NR1H4 (nuclear receptor subfamily 1 group H member 4)
- symbol:
- NR1H4
- locus group:
- protein-coding gene
- location:
- 12q23.1
- gene_family:
- Nuclear hormone receptors
- alias symbol:
- FXR|RIP14|HRR1|HRR-1
- alias name:
- farnesoid X receptor|bile acid rec…
- entrez id:
- 9971
- ensembl gene id:
- ENSG00000012504
- ucsc gene id:
- uc001thp.3
- refseq accession:
- NM_005123
- hgnc_id:
- HGNC:7967
- approved reserved:
- 1999-09-17
NR1H4基因编码法尼醇X受体（FXR），属于核受体超家族中的NR1亚家族。FXR主要在肝脏、肠道和肾脏中表达，作为胆汁酸的内源性受体，在胆汁酸代谢、脂质代谢和葡萄糖稳态中发挥核心调控作用。FXR通过与靶基因启动子区的FXRE反应元件结合，调控多种代谢相关基因的表达，包括胆汁酸合成限速酶CYP7A1、胆汁酸转运蛋白BSEP和脂蛋白代谢相关基因。当胆汁酸水平升高时，FXR被激活并抑制CYP7A1表达，形成负反馈调节环路。NR1H4基因突变可导致胆汁淤积性疾病如进行性家族性肝内胆汁淤积症5型（PFIC5），表现为严重胆汁淤积和肝衰竭。FXR功能异常还与非酒精性脂肪性肝病、胆结石、炎症性肠病和糖尿病等代谢性疾病密切相关。FXR过表达可增强胆汁酸排泄、改善胰岛素抵抗并具有抗炎作用，而敲除FXR的小鼠会出现胆汁酸代谢紊乱、高甘油三酯血症和自发肝肿瘤。FXR与同家族的LXR、PPAR等核受体存在交叉调控，共同构成复杂的代谢调控网络。该基因家族成员均具有典型的核受体结构域，通过配体激活后调控下游靶基因表达，在代谢平衡维持中起关键作用。目前FXR激动剂如奥贝胆酸已被批准用于原发性胆汁性胆管炎的治疗，并正在其他代谢性疾病中进行临床试验。
This gene encodes a ligand-activated transcription factor, which shares structural features in common with nuclear hormone receptor family, such as a DNA-binding domain that targets the receptor to specific DNA sequences, and a ligand-binding domain, which interacts directly with the ligand and contains a ligand-dependent transcriptional activation domain. This protein functions as a receptor for bile acids, and when bound to bile acids, regulates the expression of genes involved in bile acid synthesis and transport. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]
这个基因编码的配体激活的转录因子，这股在共同的结构特征与核激素受体家族，如靶向该受体对特定的DNA序列的DNA结合结构域和配体结合结构域，其直接与配体相互作用，并包含一个配体依赖性转录激活结构域。这种蛋白作为结合到胆汁酸为胆汁酸的受体，而当，调节参与胆汁酸合成和转运的基因的表达。编码不同同种型的可变剪接转录物变体已被用于这个基因说明。 [由RefSeq的，2011年8月提供]
基因本体信息
NR1H4基因（以及对应的蛋白质）的细胞分布位置：
- 质膜
- 细胞质
- 细胞外
- 高尔基体
- 囊泡
- 细胞骨架
- 内质网
- 细胞核
- 内体
- 溶酶体
- 线粒体
NR1H4基因的本体（GO）信息：
| 名称 |
|---|
| 4976 Bile secretion [PATH:hsa04976] |
| 名称 |
|---|
| Bile acid and bile salt metabolism |
| Biological oxidations |
| Cytochrome P450 - arranged by substrate type |
| Endogenous sterols |
| Fatty acid, triacylglycerol, and ketone body metabolism |
| Gene Expression |
| Generic Transcription Pathway |
| Metabolism |
| Metabolism of lipids and lipoproteins |
| Nuclear Receptor transcription pathway |
| Phase 1 - Functionalization of compounds |
| PPARA activates gene expression |
| Recycling of bile acids and salts |
| Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha) |
| Synthesis of bile acids and bile salts |
| Synthesis of bile acids and bile salts via 27-hydroxycholesterol |
| Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol |
| 疾病名称 | 关系值 | NofPmids | NofSnps | 来源 |
| Liver carcinoma | 0.201357209 | 6 | 0 | BeFree_CTD_human_MGD |
| Liver diseases | 0.125991584 | 5 | 0 | BeFree_CTD_human_LHGDN |
| Cholestasis | 0.124624443 | 10 | 0 | BeFree_CTD_human_LHGDN |
| Liver neoplasms | 0.120814326 | 6 | 0 | BeFree_CTD_human |
| Crohn Disease | 0.120542884 | 3 | 0 | BeFree_CTD_human |
| Cholestasis of pregnancy | 0.120542884 | 2 | 0 | BeFree_ORPHANET |
| Intestinal Neoplasms | 0.12 | 1 | 0 | CTD_human |
| Drug-Induced Liver Injury | 0.12 | 1 | 0 | CTD_human |
| Extravasation of Diagnostic and Therapeutic Materials | 0.12 | 1 | 0 | CTD_human |
| Intrahepatic Cholestasis | 0.087815732 | 3 | 0 | GAD_LHGDN_RGD |
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