RHO rs28936681: Understanding the p.Pro23His Variant
The rs28936681 variant in the RHO gene, commonly known as p.Pro23His, is a rare genetic alteration associated with autosomal dominant retinitis pigmentosa. This condition involves the progressive degeneration of rod photoreceptors in the retina, which are essential for vision in low-light conditions.
What each genotype means
Typical rhodopsin function
This genotype represents the common, wild-type sequence for the RHO gene. Individuals with this profile do not carry the specific p.Pro23His mutation associated with autosomal dominant retinitis pigmentosa.
This is the most common genotype found in the general population worldwide.
Increased risk of retinitis pigmentosa
This genotype indicates the presence of the p.Pro23His missense mutation, which is a known cause of autosomal dominant retinitis pigmentosa. This variant is a common founder mutation in North American populations of European descent and is associated with progressive rod photoreceptor degeneration.
This genotype is very rare in the general global population, with a minor allele frequency typically reported below 0.00005 in gnomAD, though it is more frequently identified in specific clinical cohorts.
High risk of retinal degeneration
This genotype indicates that both copies of the RHO gene carry the p.Pro23His mutation. While this variant is typically associated with autosomal dominant inheritance, the presence of two copies may lead to more severe or early-onset clinical manifestations of retinal degeneration.
This genotype is extremely rare and is not typically observed in general population databases.
What is the rs28936681 Variant?
The rs28936681 variant is a specific single-nucleotide polymorphism (SNP) located within the RHO gene on chromosome 3. In clinical and research literature, this variant is frequently referred to as p.Pro23His or c.68C>A. This notation indicates that at position 23 of the rhodopsin protein, the amino acid proline is replaced by histidine. This change occurs because of a single nucleotide substitution in the DNA sequence. Because the RHO gene provides instructions for making the rhodopsin protein, which is critical for the phototransduction process in the eye, alterations at this specific site can disrupt the protein's normal structure and function. This variant is categorized as a missense mutation, meaning it results in the production of a protein with an incorrect amino acid, which may lead to cellular stress or dysfunction within the retina.
The Role of the RHO Gene
The RHO gene encodes the protein rhodopsin, which is found in rod photoreceptor cells located in the retina at the back of the eye. Rhodopsin is a G-protein-coupled receptor that acts as a light-sensitive pigment. When light enters the eye and strikes the retina, it interacts with the 11-cis retinal molecule bound to rhodopsin, triggering a chemical cascade known as phototransduction. This process converts light energy into electrical signals that are sent to the brain, allowing us to see, particularly in dim or low-light environments. Because rod cells are highly specialized for night vision, the integrity of the rhodopsin protein is vital for maintaining healthy visual function. When the RHO gene is mutated, the resulting rhodopsin protein may be unstable or misfolded, leading to the gradual death of rod cells, a hallmark of retinitis pigmentosa.
Research and Clinical Associations
Research has established a strong association between the p.Pro23His variant and autosomal dominant retinitis pigmentosa (adRP). In this inheritance pattern, a single copy of the altered gene is sufficient to cause the condition. Studies suggest that the misfolded rhodopsin protein can accumulate within the cell, causing toxic stress that eventually leads to the degeneration of rod photoreceptors. While this variant is a well-documented cause of adRP, the clinical presentation can vary between individuals. Current research is focused on understanding the mechanisms of this degeneration and developing potential gene-based therapies to restore or preserve visual function. It is important to note that while the association with adRP is recognized, the severity and rate of vision loss can differ, and clinical management is typically handled by ophthalmologists specializing in inherited retinal diseases.
Population Frequency and Distribution
The rs28936681 variant is considered very rare in the general global population, with a minor allele frequency (MAF) typically reported as less than 0.00005 in large-scale databases like gnomAD. Despite its rarity worldwide, the variant has been identified as being enriched in specific North American cohorts, particularly those studied in the context of retinitis pigmentosa. Population genetics modeling and literature-based meta-analyses have been used to estimate the prevalence of this variant in the United States. These studies suggest that while the number of clinically diagnosed patients is relatively small, the genetic prevalence may be higher than previously anticipated, with the variant appearing across diverse ancestral backgrounds. Because it is a rare variant, its distribution is not uniform, and it is often identified through targeted genetic testing in families with a history of inherited retinal degeneration.
Navigating Genetic Information
If you or a family member have been identified as carrying the rs28936681 variant, it is essential to consult with a medical geneticist or an ophthalmologist who specializes in inherited retinal diseases. This information is for educational purposes and should not be used to diagnose or treat any medical condition. Genetic testing results can be complex, and a professional can help interpret what this means for your specific health situation and family history. While research into treatments for retinitis pigmentosa is ongoing, including clinical trials for various therapeutic approaches, there is currently no universal cure. A healthcare provider can offer guidance on the latest clinical research, potential participation in trials, and strategies for managing vision health. Always discuss any concerns about your vision or genetic findings with a qualified clinician who can provide personalized medical advice.
How common is this variant?
The rs28936681 variant is very rare worldwide (gnomAD MAF < 0.00005), though it is notably enriched in specific North American retinitis pigmentosa cohorts.
Frequently asked questions
What is the link between RHO and retinitis pigmentosa?
The RHO gene provides instructions for making rhodopsin, a protein essential for vision in low light. Mutations in this gene can cause the protein to misfold, leading to the death of rod photoreceptor cells, which results in the vision loss characteristic of retinitis pigmentosa.
Is the p.Pro23His variant inherited?
Yes, this variant is typically inherited in an autosomal dominant pattern. This means that an individual only needs to inherit one copy of the altered gene from one parent to be at risk for developing the associated condition.
Can I be tested for the rs28936681 variant?
Genetic testing for specific variants is available through clinical laboratories, often ordered by a medical geneticist or ophthalmologist. If you have a family history of retinal disease, a doctor can determine if testing is appropriate for you.
Are there treatments for RHO-associated retinitis pigmentosa?
Currently, there is no cure for RHO-associated retinitis pigmentosa, but research into gene-based therapies and other treatments is ongoing. Patients should consult with a retinal specialist to discuss the latest clinical trials and management options.
Sources & further reading
Educational information only, last refreshed 9/22/2026. 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.
Classic Pro23His (p.P23H) mutation in rhodopsin causing autosomal dominant retinitis pigmentosa.
A missense substitution (p.Arg135Trp) within rhodopsin's cytoplasmic loop that causes severe autosomal dominant retinitis pigmentosa through defective phototransduction signaling.