AAAS

Summary

AAAS (aladin WD repeat nucleoporin, HGNC:13666) is a protein-coding gene on chromosome 12q13.13, encoding Aladin (Q9NRG9). Plays a role in the normal development of the peripheral and central nervous system. It is a selective cancer dependency (DepMap: 14.2% of cell lines).

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.

Source: NCBI Gene 8086 — RefSeq curated summary.

At a glance

• Gene–disease (curated): triple-A syndrome (Definitive, GenCC)
• Clinical variants (ClinVar): 584 total — 65 pathogenic, 35 likely-pathogenic (top 6% of genes corpus-wide)
• GTEx eGene: eQTL in 43 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 51
• Cancer dependency (DepMap): dependent in 14.2% of screened cell lines
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.92 (unconstrained)
• MANE Select transcript: NM_015665

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13666
Approved symbol	AAAS
Name	aladin WD repeat nucleoporin
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000094914
Ensembl biotype	protein_coding
OMIM	605378
Entrez	8086

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 12 protein_coding, 10 retained_intron, 7 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay

MANE Select: ENST00000209873

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 7, TSL 3: 4, TSL 4: 1, TSL 5: 6

ENST00000209873, ENST00000394384, ENST00000546393, ENST00000546562, ENST00000546572, ENST00000547238, ENST00000547520, ENST00000547757, ENST00000547761, ENST00000548258, ENST00000548880, ENST00000548931, ENST00000549450, ENST00000549821, ENST00000549983, ENST00000550033, ENST00000550286, ENST00000551724, ENST00000552161, ENST00000552876, ENST00000672797, ENST00000672900, ENST00000910147, ENST00000910148, ENST00000922444, ENST00000968131, ENST00000978447, ENST00000978448, ENST00000978449, ENST00000978450, ENST00001044418, ENST00001082408, ENST00001139504

RefSeq mRNA: 2 — MANE Select: NM_015665 NM_001173466, NM_015665

CCDS: CCDS53797, CCDS8856

Canonical transcript exons

ENST00000209873 — 16 exons

Exon	Start	End
ENSE00001555195	53321343	53321610
ENSE00002374010	53307460	53307713
ENSE00003461117	53308052	53308133
ENSE00003486542	53315094	53315140
ENSE00003489674	53314751	53314849
ENSE00003529116	53320565	53320692
ENSE00003530682	53309157	53309281
ENSE00003563269	53308282	53308349
ENSE00003582842	53308435	53308528
ENSE00003595054	53308960	53309020
ENSE00003637853	53314298	53314441
ENSE00003642453	53315335	53315426
ENSE00003655335	53308725	53308815
ENSE00003656148	53315727	53315782
ENSE00003659272	53309601	53309721
ENSE00003663618	53307845	53307929

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 96.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.1649 / max 243.7495, expressed in 1814 samples.

Highest expression (Bgee): adrenal gland cortex, adrenal gland, uterine tube, adenohypophysis, apex of heart.

Genetic regulation across tissues (GTEx eQTL / sQTL)

AAAS is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 43 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 44 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	eqtl	3.6e-60	+1.04	12:53317150:T:C
Artery Tibial	eqtl	8.4e-50	+0.77	12:53317250:T:C
Thyroid	eqtl	3.3e-34	+0.84	12:53317150:T:C
Esophagus Muscularis	eqtl	5.1e-32	+0.84	12:53317150:T:C
Colon Sigmoid	eqtl	7.6e-27	+0.78	12:53317150:T:C
Esophagus Gastroesophageal Junction	eqtl	3.6e-25	+0.90	12:53317150:T:C
Adipose Subcutaneous	eqtl	3.6e-22	+0.73	12:53317150:T:C
Artery Aorta	eqtl	4.1e-21	+0.77	12:53317150:T:C
Testis	eqtl	2.4e-20	+0.75	12:53317250:T:C
Prostate	eqtl	3.2e-17	+0.91	12:53317150:T:C
Lung	eqtl	4.9e-17	+0.56	12:53320712:A:G
Cells Cultured fibroblasts	eqtl	1.6e-16	+0.61	12:53329584:G:A
Breast Mammary Tissue	eqtl	1.8e-16	+0.74	12:53317150:T:C
Adipose Visceral Omentum	eqtl	3.0e-16	+0.59	12:53317150:T:C
Brain Frontal Cortex BA9	eqtl	3.1e-15	+1.15	12:53317150:T:C
Heart Atrial Appendage	eqtl	5.7e-15	+0.75	12:53317150:T:C
Colon Transverse	eqtl	8.5e-15	+0.69	12:53326934:C:CTTGAT
Pituitary	eqtl	8.6e-15	+0.91	12:53317150:T:C
Artery Coronary	eqtl	1.0e-13	+0.94	12:53317150:T:C
Brain Cortex	eqtl	3.9e-13	+1.13	12:53317150:T:C

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
131229	37.1638	1807
131228	3.0011	1228

Top tissues by expression

showing 100 of 279 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	96.35	gold quality
right adrenal gland	UBERON:0001233	96.31	gold quality
right uterine tube	UBERON:0001302	96.29	gold quality
adenohypophysis	UBERON:0002196	96.08	gold quality
left adrenal gland cortex	UBERON:0035825	95.89	gold quality
left adrenal gland	UBERON:0001234	95.77	gold quality
apex of heart	UBERON:0002098	95.71	gold quality
adrenal cortex	UBERON:0001235	95.36	gold quality
pituitary gland	UBERON:0000007	95.27	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.92	gold quality
lower esophagus	UBERON:0013473	94.90	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.90	gold quality
right testis	UBERON:0004534	94.71	gold quality
ganglionic eminence	UBERON:0004023	94.64	gold quality
left testis	UBERON:0004533	94.38	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.18	gold quality
adrenal gland	UBERON:0002369	94.17	gold quality
ventricular zone	UBERON:0003053	93.87	gold quality
body of uterus	UBERON:0009853	93.76	gold quality
right coronary artery	UBERON:0001625	93.74	gold quality
popliteal artery	UBERON:0002250	93.54	gold quality
tibial artery	UBERON:0007610	93.53	gold quality
right lobe of thyroid gland	UBERON:0001119	93.51	gold quality
right ovary	UBERON:0002118	93.51	gold quality
endocervix	UBERON:0000458	93.43	gold quality
body of stomach	UBERON:0001161	93.40	gold quality
left ovary	UBERON:0002119	93.40	gold quality
metanephros cortex	UBERON:0010533	93.39	gold quality
aorta	UBERON:0000947	93.35	gold quality
ascending aorta	UBERON:0001496	93.27	gold quality
thoracic aorta	UBERON:0001515	93.26	gold quality
body of pancreas	UBERON:0001150	93.07	gold quality
descending thoracic aorta	UBERON:0002345	93.03	gold quality
left coronary artery	UBERON:0001626	93.00	gold quality
left lobe of thyroid gland	UBERON:0001120	92.82	gold quality
mucosa of stomach	UBERON:0001199	92.81	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.76	gold quality
coronary artery	UBERON:0001621	92.65	gold quality
lower esophagus mucosa	UBERON:0035834	92.58	gold quality
ectocervix	UBERON:0012249	92.56	gold quality
fundus of stomach	UBERON:0001160	92.49	gold quality
left uterine tube	UBERON:0001303	92.36	gold quality
testis	UBERON:0000473	92.34	gold quality
right lobe of liver	UBERON:0001114	92.34	gold quality
granulocyte	CL:0000094	92.32	gold quality
esophagus	UBERON:0001043	92.32	gold quality
right atrium auricular region	UBERON:0006631	92.31	gold quality
cerebellar hemisphere	UBERON:0002245	92.20	gold quality
transverse colon	UBERON:0001157	92.18	gold quality
peripheral nervous system	UBERON:0000010	92.12	gold quality
tibial nerve	UBERON:0001323	92.12	gold quality
cerebellar cortex	UBERON:0002129	92.11	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.08	gold quality
mucosa of transverse colon	UBERON:0004991	91.93	gold quality
stomach	UBERON:0000945	91.92	gold quality
minor salivary gland	UBERON:0001830	91.68	gold quality
thyroid gland	UBERON:0002046	91.67	gold quality
spleen	UBERON:0002106	91.63	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.63	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.55	gold quality
omental fat pad	UBERON:0010414	91.39	gold quality
peritoneum	UBERON:0002358	91.36	gold quality
heart left ventricle	UBERON:0002084	91.35	gold quality
cortical plate	UBERON:0005343	91.33	gold quality
cardiac atrium	UBERON:0002081	91.22	gold quality
cardiac ventricle	UBERON:0002082	91.08	gold quality
gastrocnemius	UBERON:0001388	90.89	gold quality
cerebellum	UBERON:0002037	90.82	gold quality
rectum	UBERON:0001052	90.68	gold quality
saliva-secreting gland	UBERON:0001044	90.67	gold quality
right frontal lobe	UBERON:0002810	90.63	gold quality
adipose tissue of abdominal region	UBERON:0007808	90.63	gold quality
heart	UBERON:0000948	90.62	gold quality
muscle of leg	UBERON:0001383	90.57	gold quality
small intestine	UBERON:0002108	90.52	gold quality
right lung	UBERON:0002167	90.52	gold quality
skin of abdomen	UBERON:0001416	90.44	gold quality
spinal cord	UBERON:0002240	90.35	gold quality
pancreas	UBERON:0001264	90.32	gold quality
skin of leg	UBERON:0001511	90.31	gold quality
esophagus mucosa	UBERON:0002469	90.31	gold quality
upper lobe of left lung	UBERON:0008952	90.17	gold quality
stromal cell of endometrium	CL:0002255	90.15	gold quality
lymph node	UBERON:0000029	89.86	gold quality
ovary	UBERON:0000992	89.85	gold quality
gall bladder	UBERON:0002110	89.82	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.72	gold quality
mouth mucosa	UBERON:0003729	89.67	gold quality
smooth muscle tissue	UBERON:0001135	89.61	gold quality
putamen	UBERON:0001874	89.55	gold quality
colon	UBERON:0001155	89.54	gold quality
vena cava	UBERON:0004087	89.43	silver quality
intestine	UBERON:0000160	89.40	gold quality
caudate nucleus	UBERON:0001873	89.40	gold quality
large intestine	UBERON:0000059	89.16	gold quality
amygdala	UBERON:0001876	89.13	gold quality
anterior cingulate cortex	UBERON:0009835	89.13	gold quality
cingulate cortex	UBERON:0003027	89.08	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.05	gold quality
nucleus accumbens	UBERON:0001882	88.96	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.77

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Thymus	tissue	23.5
Tonsil	tissue	20.2	high
Bone marrow	tissue	18.0	medium
Salivary gland	tissue	17.4	medium
Tongue	tissue	17.3
Parathyroid gland	tissue	16.9	not detected
Vagina	tissue	16.7	not detected
Lymph node	tissue	16.5	high
Placenta	tissue	16.4	high
Pancreas	tissue	15.8	not detected
Smooth muscle	tissue	15.7	medium
Choroid plexus	tissue	15.3
Ovary	tissue	15.1	medium
Fallopian tube	tissue	15.0	not detected
Testis	tissue	14.8	high
Heart muscle	tissue	14.6	medium
Rectum	tissue	14.2	low
Corpus callosum	tissue	14.1
Skin 1	tissue	13.8	not detected
Pituitary gland	tissue	13.7
Skeletal muscle	tissue	13.7	medium
Appendix	tissue	13.0	not detected
Cervix	tissue	12.8	not detected
Colon	tissue	12.8	low
Liver	tissue	12.7	medium
Adrenal gland	tissue	12.7	high
Cerebellum	tissue	12.5	high
Spleen	tissue	12.1	high
Duodenum	tissue	11.6	low
Retina	tissue	11.4
Frontal cortex	tissue	11.4
Thyroid gland	tissue	11.4	high
Caudate putamen	tissue	11.3
Seminal vesicle	tissue	11.0	medium
Endometrium 1	tissue	10.9	medium
Locus coeruleus	tissue	10.8
Nucleus accumbens	tissue	10.7
Medulla oblongata	tissue	10.6
Spinal cord	tissue	10.4
Prostate	tissue	10.3	low
Stomach 1	tissue	10.2	not detected
Small intestine	tissue	10.0	not detected
Lung	tissue	9.9	not detected
Periaqueductal gray	tissue	9.8
Substantia nigra	tissue	9.7
Thalamus	tissue	9.6
Breast	tissue	9.5	medium
Esophagus	tissue	9.5	not detected
Superior colliculi	tissue	9.5
Postcentral gyrus	tissue	9.5
Olfactory bulb	tissue	9.3
Midbrain	tissue	9.2
Adipose tissue	tissue	9.1	not detected
Urinary bladder	tissue	9.0	not detected
Gallbladder	tissue	8.8	not detected
Ventral forebrain	tissue	8.7
Pons	tissue	8.6
Hippocampus	tissue	8.6	high
Amygdala	tissue	8.5
Cerebral cortex	tissue	8.3	high

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Corpus callosum, genu (white matter) (18.8), Parieto-temporal junction (white matter) (18.7), Corpus callosum, splenium (white matter) (17.0), Temporal white matter (16.9), Piriform cortex (15.7).

Regulation

Is transcription factor: no

Functional genomics

gnomAD constraint: pLI 8.92e-16, LOEUF 0.921, missense Z 0.887 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000209873 — one region, missense o/e 0.96. DepMap (CRISPR cell-line fitness): dependent in 14.2% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): LPS853 (-1.441), KMS-26 (-1.362), LO68 (-1.275), GB-1 (-1.24), LN-443 (-1.172), BC-2 (-1.154), MGH-ICC10 (-1.153), GI-1 (-1.134), EFM-19 (-1.108), PCI-38 (-1.082), SF539 (-1.074), MGH-ICC10-6 (-1.038), KMS-34 (-1.035), 94T778 (-1.024), LP-1 (-1.019).

Literature-anchored findings (GeneRIF, showing 35)

• a homozygous G –>A transition in exon 9 of the newly identified AAAS gene, resulting in a stop codon (W295X) and predicting a truncated protein with loss of function (PMID:11815731)
• plays a cell type-specific role in regulating nucleocytoplasmic transport and that this function is essential for the proper maintenance andor development of certain tissues; NPC targeting is essential for the function of ALADIN (PMID:12730363)
• myoclonus and generalized digestive dysmotility in triple a syndrome is connected to AAAS gene mutation (PMID:15022193)
• In addition to known ophthalmic manifestations, triple-A syndrome can present with accommodative dysregulation and ocular signs of autonomic dysfunction. (PMID:15217518)
• Further studies have to investigate the role of ALADIN at NPCs and to identify interacting proteins. Functional analyses of ALADIN may permit further understanding of its role for adrenocortical function and neurodevelopment. (PMID:15666842)
• Widespread but not ubiquitous or uniform expression of AAAS mRNA in the developing rat embryo. (PMID:15680696)
• Data do not support a pathogenetic role for common AAAS gene mutations in patients with idiopathic achalasia as seen in Allgrove syndrome. (PMID:15843079)
• novel splice variant AAAS-v2 encodes a 513-amino acid polypeptide, which contains three WD40 domains; AAAS-v2 and AAAS-v1 were ubiquitously detected in human tissues (PMID:16022285)
• 3 subjects with classic AAAS did not have mutations in AAAS gene on both alleles. This supports the notion of genetic heterogeneity for this disorder, although other genetic mechanisms cannot be excluded. (PMID:16098009)
• The mutation of the AAAS gene is a novel mutation and this case adds to the clinical and molecular spectrum of triple A syndrome and may provide a new insight into the functions of AAAS gene. (PMID:16543750)
• With transfection experiments, we analyzed the cellular localization of the wild-type and 17 natural mutant variants (9 missense, 5 nonsense, 3 frameshift mutations) of ALADIN. (PMID:16609705)
• novel homozygous mutation within intron 5 (IVS5+1G–>A) illustrates the heterogenous nature and the intrafamilial phenotypic variability of Allgrove syndrome (PMID:16938764)
• Report a case of adult onset Allgrove syndrome had no mutation in the ALADIN gene on chromosome 12q13. (PMID:18175081)
• The prognosis of patients with triple A syndrome depends on the identification and treatment of adrenal insufficiency. (PMID:19011813)
• AAAS gene analysis demonstrated a homozygous A to G mutation at nucleotide position 122 in exon 1 in DNA from the patient. (PMID:19172511)
• The study shows that ALADIN is a protein with a molecular weight of 60 kDa, and expressed in the adrenal gland, pituitary gland and pancreas. ALADIN is localized in the nuclear membrane. (PMID:19322026)
• NDC1-mediated localization of ALADIN to nuclear pore complexes is essential for selective nuclear protein import; abrogation of the interaction between ALADIN and NDC1 may be important for the development of triple-A syndrome. (PMID:19703420)
• ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated. (PMID:19782045)
• ALADIN interact with FTH1 and FTH1 nuclear translocation is enhanced when ALADIN is coexpressed. (PMID:19855093)
• Study broadened the allelic and phenotypic spectrum of Allgrove syndrome due to AAAS mutations; the recurrence of the Leu469Pro mutation highlights a possible major role for this alteration in the Italian population. (PMID:20447142)
• In all children with mutation in AAAS gene, regular follow up of adrenal function is necessary to avoid adrenal crisis and start substitution therapy as soon as adrenal insufficiency is noted. (PMID:20499090)
• Sequencing of the AAAS gene detected a compound heterozygous mutation consisting of a novel mutation p.Ser296Tyr (c.887C>A) in exon 9 and a previously described p.Ser263Pro (c.787T>C) missense mutation in exon 8 in both siblings triple A syndrome. (PMID:20931227)
• identification of two novel mutations in the AAAS gene associated with achalasia adrenocortical insufficiency alacrimia syndrome (PMID:21565631)
• The compromising c.43C>A mutation is predicted to cause a p.Gln15Lys amino acid substitution in the ALADIN protein. (PMID:23073554)
• Data suggest ALADIN is involved in resistance to oxidative stress in adrenocortical cells/neurons; ALADIN knockdown down-regulates StAR (steroidogenic acute regulatory protein) and P45011beta (cytochrome P450 family 11 subfamily B polypeptide 1). (PMID:23825130)
• Triple A syndrome with a novel indel mutation in the AAAS gene and delayed puberty. (PMID:25781531)
• down-regulating ALADIN results in decreased oxidative stress response leading to alteration in steroidogenesis, highlighting our knock-down cell model as an important in-vitro tool for studying the adrenal phenotype in triple A syndrome (PMID:25867024)
• This study demonstrated that a single splicing mutation affects the AAAS transcripts and consequently the ALADIN protein structure and function. (PMID:27414811)
• Nine different AAAS mutations were found, including one new mutation: c.755G>C, p.(Trp252Ser) in a French cohort of Triple A syndrome patients. (PMID:29237697)
• Clinical and genetic characteristics of six patients with triple A syndrome and AAAS mutations are described. (PMID:29255950)
• Mutation in AAAS gene is associated with triple A syndrome. (PMID:29874194)
• AAAS mutations were identified in two families with hereditary spastic paraplegia. (PMID:30381913)
• A homozygous deletion of the entire AAAS gene was identified in a patient with triple A syndrome. (PMID:31071487)
• Triple A (Allgrove) syndrome due to AAAS gene mutation with a rare association of amyotrophy. (PMID:32700293)
• Biallelic NDC1 variants that interfere with ALADIN binding are associated with neuropathy and triple A-like syndrome. (PMID:39003500)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	aaas	ENSDARG00000102274
mus_musculus	Aaas	ENSMUSG00000036678
rattus_norvegicus	Aaas	ENSRNOG00000013445
drosophila_melanogaster	Aladin	FBGN0030122
drosophila_melanogaster	CG13137	FBGN0032188

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2443767) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 5 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased body weight	1
decreased locomotor activity	1
decreased exploration in new environment	1
abnormal motor coordination/balance	1
female infertility	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Arabidopsis thaliana	Q8GWR1	31.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SP7	protein-coding	121340
PFDN5	protein-coding	5204
MYG1	protein-coding	60314
SLC61A1	protein-coding	84975
ESPL1	protein-coding	9700
AMHR2	protein-coding	269
SP1	protein-coding	6667
PRR13	protein-coding	54458

Protein

Protein identifiers

Aladin — Q9NRG9 (reviewed: Q9NRG9)

Alternative names: Adracalin

All UniProt accessions (4): Q9NRG9, F8VUB6, F8VZ44, H3BU82

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the normal development of the peripheral and central nervous system. 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.

Subunit / interactions. Interacts with NDC1, the interaction is required for nuclear pore localization. Interacts with the inactive form aurora kinase AURKA. Interacts with PGRMC2.

Subcellular location. Nucleus. Nuclear pore complex. Cytoplasm. Cytoskeleton. Spindle pole. Nucleus envelope.

Tissue specificity. Widely expressed. Particularly abundant in cerebellum, corpus callosum, adrenal gland, pituitary gland, gastrointestinal structures and fetal lung.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Ubiquitously expressed.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NRG9-1	1, AAAS-v1	yes
Q9NRG9-2	2, AAAS-v2

RefSeq proteins (2): NP_001166937, NP_056480* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR045139	Aladin	Family
IPR057403	Beta-prop_Aladin	Domain

Pfam: PF25460

UniProt features (30 total): modified residue 7, repeat 7, sequence variant 7, sequence conflict 3, initiator methionine 1, chain 1, short sequence motif 1, compositionally biased region 1, splice variant 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
7R5K	Human nuclear pore complex (constricted)	ELECTRON MICROSCOPY	12
7R5J	Human nuclear pore complex (dilated)	ELECTRON MICROSCOPY	50

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRG9-F1	75.45	0.27

Human Protein Atlas

Protein class: Metabolic proteins, Transporters, Transporter channels and pores, Predicted intracellular proteins, Disease related genes, Potential drug targets, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nuclear membrane; centrosome; cytosol; end piece; nucleoplasm

Antibody reliability (HPA): IH approved · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (7)

Type	Positions
N-acetylcysteine	2
Phosphoserine	33, 495, 511, 522, 525, 541

Function

Pathways and Gene Ontology

Reactome pathways

29 curated (TAS) of 82; 29 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

showing 60 of 82 pathways:

ID	Pathway	Evidence
R-HSA-5619107	Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC) ⚕	curated
R-HSA-9609690	HCMV Early Events ⚕	curated
R-HSA-9610379	HCMV Late Events ⚕	curated
R-HSA-168333	NEP/NS2 Interacts with the Cellular Export Machinery ⚕	curated
R-HSA-168276	NS1 Mediated Effects on Host Pathways ⚕	curated
R-HSA-165054	Rev-mediated nuclear export of HIV RNA ⚕	curated
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses ⚕	curated
R-HSA-168271	Transport of Ribonucleoproteins into the Host Nucleus ⚕	curated
R-HSA-168325	Viral Messenger RNA Synthesis ⚕	curated
R-HSA-180910	Vpr-mediated nuclear import of PICs ⚕	curated
R-HSA-1855196	IP3 and IP4 transport between cytosol and nucleus	curated
R-HSA-1855229	IP6 and IP7 transport between cytosol and nucleus	curated
R-HSA-1855170	IPs transport between nucleus and cytosol	curated
R-HSA-1169408	ISG15 antiviral mechanism	curated
R-HSA-3301854	Nuclear Pore Complex (NPC) Disassembly	curated
R-HSA-8980692	RHOA GTPase cycle	curated
R-HSA-170822	Regulation of Glucokinase by Glucokinase Regulatory Protein	curated
R-HSA-3371453	Regulation of HSF1-mediated heat shock response	curated
R-HSA-3108214	SUMOylation of DNA damage response and repair proteins	curated
R-HSA-4570464	SUMOylation of RNA binding proteins	curated
R-HSA-4085377	SUMOylation of SUMOylation proteins	curated
R-HSA-4551638	SUMOylation of chromatin organization proteins	curated
R-HSA-3232142	SUMOylation of ubiquitinylation proteins	curated
R-HSA-159231	Transport of Mature mRNA Derived from an Intronless Transcript	curated
R-HSA-159236	Transport of Mature mRNA derived from an Intron-Containing Transcript	curated
R-HSA-159230	Transport of the SLBP Dependant Mature mRNA	curated
R-HSA-159227	Transport of the SLBP independent Mature mRNA	curated
R-HSA-191859	snRNP Assembly	curated
R-HSA-6784531	tRNA processing in the nucleus	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5619115	Disorders of transmembrane transporters ⚕	—
R-HSA-168274	Export of Viral Ribonucleoproteins from Nucleus ⚕	—
R-HSA-9609646	HCMV Infection ⚕	—
R-HSA-162906	HIV Infection ⚕	—
R-HSA-162587	HIV Life Cycle ⚕	—
R-HSA-162909	Host Interactions of HIV factors ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-168255	Influenza Infection ⚕	—
R-HSA-168273	Influenza Viral RNA Transcription and Replication ⚕	—
R-HSA-177243	Interactions of Rev with host cellular proteins ⚕	—
R-HSA-176033	Interactions of Vpr with host cellular proteins ⚕	—
R-HSA-162599	Late Phase of HIV Life Cycle ⚕	—
R-HSA-180746	Nuclear import of Rev protein ⚕	electronic
R-HSA-9679506	SARS-CoV Infections ⚕	—
R-HSA-9694516	SARS-CoV-2 Infection ⚕	—
R-HSA-9705683	SARS-CoV-2-host interactions ⚕	—
R-HSA-5619102	SLC transporter disorders ⚕	—
R-HSA-9824446	Viral Infection Pathways ⚕	—
R-HSA-1169410	Antimicrobial mechanism of IFN-stimulated genes	—
R-HSA-1640170	Cell Cycle	—
R-HSA-69278	Cell Cycle, Mitotic	—
R-HSA-3371556	Cellular response to heat stress	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-2262752	Cellular responses to stress	—
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-211000	Gene Silencing by RNA	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-70326	Glucose metabolism	—
R-HSA-70171	Glycolysis	—
R-HSA-168256	Immune System	—

MSigDB gene sets: 344 (showing top): GOBP_CHROMOSOME_ORGANIZATION, REACTOME_INTERACTIONS_OF_VPR_WITH_HOST_CELLULAR_PROTEINS, GOBP_COGNITION, GOBP_BEHAVIOR, GCM_GSPT1, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, REACTOME_VIRAL_MESSENGER_RNA_SYNTHESIS, GOBP_GROWTH, GCM_BCL2L1, GOBP_NUCLEAR_TRANSPORT, GOBP_MITOTIC_SPINDLE_ASSEMBLY, REACTOME_HIV_INFECTION, GOBP_ORGANELLE_FISSION, GOBP_REGULATION_OF_NUCLEOCYTOPLASMIC_TRANSPORT, GOBP_AMIDE_METABOLIC_PROCESS

GO Biological Process (6): microtubule bundle formation (GO:0001578), nucleocytoplasmic transport (GO:0006913), protein transport (GO:0015031), regulation of nucleocytoplasmic transport (GO:0046822), mRNA transport (GO:0051028), mitotic spindle assembly (GO:0090307)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (8): spindle pole (GO:0000922), nucleus (GO:0005634), nuclear envelope (GO:0005635), nuclear pore (GO:0005643), nucleoplasm (GO:0005654), membrane (GO:0016020), nuclear membrane (GO:0031965), mitotic spindle (GO:0072686)

Reactome top-level categories

14 top-level categories:

Category	Pathways
Transport of Mature mRNAs Derived from Intronless Transcripts	3
Inositol phosphate metabolism	3
Interactions of Rev with host cellular proteins	2
Influenza Infection	2
SUMO E3 ligases SUMOylate target proteins	2
Antimicrobial mechanism of IFN-stimulated genes	1
Transport of Mature Transcript to Cytoplasm	1
Late Phase of HIV Life Cycle	1
Influenza Viral RNA Transcription and Replication	1
Export of Viral Ribonucleoproteins from Nucleus	1
Glycolysis	1
Interactions of Vpr with host cellular proteins	1
Metabolism of non-coding RNA	1
Nuclear Envelope Breakdown	1

GO top-level categories

23 GO namespaces:

Category	Terms
cellular anatomical structure	3
spindle	2
nucleus	2
nuclear envelope	2
microtubule cytoskeleton organization	1
nuclear transport	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
nucleocytoplasmic transport	1
regulation of intracellular transport	1
RNA transport	1
mitotic sister chromatid segregation	1
mitotic spindle organization	1
spindle assembly	1
mitotic nuclear division	1
binding	1
intracellular membrane-bounded organelle	1
endomembrane system	1
organelle envelope	1
nuclear protein-containing complex	1
nuclear lumen	1
organelle membrane	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 11 of 15 annotations. The rest are phylogenetic / computational / electronic (IEA).

11 experimentally-supported GO terms:

GO term	NS	Evidence
microtubule bundle formation	BP	mutant phenotype
mitotic spindle assembly	BP	mutant phenotype
nucleocytoplasmic transport	BP	direct assay
membrane	CC	high-throughput assay
mitotic spindle	CC	direct assay
nuclear envelope	CC	direct assay
nuclear membrane	CC	direct assay
nuclear pore	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	high-throughput assay
spindle pole	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 846 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AAAS	POMC	P01189	736
AAAS	NDC1	Q9BTX1	687
AAAS	MC2R	Q01718	634
AAAS	NUP155	O75694	628
AAAS	NUP54	Q7Z3B4	593
AAAS	NUP205	Q92621	589
AAAS	NUP35	Q8NFH5	588
AAAS	SEH1L	Q96EE3	579
AAAS	NUP88	Q99567	560
AAAS	NUP37	Q8NFH4	559
AAAS	NUP50	Q9UKX7	559
AAAS	NUP160	Q12769	545
AAAS	NUP85	Q9BW27	533
AAAS	GLE1	Q53GS7	514
AAAS	NUP188	Q5SRE5	513

IntAct

Human interaction partners of AAAS in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

Partner	Interaction type	MIscore	Records
NUDC	physical association	0.400	1
NUDCD3	physical association	0.400	1
NUP133	physical association	0.370	1
REL	physical association	0.370	1
LORICRIN	association	0.350	1

BioGRID (223 interactions; top human partners by supporting records): NUP35 (Affinity Capture-MS; 3 records), NUP155 (Proximity Label-MS; 2 records), PARK2 (Affinity Capture-MS; 2 records), RHOA (Affinity Capture-MS; 2 records), SEC61B (Proximity Label-MS; 2 records), SLC39A4 (Affinity Capture-MS; 2 records), ABHD14A (Affinity Capture-MS), AKAP1 (Proximity Label-MS), ALK (Proximity Label-MS), AMBRA1 (Proximity Label-MS), ANLN (Affinity Capture-MS), AR (Affinity Capture-MS), ATG9A (Proximity Label-MS), BAG2 (Affinity Capture-MS), BCAP31 (Proximity Label-MS)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
AAAS	“form complex”	NPC	binding

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
Nuclear pore complex	31	NUP155, NUP188, NUP58, NUP62, SEH1L, NUP85, AAAS, NUP214, NUP42, NUP88, NUP98, NUP50, NUP54, AHCTF1, NUP35, GLE1, NDC1, NUP107, NUP133, NUP160, NUP37, NUP43, TPR, RANBP2, NUP153, NUP210, POM121, SEC13, NUP205, NUP93, RAE1

Disease & clinical

Genetic variants

Variant evidence for AAAS: 584 ClinVar records (100 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

584 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	65
Likely pathogenic	35
Uncertain significance	142
Likely benign	271
Benign	22

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 100 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
5044	NM_015665.6(AAAS):c.43C>A (p.Gln15Lys)	Pathogenic	criteria provided, multiple submitters, no conflicts	21
264994	NM_015665.6(AAAS):c.1331+1G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	17
5040	NM_015665.6(AAAS):c.1432C>T (p.Arg478Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	11
264992	NM_015665.6(AAAS):c.1066_1067del (p.Leu356fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
264990	NM_015665.6(AAAS):c.1159C>T (p.Gln387Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
429542	NM_015665.6(AAAS):c.1191dup (p.Glu398fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
264988	NM_015665.6(AAAS):c.57_58del (p.Tyr19_Glu20delinsTer)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
841221	NM_015665.6(AAAS):c.688C>T (p.Arg230Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
1322889	NM_015665.6(AAAS):c.856C>T (p.Arg286Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
2159758	NM_015665.6(AAAS):c.855_856delinsTT (p.Arg286Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
429876	NM_015665.6(AAAS):c.885G>A (p.Trp295Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2581608	NM_015665.6(AAAS):c.355C>T (p.Arg119Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2735885	NM_015665.6(AAAS):c.1024C>T (p.Arg342Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2735886	NM_015665.6(AAAS):c.771del (p.Arg258fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2735890	NM_015665.6(AAAS):c.580C>T (p.Arg194Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2

Per-variant reference — Sugi Variant

Explore AAAS’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 1,162):

Position(s)	Effect	Δscore	Sites
12:53308529	acceptor_loss	1.0000	2
12:53309155–53309156	donor_loss	1.0000	5
12:53309282–53309283	acceptor_loss	1.0000	3
12:53315725	donor_loss	1.0000	2
12:53308134–53308135	acceptor_loss	0.9900	6
12:53308350–53308351	acceptor_loss	0.9900	5
12:53308429	donor_gain	0.9900
12:53308433–53308434	donor_loss	0.9900	5
12:53308438	donor_gain	0.9900
12:53308530	acceptor_loss	0.9900	2

AlphaMissense

1,158 missense substitutions predicted likely pathogenic (of 3,495 scored), across 318 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F460	8	0.979	0.998
H160	8	0.974	0.997
D405	8	0.964	0.992
F431	8	0.948	0.997
F486	8	0.948	0.998
F7	8	0.935	0.979
F311	8	0.935	0.993
H190	8	0.927	0.991
F69	8	0.926	0.991
D223	8	0.925	0.987
F345	8	0.920	0.990
D173	8	0.919	0.996
F358	8	0.917	0.981
D172	8	0.907	0.982
F439	8	0.892	0.979
H244	8	0.798	0.889
W201	7	0.997	1.000
W220	7	0.997	0.999
W252	7	0.993	0.999
W272	7	0.993	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000931

Disease associations

OMIM: gene MIM:605378 | disease phenotypes: MIM:231550, MIM:145290

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
triple-A syndrome	Definitive	Autosomal recessive	5

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (15 panels, 14 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

15 panels:

Panel	Rating
Adult-onset neurological disorders	green
Ataxia and cerebellar anomalies - childhood onset	green
Congenital adrenal hypoplasia	green
DDG2P	green
Familial dysautonomia	green
Fetal anomalies	green
Hereditary ataxia	green
Hereditary ataxia and cerebellar anomalies, childhood onset	green
Hereditary ataxia, adult onset	green
Hereditary neuropathy or pain disorder	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Paediatric disorders	green
Dystonia, chorea or related movement disorder, childhood onset	amber

Mondo (6): triple-A syndrome (MONDO:0009279), neurodevelopmental disorder (MONDO:0700092), hyperreflexia (MONDO:0007774), achalasia-alacrima syndrome (MONDO:0800195), microcephaly (MONDO:0001149), congenital nervous system disorder (MONDO:0002320)

Orphanet (1): Triple A syndrome (Orphanet:869)

HPO phenotypes

51 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000407	Sensorineural hearing impairment
HP:0000505	Visual impairment
HP:0000522	Alacrima
HP:0000648	Optic atrophy
HP:0000649	Abnormality of visual evoked potentials
HP:0000846	Adrenal insufficiency
HP:0000953	Hyperpigmentation of the skin
HP:0000972	Palmoplantar hyperkeratosis
HP:0000982	Palmoplantar keratoderma
HP:0001097	Keratoconjunctivitis sicca
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001278	Orthostatic hypotension
HP:0001324	Muscle weakness
HP:0001347	Hyperreflexia
HP:0001531	Failure to thrive in infancy
HP:0001611	Hypernasal speech
HP:0001761	Pes cavus
HP:0001824	Weight loss
HP:0001943	Hypoglycemia
HP:0002013	Vomiting
HP:0002093	Respiratory insufficiency
HP:0002173	Hypoglycemic seizures
HP:0002376	Developmental regression
HP:0002571	Achalasia
HP:0002615	Hypotension
HP:0003154	Increased circulating ACTH level
HP:0003487	Babinski sign
HP:0003621	Juvenile onset
HP:0003676	Progressive
HP:0004319	Decreased circulating aldosterone concentration
HP:0004322	Short stature
HP:0007002	Motor axonal neuropathy
HP:0007440	Generalized hyperpigmentation
HP:0007556	Plantar hyperkeratosis
HP:0008163	Decreased circulating cortisol level
HP:0008259	Adrenocorticotropin receptor defect
HP:0008872	Feeding difficulties in infancy
HP:0009916	Anisocoria
HP:0010486	Abnormality of the hypothenar eminence
HP:0011462	Young adult onset
HP:0011463	Childhood onset
HP:0012332	Abnormal autonomic nervous system physiology
HP:0012735	Cough
HP:0012804	Corneal ulceration
HP:0031078	Impaired cortisol response to corticotropin releasing hormone stimulation test

MeSH disease descriptors

4 disease descriptors:

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625
D012021	Reflex, Abnormal	C10.597.704; C23.888.592.717; E01.370.376.550.650.655; E01.370.600.550.650.655; G11.561.731.587
C536008	Achalasia Addisonianism Alacrimia syndrome *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724744 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.27	Kd	53.65	nM	CHEMBL5653589
7.27	ED50	53.65	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 8 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147763: Binding affinity to human AAAS incubated for 45 mins by Kinobead based pull down assay	kd	0.0537	uM

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
bisphenol A	affects cotreatment, increases methylation, decreases methylation, increases expression	2
Paraquat	affects response to substance	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
pirinixic acid	affects binding, decreases expression, increases activity	1
beta-lapachone	increases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
bisphenol S	increases methylation	1
LDN 193189	decreases expression, affects cotreatment	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	increases oxidation, affects cotreatment, increases abundance	1
Arsenic	decreases expression, increases abundance, affects cotreatment	1
Coumestrol	increases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Smoke	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650805	Binding	Binding affinity to human AAAS incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Cellosaurus cell lines

1 cell lines: 1 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_JL93	GM12123	Finite cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 223 trials:

NCT	Phase	Status	Title
NCT04586348	Phase 4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	Phase 4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	Phase 3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	Phase 3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	Phase 3	RECRUITING	Reducing Missed Appointments
NCT07377032	Phase 3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	Phase 2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	Phase 2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	Phase 2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	Phase 1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	Phase 1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	Phase 1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT02179801	Not specified	UNKNOWN	Screening Cardiovascular Patients for Aortic aNeurysms (SCAN)
NCT02393716	Not specified	TERMINATED	Endurant Evo US Clinical Trial
NCT02461524	Not specified	TERMINATED	Endurant Evo International Clinical Trial
NCT02485496	Not specified	TERMINATED	E-tegra Stent Graft System in the Treatment of Infra-renal Abdominal Aortic Aneurysms
NCT02692664	Not specified	COMPLETED	Prospective Multicenter Study for the Endovascular Treatment of Iliac Aneurysm With the Branched E-liac Stent Graft
NCT03407664	Not specified	UNKNOWN	NHS AAA Screening Programme Data Linkage With HES and ONS Datasets
NCT03762525	Not specified	COMPLETED	Iliac Branch Device Movement During Cardiac Cycle (IBD-dynamics)
NCT04080557	Not specified	COMPLETED	Abdominal Aortic Aneurysm Patients Remain at Risk for Delirium on the Surgical Ward After Intensive Care Unit Dismissal
NCT05064540	Not specified	RECRUITING	JAGUAR Trial: ObJective Analysis to GaUge EVAR Outcomes Through Randomization
NCT05133492	Not specified	ACTIVE_NOT_RECRUITING	First In Human Study for Small to Medium-sized Abdominal Aortic Aneurysm (AAA)
NCT05376514	Not specified	COMPLETED	Central Blood Pressure and Variability Evaluation
NCT05409118	Not specified	WITHDRAWN	JAGUAR Trial (Outside United States; OUS): ObJective Analysis to GaUge EVAR Outcomes Through Randomization
NCT01783041	Phase 2/3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	Phase 2/3	COMPLETED	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	Early Phase 1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	COMPLETED	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice
NCT03381027	Not specified	COMPLETED	BABY SMART (Study of Massage Therapy, Sleep And neurodevelopMenT)
NCT03388294	Not specified	COMPLETED	Evaluation of a Novel Intervention for Infants At Risk for Neurodevelopmental Disorders
NCT03410810	Not specified	UNKNOWN	Childhood Outcomes of Preterm Brain Abnormalities
NCT03492060	Not specified	RECRUITING	Longitudinal Study of Neurogenetic Disorders
NCT03577756	Not specified	COMPLETED	Neurodevelopmental Assessment of Infants With Cystic Fibrosis
NCT03654248	Not specified	COMPLETED	Let’s Get Organized in Adult Psychiatric/habilitation Care
NCT03659279	Not specified	COMPLETED	Let’s Get Organized Feasibility Study
NCT03722615	Not specified	COMPLETED	Epidemiology of Congenital Cytomegalovirus in a High HIV Prevalence Setting, South Africa

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for AAAS across ~30M SureChEMBL compounds — explore on Sugi Predict.