RHO rs28936678: Understanding the Pro23His Variant
The rs28936678 variant, commonly known as the Pro23His (p.P23H) mutation, is a specific change in the RHO gene. It is primarily associated with autosomal dominant retinitis pigmentosa (adRP), a condition characterized by progressive vision loss.
What each genotype means
Typical rhodopsin profile
This genotype represents the common, non-variant form of the RHO gene at this position. It is not associated with the specific Pro23His (p.P23H) mutation linked to autosomal dominant retinitis pigmentosa.
This is the most common genotype found in the general population.
Increased risk of retinitis pigmentosa
This genotype corresponds to the Pro23His (p.P23H) mutation, which is a well-documented cause of autosomal dominant retinitis pigmentosa. Individuals with this variant may experience progressive vision loss, often beginning with night blindness, due to the impact of this mutation on rhodopsin protein function.
This genotype is very rare in the general population but is notably enriched in North American cohorts diagnosed with autosomal dominant retinitis pigmentosa.
High risk of retinitis pigmentosa
This genotype indicates the presence of the Pro23His (p.P23H) mutation on both copies of the RHO gene. Given the autosomal dominant nature of this condition, this genotype is associated with a high likelihood of developing retinitis pigmentosa, characterized by progressive photoreceptor degeneration and vision loss.
This genotype is extremely rare and is not typically observed in the general population.
What is the rs28936678 Variant?
The rs28936678 variant is a single nucleotide polymorphism (SNP) located within the RHO gene. In scientific literature, this specific change is frequently referred to as the Pro23His or p.P23H mutation, indicating that the amino acid proline at position 23 of the rhodopsin protein has been replaced by histidine. This change occurs due to a specific nucleotide substitution, often documented as c.68C>A. Because this variant is located in a gene critical for the function of light-sensitive cells in the eye, it has been the subject of extensive study in the field of ophthalmic genetics. It is classified as a pathogenic variant in the context of inherited retinal diseases, specifically those following an autosomal dominant inheritance pattern, meaning that inheriting a single copy of the variant from one parent is typically sufficient to manifest the associated clinical features.
The Role of the RHO Gene
The RHO gene provides instructions for making a protein called rhodopsin. Rhodopsin is a light-sensitive pigment found in rod cells, which are specialized photoreceptor cells located in the retina at the back of the eye. These cells are essential for vision in low-light conditions, often referred to as night vision. When light enters the eye and strikes the retina, it interacts with the rhodopsin protein, triggering a chemical cascade that sends electrical signals to the brain, which are then interpreted as visual images. Because rhodopsin is fundamental to the visual transduction process, any structural alteration to the protein—such as the one caused by the Pro23His mutation—can disrupt the stability or function of rod cells. Over time, this dysfunction leads to the progressive degeneration of these cells, which is the hallmark of retinitis pigmentosa.
Research and Clinical Associations
Research has consistently associated the rs28936678 variant with autosomal dominant retinitis pigmentosa (adRP). It is considered one of the most well-studied mutations in the RHO gene, serving as a foundational example for understanding the molecular mechanisms of inherited retinal dystrophies. Studies have utilized various models, including animal models and functional assays, to demonstrate how this mutation affects protein folding and cellular health. While the association with adRP is strong, the clinical presentation can vary between individuals, even within the same family. It is important to note that while this variant is a known cause of retinal degeneration, the field of ophthalmic genetics is complex, and researchers continue to investigate how other genetic and environmental factors might influence the severity and progression of vision loss in individuals carrying this specific mutation.
Population Frequency and Distribution
The rs28936678 variant is considered very rare in the general population. However, it is notably enriched in certain cohorts, particularly among North American cases of autosomal dominant retinitis pigmentosa. Because it is so rare, it is not typically found in large-scale, general population genetic databases at high frequencies. Recent studies have attempted to estimate the genetic prevalence of this variant in the United States, suggesting that while the number of affected individuals is relatively small, the variant represents a significant portion of RHO-associated adRP cases. The distribution of this variant is not uniform across all ancestries, and researchers emphasize that clinical prevalence estimates can differ based on the methodology used, such as literature-based meta-analyses versus population genetics modeling.
Navigating Genetic Information
Understanding your genetic status regarding the rs28936678 variant requires careful interpretation. If you or a family member have been identified as a carrier of this variant, it is essential to consult with a medical geneticist or an ophthalmologist specializing in inherited retinal diseases. This information is not a diagnosis in itself, but rather a piece of data that should be discussed within the context of a comprehensive clinical eye examination and family history. There is currently significant research into gene-based therapies and clinical trials for RHO-associated conditions, making it a rapidly evolving field. You should never make medical decisions based solely on genetic test results without professional guidance. A healthcare provider can help you understand the implications of this finding, discuss potential management strategies, and provide information on the latest developments in clinical research.
How common is this variant?
The rs28936678 variant is very rare in the general population but is notably enriched in North American cohorts diagnosed with autosomal dominant retinitis pigmentosa.
Frequently asked questions
What is the link between RHO and retinitis pigmentosa?
The RHO gene produces rhodopsin, a protein essential for rod cell function in the eye. Mutations in this gene, such as rs28936678, can cause the protein to function incorrectly, leading to the progressive death of rod cells and the vision loss characteristic of retinitis pigmentosa.
Is the Pro23His mutation common?
No, the Pro23His mutation is considered very rare in the general population. It is, however, a well-documented cause of autosomal dominant retinitis pigmentosa, particularly in North American patient populations.
Can I be tested for the rs28936678 variant?
Genetic testing for specific variants is available through clinical laboratories, usually ordered by a physician or genetic counselor. If you are concerned about inherited eye conditions, you should speak with an ophthalmologist or a genetic specialist.
What should I do if I have this variant?
If you have been identified as a carrier of this variant, you should schedule an appointment with an ophthalmologist who specializes in retinal diseases. They can perform a clinical evaluation to assess your eye health and discuss appropriate monitoring or potential participation in clinical research.
Sources & further reading
Educational information only, last refreshed 9/18/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Pathogenic missense variant causing rhodopsin Pro23His substitution that leads to autosomal dominant retinitis pigmentosa and progressive night blindness.
Constitutively active rhodopsin variant (Gly90Asp) causing autosomal dominant congenital stationary night blindness (CSNB).
Encodes the Pro23His (P23H) substitution in rhodopsin, the most common autosomal dominant retinitis pigmentosa allele in North America.
A non-synonymous variant altering rhodopsin protein structure that causes autosomal dominant retinitis pigmentosa with progressive rod photoreceptor loss.
Rhodopsin missense variant (p.Pro23His) responsible for classical autosomal dominant retinitis pigmentosa with rod photoreceptor degeneration.
A missense substitution (p.Arg135Trp) within rhodopsin's cytoplasmic loop that causes severe autosomal dominant retinitis pigmentosa through defective phototransduction signaling.