AAAS

aladin WD repeat nucleoporin, the group of WD repeat domain containing|Nucleoporins

Basic information

Region (hg38): 12:53307455-53324864

Links

ENSG00000094914 ∙ NCBI:8086 ∙ OMIM:605378 ∙ HGNC:13666 ∙ Uniprot:Q9NRG9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• triple-A syndrome (Definitive), mode of inheritance: AR
• triple-A syndrome (Definitive), mode of inheritance: AR
• triple-A syndrome (Strong), mode of inheritance: AR
• triple-A syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Achalasia-addisonianism-alacrimia syndrome	AR	Endocrine	Surveillance and treatment/preventive measures (with substitution therapy) to avoid sequelae of adrenal insufficiency, including adrenal crisis, may be beneficial	Dermatologic; Endocrine; Gastrointestinal; Neurologic; Ophthalmologic	78049; 6243664; 3565479; 1537368; 8006362; 7895750; 8757578; 11062474; 11159947; 11914417; 12429595; 12752575; 16264411; 16938764; 8628786; 19172511; 18172684; 20051279; 20200814; 20499090; 20447142; 21565631

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AAAS gene.

• not provided (186 variants)
• Glucocorticoid deficiency with achalasia (89 variants)
• Inborn genetic diseases (30 variants)
• not specified (8 variants)
• Achalasia-alacrima syndrome (1 variants)
• Abnormality of the nervous system (1 variants)
• AAAS-related condition (1 variants)
• Neurodevelopmental disorder (1 variants)
• Microcephaly (1 variants)
• Babinski sign;Spastic paraparesis;Hyperreflexia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AAAS gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	44	2	51
missense	4	6	80	2		92
nonsense	15	3	1			19
start loss						0
frameshift	12	4	1			17
inframe indel			1			1
splice donor/acceptor (+/-2bp)	2	7	1			10
splice region			2	10		12
non coding			4	17	15	36
Total	33	20	93	63	17

Highest pathogenic variant AF is 0.000184

Variants in AAAS

This is a list of pathogenic ClinVar variants found in the AAAS region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-53307457-G-A		Glucocorticoid deficiency with achalasia	Likely benign (Jun 14, 2016)
12-53307478-CTTAT-C			Likely benign (Nov 16, 2020)
12-53307490-T-TA		not specified	Uncertain significance (Aug 02, 2023)
12-53307495-G-A			Likely benign (Jan 20, 2024)
12-53307516-C-T			Likely benign (Dec 17, 2022)
12-53307532-C-T			Uncertain significance (Nov 01, 2023)
12-53307533-C-T		Glucocorticoid deficiency with achalasia	Benign/Likely benign (Jan 31, 2024)
12-53307534-T-C			Likely benign (Sep 13, 2023)
12-53307539-G-A		Glucocorticoid deficiency with achalasia	Uncertain significance (Jun 14, 2016)
12-53307549-A-G			Likely benign (Jul 10, 2018)
12-53307553-G-C		Inborn genetic diseases	Uncertain significance (Sep 01, 2021)
12-53307564-G-A		Glucocorticoid deficiency with achalasia	Conflicting classifications of pathogenicity (Dec 19, 2023)
12-53307573-A-G		Glucocorticoid deficiency with achalasia • AAAS-related disorder	Benign/Likely benign (Jan 31, 2024)
12-53307575-T-G			Uncertain significance (Feb 28, 2022)
12-53307576-A-C			Uncertain significance (Feb 24, 2022)
12-53307579-G-A			Likely benign (Sep 28, 2023)
12-53307582-G-A			Likely benign (May 31, 2023)
12-53307600-G-C			Likely benign (Jan 27, 2024)
12-53307612-A-T			Likely benign (Dec 21, 2022)
12-53307613-G-A		Inborn genetic diseases	Uncertain significance (Mar 04, 2024)
12-53307613-G-C			Uncertain significance (Jul 16, 2022)
12-53307615-A-G		Glucocorticoid deficiency with achalasia	Benign/Likely benign (Jan 31, 2024)
12-53307632-G-A		Glucocorticoid deficiency with achalasia	Uncertain significance (Jun 14, 2016)
12-53307651-A-G			Likely benign (May 28, 2023)
12-53307652-C-T		Inborn genetic diseases	Uncertain significance (Jul 15, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AAAS	protein_coding	protein_coding	ENST00000209873	16	17409

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.44e-13	0.635	125582	0	166	125748	0.000660

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.363	316	298	1.06	0.0000175	3476
Missense in Polyphen		80	77.742	1.0291		947
Synonymous	0.239	114	117	0.972	0.00000618	1175
Loss of Function	1.61	25	35.3	0.707	0.00000224	341

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00303	0.00303
Ashkenazi Jewish	0.00	0.00
East Asian	0.000217	0.000217
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000669	0.000668
Middle Eastern	0.000217	0.000217
South Asian	0.000654	0.000653
Other	0.000652	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in the normal development of the peripheral and central nervous system.
• Pathway: RNA transport - Homo sapiens (human);tRNA processing;Disease;Gene expression (Transcription);Regulation of HSF1-mediated heat shock response;Metabolism of carbohydrates;Rev-mediated nuclear export of HIV RNA;Late Phase of HIV Life Cycle;HIV Life Cycle;Interactions of Rev with host cellular proteins;Host Interactions of HIV factors;HIV Infection;snRNP Assembly;Vpr-mediated nuclear import of PICs;SUMOylation of DNA damage response and repair proteins;Transport of Ribonucleoproteins into the Host Nucleus;Viral Messenger RNA Synthesis;Export of Viral Ribonucleoproteins from Nucleus;SUMOylation of chromatin organization proteins;Influenza Viral RNA Transcription and Replication;Cellular responses to stress;SUMOylation of RNA binding proteins;Post-translational protein modification;SUMOylation of DNA replication proteins;SUMO E3 ligases SUMOylate target proteins;NEP/NS2 Interacts with the Cellular Export Machinery;Metabolism of proteins;Influenza Life Cycle;Influenza Infection;Metabolism of RNA;Infectious disease;Metabolism;Transport of the SLBP independent Mature mRNA;Transport of the SLBP Dependant Mature mRNA;Transport of Mature mRNA Derived from an Intronless Transcript;Transport of Mature mRNAs Derived from Intronless Transcripts;SUMOylation;Cellular responses to external stimuli;Regulation of Glucokinase by Glucokinase Regulatory Protein;Glycolysis;Nuclear Pore Complex (NPC) Disassembly;tRNA processing in the nucleus;Transport of Mature mRNA derived from an Intron-Containing Transcript;Metabolism of non-coding RNA;Cellular response to heat stress;Nuclear Envelope Breakdown;Mitotic Prophase;M Phase;Nuclear import of Rev protein;Glucose metabolism;Transcriptional regulation by small RNAs;Cell Cycle;Interactions of Vpr with host cellular proteins;Cell Cycle, Mitotic;Transport of Mature Transcript to Cytoplasm;Processing of Capped Intron-Containing Pre-mRNA;Gene Silencing by RNA (Consensus)

Intolerance Scores

• loftool: 0.178
• rvis_EVS: -0.91
• rvis_percentile_EVS: 9.96

Haploinsufficiency Scores

• pHI: 0.609
• hipred: N
• hipred_score: 0.266
• ghis: 0.609

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.538

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Aaas
• Phenotype: reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); growth/size/body region phenotype

Gene ontology

• Biological process: mRNA export from nucleus;nucleocytoplasmic transport;learning;fertilization;viral process;regulation of nucleocytoplasmic transport
• Cellular component: nucleus;nuclear envelope;nuclear pore;nucleoplasm;centrosome;cytosol;membrane;nuclear membrane
• Molecular function: molecular_function