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Atlas / Disease / Postural orthostatic tachycardia syndrome

Postural orthostatic tachycardia syndrome

disease
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Also known as familial orthostatic tachycardia due to norepinephrine transporter deficiencyirritable heartorthostatic intolerance due to NET deficiencyPOTSsoldiers heart

Summary

Postural orthostatic tachycardia syndrome (MONDO:0011479) is a disease with 1 cohort gene and 63 clinical trials. Top therapeutic interventions include pyridostigmine, bisoprolol, and propranolol.

At a glance

  • Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
  • Cohort genes: 1
  • Clinical trials: 63

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

TypeClassValueGeographyValidation
Cases/families2WorldwideValidated
Point prevalence<1 / 1 000 000WorldwideValidated

Identifiers

Disease identifiers

FieldValue
Canonical namepostural orthostatic tachycardia syndrome
Mondo IDMONDO:0011479
EFOEFO:1000645
MeSHD054972
OMIM604715
Orphanet443236
DOIDDOID:0111154
ICD-111533647472
NCITC85020
SNOMED CT371073003
UMLSC1299624
MedGen226970
GARD0013591
Is cancer (heuristic)no

Also known as: familial orthostatic tachycardia due to norepinephrine transporter deficiency · irritable heart · orthostatic intolerance due to NET deficiency · POTS · soldiers heart

Data availability: 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › heart conduction disease › postural orthostatic tachycardia syndrome

Related subtypes (9): short QT syndrome, atrioventricular block, sinoatrial node disorder, Wolff-Parkinson-White syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, progressive familial heart block, sinoatrial block, NKX2.5-related congenital, conduction and myopathic heart disease

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

GeneClassificationInheritanceDiseaseRecords
SLC6A2SupportiveAutosomal dominantpostural orthostatic tachycardia syndrome9

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
SLC6A2Orphanet:443236Postural orthostatic tachycardia syndrome due to NET deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
SLC6A2HGNC:11048ENSG00000103546P23975Sodium-dependent noradrenaline transportergencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
SLC6A2Sodium-dependent noradrenaline transporterMediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline), the primary signaling neurotransmitter in the autonomic sympathetic nervous system.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

FamilyGenesFoldFDR
Other/Unknown11.8×0.558

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
SLC6A2Other/UnknownnoNa/ntran_symport, Na/ntran_symport_noradrenaline, SNS_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)1
unknown0

Top tissues across cohort

TissueCohort genes
buccal mucosa cell1
decidua1
placenta1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
SLC6A2121ubiquitousmarkerplacenta, buccal mucosa cell, decidua

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
SLC6A21,213

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
SLC6A2P2397536

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Defective SLC6A2 causes orthostatic intolerance (OI)12855.0×0.003SLC6A2
SLC-mediated transport of neurotransmitters1407.9×0.010SLC6A2
SLC transporter disorders1203.9×0.011SLC6A2
R-HSA-4253661181.3×0.011SLC6A2
Disorders of transmembrane transporters1139.3×0.011SLC6A2
SLC-mediated transmembrane transport159.2×0.023SLC6A2
Transport of small molecules125.1×0.045SLC6A2
Disease113.1×0.076SLC6A2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
obsolete norepinephrine transport11872.4×0.002SLC6A2
dopamine uptake involved in synaptic transmission11872.4×0.002SLC6A2
norepinephrine uptake11872.4×0.002SLC6A2
obsolete monoamine transport11203.7×0.002SLC6A2
response to pain1887.0×0.002SLC6A2
neuron cellular homeostasis1455.5×0.004SLC6A2
neurotransmitter transport1421.3×0.004SLC6A2
amino acid transport1312.1×0.004SLC6A2
sodium ion transmembrane transport1203.0×0.006SLC6A2
chemical synaptic transmission177.3×0.014SLC6A2
response to xenobiotic stimulus169.1×0.014SLC6A2

Therapeutics

Drugs indicated for this disease

0 approved, 2 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
Albumin HumanPhase 3 (in late-stage trials)
IvabradinePhase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Efgartigimod Alfa, Metoprolol, Progesterone, Sucrose.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

SymbolExample approved molecule
SLC6A2CETIRIZINE

Top cohort targets by molecule count

SymbolMoleculesMax phase
SLC6A24714

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
CETIRIZINE4SLC6A2
BEPRIDIL4SLC6A2
CANDESARTAN CILEXETIL4SLC6A2
BEXAROTENE4SLC6A2
CLOTRIMAZOLE4SLC6A2
AMINOCAPROIC ACID4SLC6A2
SIMVASTATIN4SLC6A2
NABUMETONE4SLC6A2
METAXALONE4SLC6A2
ACETOPHENAZINE4SLC6A2
MESORIDAZINE4SLC6A2
PHENELZINE4SLC6A2
NIRAPARIB4SLC6A2
INDACATEROL4SLC6A2
IMIPRAMINE4SLC6A2
EPINASTINE4SLC6A2
RIMONABANT4SLC6A2
ARIPIPRAZOLE4SLC6A2
AMOXAPINE4SLC6A2
IDARUBICIN4SLC6A2
DESVENLAFAXINE4SLC6A2
EZETIMIBE4SLC6A2
PONATINIB4SLC6A2
DESLORATADINE4SLC6A2
RUCAPARIB4SLC6A2
DULOXETINE4SLC6A2
CELECOXIB4SLC6A2
UMECLIDINIUM4SLC6A2
TRIMETREXATE4SLC6A2
PHENIRAMINE4SLC6A2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

SymbolAssaysType breakdown
SLC6A2929Binding:885, ADMET:25, Functional:15, Toxicity:3, Unclassified:1

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

SymbolChEMBL assays
SLC6A2929

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

CompoundMax phaseCohort target (bioactivity)
CETIRIZINE4SLC6A2
BEPRIDIL4SLC6A2
CANDESARTAN CILEXETIL4SLC6A2
BEXAROTENE4SLC6A2
CLOTRIMAZOLE4SLC6A2
AMINOCAPROIC ACID4SLC6A2
SIMVASTATIN4SLC6A2
NABUMETONE4SLC6A2
METAXALONE4SLC6A2
ACETOPHENAZINE4SLC6A2
MESORIDAZINE4SLC6A2
PHENELZINE4SLC6A2
NIRAPARIB4SLC6A2
INDACATEROL4SLC6A2
IMIPRAMINE4SLC6A2
EPINASTINE4SLC6A2
RIMONABANT4SLC6A2
ARIPIPRAZOLE4SLC6A2
AMOXAPINE4SLC6A2
IDARUBICIN4SLC6A2
DESVENLAFAXINE4SLC6A2
EZETIMIBE4SLC6A2
PONATINIB4SLC6A2
DESLORATADINE4SLC6A2
RUCAPARIB4SLC6A2
DULOXETINE4SLC6A2
CELECOXIB4SLC6A2
UMECLIDINIUM4SLC6A2
TRIMETREXATE4SLC6A2
PHENIRAMINE4SLC6A2

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1SLC6A2
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 63.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified46
PHASE27
PHASE43
PHASE32
PHASE1/PHASE22
PHASE12
EARLY_PHASE11

Top trials by phase / activity

NCTPhaseStatusTitle
NCT05363514PHASE4NOT_YET_RECRUITINGLow Dose Naltrexone Use in Patients With POTS
NCT02171988PHASE4COMPLETEDEffect of Medical Treatment and Prognosis of Postural Orthostatic Tachycardia Syndrome (POTS)
NCT05481177PHASE4UNKNOWNIvabradine for Long-Term Effects of COVID-19 With POTS Cohort
NCT03182725PHASE3COMPLETEDEffect of Ivabradine on Patients With Postural Orthostatic Tachycardia Syndrome
NCT03365414PHASE3WITHDRAWNA Study to Systematically Assess the Efficacy and Safety of Intravenous Albumin Infusions in Severe POTS
NCT06593600PHASE2ACTIVE_NOT_RECRUITINGStudy of Natriuretic Peptide Receptor 1 (NPR1) Antagonist in Adult Patients With Postural Orthostatic Tachycardia Syndrome (POTS)
NCT07585513PHASE2NOT_YET_RECRUITINGBeta-3 Enhanced Autonomic Therapy for POTS
NCT00865917PHASE2UNKNOWNCardiovascular Effects of Selective I(f)-Channel Blockade
NCT01978535PHASE1/PHASE2TERMINATEDIron Sucrose in Adolescents With Iron Deficiency and Postural Orthostatic Tachycardia Syndrome (POTS)
NCT03070730PHASE1/PHASE2TERMINATEDHemodynamic Response of Neuropathic And Non-Neuropathic POTS Patients To Adrenoreceptor Agonist And Antagonist
NCT03674541PHASE2COMPLETEDThe Exercise Response to Pharmacologic Cholinergic Stimulation in Myalgic Encephalomyelitis / Chronic Fatigue Syndrome
NCT04855266PHASE2WITHDRAWNIron Sucrose in Patients With Iron Deficiency and POTS
NCT05633407PHASE2COMPLETEDEfficacy and Safety Study of Efgartigimod in Adults With Post-COVID-19 POTS
NCT06133075PHASE2COMPLETEDUsing Mirabegron to Increase BP in Patients With POTS
NCT00962949PHASE1COMPLETEDThe Renin-Aldosterone Axis in Postural Tachycardia Syndrome
NCT01771484PHASE1TERMINATEDHigh Sodium Diet and External Abdominal Compression in POTS
NCT03261570EARLY_PHASE1COMPLETEDCardiovagal Baroreflex Deficits Impair Neurovascular Coupling and Cognition in POTS
NCT00608725Not specifiedACTIVE_NOT_RECRUITINGPathophysiology of Orthostatic Intolerance
NCT00962728Not specifiedACTIVE_NOT_RECRUITINGBreathing Device in Postural Orthostatic Tachycardia Syndrome (POTS)
NCT02196376Not specifiedACTIVE_NOT_RECRUITINGAssessment of Antibodies and Inflammatory Markers in Postural Tachycardia Syndrome
NCT02281097Not specifiedACTIVE_NOT_RECRUITINGTransdermal Vagal Stimulation for POTS
NCT02725060Not specifiedENROLLING_BY_INVITATIONAutoimmune Basis for Postural Tachycardia Syndrome
NCT04881318Not specifiedRECRUITINGCompression Garments in the Community With POTS
NCT05094622Not specifiedACTIVE_NOT_RECRUITINGPhysical Training in Patients With POTS After Covid-19
NCT05212129Not specifiedRECRUITINGAuricular Vagal Nerve Stimulation for Hypermobile Ehlers-Danlos Syndrome
NCT05344599Not specifiedACTIVE_NOT_RECRUITINGEvaluating the Prevalence of Acute Hepatic Porphyria in Postural Tachycardia Syndrome
NCT05555771Not specifiedRECRUITINGPaediatric Syncope in the Emergency Department
NCT05633693Not specifiedRECRUITINGPostural Sway and Counterpressure Maneuvers for Pediatric Syncope
NCT05741112Not specifiedRECRUITINGThe Long COVID-19 Wearable Device Study
NCT05796154Not specifiedNOT_YET_RECRUITINGPOTS Stroke Volume
NCT05877534Not specifiedENROLLING_BY_INVITATIONEffects of Individual Tailored Physical Exercise in Patients With POTS After COVID-19 - a Randomized Controlled Study
NCT05914649Not specifiedRECRUITINGNC Testing in LC & POTS
NCT05924646Not specifiedRECRUITINGCAlgary SAlt for POTS
NCT06292104Not specifiedRECRUITINGPhenotyping of Postural Orthostatic Tachycardia Syndrome (POTS)
NCT06936319Not specifiedRECRUITINGCounterpressure Maneuvers in Postural Orthostatic Tachycardia Syndrome
NCT06992531Not specifiedNOT_YET_RECRUITINGAuto-immune Contribution in Symptom-based Sensory and Autonomic Disorders
NCT06996314Not specifiedNOT_YET_RECRUITINGEffects of Auricular Vagus Nerve Stimulation Combined With Slow-paced Breathing on Individuals With Postural Orthostatic Tachycardia Syndrome.
NCT07005947Not specifiedACTIVE_NOT_RECRUITINGLong COVID-19 Cutaneous Signatures: An ARPA Funded Research Project
NCT07019519Not specifiedRECRUITINGPOTS-FLOW: Interplay Between Gut Hormones and Autonomic Postprandial Blood Flow Regulation in Patients With POTS
NCT07026643Not specifiedNOT_YET_RECRUITINGaVNT in POTS - Pilot

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
PYRIDOSTIGMINE44
BISOPROLOL43
PROPRANOLOL43
IVABRADINE42
MIRABEGRON42
ALBUMIN HUMAN41
ANGIOTENSIN II41
ATENOLOL41
DROXIDOPA41
EFGARTIGIMOD ALFA41
ISOPROTERENOL41
MICROCRYSTALLINE CELLULOSE31
POWDERED CELLULOSE31
DEXPROPRANOLOL21
ESATENOLOL21
CHEMBL123000401
CHEMBL159385101

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

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This page pulls from 72 datasets indexed by BioBTree:

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