AAAS
MCID: ACH022
MIFTS: 66

Achalasia-Addisonianism-Alacrima Syndrome (AAAS)

Categories: Endocrine diseases, Eye diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases
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Aliases & Classifications for Achalasia-Addisonianism-Alacrima Syndrome

MalaCards integrated aliases for Achalasia-Addisonianism-Alacrima Syndrome:

Name: Achalasia-Addisonianism-Alacrima Syndrome 57 42 58 73
Allgrove Syndrome 57 11 19 42 58 73 53
Achalasia-Addisonianism-Alacrimia Syndrome 57 11 75 12 38
Triple-a Syndrome 57 11 73 14 75
Alacrima-Achalasia-Adrenal Insufficiency Neurologic Disorder 57 19 42 73
Triple a Syndrome 19 42 58 75
Aaa Syndrome 19 42 58 75
Glucocorticoid Deficiency with Achalasia 28 5 71
Aaas 57 11 73
Glucocorticoid Deficiency and Achalasia 57 73
Alacrima-Achalasia-Addisonianism 57 73
Addisonian-Achalasia Syndrome 57 73
Hypoadrenalism with Achalasia 57 73
Aaa 19 42
Acth-Resistant Adrenal Insufficiency with Achalasia and Alacrima 73
Acth-Resistant Adrenal Insufficiency, Achalasia and Alacrima 57
Adrenal Insufficiency-Achalasia-Alacrima Syndrome 58
Achalasia Addisonianism Alacrimia Syndrome 19
Adrenal Cortical Hypofunction 71
Addisonian Achalasia Syndrome 19
Achalasia-Addisonian Syndrome 42
Achalasia Alacrima Syndrome 19
Achalasia-Alacrima Syndrome 42
Adrenal Gland Hypofunction 71
Quaternary a Syndrome 58
Allgrove's Syndrome 73
Double a Syndrome 58
2a Syndrome 58
3a Syndrome 58
4a Syndrome 58

Characteristics:


Inheritance:

Achalasia-Addisonianism-Alacrima Syndrome: Autosomal recessive 57
Triple a Syndrome: Autosomal recessive 58

Prevelance:

Triple a Syndrome: <1/1000000 (Worldwide) 58

Age Of Onset:

Triple a Syndrome: All ages 58

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
progressive disorder
onset in early childhood
adrenal insufficiency usually develops later (first decade)
neurologic symptoms may develop decades later
variable neurologic phenotype


HPO:

30
achalasia-addisonianism-alacrima syndrome:
Onset and clinical course progressive


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


Summaries for Achalasia-Addisonianism-Alacrima Syndrome

MedlinePlus Genetics: 42 Triple A syndrome is an inherited condition characterized by three specific features: achalasia, Addison disease, and alacrima. Achalasia is a disorder that affects the ability to move food through the esophagus, the tube that carries food from the throat to the stomach. It can lead to severe feeding difficulties and low blood sugar (hypoglycemia). Addison disease, also known as primary adrenal insufficiency, is caused by abnormal function of the small hormone-producing glands on top of each kidney (adrenal glands). The main features of Addison disease include fatigue, loss of appetite, weight loss, low blood pressure, and darkening of the skin. The third major feature of triple A syndrome is a reduced or absent ability to secrete tears (alacrima). Most people with triple A syndrome have all three of these features, although some have only two.Many of the features of triple A syndrome are caused by dysfunction of the autonomic nervous system. This part of the nervous system controls involuntary body processes such as digestion, blood pressure, and body temperature. People with triple A syndrome often experience abnormal sweating, difficulty regulating blood pressure, unequal pupil size (anisocoria), and other signs and symptoms of autonomic nervous system dysfunction (dysautonomia).People with this condition may have other neurological abnormalities, such as developmental delay, intellectual disability, speech problems (dysarthria), and a small head size (microcephaly). In addition, affected individuals commonly experience muscle weakness, movement problems, and nerve abnormalities in their extremities (peripheral neuropathy). Some develop optic atrophy, which is the degeneration (atrophy) of the nerves that carry information from the eyes to the brain. Many of the neurological symptoms of triple A syndrome worsen over time.People with triple A syndrome frequently develop a thickening of the outer layer of skin (hyperkeratosis) on the palms of their hands and the soles of their feet. Other skin abnormalities may also be present in people with this condition.Alacrima is usually the first noticeable sign of triple A syndrome, as it becomes apparent early in life that affected children produce little or no tears while crying. They develop Addison disease and achalasia during childhood or adolescence, and most of the neurologic features of triple A syndrome begin during adulthood. The signs and symptoms of this condition vary among affected individuals, even among members of the same family.

MalaCards based summary: Achalasia-Addisonianism-Alacrima Syndrome, also known as allgrove syndrome, is related to congenital nervous system abnormality and familial glucocorticoid deficiency, and has symptoms including ataxia and muscle weakness. An important gene associated with Achalasia-Addisonianism-Alacrima Syndrome is AAAS (Aladin WD Repeat Nucleoporin), and among its related pathways/superpathways are Gene expression (Transcription) and Metabolism of proteins. The drugs Racepinephrine and Dexamethasone acetate have been mentioned in the context of this disorder. Affiliated tissues include adrenal gland, eye and skin, and related phenotypes are seizure and achalasia

GARD: 19 Triple A syndrome is an inherited condition characterized by three specific features: achalasia, Addison disease, and alacrima (a reduced or absent ability to secrete tears). Most people with Triple A syndrome have all three of these features, although some have only two. Several authors published descriptions of a more global autonomic disturbance associated with the original three characteristics, leading one author to suggest the name 4A syndrome (adrenal insufficiency, achalasia, alacrima, autonomic abnormalities). Specific autonomic disturbances described in this syndrome include abnormal pupillary reflexes, poor heart rate variability, and orthostatic hypotension. Affected individuals may also have developmental delay, intellectual disability, speech problems, a small head size, muscle weakness, movement problems, peripheral neuropathy, and optic atrophy. Triple A syndrome is caused by genetic changes in the AAAS gene and is inherited in an autosomal recessive pattern.

UniProtKB/Swiss-Prot: 73 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.

Disease Ontology: 11 A syndrome characterized by achalasia, adrenal insufficiency and alacrima and has material basis in mutations in the AAAS gene that encodes ALADIN within the nuclear envelope and results in dysfunction of the autonomic nervous system.

Orphanet: 58 Triple A syndrome is a very rare multisystem disease characterized by adrenal insufficiency with isolated glucocorticoid deficiency, achalasia, alacrima, autonomic dysfunction and neurodegeneration.

Wikipedia: 75 Triple-A syndrome or AAA syndrome is a rare autosomal recessive congenital disorder. In most cases,... more...

More information from OMIM: 231550

Related Diseases for Achalasia-Addisonianism-Alacrima Syndrome

Diseases related to Achalasia-Addisonianism-Alacrima Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 526)
# Related Disease Score Top Affiliating Genes
1 congenital nervous system abnormality 31.6 TRAPPC11 POMC NUP133 APTX AAAS
2 familial glucocorticoid deficiency 31.3 TXNRD2 POMC NR0B1 NNT MRAP MC2R
3 glucocorticoid deficiency 1 30.7 POMC MRAP MC2R
4 adrenal hypoplasia, congenital 30.5 POMC NR0B1 MC2R
5 achalasia 30.3 TRAPPC11 MC2R GMPPA AAAS
6 hypoadrenocorticism, familial 30.3 POMC NR0B1 MC2R
7 adrenal insufficiency, congenital, with 46,xy sex reversal, partial or complete 30.0 POMC NR0B1 NNT MC2R
8 pituitary-dependent cushing's disease 30.0 POMC MC2R
9 lipoid congenital adrenal hyperplasia 30.0 POMC NR0B1 MRAP MC2R
10 aortic aneurysm, familial abdominal, 1 11.7
11 aortic aneurysm 11.4
12 alacrima, achalasia, and mental retardation syndrome 11.2
13 multiple endocrine neoplasia, type iia 11.1
14 syndromic x-linked intellectual disability 17 11.1
15 gmppa-cdg 11.1
16 nervous system disease 11.0
17 accommodative spasm 10.9
18 polycystic liver disease 10.9
19 polycystic kidney disease 10.9
20 fissured tongue 10.9
21 diabetic polyneuropathy 10.9
22 hypoglossal nerve disease 10.9
23 schwannoma of twelfth cranial nerve 10.9
24 autosomal dominant polycystic kidney disease 10.9
25 vascular disease 10.7
26 multiple endocrine neoplasia 10.5
27 paraplegia 10.4
28 thyroid carcinoma 10.4
29 hereditary spastic paraplegia 10.4
30 thyroid carcinoma, familial medullary 10.4
31 spastic paraplegia 20, autosomal recessive 10.4
32 thyroid gland medullary carcinoma 10.3
33 waterhouse-friderichsen syndrome 10.3 POMC MC2R
34 adrenal rest tumor 10.3 POMC MC2R
35 pheochromocytoma 10.3
36 corticosteroid-binding globulin deficiency 10.3 POMC MC2R
37 spastic paraplegia 7, autosomal recessive 10.3
38 46,xy sex reversal 10.3 POMC NR0B1 MC2R
39 cranioectodermal dysplasia 4 10.3 NUP62 GLE1
40 optic atrophy 1 10.3
41 spinocerebellar ataxia 28 10.3
42 steroid inherited metabolic disorder 10.3 POMC NR0B1 MC2R
43 adrenal cortical hypofunction 10.2 POMC NR0B1 MC2R
44 dystonia 10.2
45 corticosterone methyloxidase type i deficiency 10.2 POMC NR0B1
46 adrenal cortex disease 10.2 POMC NR0B1 MC2R
47 adrenal gland disease 10.2 POMC NR0B1 MC2R
48 adrenal carcinoma 10.2 POMC NR0B1 MC2R
49 17-beta hydroxysteroid dehydrogenase iii deficiency 10.2 POMC NR0B1
50 graves disease 1 10.2 TXNRD2 POMC

Graphical network of the top 20 diseases related to Achalasia-Addisonianism-Alacrima Syndrome:



Diseases related to Achalasia-Addisonianism-Alacrima Syndrome

Symptoms & Phenotypes for Achalasia-Addisonianism-Alacrima Syndrome

Human phenotypes related to Achalasia-Addisonianism-Alacrima Syndrome:

58 30 (show all 37)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizure 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0001250
2 achalasia 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0002571
3 generalized hyperpigmentation 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0007440
4 adrenal insufficiency 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000846
5 visual impairment 58 30 Frequent (33%) Frequent (79-30%)
HP:0000505
6 short stature 58 30 Frequent (33%) Frequent (79-30%)
HP:0004322
7 palmoplantar keratoderma 58 30 Frequent (33%) Frequent (79-30%)
HP:0000982
8 hyperreflexia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001347
9 ataxia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001251
10 hypotonia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001252
11 respiratory insufficiency 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002093
12 developmental regression 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002376
13 microcephaly 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000252
14 sensorineural hearing impairment 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000407
15 optic atrophy 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000648
16 anterior hypopituitarism 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000830
17 iris coloboma 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000612
18 pes cavus 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001761
19 abnormality of the calf musculature 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001430
20 motor axonal neuropathy 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0007002
21 abnormality of the hypothenar eminence 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0010486
22 intellectual disability 30 HP:0001249
23 dysarthria 30 HP:0001260
24 muscle weakness 30 HP:0001324
25 global developmental delay 30 HP:0001263
26 abnormality of visual evoked potentials 30 HP:0000649
27 babinski sign 30 HP:0003487
28 alacrima 30 HP:0000522
29 orthostatic hypotension 30 HP:0001278
30 plantar hyperkeratosis 58 Occasional (29-5%)
31 palmoplantar hyperkeratosis 30 HP:0000972
32 decreased circulating aldosterone level 30 HP:0004319
33 hyperpigmentation of the skin 30 HP:0000953
34 decreased circulating cortisol level 30 HP:0008163
35 abnormal autonomic nervous system physiology 30 HP:0012332
36 anisocoria 30 HP:0009916
37 adrenocorticotropin receptor defect 30 HP:0008259

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Neurologic Central Nervous System:
hyperreflexia
ataxia
dysarthria
muscle weakness
anisocoria
more
Head And Neck Eyes:
optic atrophy
alacrima
anisocoria due to autonomic dysfunction

Abdomen Gastrointestinal:
achalasia

Skin Nails Hair Skin:
hyperpigmentation
hyperkeratosis of the palms and soles
abnormal sweating due to autonomic dysfunction

Muscle Soft Tissue:
distal muscle weakness and atrophy

Laboratory Abnormalities:
schirmer test shows alacrima

Head And Neck Head:
microcephaly

Growth Height:
short stature

Neurologic Peripheral Nervous System:
motor axonal neuropathy

Cardiovascular:
abnormal cardiovascular reflexes due to autonomic dysfunction
postural hypotension

Endocrine Features:
adrenocorticotropic hormone (acth)-resistant adrenal insufficiency
glucocorticoid insufficiency
mineralocorticoid insufficiency (in 15%)

Clinical features from OMIM®:

231550 (Updated 08-Dec-2022)

UMLS symptoms related to Achalasia-Addisonianism-Alacrima Syndrome:


ataxia; muscle weakness

GenomeRNAi Phenotypes related to Achalasia-Addisonianism-Alacrima Syndrome according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Nucleoplasmic pre-40S maturation defects GR00209-A-1 8.62 NUP155 NUP62

MGI Mouse Phenotypes related to Achalasia-Addisonianism-Alacrima Syndrome:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.97 AAAS APTX GMPPA LIG1 MC2R MRAP
2 endocrine/exocrine gland MP:0005379 9.65 AAAS LIG1 MC2R MRAP NDC1 NNT
3 mortality/aging MP:0010768 9.44 APTX GLE1 LIG1 MC2R MRAP NUP133

Drugs & Therapeutics for Achalasia-Addisonianism-Alacrima Syndrome

Drugs for Achalasia-Addisonianism-Alacrima Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 19)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Racepinephrine Approved, Vet_approved Phase 4 51-43-4, 329-65-7 838 5816
2
Dexamethasone acetate Approved, Investigational, Vet_approved Phase 4 1177-87-3 3680
3
Dexamethasone Approved, Investigational, Vet_approved Phase 4 50-02-2 3003 5743
4
Prednisone Approved, Vet_approved Phase 4 53-03-2 5865
5
Hydrocortisone succinate Approved Phase 4 2203-97-6 3643
6
Hydrocortisone acetate Approved, Vet_approved Phase 4 50-03-3
7
Hydrocortisone Approved, Vet_approved Phase 4 50-23-7 3640 5754
8
Tetracosactide Approved Phase 4 16960-16-0 16133802 16129617
9 Epinephryl borate Phase 4
10 Hormones Phase 4
11 Hormone Antagonists Phase 4
12 Antineoplastic Agents, Hormonal Phase 4
13 glucocorticoids Phase 4
14 Anti-Inflammatory Agents Phase 4
15 Hydrocortisone 17-butyrate 21-propionate Phase 4
16 Melanocyte-Stimulating Hormones
17 Adrenocorticotropic Hormone
18
beta-Endorphin
19 Corticotropin-Releasing Hormone

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Dexamethasone-suppression-test Predicts Later Development of Adrenal Insufficiency After a 14 Days' Course of Prednisone in Healthy Volunteers Completed NCT00975078 Phase 4 prednisone
2 Dose Response Relationship for Single Doses of Corticotropin Releasing Hormone (CRH) in Normal Volunteers and in Patients With Adrenal Insufficiency Completed NCT00001180 Ovine Corticotropin-Releasing Hormone (oCRH)
3 To Find Out the Genetic Relationship Between the Early-Onset Achalasia and AAAS Gene Completed NCT00856921
4 Coordination of Rare Diseases at Sanford Recruiting NCT01793168

Search NIH Clinical Center for Achalasia-Addisonianism-Alacrima Syndrome

Inferred drug relations via UMLS 71 / NDF-RT 50 :


Cortisone
cortisone acetate
Hydrocortisone
hydrocortisone acetate
HYDROCORTISONE ACETATE PWDR
HYDROCORTISONE ACETONIDE
Hydrocortisone butyrate
hydrocortisone cypionate
hydrocortisone probutate
HYDROCORTISONE PWDR
Hydrocortisone sodium phosphate
Hydrocortisone sodium succinate
hydrocortisone valerate
HYDROCORTISONE,NONSTERILE PWDR
prasterone
prednisolone
prednisolone acetate
PREDNISOLONE ACETATE PWDR
PREDNISOLONE PWDR
Prednisolone sodium phosphate
prednisolone tebutate
Prednisone
PREDNISONE PWDR
Triamcinolone
Triamcinolone Acetonide
TRIAMCINOLONE ACETONIDE PWDR
triamcinolone diacetate
triamcinolone hexacetonide

Genetic Tests for Achalasia-Addisonianism-Alacrima Syndrome

Genetic tests related to Achalasia-Addisonianism-Alacrima Syndrome:

# Genetic test Affiliating Genes
1 Glucocorticoid Deficiency with Achalasia 28 AAAS

Anatomical Context for Achalasia-Addisonianism-Alacrima Syndrome

Organs/tissues related to Achalasia-Addisonianism-Alacrima Syndrome:

MalaCards : Adrenal Gland, Eye, Skin, Kidney, Heart, Brain, Smooth Muscle

Publications for Achalasia-Addisonianism-Alacrima Syndrome

Articles related to Achalasia-Addisonianism-Alacrima Syndrome:

(show top 50) (show all 3924)
# Title Authors PMID Year
1
Mutant WD-repeat protein in triple-A syndrome. 53 62 57 5
11062474 2000
2
Loss of the nucleoporin Aladin in central nervous system and fibroblasts of Allgrove Syndrome. 62 57 5
31600784 2019
3
Axonal neuropathy with unusual pattern of amyotrophy and alacrima associated with a novel AAAS mutation p.Leu430Phe. 62 57 5
18628786 2008
4
Triple A syndrome: genotype-phenotype assessment. 62 57 5
12752575 2003
5
Progressive bulbospinal amyotrophy in triple A syndrome with AAAS gene mutation. 62 57 5
11914417 2002
6
Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene. 62 57 5
11159947 2001
7
Spectrum of mutations of the AAAS gene in Allgrove syndrome: lack of mutations in six kindreds with isolated resistance to corticotropin. 53 62 5
11701718 2001
8
Molecular insights into inherited ACTH resistance syndromes. 53 62 57
18407210 1994
9
Allgrove syndrome: an autosomal recessive syndrome of ACTH insensitivity, achalasia and alacrima. 53 62 57
1850671 1991
10
Clinical heterogeneity and molecular profile of triple A syndrome: a study of seven cases. 62 5
29874194 2018
11
Allgrove syndrome and motor neuron disease. 62 5
30069287 2018
12
Long-term clinical follow-up and molecular genetic findings in eight patients with triple A syndrome. 62 5
22538409 2012
13
AAA syndrome--adrenal insufficiency, alacrima and achalasia. 62 5
21865313 2012
14
Triple A syndrome mimicking ALS. 62 5
18615337 2008
15
Allgrove syndrome in a Mexican American family is caused by an ancestral mutation derived from North Africa. 62 5
18261130 2008
16
Cellular localization of 17 natural mutant variants of ALADIN protein in triple A syndrome - shedding light on an unexpected splice mutation. 62 5
16609705 2006
17
Genotypic heterogeneity and clinical phenotype in triple A syndrome: a review of the NIH experience 2000-2005. 62 57
16098009 2005
18
The triple A syndrome is due to mutations in ALADIN, a novel member of the nuclear pore complex. 62 5
15666842 2004
19
Estimating the age of rare disease mutations: the example of Triple-A syndrome. 62 5
15173230 2004
20
The nuclear pore complex protein ALADIN is mislocalized in triple A syndrome. 62 5
12730363 2003
21
Clinical and genetic characterization of families with triple A (Allgrove) syndrome. 62 5
12429595 2002
22
Progressive bulbospinal amyotrophy in triple A syndrome with AAAS gene mutation. 62 57
12473793 2002
23
A case of Allgrove (Triple A) syndrome associated with renal ectopia. 62 57
12150219 2002
24
Linkage disequilibrium in inbred North African families allows fine genetic and physical mapping of triple A syndrome. 62 57
10951524 2000
25
Segregation of Allgrove (triple-A) syndrome in Puerto Rican kindreds with chromosome 12 (12q13) polymorphic markers. 62 57
9285947 1997
26
Linkage of the gene for the triple A syndrome to chromosome 12q13 near the type II keratin gene cluster. 62 57
8968764 1996
27
Allgrove syndrome: documenting cholinergic dysfunction by autonomic tests. 62 57
8757578 1996
28
The "4A" syndrome: adrenocortical insufficiency associated with achalasia, alacrima, autonomic and other neurological abnormalities. 62 57
7895750 1995
29
Familial glucocorticoid deficiency with achalasia of the cardia associated with mixed neuropathy, long-tract degeneration and mild dementia. 62 57
1537368 1992
30
Three sibs with achalasia and alacrimia: a separate entity different from triple-A syndrome. 62 57
2817011 1989
31
Familial glucocorticoid deficiency with achalasia of the cardia and deficient tear production. 62 57
78049 1978
32
Familial adrenal insufficiency, achalasia, alacrima, peripheral neuropathy, microcephaly, normal plasma very long chain fatty acids, and normal muscle mitochondrial respiratory chain enzymes. 57
8006362 1994
33
Familial achalasia with absent tear production. 57
3351712 1988
34
Familial achalasia associated with adrenocortical insufficiency, alacrima, and neurological abnormalities. 57
3565479 1987
35
Infantile achalasia associated with deficient tear production. 57
4067228 1985
36
Glucocorticoid and partial mineralocorticoid deficiency associated with achalasia. 57
6243664 1980
37
Familial achalasia with pulmonary complications in children. 57
4695913 1973
38
Hereditary adrenocortical unresponsiveness to adrenocorticotropic hormone. 57
4342294 1972
39
The transmembrane nucleoporin NDC1 is required for targeting of ALADIN to nuclear pore complexes. 53 62
19703420 2009
40
Tissue-specific expression and subcellular localization of ALADIN, the absence of which causes human triple A syndrome. 53 62
19322026 2009
41
Heterogeneity in the molecular basis of ACTH resistance syndrome. 53 62
18426811 2008
42
[Allgrove syndrome in the mainland of China: clinical report and mutation analysis]. 53 62
17880786 2007
43
Allgrove syndrome with features of familial dysautonomia: a novel mutation in the AAAS gene. 53 62
16938764 2006
44
Mutations of the AAAS gene in an Indian family with Allgrove's syndrome. 53 62
16937455 2006
45
Triple-A syndrome--the first Chinese patient with novel mutations in the AAAS gene. 53 62
16789645 2006
46
Familial occurrence of adrenocortical insufficiency in two brothers with Allgrove syndrome. A case report of 4A (Allgrove) syndrome with epilepsy and a new AAAS gene mutation. 53 62
16264411 2005
47
Molecular cloning and characterization of AAAS-V2, a novel splice variant of human AAAS. 53 62
16022285 2005
48
Idiopathic achalasia is not allelic to alacrima achalasia adrenal insufficiency syndrome at the ALADIN locus. 53 62
15843079 2005
49
The diagnosis of adrenal insufficiency in a patient with Allgrove syndrome and a novel mutation in the ALADIN gene. 53 62
15690314 2005
50
Two cases of Allgrove syndrome with mutations in the AAAS gene. 53 62
15516781 2004

Variations for Achalasia-Addisonianism-Alacrima Syndrome

ClinVar genetic disease variations for Achalasia-Addisonianism-Alacrima Syndrome:

5 (show top 50) (show all 130)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 AAAS NM_015665.6(AAAS):c.980dup (p.Ser328fs) DUP Pathogenic
5041 rs387906326 GRCh37: 12:53702759-53702760
GRCh38: 12:53308975-53308976
2 AAAS NM_015665.6(AAAS):c.400-2A>G SNV Pathogenic
5042 rs1565781382 GRCh37: 12:53708926-53708926
GRCh38: 12:53315142-53315142
3 AAAS NM_015665.6(AAAS):c.1087+1G>A SNV Pathogenic
5046 rs1035139364 GRCh37: 12:53702508-53702508
GRCh38: 12:53308724-53308724
4 overlap with 2 genes NC_000012.12:g.53306793_53321761del DEL Pathogenic
619949 GRCh37:
GRCh38: 12:53306793-53321761
5 AAAS NM_015665.6(AAAS):c.211del (p.His71fs) DEL Pathogenic
1322028 GRCh37: 12:53714389-53714389
GRCh38: 12:53320605-53320605
6 AAAS NM_015665.6(AAAS):c.429del (p.Phe143fs) DEL Pathogenic
1322063 GRCh37: 12:53708895-53708895
GRCh38: 12:53315111-53315111
7 AAAS NM_015665.6(AAAS):c.43C>T (p.Gln15Ter) SNV Pathogenic
1322120 GRCh37: 12:53715207-53715207
GRCh38: 12:53321423-53321423
8 AAAS NM_015665.6(AAAS):c.1421G>A (p.Trp474Ter) SNV Pathogenic
1324426 GRCh37: 12:53701493-53701493
GRCh38: 12:53307709-53307709
9 AAAS NM_015665.6(AAAS):c.1331+1G>T SNV Pathogenic
1322225 GRCh37: 12:53701835-53701835
GRCh38: 12:53308051-53308051
10 AAAS NM_015665.6(AAAS):c.1261dup (p.Val421fs) DUP Pathogenic
1322301 GRCh37: 12:53701905-53701906
GRCh38: 12:53308121-53308122
11 AAAS NM_015665.6(AAAS):c.500C>T (p.Ala167Val) SNV Pathogenic
1322555 GRCh37: 12:53708580-53708580
GRCh38: 12:53314796-53314796
12 AAAS NM_015665.6(AAAS):c.1101del (p.Cys368fs) DEL Pathogenic
1322618 GRCh37: 12:53702299-53702299
GRCh38: 12:53308515-53308515
13 AAAS NM_015665.6(AAAS):c.602G>A (p.Trp201Ter) SNV Pathogenic
1322676 GRCh37: 12:53708169-53708169
GRCh38: 12:53314385-53314385
14 AAAS NM_015665.6(AAAS):c.352del (p.Cys118fs) DEL Pathogenic
1322731 GRCh37: 12:53709166-53709166
GRCh38: 12:53315382-53315382
15 AAAS NM_015665.6(AAAS):c.1366C>T (p.Gln456Ter) SNV Pathogenic
1324905 GRCh37: 12:53701679-53701679
GRCh38: 12:53307895-53307895
16 AAAS NM_015665.6(AAAS):c.709C>T (p.Gln237Ter) SNV Pathogenic
1323113 GRCh37: 12:53703486-53703486
GRCh38: 12:53309702-53309702
17 AAAS NM_015665.6(AAAS):c.884G>A (p.Trp295Ter) SNV Pathogenic
1323153 GRCh37: 12:53702992-53702992
GRCh38: 12:53309208-53309208
18 AAAS NM_015665.6(AAAS):c.1389del (p.Phe464fs) DEL Pathogenic
1323201 GRCh37: 12:53701656-53701656
GRCh38: 12:53307872-53307872
19 AAAS NM_015665.6(AAAS):c.1368_1372del (p.Gln456fs) DEL Pathogenic
1323239 GRCh37: 12:53701673-53701677
GRCh38: 12:53307889-53307893
20 AAAS NM_015665.6(AAAS):c.1190del (p.Gly397fs) DEL Pathogenic
1323273 GRCh37: 12:53702125-53702125
GRCh38: 12:53308341-53308341
21 AAAS NM_015665.6(AAAS):c.689+1G>A SNV Pathogenic
1325377 GRCh37: 12:53708081-53708081
GRCh38: 12:53314297-53314297
22 AAAS NM_015665.6(AAAS):c.546-2A>C SNV Pathogenic
1323296 GRCh37: 12:53708227-53708227
GRCh38: 12:53314443-53314443
23 AAAS NM_015665.6(AAAS):c.1264_1273del (p.Gln422fs) DEL Pathogenic
1323310 GRCh37: 12:53701894-53701903
GRCh38: 12:53308110-53308119
24 AAAS NM_015665.6(AAAS):c.928_931del (p.Val310fs) DEL Pathogenic
1323349 GRCh37: 12:53702945-53702948
GRCh38: 12:53309161-53309164
25 AAAS NM_015665.6(AAAS):c.922del (p.Ser308fs) DEL Pathogenic
1323376 GRCh37: 12:53702954-53702954
GRCh38: 12:53309170-53309170
26 AAAS NM_015665.6(AAAS):c.355C>T (p.Arg119Ter) SNV Pathogenic
1323456 GRCh37: 12:53709163-53709163
GRCh38: 12:53315379-53315379
27 AAAS NM_015665.6(AAAS):c.470_471del (p.Phe157fs) DEL Pathogenic
1323479 GRCh37: 12:53708609-53708610
GRCh38: 12:53314825-53314826
28 AAAS NM_015665.6(AAAS):c.901A>T (p.Lys301Ter) SNV Pathogenic
1323506 GRCh37: 12:53702975-53702975
GRCh38: 12:53309191-53309191
29 AAAS NM_015665.6(AAAS):c.852G>A (p.Trp284Ter) SNV Pathogenic
1323528 GRCh37: 12:53703024-53703024
GRCh38: 12:53309240-53309240
30 AAAS NM_015665.6(AAAS):c.771del (p.Arg258fs) DEL Pathogenic
1323549 GRCh37: 12:53703424-53703424
GRCh38: 12:53309640-53309640
31 AAAS NM_015665.6(AAAS):c.577C>T (p.Gln193Ter) SNV Pathogenic
1323584 GRCh37: 12:53708194-53708194
GRCh38: 12:53314410-53314410
32 AAAS NM_015665.6(AAAS):c.1104dup (p.Val369fs) DUP Pathogenic
1323636 GRCh37: 12:53702295-53702296
GRCh38: 12:53308511-53308512
33 AAAS NM_015665.6(AAAS):c.1024C>T (p.Arg342Ter) SNV Pathogenic
1323671 GRCh37: 12:53702572-53702572
GRCh38: 12:53308788-53308788
34 AAAS NM_015665.6(AAAS):c.1310_1311del (p.Pro437fs) DEL Pathogenic
1323704 GRCh37: 12:53701856-53701857
GRCh38: 12:53308072-53308073
35 AAAS NM_015665.6(AAAS):c.464G>C (p.Arg155Pro) SNV Pathogenic
1323730 GRCh37: 12:53708616-53708616
GRCh38: 12:53314832-53314832
36 AAAS NM_015665.6(AAAS):c.788C>T (p.Ser263Leu) SNV Pathogenic
1323772 GRCh37: 12:53703407-53703407
GRCh38: 12:53309623-53309623
37 AAAS NM_015665.6(AAAS):c.1191dup (p.Glu398fs) DUP Pathogenic
429542 rs746305979 GRCh37: 12:53702123-53702124
GRCh38: 12:53308339-53308340
38 AAAS NM_015665.6(AAAS):c.433C>T (p.Gln145Ter) SNV Pathogenic
1322773 GRCh37: 12:53708891-53708891
GRCh38: 12:53315107-53315107
39 AAAS NM_015665.6(AAAS):c.1304del (p.Asn435fs) DEL Pathogenic
1322856 GRCh37: 12:53701863-53701863
GRCh38: 12:53308079-53308079
40 AAAS NM_015665.6(AAAS):c.446+1G>A SNV Pathogenic
1322914 GRCh37: 12:53708877-53708877
GRCh38: 12:53315093-53315093
41 AAAS NM_015665.6(AAAS):c.1061_1062dup (p.Ser355fs) DUP Pathogenic
1322989 GRCh37: 12:53702533-53702534
GRCh38: 12:53308749-53308750
42 AAAS NM_015665.6(AAAS):c.618del (p.Ser207fs) DEL Pathogenic
1323071 GRCh37: 12:53708153-53708153
GRCh38: 12:53314369-53314369
43 AAAS NM_015665.6(AAAS):c.399+1G>A SNV Pathogenic
1119991 GRCh37: 12:53709118-53709118
GRCh38: 12:53315334-53315334
44 AAAS NM_015665.6(AAAS):c.250del (p.Trp84fs) DEL Pathogenic
1119992 GRCh37: 12:53714350-53714350
GRCh38: 12:53320566-53320566
45 AAAS NM_015665.6(AAAS):c.123+2T>C SNV Pathogenic
1322972 GRCh37: 12:53715125-53715125
GRCh38: 12:53321341-53321341
46 AAAS NM_015665.6(AAAS):c.580C>T (p.Arg194Ter) SNV Pathogenic
1323932 GRCh37: 12:53708191-53708191
GRCh38: 12:53314407-53314407
47 AAAS NM_015665.6(AAAS):c.1357_1358dup (p.Gln454fs) DUP Pathogenic
1685479 GRCh37: 12:53701686-53701687
GRCh38: 12:53307902-53307903
48 AAAS NM_015665.6(AAAS):c.887C>A (p.Ser296Tyr) SNV Pathogenic
1685480 GRCh37: 12:53702989-53702989
GRCh38: 12:53309205-53309205
49 AAAS NM_015665.6(AAAS):c.43C>A (p.Gln15Lys) SNV Pathogenic
5044 rs121918549 GRCh37: 12:53715207-53715207
GRCh38: 12:53321423-53321423
50 AAAS NM_015665.6(AAAS):c.1331+1G>A SNV Pathogenic
264994 rs150511103 GRCh37: 12:53701835-53701835
GRCh38: 12:53308051-53308051

UniProtKB/Swiss-Prot genetic disease variations for Achalasia-Addisonianism-Alacrima Syndrome:

73
# Symbol AA change Variation ID SNP ID
1 AAAS p.Gln15Lys VAR_012804 rs121918549
2 AAAS p.His160Arg VAR_012805 rs1297831120
3 AAAS p.Ser263Pro VAR_012806 rs121918550

Expression for Achalasia-Addisonianism-Alacrima Syndrome

Search GEO for disease gene expression data for Achalasia-Addisonianism-Alacrima Syndrome.

Pathways for Achalasia-Addisonianism-Alacrima Syndrome

Pathways related to Achalasia-Addisonianism-Alacrima Syndrome according to GeneCards Suite gene sharing:

(show all 25)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.94 POMC NUP62 NUP35 NUP210 NUP188 NUP155
2
Show member pathways
13.84 POMC NUP62 NUP35 NUP210 NUP188 NUP155
3
Show member pathways
13.76 AAAS NDC1 NNT NUP133 NUP155 NUP188
4
Show member pathways
13.74 AAAS LIG1 MC2R NDC1 NUP133 NUP155
5
Show member pathways
13.46 AAAS LIG1 NDC1 NUP133 NUP155 NUP188
6
Show member pathways
13.43 TXNRD2 NUP62 NUP35 NUP210 NUP188 NUP155
7
Show member pathways
13.4 AAAS GLE1 NDC1 NUP133 NUP155 NUP188
8
Show member pathways
13.39 NUP62 NUP35 NUP210 NUP188 NUP155 NUP133
9
Show member pathways
13.27 POMC NUP62 NUP35 NUP210 NUP188 NUP155
10
Show member pathways
13.17 NUP62 NUP35 NUP210 NUP188 NUP155 NUP133
11
Show member pathways
12.99 NUP62 NUP35 NUP210 NUP188 NUP155 NUP133
12
Show member pathways
12.9 NUP62 NUP35 NUP188 NUP155 NUP133 NDC1
13
Show member pathways
12.88 NUP62 NUP35 NUP210 NUP188 NUP155 NUP133
14
Show member pathways
12.71 AAAS NDC1 NUP133 NUP155 NUP188 NUP210
15
Show member pathways
12.67 NUP62 NUP35 NUP210 NUP188 NUP155 NUP133
16
Show member pathways
12.52 NUP62 NUP35 NUP210 NUP188 NUP155 NUP133
17
Show member pathways
12.48 AAAS NDC1 NUP133 NUP155 NUP188 NUP210
18
Show member pathways
12.46 NDC1 NUP133 NUP155 NUP188 NUP35 NUP62
19
Show member pathways
12.41 NUP62 NUP35 NUP210 NUP188 NUP155 NUP133
20
Show member pathways
12.3 NUP62 NUP35 NUP210 NUP188 NUP155 NUP133
21
Show member pathways
12.1 AAAS NDC1 NUP133 NUP155 NUP188 NUP210
22
Show member pathways
11.99 NUP62 NUP35 NUP210 NUP188 NUP155 NUP133
23
Show member pathways
11.76 NUP62 NUP35 NUP210 NUP188 NUP155 NUP133
24
Show member pathways
11.48 NUP62 NUP35 NUP210 NUP188 NUP155 NUP133
25
Show member pathways
10.87 NUP62 NUP210

GO Terms for Achalasia-Addisonianism-Alacrima Syndrome

Cellular components related to Achalasia-Addisonianism-Alacrima Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nuclear membrane GO:0031965 10.06 NUP62 NUP35 NUP210 NUP155 NUP133 NDC1
2 nuclear envelope GO:0005635 9.96 AAAS GLE1 NDC1 NUP133 NUP155 NUP188
3 nuclear pore central transport channel GO:0044613 9.62 NUP62 NUP35
4 nuclear pore GO:0005643 9.58 NUP62 NUP35 NUP210 NUP188 NUP155 NUP133
5 nuclear pore inner ring GO:0044611 9.56 NUP188 NUP155

Biological processes related to Achalasia-Addisonianism-Alacrima Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein import into nucleus GO:0006606 9.97 NUP62 NUP188 NUP155 NUP133
2 protein transport GO:0015031 9.97 AAAS GLE1 NDC1 NUP133 NUP155 NUP62
3 mRNA export from nucleus GO:0006406 9.85 NUP155 NUP133 GLE1
4 mRNA transport GO:0051028 9.83 AAAS GLE1 NDC1 NUP133 NUP155 NUP188
5 RNA export from nucleus GO:0006405 9.8 NUP62 NUP188 NUP155
6 DNA ligation GO:0006266 9.73 LIG1 APTX
7 nuclear pore organization GO:0006999 9.73 NUP35 NUP133 NDC1
8 transcription-dependent tethering of RNA polymerase II gene DNA at nuclear periphery GO:0000972 9.71 NUP155 NUP133
9 nucleocytoplasmic transport GO:0006913 9.58 NUP62 NUP35 NUP210 NUP188 NUP155 NUP133

Molecular functions related to Achalasia-Addisonianism-Alacrima Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 type 1 melanocortin receptor binding GO:0070996 9.56 POMC MRAP
2 type 4 melanocortin receptor binding GO:0031782 9.46 POMC MRAP
3 structural constituent of nuclear pore GO:0017056 9.4 NUP62 NUP35 NUP188 NUP155 NUP133 NDC1
4 type 3 melanocortin receptor binding GO:0031781 9.26 POMC MRAP

Sources for Achalasia-Addisonianism-Alacrima Syndrome

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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