SLC39A14 gene encodes a broad-scope metal ion transporter, which is involved in the transport of iron, manganese, and cadmium. It is particularly responsible for zinc transportation and maintaining cellular zinc ion homeostasis. Alternatively spliced transcript variants encode multiple isoforms of the SLC39A14 protein that vary in their tissue specificity. While the gene is ubiquitously expressed, isoform 1 is seen to be highly expressed in the liver, pancreas, thyroid gland, heart as well as fetal liver and fetal heart.
Homozygous truncating and missense mutations in the SLC39A14 gene have been associated with Hypermanganesemia with Dystonia 2 (HMNDYT2), an autosomal recessive disorder characterized by developmental regression, intellectual disability, and abnormal movements such as dystonia, spasticity, bulbar dysfunction and parkinsonism. These are loss-of-function mutations that impair the hepatic uptake of manganese resulting in the hypermanganesemia and downstream neurotoxic effects seen in this disorder.