On this page
RP2
RP2 activator of ARL3 GTPase
RP2 is located on the short (p) arm of chromosome X, at band Xp11.3. Arm ratio per GRCh38 - banding schematic.
Explore chromosome X in the library →Available at Jeen Health
Clinical tests that include this
Overview
The RP2 gene is located on the X chromosome and encodes a protein that plays an essential role in maintaining normal vision. Although the RP2 protein is active in cells throughout the body, its function is particularly important in the retina, the light-sensitive tissue at the back of the eye. Pathogenic variants in RP2 account for approximately 10 to 15 percent of X-linked retinitis pigmentosa cases, a hereditary condition characterised by progressive vision loss. Because RP2 is located on the X chromosome, males who inherit a pathogenic variant typically develop the condition, whilst females who carry one altered copy are usually unaffected or experience milder symptoms. Understanding RP2 function and variant effects helps inform genetic screening for X-linked retinal disorders.
What the gene does
The RP2 protein is expressed in cells throughout the body, but its role is best understood in the context of retinal health. The full name of the gene, RP2 activator of ARL3 GTPase, indicates that the protein functions by activating ARL3, a small GTPase involved in regulating cellular transport processes. Within the retina's photoreceptor cells, which detect light and enable vision, research suggests the RP2 protein helps coordinate the movement of other proteins to their proper locations. This trafficking role appears critical for maintaining the structure and viability of photoreceptors over time. Whilst the precise molecular mechanisms remain under investigation, evidence indicates that RP2 supports the delivery of proteins within these specialised cells. Outside the retina, the function of RP2 in other cell types has not been fully characterised, although its widespread expression suggests it may support fundamental cellular processes beyond vision.
Video: Genetics 101
Chromosome location
RP2 is located on the short arm of the X chromosome at position Xp11.3. This chromosomal location places RP2 among other genes subject to X-linked inheritance patterns. Because males possess only one X chromosome, a single pathogenic variant in RP2 is sufficient to cause disease, whereas females, who have two X chromosomes, typically require variants in both copies to be affected.
Protein structure
The RP2 protein comprises 350 amino acids and includes two notable regions. The N-terminal portion contains a disordered region spanning amino acids 1 to 31, which may contribute to protein flexibility and regulatory interactions. This is followed by a C-CAP/cofactor C-like domain extending from amino acids 24 to 179, which is thought to mediate interactions with other cellular proteins and participate in the protein's regulatory functions.
Key variants
More than 70 mutations in the RP2 gene have been identified in individuals with X-linked retinitis pigmentosa. Variants in RP2 account for approximately 10 to 15 percent of all X-linked retinitis pigmentosa cases. Most pathogenic changes result in the production of an abnormally short or nonfunctional protein, disrupting normal retinal cell processes. The specific nature and location of variants within the gene can influence the severity and progression of vision loss, although genotype-phenotype correlations continue to be refined through ongoing research.
No pathogenic or likely-pathogenic ClinVar variants recorded yet for this gene.
Associated conditions
Pathogenic variants in RP2 cause X-linked retinitis pigmentosa, a progressive inherited retinal disorder. Males with a pathogenic RP2 variant typically develop night blindness during early childhood, reflecting the initial loss of rod photoreceptor function. As the condition progresses, cone photoreceptors are also affected, leading to gradual loss of daytime vision and peripheral visual field constriction. Females who carry one pathogenic RP2 variant are usually unaffected or may experience mild visual symptoms later in life, due to random X-chromosome inactivation patterns.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic RP2 variants typically follow x-linked inheritance.
X-linked recessive: sons of a carrier mother have a 50% chance of being affected. Daughters have a 50% chance of being carriers.
UK clinical status
RP2 is included on the NHS Genomic Medicine Service national panel for Retinal Disorders, classified with a green rating, indicating strong evidence supporting its role in inherited retinal disease. This inclusion reflects the gene's established clinical relevance for diagnosing X-linked retinitis pigmentosa within the NHS framework.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
How is X-linked retinitis pigmentosa inherited?
X-linked retinitis pigmentosa follows an X-linked inheritance pattern, meaning the responsible gene is located on the X chromosome. Males, who have one X chromosome, develop the condition if they inherit a pathogenic variant, whilst females, with two X chromosomes, are typically unaffected carriers or experience milder symptoms.
Why does RP2-related retinitis pigmentosa primarily affect males?
Because RP2 is located on the X chromosome, males inherit only one copy of the gene. A single pathogenic variant is sufficient to cause disease in males, whereas females usually have a second, functional copy that compensates for the altered one.
What proportion of X-linked retinitis pigmentosa is caused by RP2 variants?
RP2 variants account for approximately 10 to 15 percent of X-linked retinitis pigmentosa cases, making it one of several genes responsible for this form of inherited retinal disease.