AAAS Gene - Aladin WD Repeat Protein
AAAS gene encodes the Aladin protein, essential for nuclear pore complex function and associated with triple A syndrome.
Gene Information Card
| Symbol | AAAS |
|---|---|
| Full Name | Aladin WD repeat containing protein |
| Gene Type | Protein coding |
| Chromosomal Location | 12q13.13 |
| NCBI Gene ID | 8086 ncbi.nlm.nih.gov/gene/8086 |
| Ensembl ID | ENSG00000166821 |
| UniProt ID | Q9NRG9 |
| OMIM ID | 605378 |
| HGNC ID | 13666 |
| Aliases | ADRALN, AAA, AAASb, GL003 |
Description
The AAAS gene encodes the Aladin protein, a member of the WD repeat family of proteins. Aladin is a component of the nuclear pore complex, involved in nucleocytoplasmic transport. Mutations in AAAS cause triple A syndrome (achalasia-addisonianism-alacrima syndrome), an autosomal recessive disorder characterized by adrenal insufficiency, achalasia, and alacrima. The gene is located on chromosome 12q13.13 and is expressed in various tissues, with highest levels in adrenal gland, brain, and gastrointestinal tract.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Triple A syndrome (Achalasia-Addisonianism-Alacrima syndrome) | Loss-of-function mutations in AAAS disrupt nuclear pore complex function, impairing nucleocytoplasmic transport and leading to cellular dysfunction in adrenal, esophageal, and lacrimal tissues. | OMIM #231550; ClinVar pathogenic variants |
| Adrenal insufficiency | AAAS mutations cause progressive adrenal failure due to impaired transport of proteins required for steroidogenesis. | OMIM #231550; NCBI GeneReviews |
| Achalasia | Loss of Aladin function affects esophageal motility via autonomic nervous system dysfunction. | OMIM #231550; PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adrenal gland | 12.5 | Medium |
| Brain (cerebellum) | 8.3 | Medium |
| Esophagus | 6.1 | Low |
| Lacrimal gland | 5.8 | Low |
| Liver | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.1 | Embryonic kidney cells |
| HeLa | 7.4 | Cervical cancer cells |
| SH-SY5Y | 6.9 | Neuroblastoma cells |
| HepG2 | 5.3 | Hepatocellular carcinoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1331+1G>A | Splice site | Common in triple A syndrome | Loss of function |
| c.938C>T (p.Ser313Leu) | Missense | Reported in multiple families | Loss of function |
| c.43C>T (p.Arg15*) | Nonsense | Rare | Loss of function |
| c.1364_1365delAG | Frameshift | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most AAAS mutations are loss-of-function, leading to reduced or absent Aladin protein, impairing nuclear pore complex assembly and nucleocytoplasmic transport.
Gain of Function (GOF)
No gain-of-function mutations reported in AAAS.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • nuclear pore complex (GO:0005643) | • protein transport (GO:0015031) |
| • nucleocytoplasmic transport (GO:0006913) | • WD repeat domain binding (GO:0051059) |
| • cytoplasm (GO:0005737) | • nucleus (GO:0005634) |
Pathways
• Nuclear pore complex assembly
• Nucleocytoplasmic transport
• mRNA export from nucleus
Protein Summary
The Aladin protein (UniProt Q9NRG9) is a 546-amino acid WD repeat-containing protein localized to the nuclear pore complex. It consists of multiple WD40 repeats that form a beta-propeller structure, facilitating protein-protein interactions essential for nuclear pore assembly and transport. Aladin is critical for the nuclear import of proteins involved in adrenal steroidogenesis and neuronal function. Loss of Aladin leads to triple A syndrome, characterized by achalasia, adrenal insufficiency, and alacrima.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AAAS Knockout HEK293 Cell Line | EDJ-KQ6169 | Human | 8086 | Details Get a Quote |
| AAAS Knockout A-549 Cell Line | EDJ-KQ29988 | Human | 8086 | Details Get a Quote |
| AAAS Knockout HeLa Cell Line | EDJ-KQ29989 | Human | 8086 | Details Get a Quote |
| AAAS Knockout HCT 116 Cell Line | EDJ-KQ28678 | Human | 8086 | Details Get a Quote |
