Table 3.

Summary of ZIP12 in the nervous system and in other tissues or diseases

Tissue/organ, physiological system, or disease	Citations
Brain and nervous system
Expression pattern: ZIP12 expression is highest in the brain and nervous system across vertebrates.	Chowanadisai et al., 2013a; Chowanadisai, 2014
Neural cell development: ZIP12 is necessary for neurite extension mouse Neuro-2a cells and primary mouse neurons. ZIP12 is also necessary for cellular respiration and mitochondrial function. ZIP12-deleted cells have reduced cellular respiration and are sensitive to rotenone and sodium azide. ZIP12-deleted cells have increased superoxide generation and higher oxidative damage. Exposing ZIP12-deleted cells to antioxidant chemicals can restore neurite length.	Chowanadisai et al., 2013a; Strong et al., 2020
Embryonic development: ZIP12 is expressed in the forebrain, midbrain, and eye of Xenopus tropicalis during nervous system development. ZIP12 is also expressed at the anterior neuropore during neural tube closure. Embryos injected with antisense morpholinos targeting ZIP12 have impaired neurulation, lack eyes, and premature lethality.	Chowanadisai et al., 2013a
Human brain MRI patterns: ZIP12 polymorphisms and rare mutations are linked to altered swMRI intensity and T1 FAST MRI in the human brain. Polymorphisms rs10430577 and rs10430578 are the lead SNPs most associated with swMRI intensity in the caudate, putamen, and pallidum and T1 FAST MRI. Missense ZIP12 mutations (rs10764176, rs72778328) associated with swMRI have reduced zinc transport activity.	Elliott et al., 2018; Cirulli et al., 2020; Strong et al., 2020
Schizophrenia: A non-coding polymorphism in ZIP12 has been reported in in patients with schizophrenia. ZIP12 mRNA is higher in frontal lobe, superior frontal gyrus, and inferior frontal gyrus of brains from schizophrenic subjects.	Bly, 2006; Scarr et al., 2016
Autism: One person (Han Chinese) with autism had a heterozygous deletion in SLC39A12. In a separate study, a premature stop codon was detected in one copy of SLC39A12 in a person with autism.	Gazzellone et al., 2014; Krumm et al., 2015
Other tissues and physiological systems or diseases
Lung and pulmonary hypertension: Fisher 344 (F344) rats are resistant to hypoxia-induced pulmonary hypertension, and Wistar Kyoto (WKY) rats are susceptible. A ZIP12 frameshift mutation present in F344 rats has reduced cellular zinc uptake activity. ZIP12 knockout rats also are resistant to hypoxia-induced pulmonary hypertension and vascular remodeling. Rats, cattle, and humans have increased ZIP12 protein when housed in hypoxic environments, which is due to a hypoxia response element (HRE) is present within a SLC39A12 intron. ZIP12 expression increased in human vascular endothelial and smooth muscle cells after exposure to zinc chelator TPEN.	Zhao et al., 2015; Abdo et al., 2020
Cancer: ZIP12 missense mutations were found in two studies on esophageal adenocarcinoma. ZIP12 mRNA was elevated in non-small cell lung cancer biopsies. ZIP12 protein abundance was lower in the breast cancer lines relative to a non-malignant mammary cell line.	Dulak et al., 2013; Murugaesu et al., 2015; Huang et al., 2016; Chandler et al., 2016
Ascites syndrome: ZIP12 mRNA and protein increased in lung and liver of chickens after ascites syndrome by intravenous cellulose microparticle injection.	Cui et al., 2019
Immune system: The restoration of zinc to zinc-deficient T-cells induces ZIP12 expression, which may promote cytokine production by the immune system. In broiler male chicks, ZIP12 mRNA expression in the duodenum, a region of the small intestine, decreases in response to an oral challenge with Salmonella.	Daaboul et al., 2012; Wu et al., 2020
Fertility and reproduction: SLC39A12 (ZIP12) may be a candidate gene that affects fertility in female Chinese and Nordic Holstein cows. ZIP12 mRNA is more abundant in mouse oocytes compared to cumulus cells.	Liu et al., 2017; Lisle et al., 2013
Endurance: An intronic polymorphism in SLC39A12 is linked to endurance racing performance in Arabian horses.	Ricard et al., 2017
Glucose metabolism: Two SNPs in SLC39A12, rs2497753 and rs9418383, were reported to be associated with elevated fasting plasma glucose and IgG glycosylation in 511 Chinese adults.	Ge et al., 2018