. 2016 Oct 31;2016:6762343. doi: 10.1155/2016/6762343

Table 1.

Zn transporters in physiology and pathophysiology.

Gene symbol	Protein name	Mutation type	Phenotype and disorder	Reference
SLC39A1	ZIP1	KO	Abnormal embryonic development	[15]

SLC39A2	ZIP2	KO	Abnormal embryonic development	[16]

SLC39A3^∗1	ZIP3	KO	Abnormal embryonic and T-cell development	[14]

SLC39A4^∗2	ZIP4	KO	Embryonic lethality	[18, 20–22, 60]
SLC39A4^∗2	ZIP4	Mutation	AE	[18, 20–22, 60]

SLC39A5	ZIP5	Mutation	Autosomal dominant nonsyndromic high myopia	[23]

SLC39A8^∗3	ZIP8	Hypomorphic mutation	Impaired multiple-organ organogenesis and hematopoiesis	[24–26, 61]
		Hypomorphic mutation	Abnormal innate immune function
		KO	Osteoarthritis
		SNP	Schizophrenia

SLC39A10^∗4	ZIP10	KO	Abnormal early B-cell development	[27, 28]
SLC39A10^∗4	ZIP10	KO	Impaired humoral immune response	[27, 28]

SLC39A12	ZIP12	KO	Attenuation of pulmonary hypertension in a hypoxic atmosphere	[29]

SLC39A13	ZIP13	KO	Connective tissue dysplasia	[34, 62]
SLC39A13	ZIP13	Mutation	SCD-EDS	[34, 62]

SLC39A14	ZIP14	KO	Growth retardation and impaired gluconeogenesis	[35–38]
			Impaired hepatocyte proliferation during liver regeneration after hepatectomy
			Decreased insulin signaling, hypertrophied adipocytes, and increased adipose cytokine production and plasma leptin
		Mutation	Parkinsonism-dystonia and neurodegeneration with hypermanganesemia in childhood

SLC30A1	ZnT1	KO	Embryonic lethality	[39, 63]
SLC30A1	ZnT1	KO	Abnormal vulva formation	[39, 63]

SLC30A2	ZnT2	Mutation KO	Low Zn in milk	[40–43]

SLC30A3	ZnT3	KO	Prone to seizures Alzheimer's disease-like abnormalities	[45, 64]

SLC30A4	ZnT4	Mutation	Lethal milk: lm Low Zn in milk	[46]

SLC30A5	ZnT5	KO	Growth retardation, osteopenia, hypodontia, and male-specific cardiac death	[47, 48]
SLC30A5	ZnT5	KO	Impaired mast-cell functions	[47, 48]

SLC30A7	ZnT7	KO	Reduced body fat accumulation	[49, 50]
SLC30A7	ZnT7	KO	Insulin resistance, glucose intolerance, and hyperglycemia on a high-fat diet	[49, 50]

SLC30A8	ZnT8	KO	Type 2 diabetes mellitus	[51–56]
SLC30A8	ZnT8	SNP	Type 1 and 2 diabetes mellitus	[51–56]

SLC30A10	ZnT10	Mutation	Parkinsonism, dystonia, hypermanganesemia, polycythemia, and chronic liver disease	[57–59]

^∗1Mice with a targeted ZIP3 deletion show lower DP thymocyte counts but increased number of CD4⁺ SP or CD8⁺ SP thymocytes under a Zn-limiting condition.

^∗2Patients with ZIP4 mutation (AE) show severe ZnD symptoms characterized by immunodeficiency with thymic atrophy and lymphopenia, and by recurrent infections. Epidermal LCs, which inhibit ICD triggered by the ATP release from epidermal keratinocytes, are significantly reduced in the lesions of AE patients, resulting in inflammatory skin manifestations. However, oral Zn supplementation allows LCs to recolonize and improve clinical symptoms in these patients.

^∗3Fetal fibroblasts from ZIP8 hypomorphic mice exhibit dysregulated Zn uptake and increased NF-κB activation due to insufficient control of IκB kinase. Consistent with this, mice given ZnD dietary intakes develop excessive inflammation to polymicrobial sepsis.

^∗4Mice with a targeted disruption of ZIP10 show impaired early B-cell development and antibody response, due to increased caspase activity and decreased CD45R PTPase activity, respectively.