SLC39A8 is an evolutionarily highly conserved gene that encodes the ZIP8 metal cation transporter in all vertebrates. SLC39A8 is ubiquitously expressed, including pluripotent embryonic stem cells; SLC39A8 expression occurs in every cell type examined. Uptake of ZIP8-mediated Mn2+, Zn2+, Fe2+, Se4+, and Co2+ represents endogenous functions-moving these cations into the cell. By way of mouse genetic differences, the phenotype of "subcutaneous cadmium-induced testicular necrosis" was assigned to the Cdm locus in the 1970s. This led to identification of the mouse Slc39a8 gene, its most closely related Slc39a14 gene, and creation of Slc39a8-overexpressing, Slc39a8(neo/neo) knockdown, and cell type-specific conditional knockout mouse lines; the Slc39a8(-/-) global knockout mouse is early-embryolethal. Slc39a8(neo/neo) hypomorphs die between gestational day 16.5 and postnatal day 1-exhibiting severe anemia, dysregulated hematopoiesis, hypoplastic spleen, dysorganogenesis, stunted growth, and hypomorphic limbs. Not surprisingly, genome-wide association studies subsequently revealed human SLC39A8-deficiency variants exhibiting striking pleiotropy-defects correlated with clinical disorders in virtually every organ, tissue, and cell-type: numerous developmental and congenital disorders, the immune system, cardiovascular system, kidney, lung, liver, coagulation system, central nervous system, musculoskeletal system, eye, and gastrointestinal tract. Traits with which SLC39A8-deficiency variants are currently associated include Mn2+-deficient hypoglycosylation; numerous birth defects; Leigh syndrome-like mitochondrial redox deficiency; decreased serum high-density lipoprotein-cholesterol levels; increased body mass index; greater risk of coronary artery disease, hypotension, cardiovascular death, allergy, ischemic stroke, schizophrenia, Parkinson disease, inflammatory bowel disease, Crohn disease, myopia, and adolescent idiopathic scoliosis; systemic lupus erythematosus with primary Sjögren syndrome; decreased height; and inadvertent participation in the inflammatory progression of osteoarthritis.

中文翻译：

---

SLC39A8编码金属离子转运蛋白的基因：发现并在床旁工作。

SLC39A8是进化上高度保守的基因，在所有脊椎动物中均编码ZIP8金属阳离子转运蛋白。SLC39A8无处不在，包括多能胚胎干细胞。SLC39A8表达出现在每种检查的细胞类型中。ZIP8介导的Mn2 +，Zn2 +，Fe2 +，Se4 +和Co2 +的吸收代表了内源性功能-将这些阳离子移动到细胞中。通过小鼠遗传差异，在1970年代将“皮下镉诱导的睾丸坏死”的表型分配给Cdm基因座。这导致鉴定了小鼠Slc39a8基因，其最密切相关的Slc39a14基因，并创建了Slc39a8过表达，Slc39a8（neo / neo）敲除和细胞类型特异性条件敲除小鼠品系。Slc39a8（-/-）整体敲除小鼠是早期胚胎致死的。Slc39a8（neo / neo）亚型在妊娠第16.5天和出生后第1天之间死亡，表现为严重贫血，造血功能失调，脾发育不良，器官发育不良，发育不良，四肢发育不良。毫不奇怪，全基因组关联研究随后发现，人类SLC39A8缺陷型变异体表现出惊人的多效性缺陷，与几乎所有器官，组织和细胞类型的临床疾病相关：众多发育和先天性疾病，免疫系统，心血管系统，肾脏，肺，肝，凝血系统，中枢神经系统，肌肉骨骼系统，眼睛和胃肠道。目前与SLC39A8缺陷型相关的特征包括Mn2 +缺陷型低糖基化; 大量的先天缺陷；Leigh综合征样线粒体氧化还原缺乏；降低血清高密度脂蛋白胆固醇水平；体重指数增加；患冠状动脉疾病，低血压，心血管死亡，过敏，缺血性中风，精神分裂症，帕金森病，炎性肠病，克罗恩病，近视和青少年特发性脊柱侧弯的风险更大；系统性红斑狼疮伴原发性干燥综合征；高度降低；以及无意中参与了骨关节炎的炎症过程。