SLC29A3

Chr 10AR

solute carrier family 29 member 3

ENSG00000198246 UniProt: Q9BZD2 OMIM: 602782

The protein functions as a nucleoside transporter that facilitates transport of nucleosides, nucleobases, and monoamine neurotransmitters across lysosomal and mitochondrial membranes. Mutations cause histiocytosis-lymphadenopathy plus syndrome (H syndrome), characterized by cutaneous hyperpigmentation and hypertrichosis, hepatosplenomegaly, heart anomalies, and hypogonadism, as well as the related disorder PHID (pigmented hypertrichosis with insulin-dependent diabetes mellitus). The gene shows autosomal recessive inheritance and is highly constrained against loss-of-function variants.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Uniporter that mediates the facilitative transport of nucleoside across lysosomal and mitochondrial membranes (PubMed:15701636, PubMed:19164483, PubMed:20595384, PubMed:28729424). Functions as a non-electrogenic Na(+)-independent transporter (PubMed:15701636, PubMed:19164483, PubMed:28729424). Transport activity is pH-dependent and enhanced under acidic conditions, consistent with localization to acidic intracellular compartments (PubMed:15701636, PubMed:19164483, PubMed:28729424). Protons are not cotransported but likely modulate transport by altering the ionization state of the transporter which dictates its conformation, thereby regulating substrate permeability (PubMed:28729424). May direct the nucleoside transport from lysosomes to cytosol or cytosol to mitochondria to facilitate nucleic acid salvage pathways (PubMed:28729424). Transports nucleosides (adenosine, guanosine, uridine, thymidine, cytidine and inosine), deoxynucleosides (deoxyadenosine, deoxycytidine), purine nucleobases (adenine, guanine) and pyrimidine nucleobases (uracil) (PubMed:15701636, PubMed:19164483, PubMed:20595384, PubMed:28729424). Also capable of transporting monoamine neurotransmitters dopamine, serotonin, noradrenaline and tyramine, as well as ATP (PubMed:19164483). Mediates nucleoside export from lysosomes in macrophages, thereby regulating macrophage function and number (By similarity). Also functions as a lysosomal urate exporter, contributing to intracellular urate disposal (PubMed:41476938). Regulates inflammasome activation via dual roles in urate and adenosine transport (PubMed:41476938)

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