Recent advances in whole genome sequencing and exome capture techniques have exploded the field of identification of new disease in patients with genetic diseases 
. However, even patients with mutations in the same gene frequently exhibit immense clinical heterogeneity, ranging from early-onset disorders to relative less severe late onset disease. Such phenomena pose a challenge to computationally predict and interpret the effect of the mutation on the penetrance and severity of disease phenotypes.
Degeneration or dysfunction of photoreceptors is frequently associated with variable clinical presentation, likely due to their unique structure and metabolic demands 
. Photoreceptors are polarized neurons with a distinct inner segment (IS) and photoreceptive outer segment (OS), linked by a narrow bridge-like microtubule-rich structure, called connecting cilium 
. Proteins, such as rhodopsin, destined for outer segments are synthesized in the IS and are transported via trans-Golgi network to the base of cilium from where they are transported apically by microtubule-based motor assemblies 
. Additionally, there is passive motor-independent bidirectional transport of some phototransduction proteins 
. Owing to high degree of protein trafficking demands, dysfunction in protein synthesis, sorting or trafficking results in photoreceptor dysfunction and degenerative disorders 
Retinitis Pigmentosa (RP) represents one such disorder that exhibits both clinical and genetic heterogeneity in patients 
. RP is characterized by progressive loss of rod and cone photoreceptors of the retina, resulting in night blindness followed by complete blindness 
. To date, more than 200 RP-associated genes have been identified. RP is inherited in autosomal dominant, recessive as well as X-lined manner 
. X-linked RP is one of the severe forms of RP, phenotypically characterized by onset of night blindness in the second decade of life that progresses into legal blindness by the age of 40 
. There are six genetic loci and only two cloned genes for XLRP: retinitis Pigmentosa GTPase regulator and retinitis Pigmentosa 2 (RP2). While mutations in RPGR account for 70–80% of XLRP, RP2 mutations are known to occur in approximately 20% of XLRP patients 
gene (NM_006915.2)encodes a polypeptide of 350 amino acids 
. Previous biochemical and cell biological studies have revealed a potential role for RP2 in maintaining Golgi cohesion and targeting of proteins to plasma membrane 
. Some disease-associated mutations in RP2 abolish plasma membrane targeting of RP2 in cultured cells. The amino-terminal region (151 amino acids) of RP2 shares homology with tubulin-specific chaperone protein (TBCC) and also acts as a potential GTPase activating protein (GAP) for small GTPase ADP-ribosylation factor like-3 (ARL3) 
. The carboxyl-terminus of RP2 is homologous of nucleoside diphosphate kinase (NDK); however, the physiological function of this domain remains to be determined. We have recently shown that RP2 localizes to sensory cilia and interacts with polycystin-2, a protein involved in renal ciliary diseases 
We and others have reported the association of wide-spectrum of clinical phenotype in patients with RP2 mutations. These clinical features include severe to late-onset disease, typical RP, as well as macular dystrophy 
. Disease causing mutations in RP2 are presented in the form of splice site, missense, nonsense and/or frameshift variations in the coding region. These mutations seem to affect distinct protein interactions, likely due to their effect on RP2 localization or interaction with other proteins. Hence, detailed analysis of effect of RP2 mutations on its function should provide insights into associated disease progression and pathogenesis.
It has been shown that analysis of zebrafish embryos provides an excellent platform to analyze in vivo effect of silencing of genes followed by disease progression and pathogenesis 
. Moreover, rescue of the phenotypes by human mRNA provides an analytical assay system to ascertain the effect of disease-associated mutations on the function of the protein, which in turn, can provide novel insights into associated patient phenotype. In the present study, we have utilized zebrafish as a platform to assess the pathogenic potential of selected RP-associated disease mutations in RP2. Our results indicate potentially distinct effects of RP2 mutation on cone versus rod photoreceptor dysfunction, the heterogeneity frequently observed in RP2 patients.