MCID: ORT004
MIFTS: 52

Orthostatic Intolerance malady

Genetic diseases (common) category
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Summaries for Orthostatic Intolerance

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Wikipedia:65 Orthostatic intolerance (OI) is the development of symptoms when standing upright which are relieved... more...

MalaCards based summary: Orthostatic Intolerance is related to syncope and chronic orthostatic intolerance, and has symptoms including An important gene associated with Orthostatic Intolerance is SLC6A2 (solute carrier family 6 (neurotransmitter transporter), member 2), and among its related pathways are Monoamine Transport and Development Dopamine D2 receptor transactivation of EGFR. The compounds rx821002 and medetomidine hydrochloride have been mentioned in the context of this disorder. Affiliated tissues include testes, brain and spinal cord, and related mouse phenotypes are embryogenesis and vision/eye.

Description from OMIM:46 604715

Aliases & Classifications for Orthostatic Intolerance

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Orthostatic Intolerance, Aliases & Descriptions:

Name: Orthostatic Intolerance 46 62


Classifications:

Malacards categories (disease lists): (See all malacards categories)
Global: Genetic diseases (common)


Related Diseases for Orthostatic Intolerance

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Diseases in the Orthostatic Intolerance family:

Chronic Orthostatic Intolerance

Diseases related to Orthostatic Intolerance via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show top 50)    (show all 89)
idRelated DiseaseScoreTop Affiliating Genes
1syncope10.8
2chronic orthostatic intolerance10.7
3chronic fatigue syndrome10.6
4cerebritis10.6
5postural orthostatic tachycardia syndrome10.5
6acute adrenal insufficiency10.5POMC
7congestive heart failure10.5REN
8gastroschisis10.5ACHE
9gitelman syndrome10.4REN
10autonomic dysfunction10.4
11gilles de la tourette syndrome10.4ADRA2A, SLC6A2
12acute chest syndrome10.3NOS3
13achalasia10.3POMC, ACHE
14attention deficit hyperactivity disorder10.3ADRA2A, ADRA2C, SLC6A2
15pure autonomic failure10.3REN, ACHE
16glucocorticoid-remediable aldosteronism10.3REN, POMC
17hypoaldosteronism10.3POMC, REN
18low renin hypertension10.3EDN1, REN
19neuropathy10.3
20dysautonomia10.3
21conn's syndrome10.3POMC, REN
22renal hypertension10.3EDN1, REN
23hyperaldosteronism10.3REN, POMC
24hepatorenal syndrome10.3EDN1, REN
25adrenal adenoma10.2POMC, REN
26congenital heart disease10.2ADRB2, ADRB1, ECE1
27cushing's syndrome10.2REN, POMC
28congenital adrenal hyperplasia10.2REN, POMC
29prinzmetal's variant angina10.2NOS3, EDN1
30hirschsprung's disease10.2ECE1, ACHE
31hypokalemia10.2POMC, ADRB2, REN
32coronary artery vasospasm10.2EDN1, NOS3
33acute myocardial infarction10.2EDN1, ADRB1, ADRB2
34myocarditis10.2NOS2, ADRB1
35panic disorder10.2SLC6A2, POMC
36pheochromocytoma10.2SLC6A2, ADRB2, POMC
37metabolic syndrome x10.1ACHE, ADRB2, POMC
38hepatopulmonary syndrome10.1EDN1, NOS3
39behcet's disease10.1
40multiple sclerosis10.1
41parkinson's disease10.1
42spinal cord injury10.1
43marfan syndrome10.1
44sudden infant death syndrome10.1
45tonsillitis10.1
46ehlers-danlos syndrome10.1
47motion sickness10.1
48peripheral neuropathy10.1
49chronic pain10.1
50fainting10.1

Graphical network of the top 20 diseases related to Orthostatic Intolerance:



Diseases related to orthostatic intolerance

Symptoms for Orthostatic Intolerance

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Clinical features from OMIM:

604715

HPO human phenotypes related to Orthostatic Intolerance:

id Description Frequency HPO Source Accession
1 autosomal dominant inheritance HP:0000006
2 orthostatic tachycardia HP:0012173

Drugs & Therapeutics for Orthostatic Intolerance

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Drug clinical trials:

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Genetic Tests for Orthostatic Intolerance

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Anatomical Context for Orthostatic Intolerance

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MalaCards organs/tissues related to Orthostatic Intolerance:

32
Testes, Brain, Spinal cord, Heart, Tonsil, Endothelial

Animal Models for Orthostatic Intolerance or affiliated genes

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Publications for Orthostatic Intolerance

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Articles related to Orthostatic Intolerance:

(show top 50)    (show all 239)
idTitleAuthorsYear
1
Prognostic analysis of orthostatic intolerance using survival model in children. (25382320)
2014
2
Orthostatic intolerance ambulation in patients using patient controlled analgesia. (23862002)
2013
3
Common syndromes of orthostatic intolerance. (23569093)
2013
4
Does goal-directed fluid therapy affect postoperative orthostatic intolerance?: A randomized trial. (23756453)
2013
5
Syncope and orthostatic intolerance increase risk of brain lesions in migraineurs and controls. (23616159)
2013
6
Orthostatic intolerance: postural orthostatic tachycardia syndrome with overlapping vasovagal syncope. (22920009)
2012
7
Orthostatic intolerance in multifocal acquired demyelinating sensory and motor neuropathy. (22922580)
2012
8
Temporal artery flow response during the last minute of a head up tilt test, in relation with orthostatic intolerance after a 60 day head-down bedrest. (22073117)
2011
9
Gradient compression garments as a countermeasure to post-spaceflight orthostatic intolerance. (20824997)
2010
10
Physiologic neurocirculatory patterns in the head-up tilt test in children with orthostatic intolerance. (18353058)
2008
11
Effect of thigh cuffs on haemodynamic changes of the middle cerebral artery and on orthostatic intolerance induced by 10 days head-down bed rest. (18565193)
2008
12
Is fatigue in Marfan syndrome related to orthostatic intolerance? (18575928)
2008
13
Orthostatic intolerance in chronic fatigue syndrome. (17349421)
2007
14
Treatment of chronic fatigue and orthostatic intolerance with propranolol. (17517256)
2007
15
Hypocapnia is a biological marker for orthostatic intolerance in some patients with chronic fatigue syndrome. (17263876)
2007
16
Acetylcholinesterase inhibition in patients with orthostatic intolerance. (17016160)
2006
17
Orthostatic intolerance and the biopsychosocial model. (15795587)
2005
18
Chronic orthostatic intolerance and the postural tachycardia syndrome (POTS). (15580191)
2004
19
Neuroendocrine changes involved in the genesis of HD-induced orthostatic intolerance. (16231457)
2004
20
A mutation in the human norepinephrine transporter gene (SLC6A2) associated with orthostatic intolerance disrupts surface expression of mutant and wild-type transporters. (12805287)
2003
21
Nitric oxide in microgravity-induced orthostatic intolerance: relevance to spinal cord injury. (12830962)
2003
22
Clinical and physiological effects of an acute alpha-1 adrenergic agonist and a beta-1 adrenergic antagonist in chronic orthostatic intolerance. (12460877)
2002
23
Mutual information detects a decreased interdependence between RR and SAP in orthostatic intolerance after microgravity condition. (15002504)
2002
24
Selective norepinephrine reuptake inhibition as a human model of orthostatic intolerance. (11804991)
2002
25
Therapeutic strategies for orthostatic intolerance: mechanisms, observations, and making patients feel better. (11904120)
2002
26
Enhanced flow-dependent vasodilatation after bed rest, a possible mechanism for orthostatic intolerance in humans. (11606010)
2001
27
Doppler measurement of cerebral and lower limb flow during a lower body negative pressure test for predicting orthostatic intolerance. (11758026)
2001
28
Syncope resulting from autonomic insufficiency syndromes associated with orthostatic intolerance. (11233955)
2001
29
Vascular perturbations in the chronic orthostatic intolerance of the postural orthostatic tachycardia syndrome. (11007589)
2000
30
Orthostatic intolerance: a disorder of young women. (10758621)
2000
31
Clinical improvement in patients with orthostatic intolerance after treatment with bisoprolol and fludrocortisone. (11198485)
2000
32
Leg venous compliance in orthostatic intolerance before and after 14-day head-down bed rest. (11758569)
2000
33
Cardiovascular peripheral effector mechanism in postflight orthostatic intolerance: a simulation study. (12697528)
2000
34
Orthostatic intolerance and the postural tachycardia syndrome: genetic and environment pathophysiologies. Neurolab Autonomic Team. (11200979)
2000
35
The epidemic of orthostatic tachycardia and orthostatic intolerance. (10037110)
1999
36
Assessment of capillary fluid shifts during orthostatic stress in normal subjects and subjects with orthostatic intolerance. (10225610)
1999
37
Orthostatic intolerance and chronic fatigue syndrome associated with Ehlers-Danlos syndrome. (10518084)
1999
38
Ethanol ingestion prolongs orthostatic intolerance in hyperthermic humans. (9641404)
1998
39
Orthostatic intolerance, blood pressure and its variability. (9794139)
1998
40
Exercise training in orthostatic intolerance. (10024932)
1998
41
Hypovolemia in syncope and orthostatic intolerance role of the renin-angiotensin system. (9274896)
1997
42
Orthostatic intolerance and orthostatic tachycardia: a heterogeneous disorder. (7780285)
1995
43
Mechanisms of post-flight orthostatic intolerance. (11538739)
1994
44
Mechanisms of vasovagal syncope: relevance to postflight orthostatic intolerance. (8089257)
1994
45
Individual differences of cerebrovascular responses to gravitational stress--prediction of orthostatic intolerance. (11539530)
1994
46
Delayed orthostatic intolerance. (1580710)
1992
47
Initial and delayed circulatory responses to orthostatic stress in normal humans and in subjects with orthostatic intolerance. (1387890)
1992
48
Orthostatic intolerance in 6 degrees head-down tilt and lower body negative pressure loading. (11537576)
1992
49
Drug effects on orthostatic intolerance induced by bedrest. (1761730)
1991
50
Cardiovascular deconditioning during weightlessness simulation and the use of lower body negative pressure as a countermeasure to orthostatic intolerance. (11537546)
1990

Variations for Orthostatic Intolerance

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UniProtKB/Swiss-Prot genetic disease variations for Orthostatic Intolerance:

64
id Symbol AA change Variation ID SNP ID
1SLC6A2p.Ala457ProVAR_010022

Clinvar genetic disease variations for Orthostatic Intolerance:

6
id Gene Name Type Significance SNP ID Assembly Location
1SLC6A2NM_001172504.1(SLC6A2): c.1369G> C (p.Ala457Pro)single nucleotide variantPathogenicrs121918126GRCh37Chr 16, 55731917: 55731917

Expression for genes affiliated with Orthostatic Intolerance

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Expression patterns in normal tissues for genes affiliated with Orthostatic Intolerance

Search GEO for disease gene expression data for Orthostatic Intolerance.

Pathways for genes affiliated with Orthostatic Intolerance

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Pathways related to Orthostatic Intolerance according to GeneCards/GeneDecks:

(show all 28)
idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
Serotonin Transporter Activity37
9.9SLC6A2, ACHE
2
Show member pathways
Apoptosis and survival BAD phosphorylation60
Development Alpha 2 adrenergic receptor activation of ERK60
Chemotaxis CXCR4 signaling pathway60
9.6ADRA2C, ADRA2A, ADRA2B
3
Show member pathways
9.6ADRA2C, ADRA2A, ADRA2B
49.5ADRB1, ADRA2A, ADRB2
5
Show member pathways
9.4NOS3, REN
6
Show member pathways
9.4EDN1, POMC
79.3POMC, ADRB1, ADRB2
8
Show member pathways
Calcium Regulation in the Cardiac Cell37
9.3NOS3, ADRB2, ADRB1
9
Show member pathways
9.2POMC, REN, ACHE
109.1NOS3, NOS2
11
Show member pathways
9.1NOS2, NOS3
12
Show member pathways
9.1NOS2, NOS3
139.1NOS2, NOS3
14
Show member pathways
Quercetin and Nf-kB/ AP-1 induced cell apoptosis37
9.1NOS3, NOS2
15
Show member pathways
9.1ADRA2B, ADRA2A, ADRA2C, NOS3
169.1NOS3, POMC, ECE1
17
Show member pathways
8.9ADRB1, ADRA2B, ADRA2A, ADRA2C, ADRB2
18
Show member pathways
8.8POMC, ADRA2B, ADRA2A, ADRA2C, ADRB2
198.7SLC6A2, ADRB2, ADRA2C, ADRA2A, ADRA2B, ADRB1
208.6NOS3, ADRB1, ECE1, EDN1
21
Show member pathways
8.6EDN1, ADRB1, ADRA2B, ADRA2A, ADRB2
228.5EDN1, NOS2, NOS3
238.4ADRB1, ADRB2, NOS2, NOS3
24
Show member pathways
8.4ADRB1, ADRA2B, ADRA2A, ADRA2C, ADRB2, NOS3
25
Show member pathways
8.3NOS3, NOS2, ADRA2C, ADRA2A, ADRA2B
26
Show member pathways
7.9EDN1, POMC, ADRB1, ADRA2B, ADRA2A, ADRA2C
27
Show member pathways
7.6EDN1, POMC, NET1, ADRB1, ADRA2B, ADRA2A
28
Show member pathways
7.5POMC, NAT1, ADRA2A, ADRA2C, ACHE, NOS2

Compounds for genes affiliated with Orthostatic Intolerance

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Compounds related to Orthostatic Intolerance according to GeneCards/GeneDecks:

(show top 50)    (show all 227)
idCompoundScoreTop Affiliating Genes
1rx8210022810.0ADRA2A, ADRA2C, ADRA2B
2medetomidine hydrochloride6110.0ADRA2B, ADRA2C, ADRA2A
3arc-2392810.0ADRA2C, ADRA2A, ADRA2B
4brl 444082810.0ADRA2C, ADRA2A, ADRA2B
5[3h]rx8210022810.0ADRA2B, ADRA2A, ADRA2C
6brl 44408 maleate6110.0ADRA2C, ADRA2A, ADRA2B
7jp 1302 dihydrochloride6110.0ADRA2B, ADRA2A, ADRA2C
8atipamezole hydrochloride6110.0ADRA2B, ADRA2A, ADRA2C
9dexmedetomidine hydrochloride6110.0ADRA2B, ADRA2A, ADRA2C
10[3h]mk-9122810.0ADRA2C, ADRA2A, ADRA2B
11[3h]rauwolscine289.9ADRA2A, ADRA2B, ADRA2C
12(plusmn)-adrenaline289.9ADRA2B, ADRB1, ADRA2C
13xylazine44 2810.9ADRA2C, ADRA2A, ADRA2B
14tizanidine44 1110.9ADRA2C, ADRA2A, ADRA2B
15guanfacine28 44 1111.8ADRA2B, ADRA2A, ADRA2C
16wb 4101289.8ADRA2C, ADRA2A, ADRA2B
17doxepin44 28 50 1112.7ADRA2A, SLC6A2, ADRA2C, ADRA2B
18pseudoephedrine44 24 1111.7ADRB2, ADRA2A, ADRB1, SLC6A2
19phenoxybenzamine44 1110.7ADRA2B, ADRA2A, ADRA2C, ADRB2
20rauwolscine289.6ADRA2C, ADRA2A, ADRA2B
21prazosin44 28 50 1112.6ADRA2B, ADRB1, ADRA2A, ADRA2C
22(-)-noradrenaline289.5ADRA2C, ADRA2B, ADRA2A
23fenoldopam44 1110.5ADRA2B, REN, ADRA2C, ADRA2A
24labetalol44 1110.5REN, ADRB1, ADRB2
25bucindolol44 5010.4REN, ADRB1, ADRA2C, ADRB2
26asenapine28 1110.4ADRA2A, ADRA2C, ADRA2B, ADRB1, ADRB2
27risperidone44 50 28 61 24 1114.3ADRA2B, ADRA2A, ADRA2C, ADRB2, ADRB1
28metoprolol44 50 28 24 1113.1REN, NOS3, ADRB2, ADRB1
29clozapine44 28 50 1112.1ADRA2B, ADRA2A, ADRA2C, ADRB2, POMC
30muraglitazar44 5010.1REN, ADRB1, EDN1
31atenolol44 50 28 24 1112.8ADRB1, REN, ADRB2, ADRA2A, EDN1
32n(g),n(g)-dimethylarginine448.6NOS2, EDN1, NOS3
33carvedilol44 50 28 1111.5REN, ADRB1, ADRB2, NOS3, EDN1
34catecholamine448.4ADRB1, POMC, ADRA2A, ADRA2C, SLC6A2, REN
35nebivolol44 119.3EDN1, ADRB1, ADRB2, NOS2, NOS3
36clonidine44 50 28 1111.3ADRA2B, NOS3, REN, ADRA2C, ADRA2A, ADRB1
37nitroglycerin44 119.1EDN1, REN, NOS2, NOS3
38dopamine44 28 24 1111.1SLC6A2, REN, ADRB2, ADRA2C, ADRA2A, ADRB1
39forskolin44 50 1110.0POMC, ADRB1, ADRA2C, ADRB2, REN, SLC6A2
40ang ii448.0NOS2, REN, EDN1, NOS3
41cgmp44 288.9REN, NOS2, SLC6A2, NOS3, EDN1
42isoproterenol44 118.9ADRB2, ADRA2A, REN, NOS2, ADRB1, EDN1
43glucose447.9POMC, ECE1, ADRB1, ADRA2B, ADRA2A, ADRB2
44epinephrine44 24 119.8REN, EDN1, POMC, ADRB1, ADRA2A, ADRB2
45glutamate447.7ADRA2B, NOS3, NOS2, ADRB1, SLC6A2, ADRA2A
46phenylephrine44 28 24 1110.6ADRA2B, EDN1, POMC, ADRB1, ADRA2A, NOS2
47norepinephrine44 24 119.5ADRA2A, ADRA2C, ADRB2, REN, SLC6A2, ADRA2B
48acetylcholine44 50 28 24 1111.5ADRB2, SLC6A2, NOS3, NOS2, ACHE, POMC
49indomethacin44 28 61 1110.4POMC, ECE1, REN, NOS2, EDN1, NOS3
50nitric oxide44 24 119.0ADRB1, ECE1, NOS3, NOS2, REN, NAT1

GO Terms for genes affiliated with Orthostatic Intolerance

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Cellular components related to Orthostatic Intolerance according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1endosomeGO:0057689.4ADRB2, ADRA2C, ECE1
2integral component of plasma membraneGO:0058878.4ADRB1, ADRA2B, ADRA2A, ADRA2C, ADRB2, SLC6A2
3plasma membraneGO:0058866.8SLC6A2, ECE1, ADRB1, ADRA2B, ADRA2A, ADRA2C

Biological processes related to Orthostatic Intolerance according to GeneCards/GeneDecks:

(show all 35)
idNameGO IDScoreTop Affiliating Genes
1negative regulation of uterine smooth muscle contractionGO:07047310.3ADRA2C, ADRA2A
2fear responseGO:04259610.2ADRB1, ADRA2A
3heat generationGO:03164910.1ADRB1, ADRB2
4vasodilation by norepinephrine-epinephrine involved in regulation of systemic arterial blood pressureGO:00202510.1ADRB1, ADRB2
5negative regulation of smooth muscle contractionGO:04598610.1ADRB1, ADRB2
6diet induced thermogenesisGO:00202410.1ADRB2, ADRB1
7activation of MAPK activity by adrenergic receptor signaling pathwayGO:07188310.0ADRA2C, ADRA2A, ADRA2B
8epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathwayGO:03562510.0ADRA2B, ADRA2A, ADRA2C
9negative regulation of epinephrine secretionGO:03281110.0ADRA2B, ADRA2A, ADRA2C
10negative regulation of norepinephrine secretionGO:01070010.0ADRA2C, ADRA2A, ADRA2B
11activation of protein kinase B activityGO:03214810.0ADRA2B, ADRA2A, ADRA2C
12negative regulation of multicellular organism growthGO:04001510.0ADRB2, ADRB1
13female pregnancyGO:0075659.9ADRA2B, ADRA2A, ADRA2C
14negative regulation of calcium ion transportGO:0519269.9ADRA2A, NOS3
15negative regulation of cAMP biosynthetic processGO:0308189.8EDN1, ADRA2A
16regulation of sodium ion transportGO:0020289.8ADRB2, NOS3
17peptide hormone processingGO:0164869.8ECE1, POMC
18activation of adenylate cyclase activityGO:0071909.8ADRB2, ADRB1
19regulation of sensory perception of painGO:0519309.7ADRA2C, EDN1
20brown fat cell differentiationGO:0508739.7ADRB1, ADRB2
21platelet activationGO:0301689.6ADRA2C, ADRA2A, ADRA2B
22regulation of vasoconstrictionGO:0192299.5EDN1, ECE1, ADRA2A
23response to coldGO:0094099.5ADRB2, ADRB1
24arginine catabolic processGO:0065279.4NOS3, NOS2
25positive regulation of guanylate cyclase activityGO:0312849.4NOS3, NOS2
26regulation of insulin secretionGO:0507969.4ADRA2A, ADRA2C, NOS2
27nitric oxide biosynthetic processGO:0068099.4NOS2, NOS3
28regulation of blood pressureGO:0082179.3NOS3, REN, POMC
29regulation of systemic arterial blood pressure by endothelinGO:0031009.3NOS3, ECE1, EDN1
30G-protein coupled receptor signaling pathwayGO:0071869.3ADRA2C, ADRA2A, ADRA2B, EDN1
31nitric oxide mediated signal transductionGO:0072639.3NOS2, NOS3
32positive regulation of vasodilationGO:0459099.2ADRA2A, NOS2, NOS3
33cell-cell signalingGO:0072679.2EDN1, POMC, ADRA2B, ADRA2C
34negative regulation of blood pressureGO:0457769.2NOS2, NOS3
35blood coagulationGO:0075968.7ADRA2B, ADRA2A, ADRA2C, NOS2, NOS3

Molecular functions related to Orthostatic Intolerance according to GeneCards/GeneDecks:

(show all 11)
idNameGO IDScoreTop Affiliating Genes
1alpha-2A adrenergic receptor bindingGO:0316949.9ADRA2C, ADRB1
2alpha2-adrenergic receptor activityGO:0049389.8ADRA2B, ADRA2A, ADRA2C
3norepinephrine bindingGO:0513809.7ADRB2, ADRA2A, ADRB1
4epinephrine bindingGO:0513799.5ADRA2C, ADRA2A, ADRA2B, ADRB1
5nitric-oxide synthase activityGO:0045179.3NOS3, NOS2
6arginine bindingGO:0346189.2NOS2, NOS3
7tetrahydrobiopterin bindingGO:0346179.2NOS2, NOS3
8FMN bindingGO:0101819.1NOS3, NOS2
9NADPH-hemoprotein reductase activityGO:0039589.0NOS2, NOS3
10protein homodimerization activityGO:0428038.1ECE1, ADRA2A, ADRA2C, ADRB2, ACHE, NOS2
11protein bindingGO:0055156.1EDN1, ADRB1, ADRA2B, ADRA2A, ADRA2C, ADRB2

Products for genes affiliated with Orthostatic Intolerance

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