SLC29A4

Description

The SLC29A4 (solute carrier family 29 member 4) is a protein-coding gene located on chromosome 7.

SLC29A4 gene encodes the plasma membrane monoamine transporter (PMAT), also known as human equilibrative nucleoside transporter-4 (hENT4). This integral membrane protein is responsible for transporting monoamine neurotransmitters (serotonin, dopamine, norepinephrine), as well as adenosine, from synaptic spaces into presynaptic neurons or neighboring glial cells. It is highly expressed in the human brain, heart tissue, and skeletal muscle, as well as in the kidneys, liver, and small intestine. PMAT is relatively insensitive to high affinity inhibitors of the SLC6A monoamine transporters, but shows weak sensitivity to the adenosine transport inhibitor, dipyridamole. PMAT is particularly abundant in dendrites with dense monoaminergic input and significantly impacts synaptic clearance of monoamines, especially under non-homeostatic conditions. Its transport mechanism is electrogenic, using the cell's naturally negative interior to attract cationic monoamines, thereby increasing its Vmax (without changing affinity) with increasingly negative membrane potentials. PMAT preferentially transports 5-HT and DA, with a transport efficiency comparable to SERT and DAT, but a lower Km. PMAT and similar transporters like OCT3 are often referred to as uptake2 transporters.

SLC29A4 encodes an electrogenic, voltage-dependent transporter that mediates the transport of various endogenous bioactive amines, cationic xenobiotics and drugs. It utilizes the inside-negative membrane potential as a driving force to facilitate cellular uptake of organic cations. The transporter functions as a Na(+)- and Cl(-)- independent bidirectional transporter. Substrate transport is pH-dependent and enhanced under acidic conditions, likely due to allosteric changes in the transporter structure. SLC29A4 is implicated in the uptake of monoamine neurotransmitters like serotonin, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, histamine and tyramine, supporting a role in homeostatic regulation of aminergic neurotransmission in the central nervous system. It is also responsible for the uptake of bioactive amines and drugs through the blood-cerebrospinal fluid (CSF) barrier, from the CSF into choroid plexus epithelial cells, playing a significant role in the clearance of cationic neurotoxins, xenobiotics and metabolic waste in the brain. SLC29A4 is involved in bidirectional transport of the purine nucleoside adenosine and plays a role in the regulation of extracellular adenosine concentrations in cardiac tissues, particularly during ischemia. It may be involved in organic cation uptake from the tubular lumen into renal tubular cells, contributing to organic cation reabsorption in the kidney. The transporter also transports guanidine.

SLC29A4 is also known as ENT4, PMAT.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing