PRPF31

PRPF31 stands for pre-mRNA processing factor 31. PRPF31 makes a protein that helps assemble and activate the spliceosome, which trims and joins the pieces of genetic messages so that cells can read them correctly. Although this protein is used throughout the body, disease-causing changes mainly affect the retina. In most families, the problem is haploinsufficiency, which means that one working copy of the gene alone does not make enough protein for the retina to stay healthy. Laboratory studies of patient-derived cells suggest that reduced splicing function disturbs the tiny structures called cilia that photoreceptors depend on, which may help explain why the retina is especially vulnerable.

People described with PRPF31-associated retinitis pigmentosa most often notice night blindness first, followed by a gradual narrowing of the peripheral field of vision. The condition typically follows a rod-then-cone pattern, meaning the cells responsible for dim-light and peripheral vision decline before those used for central and detailed vision. In a large cohort study of 86 people from 61 families, nearly all had a typical retinitis pigmentosa pattern, while a single person showed a cone-rod pattern and one gene carrier had no signs of retinal disease. A separate natural history study (definition: A study that follows people with a condition over time without giving a new treatment, to understand how the condition normally progresses.) of 31 adults confirmed wide variability, and reported one person with an unusual pericentral form of the dystrophy. Swelling in the central retina, called cystoid macular edema, is common and can further reduce central vision. Cataract and a thin scar-like layer on the retina known as an epiretinal membrane were also frequently reported. The age of onset and the age at which vision becomes severely limited vary considerably from person to person, even within the same family. In two reported cases, PRPF31-related retinitis pigmentosa was accompanied by signs of eye inflammation that overlapped with a condition called uveitis, which shows how the diagnosis can occasionally be confused with other eye diseases.

The link between PRPF31 and retinitis pigmentosa is well established and appears in expert-reviewed genetic references. In a Portuguese registry, PRPF31 changes almost always followed an autosomal dominant (definition: An inheritance pattern where a single altered copy of a gene, from just one parent, is enough to cause the condition.) pattern and were associated exclusively with retinitis pigmentosa rather than other retinal diagnoses. PRPF31 is one of the more frequently identified causes of retinitis pigmentosa across many populations, including large East Asian cohorts, although exactly how often it appears varies from place to place. The underlying mechanism in most families is loss of a working gene copy, confirmed in one study by reduced gene activity and absent protein in affected individuals. Researchers have observed that women appear more likely than men to be affected, suggesting that sex acts as a modifier of whether and how strongly the gene change shows up. Importantly, some disease-causing changes lie in regions of the gene that standard genetic panels can miss, including deep intronic variants and larger deletions.

The reason for incomplete penetrance is not fully understood. Several factors thought to influence whether carriers develop disease, such as the activity of a neighboring gene, did not explain the pattern seen in at least one studied family, suggesting other unknown modifiers exist. One cohort noted that truly symptom-free carriers may be rare when family members are examined carefully over a lifetime. Therefore, the number of sympton-free carriers remains an open question. It is also not possible to predict from a genetic result alone how quickly one person's vision will change, because onset and progression vary widely. Some newly found gene changes are first reported as variants of uncertain significance, and additional family and clinical data are sometimes needed before their meaning becomes clear.

As of this review, no approved therapy directly targets PRPF31-related RP. Much of the current research is at an early, laboratory stage. Scientists have created stem-cell and retinal organoid (definition: A small, lab-grown model of retinal tissue, made from stem cells, used to study a disease or test treatments without involving a person.) models from patients to study how the disease begins and to test ideas for treatment. In cell studies, researchers have explored non-viral delivery methods, such as chitosan nanoparticles carrying a healthy copy of PRPF31, but these findings are preliminary and require animal testing before any human use. Other laboratory work points to disturbances in cell cilia and shared cellular stress pathways as possible future treatment targets, but these remain research findings, not available therapies. A long-term study of vitamin A and E supplementation in retinitis pigmentosa found that vitamin E should be avoided and did not confirm a general benefit of vitamin A across all genetic subtypes. Therefore, supplement decisions should be individualized with a clinician. Managing cystoid macular edema is also being studied as a way to protect central vision and potentially prepare the retina for future gene-based therapies.

• A hidden deletion causes disease through loss of protein

  Human case series with laboratory confirmation.

  What was found:

  A new deletion spanning two exons of PRPF31 caused dominant disease, with reduced gene activity and complete absence of the protein confirming haploinsufficiency.

  Why it matters:

  It shows why some patients need broader testing beyond standard panels and supports haploinsufficiency as the disease mechanism.

  Limitation: Only a small number of families were studied.

• How splicing defects may harm photoreceptor cilia

  Laboratory and cellular research.

  What was found:

  The changes disrupted microtubules and cilia, and restoring a specific enzyme rescued cilia in the lab, pointing to a possible mechanism and future target.

  Why it matters:

  Understanding why the retina is uniquely vulnerable could guide new treatment approaches.

  Limitation: These are cell-based findings only and have not been tested as a treatment in people.

• A large cohort maps the range of PRPF31-associated retinal disease

  Observational human cohort study (retrospective chart review).

  What was found:

  Almost all patients had typical retinitis pigmentosa, one had a cone-rod pattern, and one gene carrier had no retinal disease; onset and time to legal blindness varied widely, and macular swelling was common.

  Why it matters:

  It confirms that PRPF31 disease is highly variable and that visual outcomes cannot be predicted from the gene result alone.

  Limitation: Being retrospective and single-center, it may underrepresent symptom-free carriers and may not reflect all populations.

• Baseline data from a prospective natural history study

  Prospective observational natural history study (baseline data).

  What was found:

  Thirty of 31 had a classic retinitis pigmentosa pattern and one had a pericentral form; cystoid macular edema, epiretinal membrane, and cataract were frequent, and certain imaging measures tracked with vision.

  Why it matters:

  Careful baseline measurements are needed to judge whether future treatments slow the disease.

  Limitation: Only baseline results are reported, and some tests could not be completed in more advanced disease.

• Sex appears to influence who develops PRPF31 disease

  Observational human study across multiple registries.

  What was found:

  Women were significantly overrepresented among people affected by PRPF31-associated retinitis pigmentosa.

  Why it matters:

  It suggests sex is a modifier of penetrance, which may help explain why some carriers are affected and others are not.

  Limitation: It shows an association, not a cause, and does not explain the biological reason.

A distinctive feature of PRPF31 is that not everyone who inherits a disease-causing change develops symptoms, so a parent or sibling could carry the same variant yet have little or no vision loss. Because inheritance is usually autosomal dominant (definition: An inheritance pattern where a single altered copy of a gene, from just one parent, is enough to cause the condition.), each child of an affected or carrier parent has about a one-in-two chance of inheriting the change, though whether it causes vision loss cannot be predicted with certainty. For these reasons, relatives considering testing may benefit from genetic counseling that specifically addresses this uncertainty. Beyond these points, the general guidance shown on every gene page applies.

• Was my specific PRPF31 change classified as pathogenic, likely pathogenic, or of uncertain significance, and what does that mean for me?
• Given the incomplete penetrance of this gene, what does my result suggest for relatives who may carry the same change?
• Do I have any cystoid macular edema, and if so, should it be monitored or treated?
• Would additional testing, such as whole genome sequencing, add anything in my case?
• How often should my vision and retina be monitored to track any changes over time?
• Are there natural history studies or PRPF31-specific trials that might be appropriate to discuss?

A confirmed genetic diagnosis can be discussed with a retinal specialist and a genetic counselor to understand what it means for you and your family. Because some PRPF31 changes hide in noncoding DNA or involve deletions, broader testing such as whole genome sequencing may find a cause when a standard panel comes back negative. If you experience blurred central vision, it is worth asking whether cystoid macular edema is present, since it is common in this condition and may be monitored or managed. You can explore current studies, including those specific to PRPF31, using RP Hope's Clinical Trials Finder. RP Hope's guided pathway can help you find resources that fit your stage of the journey.