The human ATP-binding cassette (ABC) transporter superfamily.
The human ATP-binding cassette (ABC) transporter superfamily.
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DOI：
10.1002/humu.24418
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发表时间：
2022-09
期刊：
影响因子：
3.9
通讯作者：
Allikmets, Rando
中科院分区：
文献类型：
--
作者：
Dean, Michael;Moitra, Karobi;Allikmets, Rando
ATP结合盒（ABC）转运蛋白超家族包括跨细胞外和细胞内膜流出各种底物的膜蛋白。ABC基因突变导致21种孟德尔遗传的人类疾病或表型，包括囊性纤维化、肾上腺脑白质营养不良、视网膜变性、胆固醇和胆汁转运缺陷。为了提供研究人类ABC转运蛋白功能的工具，我们从多个基因组学数据库中编译了数据。我们分析了人类群体中ABC基因的保守性，并在脊椎动物中调查了小鼠ABC基因突变的表型。大多数小鼠ABC基因破坏突变具有模拟人类疾病的表型，表明它们是适用的模型。有趣的是，几个ABCA家族基因，其人类功能未知，在小鼠中具有胆固醇水平表型。全基因组关联研究证实并扩展了ABC性状，并提出了几个新的功能进行调查。来自不同癌症类型的肿瘤的全外显子组测序表明，ABC基因的突变在癌症中并不常见，但特定基因在选定的肿瘤类型中过表达。最后，对功能丧失突变频率的分析表明，许多人类ABC基因是必需的，变异水平较低，而其他基因则具有较高的遗传多样性。
The ATP-binding cassette (ABC) transporter superfamily comprises membrane proteins that efflux various substrates across extra- and intra-cellular membranes. Mutations in ABC genes cause 21 human disorders or phenotypes with Mendelian inheritance, including cystic fibrosis, adrenoleukodystrophy, retinal degeneration, cholesterol, and bile transport defects. To provide tools to study the function of human ABC transporters we compiled data from multiple genomics databases. We analyzed ABC gene conservation within human populations and across vertebrates surveyed phenotypes of ABC gene mutations in mice. Most mouse ABC gene disruption mutations have a phenotype that mimics human disease, indicating they are applicable models. Interestingly several ABCA family genes, whose human function is unknown, have cholesterol level phenotypes in the mouse. Genome-wide association studies confirm and extend ABC traits and suggest several new functions to investigate. Whole exome sequencing of tumors from diverse cancer types demonstrates that mutations in ABC genes are not common in cancer, but specific genes are overexpressed in select tumor types. Finally, an analysis of the frequency of loss-of-function mutations demonstrates that many human ABC genes are essential with a low level of variants, while others have a higher level of genetic diversity.
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影响因子：
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作者：
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