SLC6A2 encodes the sodium-dependent noradrenaline transporter NAT1 which terminates the action of the neurotransmitter noradrenaline (NAd) by transporting it from the synapse back to its vesicles for storage and reuse. SLC6A2 is expressed in the CNS and adrenal glands. Defects in SLC6A2 can cause orthostatic intolerance (OI; MIM:604715), a syndrome characterised by lightheadedness, fatigue and development of symptoms during upright standing, relieved by sitting back down again. Plasma NAd concentration is abnormally high. The loss-of-function A457P mutation in SLC6A2 can lead to OI. NAd is not transported back to vesciles for storage and builds up in the bloodstream (Shannon et al. 2000, Paczkowski et al. 2002).
norepinephrine:sodium symporter activity of SLC6A2 A457P [plasma membrane]
Loss of function of SLC6A2 A457P [plasma membrane]