THRB基因编码甲状腺激素受体β（Thyroid Hormone Receptor Beta），属于核受体超家族中的甲状腺激素受体家族（THR家族）。该家族成员（包括THRA和THRB）通过与甲状腺激素（T3/T4）结合，调控靶基因的转录，影响生长发育、代谢、心血管功能等生理过程。THRB主要在肝脏、心脏、大脑和骨骼肌中表达，其蛋白产物作为配体依赖的转录因子，当与甲状腺激素结合后，会改变构象并与DNA上的甲状腺激素反应元件（TREs）结合，激活或抑制下游基因（如参与脂代谢的CPT1A或线粒体功能的基因）的表达。THRB的突变可导致甲状腺激素抵抗综合征（RTHβ），表现为组织对甲状腺激素敏感性降低，临床特征包括甲状腺肿大、心动过速、发育迟缓等，但血清甲状腺激素水平升高。某些突变（如错义突变p.Arg316His）会破坏激素结合域，使受体无法正常响应激素信号。THRB过表达可能增强甲状腺激素的代谢调控作用，例如促进脂肪酸氧化，但过度激活可能导致心律失常；而表达降低则可能引发类似甲减的症状（如体重增加、血脂异常）。此外，THRB与癌症（如肝细胞癌）相关，其表达下调可能促进肿瘤进展。THR家族的共性包括：均含有DNA结合域（DBD）和配体结合域（LBD），形成二聚体（常与视黄醇X受体RXR结合）后调控转录。专业术语解释：核受体（Nuclear Receptor）——细胞内可结合激素并直接调控基因表达的蛋白质；甲状腺激素反应元件（TREs）——DNA上被甲状腺激素受体识特定序列。

由该基因编码的蛋白质是用于甲状腺素核激素受体。它是几个受体甲状腺激素之一，并且已经显示出介导甲状腺激素的生物活性。在小鼠中敲除的研究表明，在不同的受体，而具有冗余的一定程度时，可以介导的甲状腺激素不同的功能。在这个基因的突变是已知的广义甲状腺激素抵抗的原因（GTHR），其特征在于甲状腺肿和高水平的循环甲状腺激素（T3-T4）的综合症，与正常或略微升高的促甲状腺激素（TSH）。编码相同蛋白质的几个可变剪接转录物变体已经观察到这种基因。 [由RefSeq的，2008年7月提供]

The THRB gene encodes the thyroid hormone receptor beta, a ligand-dependent transcription factor belonging to the thyroid hormone receptor (THR) subfamily within the nuclear receptor superfamily. As a key regulator of physiological processes including growth, development, metabolism, and cardiovascular function, THRB is predominantly expressed in the liver, heart, brain, and skeletal muscle. Mechanistically, the receptor protein contains conserved DNA-binding and ligand-binding domains; upon binding thyroid hormones such as triiodothyronine (T3) and thyroxine (T4), it undergoes a conformational change that enables it to dimerize, typically with the retinoid X receptor (RXR), and bind to specific thyroid hormone response elements (TREs) in the promoter regions of target genes. This interaction modulates the transcription of downstream effectors involved in lipid metabolism, such as CPT1A, and mitochondrial function, thereby fine-tuning cellular energy homeostasis. Disruption of THRB function, often through missense mutations like p.Arg316His that compromise the hormone-binding domain, results in beta-thyroid hormone resistance syndrome (RTHβ), a condition characterized by tissue insensitivity to thyroid hormones, leading to clinical manifestations such as goiter, tachycardia, and developmental delays despite elevated serum thyroid hormone levels. Conversely, altered expression levels of THRB have significant pathological implications: overexpression may enhance metabolic regulation and promote fatty acid oxidation but risks inducing arrhythmias, whereas reduced expression can mimic hypothyroidism with symptoms including weight gain and dyslipidemia. Furthermore, THRB plays a critical role in oncology, particularly in hepatocellular carcinoma, where its downregulation is associated with tumor progression and poor prognosis, highlighting its dual role in maintaining metabolic stability and suppressing malignant transformation.

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