Alternative titles; symbols
HGNC Approved Gene Symbol: NRL
Cytogenetic location: 14q11.2-q12 Genomic coordinates (GRCh38) : 14:24,078,662-24,114,949 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 14q11.2-q12 | Enhanced S-cone syndrome 2 | 621371 | Autosomal recessive | 3 |
| Retinitis pigmentosa 27 | 613750 | Autosomal dominant | 3 |
The neural retina leucine zipper (NRL), a basic motif-leucine zipper (bZIP) transcription factor of the Maf- subfamily, is a phosphorylated protein that is specifically expressed in rod photoreceptors and pineal gland, but not in cones or other cell types. NRL is required for rod photoreceptor differentiation during retinal development (summary by Kanda et al., 2007).
Using subtraction cloning, Swaroop et al. (1991, 1992) identified a gene, designated NRL, that is expressed specifically in neuronal cells of retina. The NRL gene encodes a putative DNA-binding protein of the 'leucine zipper' family with strong similarity to the DNA-binding domain of the MAF oncogene product. The authors suggested that the NRL gene product might play a role in the regulation of retinal development and/or differentiation.
By Southern blot analysis of genomic DNA from a human/rodent somatic cell hybrid panel, Yang-Feng and Swaroop (1992) mapped the NRL gene to human chromosome 14 and sublocalized the gene to 14q11.1-q11.2 by in situ hybridization. Because of its specific pattern of expression, NRL was considered a candidate gene for retinal diseases.
Dahl et al. (1992) synthesized oligonucleotide primer sequences of 8 short tandem repeat polymorphism (STRP) markers that span the area 14q11.2-q32. Also synthesized were primer pair sequences for NRL that bracketed a polymorphic CA repeat fragment approximately 300 bp long. Genetic linkage studies in 17 families demonstrated the most likely position for NRL to be between D14S54 proximally and D14S50 distally. Bespalova et al. (1993) demonstrated that the homologous gene is located on mouse chromosome 14 and Farjo et al. (1993) provided molecular characterization of the murine gene.
NRL regulates the expression of several rod-specific genes, and missense mutations in the human NRL gene are associated with autosomal dominant retinitis pigmentosa. Mitton et al. (2003) used yeast 2-hybrid screening to identify FIZ1 (609133) as an NRL-interacting protein in retina. FIZ1 suppressed NRL- but not CRX (602225)-mediated transactivation of rhodopsin (180380) promoter activity in a transiently transfected monkey kidney cell line.
Using mouse microarrays, Yoshida et al. (2004) generated expression profiles of the wildtype and Nrl -/- retina at 3 distinct stages of photoreceptor differentiation. Comparative data analysis revealed 161 differentially expressed genes, of which 78 exhibited significantly lower and 83 higher expression in the Nrl -/- retina. Hierarchical clustering was used to predict the function of these genes in a temporal context. The differentially expressed genes primarily encoded proteins associated with signal transduction, transcriptional regulation, intracellular transport, and other processes, which could correspond to differences between rods and cones and/or retinal remodeling in the absence of rods. Chromatin immunoprecipitation assay showed that in addition to the rod phototransduction genes, Nrl might modulate the promoters of many functionally diverse genes in vivo.
Preceding the study of MacLaren et al. (2006), brain- and retina-derived stem cells transplanted into adult retina had shown little evidence of being able to integrate into the outer nuclear layer and differentiate into new photoreceptors. Furthermore, there had been no demonstration that transplanted cells form functional synaptic connections with other neurons in the recipient retina or restore visual function. MacLaren et al. (2006) hypothesized that committed progenitor or precursor cells at later ontogenetic stages might have a higher probability of success upon transplantation. In studies in mice, MacLaren et al. (2006) showed that adult wildtype and degenerating mammalian retinas can effectively incorporate rod photoreceptor precursor cells into the outer nuclear layer (ONL) of the retina. These cells differentiated, formed functional synaptic connections with downstream targets in the recipient retina, and contributed to visual function. Rather than the environment of the mature retina inhibiting photoreceptor maturation, they showed that transplantation of precursor cells at a specific ontogenetic stage, defined by activation of the transcription factor Nrl, results in their integration and subsequent differentiation into rod photoreceptors, even in retinal degeneration. Conversely, progenitor or stem cells that had not yet begun to express Nrl did not show this property and failed to integrate. Identification of the optimal ontogenetic stage for donor cells might facilitate the generation of appropriate cells for transplantation into humans from either embryonic or adult-derived stem cells.
Hao et al. (2014) found that developing and adult Nrl -/- mice lacked expression of a retina-specific Reep6 (609346) splice variant, Reep6.1, that includes exon 5. In contrast, expression of the Reep6.2 variant, which lacks exon 5, was intact in both early retina and liver of Nrl -/- mice. Hao et al. (2014) showed that Nrl bound an enhancer element in Reep6 intron 1 and, along with Nono (300084), promoted inclusion of exon 5 in Reep6.1 transcripts. Nrl had no effect on expression of the Reep6.2 transcript.
Retinitis Pigmentosa 27
Farjo et al. (1997) determined the complete sequence of the human NRL gene, identified a polymorphic (CA)n repeat (identical to D14S64) within an NRL-containing cosmid, and refined the location of the NRL gene by linkage analysis. Since a locus for autosomal recessive retinitis pigmentosa was thought to map to 14q11 in Sardinian families (Wright et al., 1995), and because mutations in rhodopsin (180380), a gene regulated by the NRL protein, cause RP, NRL was considered a valid candidate gene for retinopathies. In a panel of patients representing independent families with inherited retinal degeneration, Farjo et al. (1997) sequenced genomic PCR products of the NRL gene and of the rhodopsin-NRL response element. No causative mutations were identified.
In all affected members of a large autosomal dominant retinitis pigmentosa family (RP251) showing linkage to D14S64 (RP27; 613750), Bessant et al. (1999) identified a mutation in the NRL gene (S50T; 162080.0001).
Martinez-Gimeno et al. (2001) screened for mutations in the NRL gene in a cohort of 130 index cases from Spanish families segregating autosomal dominant RP and 37 sporadic RP patients, and identified a 5-generation Spanish family with a heterozygous missense mutation (P51L; 162080.0005). The mutation segregated fully with disease in the family and was not found in control individuals. Another NRL variant, G122E, was identified in 1 of the sporadic RP patients; the authors stated that its pathogenicity remained to be demonstrated.
Hernan et al. (2012) screened the NRL gene in 50 Spanish autosomal dominant RP probands and identified a heterozygous missense mutation in 1 (M96T; 162080.0004). The 3 affected individuals in the proband's family had less severe RP with later onset of symptoms than previously reported with mutations in the NRL gene; in vitro functional analysis showed that the M96T mutant increased transactivation to a lesser degree than the S50T or P51L mutant proteins.
In a 3-generation Japanese family with retinitis pigmentosa, Mizobuchi et al. (2022) screened whole-exome sequencing data for variants in known retinal dystrophy-associated genes and identified heterozygosity for the previously reported P51L mutation in the NRL gene.
Enhanced S-Cone Syndrome 2
Nishiguchi et al. (2004) screened the NRL gene in a cohort of 749 unrelated patients with various retinal diseases and identified a sister and brother with clumped pigmentary retinal degeneration and relative preservation of blue cone function (enhanced S-cone syndrome-2; ESCS2, 621371) who were compound heterozygous for a 1-bp insertion (224insC; 162080.0002) and a missense substitution (L160P; 162080.0003). The brother had an unaffected daughter who was heterozygous for the 1-bp insertion.
From a cohort of 230 patients from 186 families living in the Netherlands and segregating autosomal recessive retinitis pigmentosa (RP), Collin et al. (2011) identified a 30-year-old Moroccan man with clumped pigmentary retinal degeneration who was homozygous for a missense mutation in the NRL gene (R170S; 162080.0006). The variant was not found in 180 Dutch control individuals; familial segregation was not analyzed. Littink et al. (2018) restudied the proband and demonstrated that he had an enhanced S-cone response.
By next-generation sequencing in 100 RP patients who were negative for mutation in known RP-associated genes, Neveling et al. (2012) identified a Moroccan boy with early-onset clumped pigmentary retinal degeneration who was compound heterozygous for mutations in the NRL gene: the previously reported R170S substitution, and a 1-bp deletion (162080.0007). Littink et al. (2018) reported that the proband's affected brother was also compound heterozygous for these mutations, and demonstrated an enhanced S-cone response in both boys.
By exome sequencing in 3 unrelated families with a clinical diagnosis of early-onset autosomal recessive retinitis pigmentosa, El-Asrag et al. (2022) identified biallelic mutations in the NRL gene. In a Pakistani family, 3 affected sibs were homozygous for a stop-loss mutation (162080.0008) that segregated with disease. A 57-year-old Spanish man was homozygous for a nonsense mutation (Q80X), and a 21-year-old Romanian woman was homozygous for a different nonsense mutation (Q182X); segregation analysis was not reported for the latter 2 families, but neither variant was present in the gnomAD database. The authors stated that the ocular phenotype in their patients was consistent with that of previous reports of patients with biallelic mutations in the NRL gene, but noted that the S-cone phenotype in these patients could not be studied due to limited patient access.
By clinical exome sequencing in 2 unrelated Italian girls from consanguineous families with ESCS, Iarossi et al. (2022) identified homozygosity for the same 1-bp deletion (162080.0009). The mutation segregated with disease in both families and was not found in the gnomAD database.
Maggi et al. (2024) reported 2 unrelated teenage patients who had early-onset severe progressive retinal dystrophy with a clumped pigmentary pattern along the temporal vascular arcades and mutation in the NRL gene. The authors stated that they were not able to ascertain whether these patients exhibited enhanced S-cone function. Patient A was a 16-year-old girl of Middle Eastern origin who was homozygous for a deletion (c.-41_-28+23del) disrupting the natural donor splice of exon 1 of transcript NM_006177.3. Her unaffected first-cousin parents were heterozygous for the deletion, which was not found in the gnomAD database. Minigene assay revealed that the variant results in 2 aberrant transcripts due to the use of alternative cryptic donor splice sites located in intron 1. Patient 2 was a Swiss boy homozygous for a previously reported nonsense mutation (Q182X) in the last exon of NRL. The mutation was present in his unaffected mother but not his father; the proband's homozygosity was attributed to the diagnosed uniparental (maternal) disomy of chromosome 14.
Mutant NRL Function
Kanda et al. (2007) reported functional analyses of 17 amino acid variations and/or mutations in the NRL gene using transfection studies of HEK293 and COS1 cells. Six mutations at residues 50 and 51, including S50T, identified in patients with autosomal dominant retinitis pigmentosa resulted in a major NRL isoform that exhibited reduced phosphorylation but enhanced transcriptional activation of the rhodopsin promoter. Truncated NRL products, including 224insC, did not localize to the nucleus because of absence of the bZIP domain. The L160P mutation did not bind to the NRL-response element and showed decreased transcriptional activity. Other sequence variations were of uncertain significance. Kanda et al. (2007) concluded that gain-of-function mutations result in autosomal dominant disease, while loss-of-function mutations result in autosomal recessive disease. The findings also suggested that differential phosphorylation of NRL fine tunes its transcriptional regulatory activity, leading to a more precise control of gene expression.
Mears et al. (2001) generated mice with deletion of the NRL gene. Nrl -/- mice had complete loss of rod function and supernormal cone function, mediated by S cones. The photoreceptors in the Nrl -/- retina had cone-like nuclear morphology and short, sparse outer segments with abnormal disks. Analysis of retinal gene expression confirmed the apparent functional transformation of rods into S cones in the Nrl -/- retina. Mears et al. (2001) suggested that NRL acts as a molecular switch during rod-cell development by directly modulating rod-specific genes while simultaneously inhibiting the S-cone pathway through the activation of NR2E3 (604485).
In all affected members of a family (RP251) with a form of autosomal dominant retinitis pigmentosa showing linkage to D14S64 (RP27; 613750), Bessant et al. (1999) identified a T-to-A transversion at nucleotide 1942 of the NRL gene, resulting in a ser50-to-thr (S50T) substitution of the NRL protein. The mutation was not seen in unaffected family members or in 250 normal controls. Ser50 is located in 1 of 2 highly conserved regions of the transactivation (TA) domain, and is present in other members of the Maf family of proteins (see 602020) that contain a TA domain. Transient expression of NRL-S50T protein in CV-1 and 293 cells resulted in increased transactivation of the RHO promoter compared with wildtype NRL. The mutation abolished an HphI site.
By screening a panel of 200 autosomal dominant retinitis pigmentosa families, Bessant et al. (2000) found the S50T mutation in 3 additional families. Comparison of marker haplotypes in affected individuals from these families revealed a common disease haplotype. The exclusion of this locus and 9 other RP loci in several families indicated the existence of at least 1 other autosomal dominant RP locus.
Bessant et al. (2003) reviewed the clinical records of 21 patients with autosomal dominant RP due to the S50T mutation in the NRL gene. This mutation is associated with selective loss of scotopic function before age 20 years. With time, the photopic system becomes affected as well, leading to loss of the photopic visual field and of visual acuity.
By functional studies in cell culture, Kanda et al. (2007) determined that the S50T mutation resulted in a protein with reduced phosphorylation and enhanced transcriptional activation.
Using a mammalian 2-hybrid system, Perveen et al. (2007) demonstrated that the transactivation domain of the NRL gene interacts with p300 (602700) and that the S50T mutation enhances that interaction.
In a sister and brother (family 7080) with clumped pigmentary retinal generation and relative preservation of blue cone function (enhanced S-cone syndrome-2; ESCS2, 621371), Nishiguchi et al. (2004) identified compound heterozygosity for NRL mutations: a 1-bp insertion (c.224insC, NM_006177), resulting in a frameshift at codon 75 and a premature stop 19 codons downstream, and a c.479T-C transition, resulting in a leu160-to-pro (L160P; 162080.0003) substitution at a highly conserved residue adjacent to an ancillary DNA-binding domain. The 1-bp insertion was interpreted as a null allele because the stop codon early in the reading frame would likely result in nonsense-mediated decay of the mutant RNA transcript and, even if the RNA were translated, the resulting protein would have no basic leucine zipper domain. An unaffected daughter of the brother was heterozygous for the 1-bp insertion.
By functional studies in cell culture, Kanda et al. (2007) determined that the 224insC mutant NRL protein did not localize to the nucleus because of the absence of the bZIP domain.
For discussion of the c.479T-C transition (c.479T-C, NM_006177) in the NRL gene, resulting in a leu160-to-pro (L160P) substitution, that was found in compound heterozygous state in a sister and brother with enhanced S-cone syndrome-2 (ESCS2; 621371) by Nishiguchi et al. (2004), see 162080.0002.
By functional studies in cell culture, Kanda et al. (2007) determined that the L160P mutant NRL protein did not bind to the NRL-response element and showed decreased transcriptional activity.
In a Spanish patient with retinitis pigmentosa (RP27; 613750), Hernan et al. (2012) identified heterozygosity for a 287T-C transition in the NRL gene, resulting in a met96-to-thr (M96T) substitution at a conserved residue. The proband's mother and a maternal aunt were also heterozygous for the mutation, which was not found in 127 controls. The 3 affected individuals had onset of night blindness in the second or third decade of life. The mutation was also present in the proband's sister and a cousin, who remained asymptomatic at ages 37 and 45 years, respectively. Hernan et al. (2012) noted that the RP phenotype in this family was less severe and had later onset of symptoms than previously reported with other NRL mutations; in vitro functional analysis demonstrated that the M96T mutant increased transactivation to a lesser degree than the S50T (162080.0001) or P51L (see Martinez-Gimeno et al., 2001) mutant proteins.
In affected members of a 5-generation Spanish family segregating autosomal dominant retinitis pigmentosa (RP27; 613750), Martinez-Gimeno et al. (2001) identified heterozygosity for a c.2316C-T transition in exon 2 of the NRL gene, resulting in a pro51-to-leu (P51L) substitution within the transactivation domain. The mutation segregated fully with disease in the family and was not found in 157 unrelated control individuals.
In a Japanese family in which 2 sisters, their father, and their paternal grandmother had retinitis pigmentosa, Mizobuchi et al. (2022) identified heterozygosity for the previously reported P51L mutation (c.152C-T, NM_001354768.3) in the NRL gene. The mutation, which occurred at a well-conserved residue, segregated with disease in the family and was not found in the jMorp database.
In a 30-year-old Moroccan man with clumped pigmentary retinal degeneration (enhanced S-cone syndrome-2; ESCS2, 621371), Collin et al. (2011) identified homozygosity for a c.508C-A transversion in the NRL gene, resulting in an arg170-to-ser (R170S) substitution at a highly conserved residue within the DNA-binding domain. The mutation was not found in 180 Dutch control individuals; familial segregation was not analyzed. Functional analysis was not reported.
In a Moroccan boy (patient 32594) with early-onset clumped pigmentary retinal degeneration, Neveling et al. (2012) identified compound heterozygosity for the previously reported R170S substitution in the NRL gene and a 1-bp deletion (c.654del; 162080.0007), causing a frameshift (C219fs). The variants segregated with disease in the family. Littink et al. (2018) reported that the proband's affected brother (patient 32595) was also compound heterozygous for these mutations, and demonstrated an enhanced S-cone response in both boys.
For discussion of the 1-bp deletion (c.654del) in the NRL gene, causing a frameshift (C219fs), that was found in compound heterozygous state in a Moroccan boy (patient 32594) with enhanced S-cone syndrome-2 (ESCS2; 621371) by Neveling et al. (2012), see 162080.0006.
In 3 sibs from a consanguineous Pakistani family (MM1) who had early-onset clumped pigmentary retinal degeneration (enhanced S-cone syndrome-2; ESCS2, 621371), El-Asrag et al. (2022) identified homozygosity for a c.713G-T transversion (c.713G-T, NM_006177.5) in the NRL gene, resulting in a ter238-to-leu substitution and extension of the protein by 57 amino acids (X238Lext57). The sibs' unaffected first-cousin parents and 2 unaffected sisters were heterozygous for the mutation, which was present at low minor allele frequency in the gnomAD database.
In 2 unrelated Italian girls from consanguineous families with enhanced S-cone syndrome-2 (ESCS2; 621371), Iarossi et al. (2022) identified homozygosity for the same 1-bp deletion in the NRL gene (c.22delC, NM_006177), causing a frameshift predicted to result in a premature termination codon (Leu8TrpfsTer11). The deletion was present in heterozygosity in the unaffected parents from both families, and was not found in the gnomAD database.
Bespalova, I. N., Farjo, Q., Mortlock, D. P., Jackson, A. U., Meisler, M. H., Swaroop, A., Burmeister, M. Mapping of the neural retina leucine zipper gene, Nrl, to mouse chromosome 14. Mammalian Genome 4: 618-620, 1993. [PubMed: 8268663] [Full Text: https://doi.org/10.1007/BF00361397]
Bessant, D. A. R., Holder, G. E., Fitzke, F. W., Payne, A. M., Bhattacharya, S. S., Bird, A. C. Phenotype of retinitis pigmentosa associated with the ser50thr mutation in the NRL gene. Arch. Ophthal. 121: 793-802, 2003. [PubMed: 12796249] [Full Text: https://doi.org/10.1001/archopht.121.6.793]
Bessant, D. A. R., Payne, A. M., Mitton, K. P., Wang, Q.-L., Swain, P. K., Plant, C., Bird, A. C., Zack, D. J., Swaroop, A., Bhattacharya, S. S. A mutation in NRL is associated with autosomal dominant retinitis pigmentosa. Nature Genet. 21: 355-356, 1999. [PubMed: 10192380] [Full Text: https://doi.org/10.1038/7678]
Bessant, D. A. R., Payne, A. M., Plant, C., Bird, A. C., Swaroop, A., Bhattacharya, S. S. NRL S50T mutation and the importance of 'founder effects' in inherited retinal dystrophies. Europ. J. Hum. Genet. 8: 783-787, 2000. [PubMed: 11039579] [Full Text: https://doi.org/10.1038/sj.ejhg.5200538]
Collin, R. W. J., van den Born, L. I., Klevering, B. J., de Castro-Miro, M., Littink, K. W., Arimadyo, K., Azam, M., Yazar, V., Zonneveld, M. N., Paun, C. C., Siemiatkowska, A. M., Strom, T. M., Hehir-Kwa, J. Y., Kroes, H. Y., de Faber, J.-T. H. N., van Schooneveld, M. J., Heckenlively, J. R., Hoyng, C. B., den Hollander, A. I., Cremers, F. P. High-resolution homozygosity mapping is a powerful tool to detect novel mutations causative of autosomal recessive RP in the Dutch population. Invest. Ophthal. Vis. Sci. 52: 2227-2239, 2011. [PubMed: 21217109] [Full Text: https://doi.org/10.1167/iovs.10-6185]
Dahl, S. P., Jackson, A., Kimberling, W. J., Blackwood, D., Swaroop, A. Genetic mapping of NRL, a human retina-specific gene located on chromosome 14. (Abstract) Am. J. Hum. Genet. 51 (suppl.): A185 only, 1992.
El-Asrag, M. E., Corton, M., McKibbin, M., Avila-Fernandez, A., Mohamed, M. D., Blanco-Kelly, F., Toomes, C., Inglehearn, C. F., Ayuso, C., Ali, M. Novel homozygous mutations in the transcription factor NRL cause non-syndromic retinitis pigmentosa. Molec. Vision 28: 48-56, 2022. [PubMed: 35693422]
Farjo, Q., Jackson, A., Pieke-Dahl, S., Scott, K., Kimberling, W. J., Sieving, P. A., Richards, J. E., Swaroop, A. Human bZIP transcription factor gene NRL: structure, genomic sequence, and fine linkage mapping at 14q11.2 and negative mutation analysis in patients with retinal degeneration. Genomics 45: 395-401, 1997. [PubMed: 9344665] [Full Text: https://doi.org/10.1006/geno.1997.4964]
Farjo, Q., Jackson, A. U., Xu, J., Gryzenia, M., Skolnick, C., Agarwal, N., Swaroop, A. Molecular characterization of the murine neural retina leucine zipper gene, Nrl. Genomics 18: 216-222, 1993. [PubMed: 8288222] [Full Text: https://doi.org/10.1006/geno.1993.1458]
Hao, H., Veleri, S., Sun, B., Kim, D. S., Keeley, P. W., Kim, J.-W., Yang, H.-J., Yadav, S. P., Manjunath, S. H., Sood, R., Liu, P., Reese, B. E., Swaroop, A. Regulation of a novel isoform of receptor expression enhancing protein REEP6 in rod photoreceptors by bZIP transcription factor NRL. Hum. Molec. Genet. 23: 4260-4271, 2014. [PubMed: 24691551] [Full Text: https://doi.org/10.1093/hmg/ddu143]
Hernan, I., Gamundi, M. J., Borras, E., Maseras, M., Garcia-Sandoval, B., Blanco-Kelly, F., Ayuso, C., Carballo, M. Novel p.M96T variant of NRL and shRNA-based suppression and replacement of NRL mutants associated with autosomal dominant retinitis pigmentosa. Clin. Genet. 82: 446-452, 2012. [PubMed: 21981118] [Full Text: https://doi.org/10.1111/j.1399-0004.2011.01796.x]
Iarossi, G., Sinibaldi, L., Passarelli, C., Coppe', A. M., Cappelli, A., Petrocelli, G., Catena, G., Perrone, C., Falsini, B., Novelli, A., Bartuli, A., Buzzonetti, L. A novel autosomal recessive variant of the NRL gene causing enhanced S-cone syndrome: a morpho-functional analysis of two unrelated pediatric patients. Diagnostics (Basel) 12: 2183, 2022. [PubMed: 36140584] [Full Text: https://doi.org/10.3390/diagnostics12092183]
Kanda, A., Friedman, J. S., Nishiguchi, K. M., Swaroop, A. Retinopathy mutations in the bZIP protein NRL alter phosphorylation and transcriptional activity. Hum. Mutat. 28: 589-598, 2007. [PubMed: 17335001] [Full Text: https://doi.org/10.1002/humu.20488]
Littink, K. W., Stappers, P. T. Y., Riemslag, F. C. C., Talsma, H. E., van Genderen, M. M., Cremers, F. P. M., Collin, R. W. J., van den Born, L. I. Autosomal recessive NRL mutations in patients with enhanced S-cone syndrome. Genes (Basel) 9: 68, 2018. Note: Erratum: Genes (Basel) 9: 145, 2018. [PubMed: 29385733] [Full Text: https://doi.org/10.3390/genes9020068]
MacLaren, R. E., Pearson, R. A., MacNeil, A., Douglas, R. H., Salt, T. E., Akimoto, M., Swaroop, A., Sowden, J. C., Ali, R. R. Retinal repair by transplantation of photoreceptor precursors. Nature 444: 203-207, 2006. [PubMed: 17093405] [Full Text: https://doi.org/10.1038/nature05161]
Maggi, J., Hanson, J. V. M., Kurmann, L., Koller, S., Feil, S., Gerth-Kahlert, C., Berger, W. Retinal dystrophy associated with homozygous variants in NRL. Genes 15: 1594, 2024. [PubMed: 39766861] [Full Text: https://doi.org/10.3390/genes15121594]
Martinez-Gimeno, M., Maseras, M., Baiget, M., Beneito, M., Antinolo, G., Ayuso, C., Carballo, M. Mutations P51L and G122E in retinal transcription factor NRL associated with autosomal dominant and sporadic retinitis pigmentosa. (Abstract) Hum. Mutat. 17: 520 only, 2001. Note: Full Article Online.
Mears, A. J., Kondo, M., Swain, P. K., Takada, Y., Bush, R. A., Saunders, T. L., Sieving, P. A., Swaroop, A. Nrl is required for rod photoreceptor development. Nature Genet. 29: 447-452, 2001. [PubMed: 11694879] [Full Text: https://doi.org/10.1038/ng774]
Mitton, K. P., Swain, P. K., Khanna, H., Dowd, M., Apel, I. J., Swaroop, A. Interaction of retinal bZIP transcription factor NRL with Flt3-interacting zinc-finger protein Fiz1: possible role of Fiz1 as a transcriptional repressor. Hum. Molec. Genet. 12: 365-373, 2003. [PubMed: 12566383] [Full Text: https://doi.org/10.1093/hmg/ddg035]
Mizobuchi, K., Hayashi, T., Matsuura, T., Nakano, T. Clinical characterization of autosomal dominant retinitis pigmentosa with NRL mutation in a three-generation Japanese family. Docum. Ophthal. 144: 227-235, 2022. [PubMed: 35653045] [Full Text: https://doi.org/10.1007/s10633-022-09874-y]
Neveling, K., Collin, R. W. J., Gilissen, C., van Huet, R. A. C., Visser, L., Kwint, M. P., Gijsen, S. J., Zonneveld, M. N., Wieskamp, N., de Ligt, J., Siemiatkowska, A. M., Hoefsloot, L. H., and 11 others. Next-generation genetic testing for retinitis pigmentosa. Hum. Mutat. 33: 963-972, 2012. Note: Erratum: Hum. Mutat. 34: 1181, 2013. [PubMed: 22334370] [Full Text: https://doi.org/10.1002/humu.22045]
Nishiguchi, K. M., Friedman, J. S., Sandberg, M. A., Swaroop, A., Berson, E. L., Dryja, T. P. Recessive NRL mutations in patients with clumped pigmentary retinal degeneration and relative preservation of blue cone function. Proc. Nat. Acad. Sci. 101: 17819-17824, 2004. [PubMed: 15591106] [Full Text: https://doi.org/10.1073/pnas.0408183101]
Perveen, R., Favor, J., Jamieson, R. V., Ray, D. W., Black, G. C. M. A heterozygous c-Maf transactivation domain mutation causes congenital cataract and enhances target gene activation. Hum. Molec. Genet. 16: 1030-1038, 2007. [PubMed: 17374726] [Full Text: https://doi.org/10.1093/hmg/ddm048]
Swaroop, A., Xu, J., Agarwal, N., Weissman, S. M. A simple and efficient cDNA library subtraction procedure: isolation of human retina-specific cDNA clones. Nucleic Acids Res. 19: 1954 only, 1991. [PubMed: 2030979] [Full Text: https://doi.org/10.1093/nar/19.8.1954]
Swaroop, A., Xu, J., Pawar, H., Jackson, A., Skolnick, C., Agarwal, N. A conserved retina-specific gene encodes a basic motif/leucine zipper domain. Proc. Nat. Acad. Sci. 89: 266-270, 1992. [PubMed: 1729696] [Full Text: https://doi.org/10.1073/pnas.89.1.266]
Wright, A. F., Mansfield, D. C., Bruford, E. A., Teague, P. W., Thomson, K. L., Riise, R., Jay, M., Patton, M. A., Jeffery, S., Schinzel, A., Tommerup, N., Fossarello, M. Genetic studies in autosomal recessive forms of retinitis pigmentosa. In: Anderson, R. E.; LaVail, M. M.; Hollyfield, J. G. (eds.): Degenerative Diseases of the Retina. New York: Plenum Press (pub.) 1995. Pp. 293-302.
Yang-Feng, T. L., Swaroop, A. Neural retina-specific leucine zipper gene NRL (D14S46E) maps to human chromosome 14q11.1-q11.2. Genomics 14: 491-492, 1992. [PubMed: 1427865] [Full Text: https://doi.org/10.1016/s0888-7543(05)80248-4]
Yoshida, S., Mears, A. J., Friedman, J. S., Carter, T., He, S., Oh, E., Jing, Y., Farjo, R., Fleury, G., Barlow, C., Hero, A. O., Swaroop, A. Expression profiling of the developing and mature Nrl -/- mouse retina: identification of retinal disease candidates and transcriptional regulatory targets of Nrl. Hum. Molec. Genet. 13: 1487-1503, 2004. [PubMed: 15163632] [Full Text: https://doi.org/10.1093/hmg/ddh160]