SLC39A4 Gene

The SLC39A4 gene (SLC39A4 stands for "Solute Carrier Family 39 Member 4") is a protein coding gene located on chromosome 8q24.3. The SLC39A4 gene encodes a member of the zinc/iron-regulated transporter-like protein (ZIP) family that is highly expressed in the duodenum and jejunum (Schmitt S et al. 2009). SLC39A4 mutations are distributed throughout the gene and include many different types of mutations. Since the initial description, >40 mutations or unclassified variants of SLC39A4 have been described in this gene.

The encoded protein is localized at cell membranes and is required for zinc uptake in the intestine. Mutations in this gene lead to the clinical picture of "acrodermatitis enteropathica". Several transcript variants encoding different isoforms have been found for the SLC39A4 gene.

Diseases associated with SLC39A7 include:

Agammaglobulinemia 9, autosomal recessive

and

Acrodermatitis enteropathica, zinc deficiency type. Acrodermatitis enteropathica (AE) is a very rare, recessively inherited disease caused by severe zinc deficiency. It typically occurs in early infancy and is characterized by perioral and acral dermatitis, alopecia, and diarrhea.

The encoded protein ZIP-4 plays an important role in cellular zinc homeostasis as a zinc transporter. It is regulated in response to zinc availability. Related metabolic pathways include the transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds, and the NRF2 pathway.

1. Kiener S et al. (2021) A missense variant in SLC39A4 in a litter of Turkish Van Cats with Acrodermatitis Enteropathica. Genes (Basel) 12:1309.
2. Schmitt S et al (2009) An update on mutations of the SLC39A4 gene in acrodermatitis enteropathica. Hum Mutat 30:926-933.