POTS is associated with pathogenic variants in the SLC6A2 gene on chromosome 16, which encodes the norepinephrine transporter. Dysfunction of the norepinephrine transporter leads to impaired norepinephrine reuptake, contributing to elevated urinary norepinephrine levels and adrenergic features characteristic of the syndrome. An autosomal dominant inheritance pattern is documented in this packet. No ClinGen gene-validity classification is captured in this packet for the SLC6A2-POTS association. POTS is described in this packet as a disorder of the autonomic nervous system, with symptom expression linked to upright posture.

The two obligate phenotypic features documented in this packet, orthostatic tachycardia and elevated urinary norepinephrine, are central to the clinical characterization of POTS. Positional onset and relief of symptoms, as described in the packet definition, are defining features of the syndrome. The SLC6A2 gene on chromosome 16 is documented as a genetic contributor to POTS in this packet. No specific diagnostic criteria thresholds or testing protocol fields are populated beyond gene and phenotype data in this packet.

No FDA-approved drug therapies are documented in this packet specifically for POTS, and no foundational therapies are listed. Clinical trials documented in the packet include an early-phase study investigating guanfacine and cromolyn sodium for POTS (NCT07757555, not yet recruiting), sponsored by Johns Hopkins University, and a registry study for tachycardia conditions (NCT05107635, recruiting), sponsored by AtriCure, Inc. These investigational efforts represent the treatment research landscape for POTS as captured in this packet.

Natural history data fields are not populated in this packet. The packet definition characterizes POTS by positional symptom onset with standing and relief upon returning to a supine or seated position. The long-term clinical course and prognostic trajectory for POTS are not captured in the available packet data fields beyond this functional description.

POTS has an active research landscape, with 10 clinical trials documented in this packet involving drug therapy, other interventions, medical devices, and procedural approaches. Sponsors include academic institutions, including Johns Hopkins University, and industry participants such as AtriCure, Inc. The Kisho literature tracker documents 447 classified publications related to POTS, with reviews and meta-analyses as the dominant publication type (142 entries) and 32 case reports. Literature encompasses biomarker research, gene therapy publications, and coverage of recent trial results. The substantial review literature base reflects ongoing synthesis and investigational activity in this field.