Orthostatic Intolerance disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

MCID: ORT004 MIFTS: 68	Orthostatic Intolerance Categories: Genetic diseases, Neuronal diseases, Rare diseases, Mental diseases, Cardiovascular diseases
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Aliases & Classifications for Orthostatic Intolerance

MalaCards integrated aliases for Orthostatic Intolerance:

Name: Orthostatic Intolerance ⁵⁷ ⁷⁶ ⁷⁵ ³⁷ ²⁹ ¹³ ⁶

Mitral Valve Prolapse ¹² ⁷⁶ ³⁷ ²⁹ ⁵⁵ ⁶ ⁴³ ⁴⁴ ¹⁵ ⁶³

Neurocirculatory Asthenia ⁵⁷ ¹² ⁴⁴ ¹⁵ ⁷³

Mitral Valve Prolapse Syndrome ⁵⁷ ⁷³

Irritable Heart ⁵⁷ ⁷³

Familial Orthostatic Tachycardia Due to Norepinephrine Transporter Deficiency ⁵⁹

Cardiovascular Malfunction Arising from Mental Factors ¹²

Postural Tachycardia Syndrome Due to Net Deficiency ⁵⁹

Orthostatic Intolerance Due to Net Deficiency ⁵⁹

Mitral Valve Prolapse, Familial, X-Linked ⁷³

Myxomatous Mitral Valve Prolapse ¹²

Systolic Click-Murmur Syndrome ¹²

Intolerance, Orthostatic ⁴⁰

Cardiovascular Neurosis ¹²

Mitral Leaflet Syndrome ¹²

Floppy Mitral Valve ¹²

Da Costa's Syndrome ¹²

Krishaber's Disease ¹²

Barlow's Syndrome ¹²

Soldiers Heart ⁵⁷

Oi ⁷⁵

Characteristics:

Orphanet epidemiological data:

⁵⁹

orthostatic intolerance due to net deficiency
Inheritance: Autosomal dominant;

HPO:

³²

orthostatic intolerance:
Inheritance autosomal dominant inheritance

Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases
Anatomical: Neuronal diseases Mental diseases Cardiovascular diseases

See all MalaCards categories (disease lists)

ICD10: ³⁴

Diseases of the circulatory system

Other and unspecified disorders of the circulatory system

Hypotension

Orthostatic hypotension

Orphanet: ⁵⁹

Rare neurological diseases

External Ids:

OMIM ⁵⁷ 604715

Disease Ontology ¹² DOID:11569 DOID:988

ICD9CM ³⁵ 306.2

MeSH ⁴⁴ D009449 D008945

SNOMED-CT ⁶⁸ 154922007 191960008 191961007 more

NCIt ⁵⁰ C50655

Orphanet ⁵⁹ ORPHA443236

ICD10 via Orphanet ³⁴ I95.1

MedGen ⁴² C1535893 C0026267 C2930833

KEGG ³⁷ H01868 H01031

SNOMED-CT via HPO ⁶⁹ 263681008

UMLS ⁷³ C0027821 C0026267 C2930833 more

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Summaries for Orthostatic Intolerance

MedlinePlus : ⁴³ Mitral valve prolapse (MVP) occurs when one of your heart's valves doesn't work properly. The flaps of the valve are "floppy" and don't close tightly. Most people who have the condition are born with it. It also tends to run in families. Most of the time, MVP doesn't cause any problems. Rarely, blood can leak the wrong way through the floppy valve. This can cause Palpitations (feelings that your heart is skipping a beat, fluttering, or beating too hard or too fast) Shortness of breath Cough Fatigue, dizziness, or anxiety Migraine headaches Chest discomfort Most people who have mitral valve prolapse (MVP) don't need treatment because they don't have symptoms and complications. If you need treatment for MVP, medicines can help relieve symptoms or prevent complications. Very few people will need surgery to repair or replace the mitral valve. MVP puts you at risk for infective endocarditis, a kind of heart infection. To prevent it, doctors used to prescribe antibiotics before dental work or certain surgeries. Now, only people at high risk of endocarditis need the antibiotics. NIH: National Heart, Lung, and Blood Institute

MalaCards based summary : Orthostatic Intolerance, also known as mitral valve prolapse, is related to mitral valve prolapse 1 and ehlers-danlos syndrome, hypermobility type, and has symptoms including angina pectoris, chest pain and edema. An important gene associated with Orthostatic Intolerance is SLC6A2 (Solute Carrier Family 6 Member 2), and among its related pathways/superpathways are Peptide ligand-binding receptors and NFAT and Cardiac Hypertrophy. The drugs Midodrine and Metoprolol have been mentioned in the context of this disorder. Affiliated tissues include heart, brain and testes, and related phenotypes are orthostatic tachycardia and cardiovascular system

UniProtKB/Swiss-Prot : ⁷⁵ Orthostatic intolerance: Syndrome characterized by lightheadedness, fatigue, altered mentation and syncope. It is associated with postural tachycardia. Plasma norepinephrine concentration is abnormally high.

Disease Ontology : ¹² A mitral valve disease where one or both of the cusps of the mitral valve bulge or collapse backward in the left atrium during systole.

PubMed Health : ⁶³ About mitral valve prolapse: Mitral (MI-tral) valve prolapse (MVP) is a condition in which the heart's mitral valve doesn't work well. The flaps of the valve are "floppy" and don't close tightly. These flaps normally help seal or open the valve.Much of the time, MVP doesn't cause any problems. Rarely, blood can leak the wrong way through the floppy valve. This can lead to palpitations, shortness of breath, chest pain, and other symptoms. (Palpitations are feelings that your heart is skipping a beat, fluttering, or beating too hard or too fast.)

Wikipedia : ⁷⁶ Mitral valve prolapse (MVP; a.k.a. floppy mitral valve syndrome, systolic click murmur syndrome or... more...

Description from OMIM: 604715

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Related Diseases for Orthostatic Intolerance

Diseases in the Orthostatic Intolerance family:

Chronic Orthostatic Intolerance

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

(show top 50) (show all 88)

#	Related Disease	Score	Top Affiliating Genes
1	mitral valve prolapse 1	35.4	DCHS1 MMVP1
2	ehlers-danlos syndrome, hypermobility type	30.6	FBN1 PLOD1
3	autonomic dysfunction	30.4	DBH ECE1
4	mitral valve prolapse 2	12.7
5	mitral valve prolapse 3	12.6
6	chronic orthostatic intolerance	12.4
7	postural orthostatic tachycardia syndrome	12.0
8	brittle bone disorder	12.0
9	osteogenesis imperfecta, type v	11.9
10	osteogenesis imperfecta, type iv	11.9
11	osteogenesis imperfecta, type ii	11.9
12	osteogenesis imperfecta, type viii	11.8
13	osteogenesis imperfecta, type iii	11.7
14	osteogenesis imperfecta, type xiii	11.7
15	osteogenesis imperfecta, type xiv	11.7
16	osteogenesis imperfecta, type xv	11.7
17	osteogenesis imperfecta, type i	11.7
18	osteogenesis imperfecta, type vii	11.7
19	osteogenesis imperfecta, type xi	11.7
20	mitral valve prolapse, familial, x-linked	11.7
21	osteogenesis imperfecta, type x	11.6
22	osteogenesis imperfecta, type vi	11.6
23	osteogenesis imperfecta, type xii	11.6
24	dentinogenesis imperfecta	11.3
25	osteogenesis imperfecta, type ix	11.1
26	platelet membrane fluidity	10.9	NOS2 NOS3
27	resting heart rate, variation in	10.8	ADRA2B ADRB1 ADRB2
28	ocular hypotension	10.8	ADRB1 ADRB2
29	persistent fetal circulation syndrome	10.8	EDN1 NOS3 POMC
30	hepatopulmonary syndrome	10.7	EDN1 NOS2 NOS3
31	coronary artery vasospasm	10.7	EDN1 MGAM NOS3
32	scleredema adultorum	10.7	FBN1 POMC
33	perinephritis	10.7	ADRB2 EDN1 MGAM
34	raynaud phenomenon	10.7	ADRA2C AGTR1 EDN1
35	impotence	10.7	EDN1 NOS2 NOS3
36	meningococcal infection	10.7	ADRB1 ADRB2 AGTR1
37	renovascular hypertension	10.6	AGTR1 EDN1 NOS3
38	ischemic optic neuropathy	10.6	AGTR1 EDN1 NOS3
39	collagen disease	10.6	EDN1 FBN1 PLOD1
40	nonarteritic anterior ischemic optic neuropathy	10.6	AGTR1 EDN1 NOS3
41	renal hypertension	10.6	AGTR1 DBH EDN1
42	portal hypertension	10.5	AGTR1 EDN1 NOS3
43	arteries, anomalies of	10.5	AGTR1 EDN1 NOS3
44	mitral valve disease	10.5	AGTR1 FBN1 NOS3
45	acute mountain sickness	10.5	ADRB2 AGTR1 EDN1 NOS3
46	congestive heart failure	10.5	ADRB1 ADRB2 AGTR1 EDN1
47	syncope	10.5
48	chronic rhinitis	10.5	ECE1 EDN1
49	renal artery disease	10.4	AGTR1 NOS3
50	cerebritis	10.3

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

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Symptoms & Phenotypes for Orthostatic Intolerance

Clinical features from OMIM:

604715

Human phenotypes related to Orthostatic Intolerance:

³²

#	Description	HPO Frequency	HPO Source Accession
1	orthostatic tachycardia ³²		HP:0012173

UMLS symptoms related to Orthostatic Intolerance:

angina pectoris, chest pain, edema

MGI Mouse Phenotypes related to Orthostatic Intolerance:

⁴⁶ (show all 12)

#	Description	MGI Source Accession	Score	Top Affiliating Genes
1	cardiovascular system	MP:0005385	10.38	ECE1 EDN1 FBN1 NOS2 NOS3 PLOD1
2	behavior/neurological	MP:0005386	10.31	ADRB2 AGTR1 DBH FBN1 NOS2 NOS3
3	homeostasis/metabolism	MP:0005376	10.31	ACHE ADRA2A ADRA2B ADRA2C ADRB1 ADRB2
4	growth/size/body region	MP:0005378	10.28	ACHE ADRA2B ADRB1 ADRB2 AGTR1 DBH
5	mortality/aging	MP:0010768	10.27	AGTR1 DBH DCHS1 ECE1 EDN1 FBN1
6	adipose tissue	MP:0005375	10.16	POMC ACHE ADRB1 ADRB2 AGTR1 DBH
7	endocrine/exocrine gland	MP:0005379	10.11	ADRB2 DBH ECE1 EDN1 FBN1 NOS2
8	nervous system	MP:0003631	10.1	EDN1 FBN1 NOS2 NOS3 POMC SLC6A2
9	muscle	MP:0005369	10.02	ACHE ADRA2B ADRB1 ADRB2 ECE1 EDN1
10	no phenotypic analysis	MP:0003012	9.7	ACHE ADRB1 ADRB2 DCHS1 FBN1 PLOD1
11	renal/urinary system	MP:0005367	9.56	ADRA2B AGTR1 DCHS1 EDN1 FBN1 NOS2
12	skeleton	MP:0005390	9.32	ADRB1 ADRB2 DBH DCHS1 ECE1 EDN1

Sources

Drugs & Therapeutics for Orthostatic Intolerance

PubMedHealth treatment related to Orthostatic Intolerance: ⁶³

Most people who have mitral valve prolapse (MVP) don't need treatment because they don't have symptoms and complications.Even people who do have symptoms may not need treatment. The presence of symptoms doesn't always mean that the backflow of blood through the valve is significant.People who have MVP and troublesome mitral valve backflow usually need treatment. MVP is treated with medicines, surgery, or both.The goals of treating MVP include:Preventing infective endocarditis (IE), arrhythmias, and other complicationsRelieving symptomsCorrecting the underlying mitral valve problem, if necessary

Drugs for Orthostatic Intolerance (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 277)

Name

Status

Phase

Clinical Trials

Cas Number

PubChem Id

Midodrine

Approved

Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable

133163-28-7, 42794-76-3

4195

Metoprolol

Approved, Investigational

Phase 4,Phase 2,Not Applicable

37350-58-6, 51384-51-1

4171

Propranolol

Approved, Investigational

Phase 4,Phase 2,Phase 1,Not Applicable,Early Phase 1

525-66-6

4946

Bisoprolol

Approved

Phase 4

66722-44-9

2405

Fludrocortisone

Approved, Investigational

Phase 4,Phase 2,Phase 3,Phase 1,Not Applicable

127-31-1

31378

Droxidopa

Approved, Investigational

Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable

23651-95-8

443940

Adrenergic Agents

Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable,Early Phase 1

Adrenergic Antagonists

Phase 4,Phase 2,Phase 1,Not Applicable,Early Phase 1

Adrenergic beta-Antagonists

Phase 4,Phase 2,Phase 1,Not Applicable,Early Phase 1

Anti-Arrhythmia Agents

Phase 4,Phase 2,Phase 1,Not Applicable,Early Phase 1

Antihypertensive Agents

Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable,Early Phase 1

Neurotransmitter Agents

Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable,Early Phase 1

Adrenergic Agonists

Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable,Early Phase 1

Adrenergic alpha-Agonists

Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable,Early Phase 1

Autonomic Agents

Phase 4,Phase 2,Phase 3,Phase 1,Not Applicable,Early Phase 1

Peripheral Nervous System Agents

Phase 4,Phase 2,Phase 3,Phase 1,Not Applicable,Early Phase 1

Vasoconstrictor Agents

Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable,Early Phase 1

Adrenergic beta-1 Receptor Antagonists

Phase 4,Phase 2,Phase 1,Not Applicable

Sympatholytics

Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable

Vasodilator Agents

Phase 4,Phase 2,Phase 1,Not Applicable,Early Phase 1

Anticonvulsants

Phase 4,Phase 2,Phase 1

Bromides

Phase 4,Phase 2,Phase 1,Early Phase 1,Not Applicable

Cholinergic Agents

Phase 4,Phase 2,Phase 1,Early Phase 1,Not Applicable

Cholinesterase Inhibitors

Phase 4,Phase 2,Phase 1,Early Phase 1,Not Applicable

Pyridostigmine Bromide

Phase 4,Phase 2,Phase 1,Early Phase 1,Not Applicable

101-26-8

Anti-Inflammatory Agents

Phase 4,Phase 2,Phase 3,Phase 1,Not Applicable

Atomoxetine Hydrochloride

Phase 4,Phase 3,Phase 2,Phase 1

Neurotransmitter Uptake Inhibitors

Phase 4,Phase 3,Phase 2,Phase 1

Antiparkinson Agents

Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable

Methylprednisolone

Approved, Vet_approved

Phase 2, Phase 3,Not Applicable

83-43-2

6741

Prednisolone

Approved, Vet_approved

Phase 2, Phase 3,Not Applicable

50-24-8

5755

Dopamine

Approved

Phase 3,Phase 2,Phase 1,Not Applicable

51-61-6, 62-31-7

681

Levodopa

Approved

Phase 3,Phase 1,Early Phase 1

59-92-7

6047

Mannitol

Approved, Investigational

Phase 3

69-65-8

453 6251

Carbidopa

Approved

Phase 2, Phase 3,Phase 3,Phase 1

28860-95-9

34359 38101

Methyldopa

Approved

Phase 3,Phase 1

555-30-6

38853

Losartan

Approved

Phase 3,Early Phase 1

114798-26-4

3961

Benzocaine

Approved, Investigational

Phase 2, Phase 3

1994-09-7, 94-09-7

2337

Metoclopramide

Approved, Investigational

Phase 3,Phase 1

364-62-5

4168

Atenolol

Approved

Phase 3,Phase 1,Phase 2

29122-68-7

2249

tannic acid

Approved, Nutraceutical

Phase 2, Phase 3

Antiemetics

Phase 2, Phase 3,Phase 3,Phase 1,Not Applicable

Antineoplastic Agents, Hormonal

Phase 2, Phase 3,Phase 1,Not Applicable

Gastrointestinal Agents

Phase 2, Phase 3,Phase 3,Phase 1,Not Applicable,Early Phase 1

glucocorticoids

Phase 2, Phase 3,Not Applicable

Hormone Antagonists

Phase 2, Phase 3,Not Applicable

Hormones

Phase 2, Phase 3,Not Applicable

Hormones, Hormone Substitutes, and Hormone Antagonists

Phase 2, Phase 3,Not Applicable

Methylprednisolone acetate

Phase 2, Phase 3,Not Applicable

Methylprednisolone Hemisuccinate

Phase 2, Phase 3,Not Applicable

Interventional clinical trials:

(show top 50) (show all 221)

#	Name	Status	NCT ID	Phase	Drugs
1	Closed Loop Stimulation for Neuromediated Syncope (SPAIN Study)	Unknown status	NCT01621464	Phase 4
2	Radical Prostatectomy and Perioperative Fluid Therapy	Completed	NCT00771966	Phase 4
3	Propranolol to Treat Fainting Due to Sympathoadrenal Imbalance	Completed	NCT00060866	Phase 4	Propranolol
4	Treatment and Prognosis of Neurogenic Orthostatic Hypotension : A Prospective Randomized Study	Completed	NCT02308124	Phase 4	Midodrine;Pyridostigmine Bromide;Midodrine + pyridostigmine
5	Tilt-Table Study of the Clinical Efficacy of Midodrine in Symptomatic Orthostatic Hypotension	Completed	NCT01518946	Phase 4	Midodrine HCl;Placebo
6	Clinical Efficacy of Midodrine in Symptomatic Orthostatic Hypotension	Completed	NCT01515865	Phase 4	Midodrine HCl;Placebo
7	Study to Assess the Benefit of Midodrine in the Treatment of Patients With Neurogenic Orthostatic Hypotension	Completed	NCT00555880	Phase 4	Midodrine hydrochloride;Placebo
8	A Study for Patients With Neurogenic Orthostatic Hypotension	Completed	NCT00046475	Phase 4	Midodrine Hydrochloride
9	Effect of Medical Treatment and Prognosis of Postural Orthostatic Tachycardia Syndrome (POTS)	Completed	NCT02171988	Phase 4	Propranolol;Bisoprolol;Propranolol+pyridostigmine;Bisoprolol+pyridostgmine
10	Clinical Trial for the Prevention of Vasovagal Syncope	Completed	NCT00118482	Phase 4	fludrocortisone acetate
11	Efficacy and Safety of Midodrine and Atomoxetine for Neurogenic OH	Recruiting	NCT03350659	Phase 4	Midodrine;Atomoxetine
12	Dawn Simulation and Postural Hypotension	Recruiting	NCT02632318	Phase 4
13	Sustained Effect of Droxidopa in Symptomatic Neurogenic Orthostatic Hypotension	Recruiting	NCT02586623	Phase 4	Droxidopa capsules;Placebo capsules
14	Assessment of Metoprolol in the Prevention of Vasovagal Syncope in Aging Subjects	Recruiting	NCT02123056	Phase 4	Metoprolol;Matching Placebo
15	Assessment of Midodrine in the Prevention of Vasovagal Syncope: The Prevention of Syncope Trial IV	Recruiting	NCT01456481	Phase 4	midodrine hydrochloride;matching placebo
16	TQL-block for Laparoscopic Hemicolectomy	Not yet recruiting	NCT03570541	Phase 4	Ropivacaine;Acetaminophen;Morphine;Saline
17	Brain Perfusion & Oxygenation in Parkinson's Disease With NOH	Not yet recruiting	NCT03229174	Phase 4	Droxidopa;Placebo
18	A Phase IV Study in Subjects With Neurogenic Orthostatic Hypotension	Terminated	NCT00046163	Phase 4	midodrine hydrochloride (ProAmatine®)
19	Effect of Methylprednisolone on Orthostatic Intolerance and Heart Rate Variability in Hip-arthroplasty Patients	Completed	NCT02445898	Phase 2, Phase 3	Methylprednisolone;Isotonic Sodium Chloride
20	Efficacy of Midodrine for the Prevention of Orthostatic Hypotension During Early Mobilization After Fast-track Hip Arthroplasty	Completed	NCT01707953	Phase 3	Midodrine;Placebo
21	Clinical Study of Droxidopa in Patients With Neurogenic Orthostatic Hypotension (NOH) (Droxi-304)	Completed	NCT01132326	Phase 3	Droxidopa
22	A Clinical Study for Patients With Neurogenic Orthostatic Hypotension (NOH) Using Droxidopa	Completed	NCT00782340	Phase 3	Placebo;Droxidopa
23	Clinical Study of Droxidopa in Patients With Neurogenic Orthostatic Hypotension (NOH)	Completed	NCT00633880	Phase 3	Placebo;Droxidopa
24	Stop Vasodepressor Drugs in Reflex Syncope	Completed	NCT02137278	Phase 3	Vasoactive drug therapies
25	Open-Label Clinical Study of Droxidopa in Patients With Neurogenic Orthostatic Hypotension (NOH)	Completed	NCT00738062	Phase 3	Droxidopa;Placebo
26	A Two Part Study (306A/306B) to Assess Droxidopa in Treatment of NOH in Patients With Parkinson's Disease	Completed	NCT01176240	Phase 3	Droxidopa
27	Efficacy of L-threo DOPS on Orthostatic Hypotension Symptoms and Other Non-motor Symptoms in Patients With MSA	Recruiting	NCT02071459	Phase 2, Phase 3	L-Threo DOPS;placebo
28	Effect of Ivabradine on Patients With Postural Orthostatic Tachycardia Syndrome	Recruiting	NCT03182725	Phase 3	Ivabradine;Placebo
29	Treatment of Post-SCI Hypotension	Recruiting	NCT02919917	Phase 2, Phase 3	Midodrine Hydrochloride;Midodrine Hydrochloride
30	Peripheral Dopamine in Postural Tachycardia Syndrome	Active, not recruiting	NCT00685919	Phase 2, Phase 3	Carbidopa;Placebo
31	Treatment of Orthostatic Hypotension	Enrolling by invitation	NCT00581477	Phase 3	droxidopa;placebo;alpha-methyldopa;carbidopa;metyrosine;levodopa;atomoxetine;metoclopramide
32	A Study to Systematically Assess the Efficacy and Safety of Intravenous Albumin Infusions in Severe POTS	Not yet recruiting	NCT03365414	Phase 3	Normal Saline 0.9% Infusion Solution Bag
33	Phase 3 Study to Evaluate the Efficacy and Safety of Droxidopa on Orthostatic Hypotension Treatment in Hemodialysis Patients	Terminated	NCT01612078	Phase 3	Droxidopa;Placebo
34	A Clinical Study of Patients With Symptomatic NOH to Assess Sustained Effects of Droxidopa Therapy	Terminated	NCT01927055	Phase 3	Droxidopa;Placebo
35	Circulating Transforming Growth Factor Beta (TGF-β) in Individuals With Marfan Syndrome	Withdrawn	NCT01361087	Phase 3
36	The Effect of Ivabradine on Patients With Postural Tachycardia Syndrome	Unknown status	NCT01761825	Phase 2	ivabradine
37	Cardiovascular Effects of Selective I(f)-Channel Blockade	Unknown status	NCT00865917	Phase 2	beta-blocker (Metoprolol);I(f)-blocker (ivabradine);Placebo
38	Fipamezole in Neurogenic Orthostatic Hypotension	Unknown status	NCT00758849	Phase 2	Placebo;Fipamezole
39	Safety and Efficacy Study of a New Device for Making Neochordae in Mitral Valve Repair	Unknown status	NCT01811537	Phase 1, Phase 2
40	Sex Hormones and Orthostatic Tolerance	Completed	NCT01153581	Phase 2	Ganirelix acetate;17β-Oestradiol;Progesterone
41	Non-Pharmacologic Therapy for Neurocardiogenic Syncope	Completed	NCT00096902	Phase 2
42	Propranolol to Treat Fainting in Children With Sympathoadrenal Imbalance	Completed	NCT00093860	Phase 2	Propranolol
43	Clinical Trial to Assess Efficacy, Safety, and Tolerability of Rasagiline Mesylate 1 mg in Patients With Multiple System Atrophy of the Parkinsonian Subtype (MSA-P)	Completed	NCT00977665	Phase 2	rasagiline mesylate;placebo
44	Acetylcholinesterase Inhibition and Orthostatic Hypotension in SCI	Completed	NCT02307526	Phase 2	Pyridostigmine Bromide
45	Intravenous Norepinephrine for Orthostatic Hypotension	Completed	NCT01285908	Phase 1, Phase 2	Intravenous Norepinephrine Infusion
46	Phase II Study of Midodrine for Neurogenic Orthostatic Hypotension	Completed	NCT00004268	Phase 2	midodrine
47	Abdominal Binder to Treat Orthostatic Hypotension (OH) in Parkinson's Disease (PD)	Completed	NCT01971008	Phase 2
48	Transcranial Electrical Stimulation for Management of Orthostatic Instability in Acute Cervical Spinal Cord Injury	Completed	NCT01874782	Phase 2
49	Safety and Efficacy of L-NAME and Midodrine to Increase MAP	Completed	NCT00835224	Phase 2	L-NAME;Midodrine;Placebo
50	A Dose Response Trial Using 5 and 10 Mg of Midodrine Hydrochloride	Completed	NCT00426842	Phase 2	Midodrine Hydrochloride

Search NIH Clinical Center for Orthostatic Intolerance

Cochrane evidence based reviews: neurocirculatory asthenia

Sources

Genetic Tests for Orthostatic Intolerance

Genetic tests related to Orthostatic Intolerance:

#	Genetic test	Affiliating Genes
1	Orthostatic Intolerance ²⁹	SLC6A2
2	Mitral Valve Prolapse ²⁹

Sources

Anatomical Context for Orthostatic Intolerance

MalaCards organs/tissues related to Orthostatic Intolerance:

⁴¹

Heart, Brain, Testes, Lung, Spinal Cord, Bone, Endothelial

Sources

Publications for Orthostatic Intolerance

Articles related to Orthostatic Intolerance:

(show top 50) (show all 964)

#	Title	Authors	Year
1	Unusual combination of mitral valve prolapse, bicuspid aortic valve, and ventricular septal defect restricted by the tricuspid septal leaflet. ( 29339711 )	KocabaA9 U....SoydaA9 A8A+nar C.	2018
2	Intravenous saline administration in patients with severe acquired brain injury and orthostatic intolerance for tilt-table mobilization. ( 29190150 )	Riberholt C....Petersen T.H.	2018
3	Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection. ( 29650052 )	Richardson A.M....Lidbury B.A.	2018
4	Orthostatic tachycardia with different onset time in patients with orthostatic intolerance. ( 29801880 )	Lee H....Kim H.A.	2018
5	Intracranial compliance is associated with symptoms of orthostatic intolerance in chronic fatigue syndrome. ( 29969498 )	Finkelmeyer A....Newton J.L.	2018
6	Orthostatic intolerance and postural tachycardia syndrome: new insights into pathophysiology and treatment. ( 29696346 )	Ruzieh M....Grubb B.P.	2018
7	The etiologic relation between disequilibrium and orthostatic intolerance in patients with myalgic encephalomyelitis (chronic fatigue syndrome). ( 29588088 )	Miwa K....Inoue Y.	2018
8	Emotional orienting during interoceptive threat in orthostatic intolerance: Dysautonomic contributions to psychological symptomatology in the postural tachycardia syndrome and vasovagal syncope. ( 29519640 )	Owens A.P....Mathias C.J.	2018
9	Pediatric Disorders of Orthostatic Intolerance. ( 29222399 )	Stewart J.M....Chelimsky T.C.	2018
10	Postural tachycardia syndrome and other forms of orthostatic intolerance in Ehlers-Danlos syndrome. ( 29519641 )	Roma M....Rowe P.C.	2018
11	Changes in the augmentation index and postoperative orthostatic intolerance in orthopedic surgery: a prospective cohort study. ( 29790120 )	Memtsoudis S.G....Danninger T.	2018
12	Prefrontal hemodynamic changes measured using near-infrared spectroscopy during the Valsalva maneuver in patients with orthostatic intolerance. ( 29392157 )	Kim Y.H....Kim B.J.	2018
13	Association of blood pressure variability with orthostatic intolerance symptoms. ( 28591231 )	Sunwoo J.S....Chu K.	2017
14	Mitral valve prolapse and Marfan syndrome. ( 28580713 )	Thacoor A.	2017
15	Orthostatic Intolerance and Postural Orthostatic Tachycardia Syndrome in Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome, Hypermobility Type: Neurovegetative Dysregulation or Autonomic Failure? ( 28286774 )	Celletti C....Strano S.	2017
16	Dominant Transmission Observed in Adolescents and Families With Orthostatic Intolerance. ( 27773421 )	Posey J.E....Butler I.J.	2017
17	Syndromes of orthostatic intolerance and syncope in young adults. ( 28674628 )	Hamrefors V....Fedorowski A.	2017
18	Early Orthostatic Hypotension and Orthostatic Intolerance-More Than an Observation or Annoyance. ( 28738118 )	Singer W....Low P.A.	2017
19	Patients with Orthostatic Intolerance: Relationship to Autonomic Function Tests results and Reproducibility of Symptoms on Tilt. ( 28720881 )	Lee H....Kim H.A.	2017
20	The effects of body weight status on orthostatic intolerance and predisposition to noncardiac syncope. ( 28112481 )	Christou G.A....Kiortsis D.N.	2017
21	Novel insights into symptomatology of moyamoya disease in pediatric patients: survey of symptoms suggestive of orthostatic intolerance. ( 28862519 )	Uchino H....Houkin K.	2017
22	Orthostatic Intolerance in Older Persons: Etiology and Countermeasures. ( 29163185 )	Goswami N....Montani J.P.	2017
23	Common origin of all three coronary arteries from the right sinus of Valsalva - first case study accompanied by mitral valve prolapse and vein anomaly, second case study followed by successful percutaneous coronary intervention of right coronary artery stenosis. ( 28515755 )	Przywara-Chowaniec B....Czarnecka A.	2017
24	Cardiovascular and Cutaneous Responses to the Combination of Alcohol and Soft Drinks: The Way to Orthostatic Intolerance? ( 29176950 )	Maufrais C....Montani J.P.	2017
25	The role of autoantibodies in the syndromes of orthostatic intolerance: a systematic review. ( 28738696 )	Ruzieh M....Grubb B.	2017
26	Truncal ataxia or disequilibrium is an unrecognised cause of orthostatic intolerance in patients with myalgic encephalomyelitis. ( 28613452 )	Miwa K....Inoue Y.	2017
27	Monitoring of cerebral oximetry during head-up tilt test in adults with history of syncope and orthostatic intolerance. ( 29036615 )	Bachus E....Fedorowski A.	2017
28	A Rare Case of Mitral Valve Prolapse in Endomyocardial Fibrosis. ( 27549547 )	Xavier J....Suryaprakash S.	2016
29	A rare case of right sided pulmonary artery agenesis associated with congenital mitral valve prolapse. ( 27481086 )	A^liaz S....Tabak L.	2016
30	Mechanisms of orthostatic intolerance during heat stress. ( 26723547 )	Schlader Z.J....Crandall C.G.	2016
31	Orthostatic intolerance symptoms are associated with depression and diminished quality of life in patients with postural tachycardia syndrome. ( 27729043 )	Moon J....Lee S.K.	2016
32	Sudden cardiac arrest and coexisting mitral valve prolapse: a case report and literature review. ( 27249812 )	Ahmed M....Fletcher N.	2016
33	Distinct neurohumoral biomarker profiles in children with hemodynamically defined orthostatic intolerance may predict treatment options. ( 26608337 )	Wagoner A.L....Diz D.I.	2016
34	Orthostatic intolerance and fatigue in the hypermobility type of Ehlers-Danlos Syndrome. ( 27094596 )	De Wandele I....Malfait F.	2016
35	Incidental left anterior descending coronary artery to pulmonary artery fistula in myxomatous mitral valve prolapse. ( 27751341 )	Aggarwal P....Bhan A.	2016
36	Antroduodenal Manometry is Abnormal in Children Presenting with Orthostatic Intolerance and Gastrointestinal Symptoms. ( 26859090 )	Moak J.P....Darbari A.	2016
37	Dizziness and Orthostatic Intolerance In Pediatric Headache Patients. ( 27017026 )	Qubty W....Kedia S.	2016
38	Postoperative orthostatic intolerance: a common perioperative problem with few available solutions. ( 27638295 )	Jans A.9....Kehlet H.	2016
39	Orthostatic hypertension: An underestimated cause of orthostatic intolerance. ( 26806722 )	Lee H....Kim H.A.	2016
40	Reduced Systolic Volume: Main Pathophysiological Mechanism in Patients with Orthostatic Intolerance? ( 27849259 )	TA!vora-Mehta M.Z....Cunha C.L.	2016
41	Orthostatic intolerance and autonomic dysfunction following bariatric surgery: A retrospective study and review of the literature. ( 27292926 )	Ponnusamy V....Mathias C.J.	2016
42	Detailed Relationship Between the Pattern of Blood Pressure Change During the Valsalva Maneuver and the Degree of Orthostatic Hypotension During the Head-Up Tilt Test in Patients With Orthostatic Intolerance: A Retrospective Case-Control Study. ( 27175668 )	Kim H.A....Lee H.	2016
43	Adolescent Chronic Fatigue and Orthostatic Intolerance: Relationships Between Parental Attributes and Child Functioning. ( 27421749 )	Kluck B.N....Weiss K.E.	2016
44	Evolution of Mitral Valve Prolapse: Insights From the Framingham Heart Study. ( 27006478 )	Delling F.N....Vasan R.S.	2016
45	Hiatal hernia, mitral valve prolapse and defecatory disorders: An underlying rectal prolapse? ( 26925980 )	Shalaby M....Sileri P.	2016
46	Genetic association analyses highlight biological pathways underlying mitral valve prolapse. ( 26301497 )	Dina C....Jeunemaitre X.	2015
47	New recessive truncating mutation in LTBP3 in a family with oligodontia, short stature, and mitral valve prolapse. ( 25899461 )	Dugan S.L....Vincent J.B.	2015
48	Cortical Morphology in Patients with Orthostatic Intolerance. ( 25895544 )	Shin K.J....Park K.M.	2015
49	Postexercise orthostatic intolerance: influence of exercise intensity. ( 26040636 )	MA1ndel T....Lucas S.J.	2015
50	Autonomic activity and biomarker behavior in supine position and after passive postural stress in different orthostatic intolerance syndromes. ( 26320094 )	Freitas J....Rocha-GonAsalves F.	2015

Sources

Genes for Orthostatic Intolerance

Genes related to Orthostatic Intolerance (5 elite genes):

(show all 29)

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubmedIds
1	SLC6A2	Solute Carrier Family 6 Member 2	Protein Coding	1710.79	Molecular basis known ⁵⁷ Pathogenic ⁶ Causative germline mutation (loss of function) ⁵⁹ Causative variation ⁷⁵ Genetic Tests ²⁹ DISEASES inferred ¹⁵ Novoseek inferred ⁵⁵ GeneCards inferred via : Disorders Publications Summaries Variants (show sections)	10684912 11875370 12391111 (more) 11804991 12805287 14726430 15894713 15612527 10851182 11875370 10684912
2	FBN1	Fibrillin 1	Protein Coding	426.18	Pathogenic ⁶ DISEASES inferred ¹⁵ Novoseek inferred ⁵⁵ GeneCards inferred via : DISEASES inferred (show sections)	19199346 14759433 20189150 (more) 9837823 12918850
3	PLOD1	Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 1	Protein Coding	400	Pathogenic ⁶
4	MMVP3	Mitral Valve Prolapse, Myxomatous 3	Genetic Locus	50	MalaCards inferred ⁵⁷
5	MMVP1	Myxomatous Mitral Valve Prolapse 1	Genetic Locus	50	MalaCards inferred ⁵⁷
6	ADRB1	Adrenoceptor Beta 1	Protein Coding	20.05	DISEASES inferred ¹⁵ GeneCards inferred via : Publications (show sections)
7	MGAM	Maltase-Glucoamylase	Protein Coding	19.22	DISEASES inferred ¹⁵ ¹⁵ GeneCards inferred via : DISEASES inferred (show sections)
8	DBH	Dopamine Beta-Hydroxylase	Protein Coding	18.38	DISEASES inferred ¹⁵ Novoseek inferred ⁵⁵ GeneCards inferred via : DISEASES inferred (show sections)	12438171
9	EDN1	Endothelin 1	Protein Coding	17.35	GeneCards inferred via : Publications (show sections)
10	AGTR1	Angiotensin II Receptor Type 1	Protein Coding	17.01	DISEASES inferred ¹⁵ Novoseek inferred ⁵⁵ GeneCards inferred via : DISEASES inferred (show sections)	11999641 17379330 18242274 (more) 10618569
11	ADRA2C	Adrenoceptor Alpha 2C	Protein Coding	17	GeneCards inferred via : Publications (show sections)
12	ADRA2B	Adrenoceptor Alpha 2B	Protein Coding	17	GeneCards inferred via : Publications (show sections)
13	ECE1	Endothelin Converting Enzyme 1	Protein Coding	17	GeneCards inferred via : Publications (show sections)
14	ADRA2A	Adrenoceptor Alpha 2A	Protein Coding	17	GeneCards inferred via : Publications (show sections)
15	NOS3	Nitric Oxide Synthase 3	Protein Coding	17	GeneCards inferred via : Publications (show sections)
16	NOS2	Nitric Oxide Synthase 2	Protein Coding	17	GeneCards inferred via : Publications (show sections)
17	ADRB2	Adrenoceptor Beta 2	Protein Coding	17	GeneCards inferred via : Publications (show sections)
18	POMC	Proopiomelanocortin	Protein Coding	17	GeneCards inferred via : Publications (show sections)
19	ACHE	Acetylcholinesterase (Cartwright Blood Group)	Protein Coding	17	GeneCards inferred via : Publications (show sections)
20	DCHS1	Dachsous Cadherin-Related 1	Protein Coding	16.29	DISEASES inferred ¹⁵ GeneCards inferred via : DISEASES inferred (show sections)
21	PDLIM1	PDZ And LIM Domain 1	Protein Coding	11.42	DISEASES inferred ¹⁵ Novoseek inferred ⁵⁵	8351994
22	SCX	Scleraxis BHLH Transcription Factor	Protein Coding	7.72	DISEASES inferred ¹⁵ ¹⁵
23	KANTR	KDM5C Adjacent Transcript	RNA Gene	6.34	DISEASES inferred ¹⁵
24	ADAMTSL4	ADAMTS Like 4	Protein Coding	6.16	DISEASES inferred ¹⁵
25	ELN	Elastin	Protein Coding	6.1	DISEASES inferred ¹⁵
26	LPXN	Leupaxin	Protein Coding	6.07	DISEASES inferred ¹⁵
27	LINC00536	Long Intergenic Non-Protein Coding RNA 536	RNA Gene	6.01	DISEASES inferred ¹⁵
28	FBN2	Fibrillin 2	Protein Coding	6	DISEASES inferred ¹⁵
29	UBAP1	Ubiquitin Associated Protein 1	Protein Coding	5.99	DISEASES inferred ¹⁵

Sources

Variations for Orthostatic Intolerance

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

⁷⁵

#	Symbol	AA change	Variation ID	SNP ID
1	SLC6A2	p.Ala457Pro	VAR_010022	rs121918126

ClinVar genetic disease variations for Orthostatic Intolerance:

⁶

(show top 50) (show all 141)

#	Gene	Variation	Type	Significance	SNP ID	Assembly	Location
1	SLC6A2	NM_001172504.1(SLC6A2): c.1369G> C (p.Ala457Pro)	single nucleotide variant	Pathogenic	rs121918126	GRCh37	Chromosome 16, 55731917: 55731917
2	SLC6A2	NM_001172504.1(SLC6A2): c.1369G> C (p.Ala457Pro)	single nucleotide variant	Pathogenic	rs121918126	GRCh38	Chromosome 16, 55698005: 55698005
3	SLC39A13	NM_152264.4(SLC39A13): c.398C> T (p.Thr133Met)	single nucleotide variant	Conflicting interpretations of pathogenicity	rs140574574	GRCh37	Chromosome 11, 47433573: 47433573
4	SLC39A13	NM_152264.4(SLC39A13): c.398C> T (p.Thr133Met)	single nucleotide variant	Conflicting interpretations of pathogenicity	rs140574574	GRCh38	Chromosome 11, 47412022: 47412022
5	BMPR2	NM_001204.6(BMPR2): c.2948G> A (p.Arg983Gln)	single nucleotide variant	Likely benign	rs148099152	GRCh38	Chromosome 2, 202559777: 202559777
6	BMPR2	NM_001204.6(BMPR2): c.2948G> A (p.Arg983Gln)	single nucleotide variant	Likely benign	rs148099152	GRCh37	Chromosome 2, 203424500: 203424500
7	SLC6A2	NM_001043.3(SLC6A2): c.52G> C (p.Asp18His)	single nucleotide variant	Uncertain significance	rs886052131	GRCh38	Chromosome 16, 55656746: 55656746
8	SLC6A2	NM_001043.3(SLC6A2): c.-182C> T	single nucleotide variant	Likely benign	rs2242446	GRCh38	Chromosome 16, 55656513: 55656513
9	SLC6A2	NM_001043.3(SLC6A2): c.-182C> T	single nucleotide variant	Likely benign	rs2242446	GRCh37	Chromosome 16, 55690425: 55690425
10	SLC6A2	NM_001043.3(SLC6A2): c.21C> A (p.Asn7Lys)	single nucleotide variant	Uncertain significance	rs11568323	GRCh38	Chromosome 16, 55656715: 55656715
11	SLC6A2	NM_001043.3(SLC6A2): c.21C> A (p.Asn7Lys)	single nucleotide variant	Uncertain significance	rs11568323	GRCh37	Chromosome 16, 55690627: 55690627
12	SLC6A2	NM_001043.3(SLC6A2): c.48G> C (p.Gly16=)	single nucleotide variant	Uncertain significance	rs551459843	GRCh38	Chromosome 16, 55656742: 55656742
13	SLC6A2	NM_001043.3(SLC6A2): c.48G> C (p.Gly16=)	single nucleotide variant	Uncertain significance	rs551459843	GRCh37	Chromosome 16, 55690654: 55690654
14	SLC6A2	NM_001043.3(SLC6A2): c.52G> C (p.Asp18His)	single nucleotide variant	Uncertain significance	rs886052131	GRCh37	Chromosome 16, 55690658: 55690658
15	SLC6A2	NM_001043.3(SLC6A2): c.275-15C> T	single nucleotide variant	Uncertain significance	rs886052132	GRCh37	Chromosome 16, 55703462: 55703462
16	SLC6A2	NM_001043.3(SLC6A2): c.275-15C> T	single nucleotide variant	Uncertain significance	rs886052132	GRCh38	Chromosome 16, 55669550: 55669550
17	SLC6A2	NM_001043.3(SLC6A2): c.866A> G (p.Asn289Ser)	single nucleotide variant	Uncertain significance	rs77951841	GRCh37	Chromosome 16, 55725912: 55725912
18	SLC6A2	NM_001043.3(SLC6A2): c.866A> G (p.Asn289Ser)	single nucleotide variant	Uncertain significance	rs77951841	GRCh38	Chromosome 16, 55692000: 55692000
19	SLC6A2	NM_001043.3(SLC6A2): c.918+11A> G	single nucleotide variant	Likely benign	rs5564	GRCh37	Chromosome 16, 55725975: 55725975
20	SLC6A2	NM_001043.3(SLC6A2): c.918+11A> G	single nucleotide variant	Likely benign	rs5564	GRCh38	Chromosome 16, 55692063: 55692063
21	SLC6A2	NM_001043.3(SLC6A2): c.1401C> T (p.Tyr467=)	single nucleotide variant	Uncertain significance	rs138435822	GRCh37	Chromosome 16, 55732392: 55732392
22	SLC6A2	NM_001043.3(SLC6A2): c.1401C> T (p.Tyr467=)	single nucleotide variant	Uncertain significance	rs138435822	GRCh38	Chromosome 16, 55698480: 55698480
23	SLC6A2	NM_001043.3(SLC6A2): c.1465G> A (p.Ala489Thr)	single nucleotide variant	Uncertain significance	rs762006683	GRCh37	Chromosome 16, 55732456: 55732456
24	SLC6A2	NM_001043.3(SLC6A2): c.1465G> A (p.Ala489Thr)	single nucleotide variant	Uncertain significance	rs762006683	GRCh38	Chromosome 16, 55698544: 55698544
25	SLC6A2	NM_001043.3(SLC6A2): c.414_415insC	insertion	Uncertain significance	rs886052137	GRCh37	Chromosome 16, 55736672: 55736673
26	SLC6A2	NM_001043.3(SLC6A2): c.*371G> A	single nucleotide variant	Likely benign	rs115138076	GRCh38	Chromosome 16, 55702717: 55702717
27	SLC6A2	NM_001043.3(SLC6A2): c.*371G> A	single nucleotide variant	Likely benign	rs115138076	GRCh37	Chromosome 16, 55736629: 55736629
28	SLC6A2	NM_001043.3(SLC6A2): c.396_397dupCC	duplication	Uncertain significance	rs886052135	GRCh38	Chromosome 16, 55702742: 55702743
29	SLC6A2	NM_001043.3(SLC6A2): c.396_397dupCC	duplication	Uncertain significance	rs886052135	GRCh37	Chromosome 16, 55736654: 55736655
30	SLC6A2	NM_001043.3(SLC6A2): c.414_415insC	insertion	Uncertain significance	rs886052137	GRCh38	Chromosome 16, 55702760: 55702761
31	SLC6A2	NM_001043.3(SLC6A2): c.*416delC	deletion	Uncertain significance	rs113163898	GRCh38	Chromosome 16, 55702762: 55702762
32	SLC6A2	NM_001043.3(SLC6A2): c.*416delC	deletion	Uncertain significance	rs113163898	GRCh37	Chromosome 16, 55736674: 55736674
33	SLC6A2	NM_001043.3(SLC6A2): c.*417T> A	single nucleotide variant	Likely benign	rs40615	GRCh38	Chromosome 16, 55702763: 55702763
34	SLC6A2	NM_001043.3(SLC6A2): c.*417T> A	single nucleotide variant	Likely benign	rs40615	GRCh37	Chromosome 16, 55736675: 55736675
35	SLC6A2	NM_001043.3(SLC6A2): c.*606T> C	single nucleotide variant	Likely benign	rs111663130	GRCh38	Chromosome 16, 55702952: 55702952
36	SLC6A2	NM_001043.3(SLC6A2): c.*606T> C	single nucleotide variant	Likely benign	rs111663130	GRCh37	Chromosome 16, 55736864: 55736864
37	SLC6A2	NM_001043.3(SLC6A2): c.919_921delACC	deletion	Uncertain significance	rs886052140	GRCh38	Chromosome 16, 55703265: 55703267
38	SLC6A2	NM_001043.3(SLC6A2): c.919_921delACC	deletion	Uncertain significance	rs886052140	GRCh37	Chromosome 16, 55737177: 55737179
39	SLC6A2	NM_001043.3(SLC6A2): c.*1017G> A	single nucleotide variant	Uncertain significance	rs886052141	GRCh38	Chromosome 16, 55703363: 55703363
40	SLC6A2	NM_001043.3(SLC6A2): c.*1017G> A	single nucleotide variant	Uncertain significance	rs886052141	GRCh37	Chromosome 16, 55737275: 55737275
41	SLC6A2	NM_001043.3(SLC6A2): c.*1175A> G	single nucleotide variant	Uncertain significance	rs886052142	GRCh38	Chromosome 16, 55703521: 55703521
42	SLC6A2	NM_001043.3(SLC6A2): c.*1175A> G	single nucleotide variant	Uncertain significance	rs886052142	GRCh37	Chromosome 16, 55737433: 55737433
43	SLC6A2	NM_001043.3(SLC6A2): c.407-12G> A	single nucleotide variant	Likely benign	rs11568343	GRCh38	Chromosome 16, 55671926: 55671926
44	SLC6A2	NM_001043.3(SLC6A2): c.407-12G> A	single nucleotide variant	Likely benign	rs11568343	GRCh37	Chromosome 16, 55705838: 55705838
45	SLC6A2	NM_001043.3(SLC6A2): c.848C> G (p.Thr283Arg)	single nucleotide variant	Likely benign	rs45564432	GRCh37	Chromosome 16, 55725894: 55725894
46	SLC6A2	NM_001043.3(SLC6A2): c.848C> G (p.Thr283Arg)	single nucleotide variant	Likely benign	rs45564432	GRCh38	Chromosome 16, 55691982: 55691982
47	SLC6A2	NM_001043.3(SLC6A2): c.1389+9G> A	single nucleotide variant	Likely benign	rs998424	GRCh37	Chromosome 16, 55731946: 55731946
48	SLC6A2	NM_001043.3(SLC6A2): c.1389+9G> A	single nucleotide variant	Likely benign	rs998424	GRCh38	Chromosome 16, 55698034: 55698034
49	SLC6A2	NM_001043.3(SLC6A2): c.1489+9G> A	single nucleotide variant	Uncertain significance	rs760893401	GRCh38	Chromosome 16, 55698577: 55698577
50	SLC6A2	NM_001043.3(SLC6A2): c.1489+9G> A	single nucleotide variant	Uncertain significance	rs760893401	GRCh37	Chromosome 16, 55732489: 55732489

Sources

Expression for Orthostatic Intolerance

Search GEO for disease gene expression data for Orthostatic Intolerance.

Sources

Pathways for Orthostatic Intolerance

Pathways related to Orthostatic Intolerance according to GeneCards Suite gene sharing:

(show all 19)

#	Super pathways	Score	Top Affiliating Genes
1	Peptide ligand-binding receptors ⁶⁶ Show member pathways Class A/1 (Rhodopsin-like receptors) ⁶⁶ Defective AVP causes neurohypophyseal diabetes insipidus (NDI) ⁶⁶ Formyl peptide receptors bind formyl peptides and many other ligands ⁶⁶ G alpha (i) signalling events ⁶⁶ GPCR ligand binding ⁶⁶ GPCRs, Class A Rhodopsin-like ¹ Neuroactive ligand-receptor interaction ³⁷ Orexin and neuropeptides FF and QRFP bind to their respective receptors ⁶⁶ Peptide GPCRs ¹ Tachykinin receptors bind tachykinins ⁶⁶ Vasopressin-like receptors ⁶⁶	13.38	ADRA2A ADRA2B ADRA2C ADRB1 ADRB2 AGTR1
2	NFAT and Cardiac Hypertrophy ⁶⁴ Show member pathways IGF1R Signaling ⁶⁴ Signaling Involved in Cardiac Hypertrophy ⁶⁴	12.72	ADRA2A ADRA2B ADRB1 ADRB2 EDN1
3	Vascular smooth muscle contraction ³⁷ Show member pathways cGMP-PKG signaling pathway ³⁷ Oxytocin signaling pathway ³⁷	12.51	ADRA2A ADRA2B ADRA2C ADRB1 ADRB2 AGTR1
4	ADP signalling through P2Y purinoceptor 12 ⁶⁶ Show member pathways Adrenaline,noradrenaline inhibits insulin secretion ⁶⁶ Beta-agonist/Beta-blocker Pathway, Pharmacodynamics ⁶¹ Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding ⁶⁶ G alpha (z) signalling events ⁶⁶ G-protein activation ⁶⁶ Signal transduction cAMP signaling ²²	12.33	ADRA2A ADRA2B ADRA2C ADRB2 POMC
5	Calcium signaling pathway ³⁷ Show member pathways Oxytocin signaling ¹	12.07	ADRB1 ADRB2 AGTR1 NOS2 NOS3
6	AMPK Enzyme Complex Pathway ⁶⁴ Show member pathways Chromatin Remodeling ⁶⁴ mitochondrial L-carnitine shuttle ¹	12	ADRA2A ADRA2B ADRA2C NOS2 NOS3
7	HIF-1 signaling pathway ³⁷	11.75	EDN1 NOS2 NOS3
8	AGE-RAGE signaling pathway in diabetic complications ³⁷	11.74	AGTR1 EDN1 NOS3
9	Integrin alphaIIb beta3 signaling ⁶⁶ Show member pathways GRB2-SOS provides linkage to MAPK signaling for Integrins ⁶⁶ p130Cas linkage to MAPK signaling for integrins ⁶⁶ Platelet Aggregation (Plug Formation) ⁶⁶	11.73	ADRA2A ADRA2B ADRA2C
10	Monoamine GPCRs ¹ Show member pathways Adrenaline signalling through Alpha-2 adrenergic receptor ⁶⁶ Adrenoceptors ⁶⁶ Amine ligand-binding receptors ⁶⁶ Dopamine receptors ⁶⁶ Histamine receptors ⁶⁶ Muscarinic acetylcholine receptors ⁶⁶ Serotonin receptors ⁶⁶	11.72	ADRA2A ADRA2B ADRA2C ADRB1 ADRB2
11	Corticotropin-releasing hormone signaling pathway ¹	11.69	ECE1 NOS3 POMC
12	Renin secretion ³⁷	11.5	ADRB1 ADRB2 AGTR1
13	Antiarrhythmic Pathway, Pharmacodynamics ⁶¹	11.42	ADRA2A ADRB1 ADRB2
14	Monoamine Transport ¹ Show member pathways Serotonin Transporter Activity ¹	11.29	ACHE DBH SLC6A2
15	Melatonin metabolism and effects ¹	11.02	ACHE ADRB1 ECE1 EDN1
16	Endothelin Pathways ¹	10.79	ADRB1 ECE1 EDN1 NOS3
17	NO-dependent CFTR activation (normal and CF) ²²	10.65	NOS2 NOS3
18	Sympathetic Nerve Pathway (Neuroeffector Junction) ⁶¹	10.53	ADRA2A ADRA2B ADRA2C ADRB1 ADRB2 DBH
19	Effects of Nitric Oxide ¹	10.43	NOS2 NOS3

Sources

GO Terms for Orthostatic Intolerance

Cellular components related to Orthostatic Intolerance according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	plasma membrane	GO:0005886	9.77	ACHE ADRA2A ADRA2B ADRA2C ADRB1 ADRB2
2	integral component of plasma membrane	GO:0005887	9.7	ADRA2A ADRA2B ADRA2C ADRB1 ADRB2 AGTR1
3	Weibel-Palade body	GO:0033093	8.62	ECE1 EDN1

Biological processes related to Orthostatic Intolerance according to GeneCards Suite gene sharing:

(show all 33)

#	Name	GO ID	Score	Top Affiliating Genes
1	cell-cell signaling	GO:0007267	9.91	ADRA2A ADRA2B ADRA2C ADRB1 ADRB2 EDN1
2	positive regulation of MAPK cascade	GO:0043410	9.86	ADRA2A ADRA2B ADRA2C ADRB2
3	platelet activation	GO:0030168	9.82	ADRA2A ADRA2B ADRA2C
4	kidney development	GO:0001822	9.81	AGTR1 DCHS1 FBN1
5	glucose homeostasis	GO:0042593	9.8	ADRA2A DBH POMC
6	regulation of blood pressure	GO:0008217	9.77	EDN1 NOS3 POMC
7	regulation of insulin secretion	GO:0050796	9.75	ADRA2A ADRA2C NOS2
8	activation of protein kinase B activity	GO:0032148	9.72	ADRA2A ADRA2B ADRA2C
9	adenylate cyclase-modulating G-protein coupled receptor signaling pathway	GO:0007188	9.72	ADRA2A ADRA2B ADRA2C ADRB1 ADRB2
10	peptide hormone processing	GO:0016486	9.66	ECE1 POMC
11	response to pain	GO:0048265	9.65	DBH SLC6A2
12	regulation of sodium ion transport	GO:0002028	9.65	ADRB2 NOS3
13	negative regulation of norepinephrine secretion	GO:0010700	9.65	ADRA2A ADRA2B ADRA2C
14	regulation of blood vessel size	GO:0050880	9.64	EDN1 NOS3
15	nitric oxide mediated signal transduction	GO:0007263	9.64	NOS2 NOS3
16	regulation of systemic arterial blood pressure by endothelin	GO:0003100	9.63	ECE1 EDN1 NOS3
17	regulation of blood vessel diameter	GO:0097746	9.62	ADRB2 AGTR1
18	negative regulation of calcium ion transport	GO:0051926	9.62	ADRA2A NOS3
19	nitric oxide biosynthetic process	GO:0006809	9.61	NOS2 NOS3
20	negative regulation of multicellular organism growth	GO:0040015	9.61	ADRB1 ADRB2
21	negative regulation of epinephrine secretion	GO:0032811	9.61	ADRA2A ADRA2B ADRA2C
22	positive regulation of guanylate cyclase activity	GO:0031284	9.6	NOS2 NOS3
23	diet induced thermogenesis	GO:0002024	9.58	ADRB1 ADRB2
24	epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathway	GO:0035625	9.58	ADRA2A ADRA2B ADRA2C
25	arginine catabolic process	GO:0006527	9.57	NOS2 NOS3
26	regulation of smooth muscle contraction	GO:0006940	9.56	ADRA2A ADRA2B ADRA2C ADRB2
27	heat generation	GO:0031649	9.54	ADRB1 ADRB2
28	norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure	GO:0002025	9.52	ADRB1 ADRB2
29	fear response	GO:0042596	9.51	ADRB1 DBH
30	adrenergic receptor signaling pathway	GO:0071875	9.46	ADRA2A ADRA2B ADRA2C ADRB2
31	adenylate cyclase-activating adrenergic receptor signaling pathway	GO:0071880	9.35	ADRA2A ADRA2B ADRA2C ADRB1 ADRB2
32	regulation of vasoconstriction	GO:0019229	9.1	ADRA2A ADRA2B ADRA2C AGTR1 ECE1 EDN1
33	G-protein coupled receptor signaling pathway	GO:0007186	10.1	ADRA2A ADRA2B ADRA2C ADRB1 ADRB2 AGTR1

Molecular functions related to Orthostatic Intolerance according to GeneCards Suite gene sharing:

(show all 16)

#	Name	GO ID	Score	Top Affiliating Genes
1	G-protein coupled receptor activity	GO:0004930	9.99	ADRA2A ADRA2B ADRA2C ADRB1 ADRB2 AGTR1
2	protein homodimerization activity	GO:0042803	9.87	ACHE ADRA2A ADRA2C ADRB2 ECE1 NOS2
3	obsolete signal transducer activity	GO:0004871	9.85	ADRA2A ADRA2B ADRB1 ADRB2 AGTR1
4	hormone activity	GO:0005179	9.71	EDN1 FBN1 POMC
5	oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen	GO:0016709	9.56	NOS2 NOS3
6	L-ascorbic acid binding	GO:0031418	9.55	DBH PLOD1
7	FMN binding	GO:0010181	9.52	NOS2 NOS3
8	arginine binding	GO:0034618	9.49	NOS2 NOS3
9	NADPH-hemoprotein reductase activity	GO:0003958	9.48	NOS2 NOS3
10	alpha-2A adrenergic receptor binding	GO:0031694	9.43	ADRA2C ADRB1
11	norepinephrine binding	GO:0051380	9.43	ADRA2A ADRB1 ADRB2
12	tetrahydrobiopterin binding	GO:0034617	9.4	NOS2 NOS3
13	nitric-oxide synthase activity	GO:0004517	9.37	NOS2 NOS3
14	adrenergic receptor activity	GO:0004935	9.35	ADRA2A ADRA2B ADRA2C ADRB1 ADRB2
15	alpha2-adrenergic receptor activity	GO:0004938	9.33	ADRA2A ADRA2B ADRA2C
16	epinephrine binding	GO:0051379	9.02	ADRA2A ADRA2B ADRA2C ADRB1 ADRB2

Sources

Sources for Orthostatic Intolerance

¹ BioSystems

² BitterDB

³ CDC

⁴ Cell Signaling Technology

⁵ ClinicalTrials

⁶ ClinVar

⁷ CNVD

⁸ Cochrane Library

⁹ Cosmic

¹⁰ dbSNP

¹¹ DGIdb

¹² Disease Ontology

¹³ diseasecard

¹⁴ DiseaseEnhancer

¹⁵ DISEASES

¹⁶ DrugBank

¹⁷ ExPASy

¹⁸ FDA Approved Drugs

¹⁹ FMA

²⁰ GeneAnalytics

²¹ GeneCards

²² GeneGo (Thomson Reuters)

²³ GeneHancer via GeneCards

²⁴ GeneReviews

²⁵ Genetics Home Reference

²⁶ GenomeRNAi

²⁷ GEO DataSets

²⁸ GO

²⁹ GTR

³⁰ HGMD

³¹ HMDB

³² HPO

³³ ICD10

³⁴ ICD10 via Orphanet

³⁵ ICD9CM

³⁶ IUPHAR

³⁷ KEGG

³⁸ LifeMap

³⁹ LncRNADisease

⁴⁰ LOVD

⁴¹ MalaCards

⁴² MedGen

⁴³ MedlinePlus

⁴⁴ MeSH

⁴⁵ MESH via Orphanet

⁴⁶ MGI

⁴⁷ miR2Disease

⁴⁸ NCBI Bookshelf

⁴⁹ NCI

⁵⁰ NCIt

⁵¹ NDF-RT

⁵² NIH Clinical Center

⁵³ NIH Rare Diseases

⁵⁴ NINDS

⁵⁵ Novoseek

⁵⁶ Novus Biologicals

⁵⁷ OMIM

⁵⁸ OMIM via Orphanet

⁵⁹ Orphanet

⁶⁰ PathCards

⁶¹ PharmGKB

⁶² PubMed

⁶³ PubMed Health

⁶⁴ QIAGEN

⁶⁵ R&D Systems

⁶⁶ Reactome

⁶⁷ Sino Biological

⁶⁸ SNOMED-CT

⁶⁹ SNOMED-CT via HPO

⁷⁰ SNOMED-CT via Orphanet

⁷¹ TGDB

⁷² Tocris

⁷³ UMLS

⁷⁴ UMLS via Orphanet

⁷⁵ UniProtKB/Swiss-Prot

⁷⁶ Wikipedia

Orthostatic Intolerance

Aliases & Classifications for Orthostatic Intolerance

MalaCards integrated aliases for Orthostatic Intolerance:

Characteristics:

Orphanet epidemiological data:

HPO:

Classifications:

External Ids:

Summaries for Orthostatic Intolerance

Related Diseases for Orthostatic Intolerance

Diseases in the Orthostatic Intolerance family:

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

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

Symptoms & Phenotypes for Orthostatic Intolerance

Clinical features from OMIM:

Human phenotypes related to Orthostatic Intolerance:

UMLS symptoms related to Orthostatic Intolerance:

MGI Mouse Phenotypes related to Orthostatic Intolerance:

Drugs & Therapeutics for Orthostatic Intolerance

PubMedHealth treatment related to Orthostatic Intolerance: 63

Drugs for Orthostatic Intolerance (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

Interventional clinical trials:

Cochrane evidence based reviews: neurocirculatory asthenia

Genetic Tests for Orthostatic Intolerance

Genetic tests related to Orthostatic Intolerance:

Anatomical Context for Orthostatic Intolerance

MalaCards organs/tissues related to Orthostatic Intolerance:

Publications for Orthostatic Intolerance

Articles related to Orthostatic Intolerance:

Genes for Orthostatic Intolerance

Genes related to Orthostatic Intolerance (5 elite genes):

Variations for Orthostatic Intolerance

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

ClinVar genetic disease variations for Orthostatic Intolerance:

Expression for Orthostatic Intolerance

Pathways for Orthostatic Intolerance

Pathways related to Orthostatic Intolerance according to GeneCards Suite gene sharing:

GO Terms for Orthostatic Intolerance

Cellular components related to Orthostatic Intolerance according to GeneCards Suite gene sharing:

Biological processes related to Orthostatic Intolerance according to GeneCards Suite gene sharing:

Molecular functions related to Orthostatic Intolerance according to GeneCards Suite gene sharing:

Sources for Orthostatic Intolerance

PubMedHealth treatment related to Orthostatic Intolerance: ⁶³