAN)
  • Mutant Allgrove syndrome protein (D9DBT1_HUMAN)
  • Mutant Allgrove syndrome protein (D9DBT2_HUMAN)
genes like me logo Genes that share domains with AAAS: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for AAAS Gene

Function for AAAS Gene

Molecular function for AAAS Gene

UniProtKB/Swiss-Prot Function:
Plays a role in the normal development of the peripheral and central nervous system (PubMed:11062474, PubMed:11159947, PubMed:16022285). Required for the correct localization of aurora kinase AURKA and the microtubule minus end-binding protein NUMA1 as well as a subset of AURKA targets which ensures proper spindle formation and timely chromosome alignment (PubMed:26246606).

Phenotypes From GWAS Catalog for AAAS Gene

Gene Ontology (GO) - Molecular Function for AAAS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003674 molecular_function ND --
GO:0005515 protein binding IEA,IPI 27754849
genes like me logo Genes that share ontologies with AAAS: view
genes like me logo Genes that share phenotypes with AAAS: view

Human Phenotype Ontology for AAAS Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for AAAS Gene

MGI Knock Outs for AAAS:
  • Aaas Aaas<tm1Ahue>

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for AAAS

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for AAAS Gene

Localization for AAAS Gene

Subcellular locations from UniProtKB/Swiss-Prot for AAAS Gene

Nucleus, nuclear pore complex. Cytoplasm, cytoskeleton, spindle pole. Nucleus envelope. Note=In metaphase cells localizes within the spindle with some accumulation around spindle poles, with the highest concentration between the centrosome and metaphase plate (PubMed:26246606). The localization to the spindle is microtubule-mediated (PubMed:26246606). {ECO:0000269 PubMed:26246606}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for AAAS gene
Compartment Confidence
cytoskeleton 5
nucleus 5
cytosol 5
plasma membrane 1
extracellular 1
mitochondrion 1
endoplasmic reticulum 1
peroxisome 0
lysosome 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Centrosome (2)
  • Cytosol (2)
  • Nuclear membrane (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for AAAS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000922 spindle pole IEA,IDA 26246606
GO:0005634 nucleus IEA,HDA 21630459
GO:0005635 nuclear envelope TAS --
GO:0005643 nuclear pore IBA,IDA 12730363
GO:0005654 nucleoplasm IDA --
genes like me logo Genes that share ontologies with AAAS: view

Pathways & Interactions for AAAS Gene

PathCards logo

SuperPathways for AAAS Gene

SuperPathway Contained pathways
1 Transport of the SLBP independent Mature mRNA
2 HIV Life Cycle
.45
3 Cell Cycle, Mitotic
.60
4 Mitotic Prophase
5 Influenza Viral RNA Transcription and Replication
genes like me logo Genes that share pathways with AAAS: view

Pathways by source for AAAS Gene

Gene Ontology (GO) - Biological Process for AAAS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001578 microtubule bundle formation IMP 26246606
GO:0006110 regulation of glycolytic process TAS --
GO:0006406 mRNA export from nucleus TAS --
GO:0006409 tRNA export from nucleus TAS --
GO:0006913 nucleocytoplasmic transport IDA 12730363
genes like me logo Genes that share ontologies with AAAS: view

No data available for SIGNOR curated interactions for AAAS Gene

Drugs & Compounds for AAAS Gene

(1) Drugs for AAAS Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with AAAS: view

Transcripts for AAAS Gene

mRNA/cDNA for AAAS Gene

2 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
22 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for AAAS

Alternative Splicing Database (ASD) splice patterns (SP) for AAAS Gene

ExUns: 1a · 1b · 1c · 1d · 1e · 1f ^ 2a · 2b · 2c ^ 3a · 3b · 3c ^ 4a · 4b ^ 5a · 5b ^ 6a · 6b ^ 7 ^ 8a · 8b · 8c ^ 9 ^ 10 ^ 11 ^ 12 ^
SP1: - - - - - - -
SP2: - - - - - - - - -
SP3: - - - - - - -
SP4:
SP5: - - - - - - -
SP6: - - - - -
SP7: - - - -
SP8: - - - -
SP9: - - -
SP10: - -
SP11:
SP12: -

ExUns: 13 ^ 14 ^ 15a · 15b ^ 16
SP1: -
SP2: -
SP3: -
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:

Relevant External Links for AAAS Gene

GeneLoc Exon Structure for
AAAS

Expression for AAAS Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for AAAS Gene

Protein differential expression in normal tissues from HIPED for AAAS Gene

This gene is overexpressed in Nasal epithelium (43.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for AAAS Gene



Protein tissue co-expression partners for AAAS Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for AAAS

SOURCE GeneReport for Unigene cluster for AAAS Gene:

Hs.369144

mRNA Expression by UniProt/SwissProt for AAAS Gene:

Q9NRG9-AAAS_HUMAN
Tissue specificity: Widely expressed (PubMed:11159947, PubMed:16022285). Particularly abundant in cerebellum, corpus callosum, adrenal gland, pituitary gland, gastrointestinal structures and fetal lung (PubMed:11159947).

Evidence on tissue expression from TISSUES for AAAS Gene

  • Nervous system(4.6)
  • Kidney(4.4)
  • Liver(4.4)
  • Adrenal gland(3)
  • Skin(2.3)

Phenotype-based relationships between genes and organs from Gene ORGANizer for AAAS Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • integumentary
  • nervous
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • cerebellum
  • cranial nerve
  • ear
  • eye
  • head
  • lacrimal apparatus
  • mouth
  • pharynx
  • skull
Thorax:
  • esophagus
  • heart
Abdomen:
  • adrenal gland
  • kidney
  • pancreas
  • stomach
Limb:
  • foot
  • hand
  • lower limb
  • upper limb
General:
  • blood vessel
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal cord
genes like me logo Genes that share expression patterns with AAAS: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for AAAS Gene

Orthologs for AAAS Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for AAAS Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia AAAS 29 30
  • 99.63 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia AAAS 29 30
  • 90.84 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia AAAS 29 30
  • 87.97 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Aaas 29 16 30
  • 87.48 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Aaas 29
  • 87.36 (n)
Chicken
(Gallus gallus)
Aves AAAS 29 30
  • 69.57 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia AAAS 30
  • 66 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia aaas 29
  • 64.45 (n)
Zebrafish
(Danio rerio)
Actinopterygii aaas 29 30
  • 60.94 (n)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP010685 29
  • 44.57 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta CG16892 29 30 31
  • 42.83 (n)
OneToMany
CG13137 30
  • 25 (a)
OneToMany
Thale Cress
(Arabidopsis thaliana)
eudicotyledons AT3G56900 29
  • 43.91 (n)
Rice
(Oryza sativa)
Liliopsida Os11g0132700 29
  • 41.83 (n)
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 42 (a)
OneToOne
Species where no ortholog for AAAS was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Oppossum (Monodelphis domestica)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for AAAS Gene

ENSEMBL:
Gene Tree for AAAS (if available)
TreeFam:
Gene Tree for AAAS (if available)
Aminode:
Evolutionary constrained regions (ECRs) for AAAS: view image
Alliance of Genome Resources:
Additional Orthologs for AAAS

Paralogs for AAAS Gene

Pseudogenes.org Pseudogenes for AAAS Gene

genes like me logo Genes that share paralogs with AAAS: view

No data available for Paralogs for AAAS Gene

Variants for AAAS Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for AAAS Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
1027994 Uncertain Significance: Glucocorticoid deficiency with achalasia 53,309,639(-) G/A
NM_015665.6(AAAS):c.772C>T (p.Arg258Trp)
MISSENSE
813665 Uncertain Significance: Microcephaly 53,314,833(-) G/A
NM_015665.6(AAAS):c.463C>T (p.Arg155Cys)
MISSENSE_VARIANT,INTRON
841221 Pathogenic: not provided 53,314,299(-) G/A
NM_015665.6(AAAS):c.688C>T (p.Arg230Ter)
NONSENSE
872168 Pathogenic: not provided 53,314,832(-) C/T
NM_015665.6(AAAS):c.464G>A (p.Arg155His)
MISSENSE_VARIANT,INTRON
881291 Uncertain Significance: Glucocorticoid deficiency with achalasia 53,308,968(-) G/A
NM_015665.6(AAAS):c.988C>T (p.Arg330Cys)
MISSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for AAAS Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for AAAS Gene

Variant ID Type Subtype PubMed ID
nsv517066 CNV loss 19592680

Variation tolerance for AAAS Gene

Residual Variation Intolerance Score: 34.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.18; 39.49% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for AAAS Gene

Human Gene Mutation Database (HGMD)
AAAS
SNPedia medical, phenotypic, and genealogical associations of SNPs for
AAAS
Leiden Open Variation Database (LOVD)
AAAS

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for AAAS Gene

Disorders for AAAS Gene

MalaCards: The human disease database

(14) MalaCards diseases for AAAS Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

Disorder Aliases PubMed IDs
achalasia-addisonianism-alacrima syndrome
  • aaas
spastic paraparesis
achalasia
  • achalasia of cardia
accommodative spasm
  • spasm of accommodation
hypoglossal nerve disease
  • disorder of 12th nerve
- elite association - COSMIC cancer census association via MalaCards
Search AAAS in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

AAAS_HUMAN
  • Achalasia-addisonianism-alacrima syndrome (AAAS) [MIM:231550]: An autosomal recessive disorder characterized by adreno-corticotropic hormone (ACTH)-resistant adrenal failure, achalasia of the esophageal cardia and alacrima. The syndrome is associated with variable and progressive neurological impairment involving the central, peripheral, and autonomic nervous system. Other features such as palmoplantar hyperkeratosis, short stature, facial dysmorphy and osteoporosis may also be present. {ECO:0000269 PubMed:11159947}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for AAAS

genes like me logo Genes that share disorders with AAAS: view

No data available for Genatlas for AAAS Gene

Publications for AAAS Gene

  1. Mutant WD-repeat protein in triple-A syndrome. (PMID: 11062474) Tullio-Pelet A … Lyonnet S (Nature genetics 2000) 2 3 4 22 72
  2. Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene. (PMID: 11159947) Handschug K … Huebner A (Human molecular genetics 2001) 3 4 22 72
  3. The nuclear pore complex protein ALADIN is anchored via NDC1 but not via POM121 and GP210 in the nuclear envelope. (PMID: 19782045) Kind B … Huebner A (Biochemical and biophysical research communications 2009) 3 4 22
  4. Molecular cloning and characterization of AAAS-V2, a novel splice variant of human AAAS. (PMID: 16022285) Li X … Mao Y (Molecular biology reports 2005) 3 4 22
  5. Proteomic analysis of the mammalian nuclear pore complex. (PMID: 12196509) Cronshaw JM … Matunis MJ (The Journal of cell biology 2002) 2 3 22

Products for AAAS Gene