RHO基因编码视紫红质（rhodopsin），是一种在视网膜视杆细胞中高度表达的G蛋白偶联受体（GPCR），属于视蛋白（opsin）基因家族。视紫红质是视觉光转导的关键分子，负责在弱光条件下感知光线。当光线照射时，视紫红质的发色团11-顺式视黄醛（11-cis-retinal）异构化为全反式视黄醛，触发构象变化并激活转导蛋白（transducin），进而启动光信号传导级联反应。RHO基因突变是常染色体显性视网膜色素变性（adRP）最常见的原因，占病例的20-30%。突变可能导致视紫红质错误折叠、异常运输或功能丧失，引发视杆细胞凋亡和进行性视力丧失。常见的致病突变包括P23H（脯氨酸23替换为组氨酸）和R135W（精氨酸135替换为色氨酸）。RHO基因过表达可能导致蛋白质错误折叠堆积，激活未折叠蛋白反应（UPR），加剧细胞应激；而表达降低则直接损害光感受器功能，导致夜盲症。视蛋白家族成员（如视锥细胞的视蛋白）均具有七次跨膜结构，依赖视黄醛发色团，但光谱敏感性不同。研究显示某些RHO突变体可能具有毒性增益功能（toxic gain-of-function），异常激活信号通路，这为基因治疗策略（如CRISPR编辑或AAV载体递送）提供了靶点。值得注意的是，RHO突变表型存在差异，部分突变导致早发型严重视网膜变性，而另一些仅引起晚发型症状，这种异质性与突变具体影响的蛋白质结构域（如胞内环、跨膜区）密切相关。

视网膜色素变性是一种遗传性疾病是西方社会失明的主要原因。它可作为常染色体显性，常染色体隐性，或X连锁隐性疾病。在常染色体显性形式，其包括占全部病例的约25％，家庭的大约30％具有在编码棒状特定感光体蛋白的视紫红质的基因突变。这是跨膜蛋白，其，光激发时，启动视觉转导级联。在这个基因的缺陷也先天性静止性夜盲的原因之一。 [由RefSeq的，2008年7月提供]

The RHO gene encodes rhodopsin, the principal photopigment of rod photoreceptor cells in the retina and a canonical member of the opsin subfamily of class A G protein-coupled receptors. Like all members of this receptor superfamily, rhodopsin is composed of seven transmembrane α-helices linked by extracellular and cytoplasmic loops, with a covalently bound 11-cis-retinal chromophore anchored in the seventh transmembrane helix that confers its exquisite spectral sensitivity to dim light. In the dark-adapted state the receptor rests in an inactive conformation; upon absorption of even a single photon, the 11-cis-retinal undergoes rapid isomerization to all-trans-retinal, driving a cascade of conformational rearrangements that convert the receptor to its active Metarhodopsin II form. This activated state engages the Gα subunit of transducin (GNAT1), which in turn stimulates phosphodiesterase-6 to hydrolyze cyclic GMP, causing closure of cGMP-gated cation channels in the outer-segment membrane and hyperpolarization of the rod cell, thereby transducing a light signal into the electrical response that is relayed through the retinal circuitry to the visual cortex. RHO is expressed almost exclusively in rod photoreceptors, where it is present in extraordinary abundance—on the order of ten million to ten million molecules per outer-segment disc—making rods the most light-sensitive cells in the human eye. Mutations in RHO constitute the single most frequent genetic cause of autosomal dominant retinitis pigmentosa (adRP), accounting for roughly twenty to thirty percent of all adRP cases, and the pathogenic spectrum encompasses missense substitutions, nonsense mutations, and small in-frame deletions. The two most prevalent missense alleles, P23H (a proline-to-histidine substitution in the first extracellular loop) and R135W (an arginine-to-tryptophan substitution in the sixth transmembrane helix), disrupt proper rhodopsin folding and trafficking, causing the misfolded protein to accumulate in the endoplasmic reticulum and chronically activate the unfolded protein response. Persistent ER stress, compounded by the toxic gain-of-function effects of certain mutants that aberrantly couple to transducin in the absence of light, ultimately engages apoptotic pathways and drives progressive rod cell death, which is followed secondarily by cone degeneration and the characteristic concentric constriction of the visual field. Conversely, hypomorphic or null mutations that reduce rhodopsin expression below a critical threshold impair the rod's capacity to generate a light response, manifesting clinically as nyctalopia and, in severe cases, congenital stationary night blindness. Phenotypic severity and age of onset vary considerably among RHO mutation carriers: mutations that perturb the cytoplasmic loops or the transducin-coupling interface tend to produce an aggressive, early-onset course with rapid photoreceptor loss, whereas those affecting the extracellular loops or the retinal-binding pocket often yield a milder, later-onset phenotype, underscoring the structure–function relationship that governs disease expression. This heterogeneity, together with the well-characterized molecular mechanisms underlying mutant rhodopsin toxicity, has made RHO one of the most intensively studied targets in retinal gene therapy, with strategies spanning antisense oligonucleotides, small-molecule chaperones, CRISPR/Cas9-mediated allele correction, and adeno-associated virus–mediated delivery of a corrected RHO transcript, all of which aim to restore proper rhodopsin homeostasis and halt the progressive photoreceptor degeneration that defines the disease.

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