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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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NRL
neural retina leucine zipper
Chromosome 14 Β· 14q11.2-q12
NCBI Gene: 4901Ensembl: ENSG00000129535.14HGNC: HGNC:8002UniProt: P54845
49PubMed Papers
2Diseases
0Drugs
33Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
nucleusnucleoplasmcytoplasmprotein bindingRetinitis pigmentosa 27Retinal degeneration autosomal recessive clumped pigment type
✦AI Summary

NRL (neural retina leucine zipper) is a Maf-family basic leucine zipper transcription factor that serves as a master regulator of rod photoreceptor specification and function 1. NRL acts as a transcriptional activator and coactivator, controlling the expression of rod-specific genes including rhodopsin (RHO) and phosphodiesterase 6B (PDE6B) 2. The protein functions synergistically with transcription factor CRX, forming protein complexes in the nucleus that enhance rod phototransduction gene expression 3. NRL binds sequence-specifically to the rhodopsin promoter and regulates transcription through interactions with RNA polymerase II 4. Beyond its transcriptional role, NRL interacts with multiple RNA-binding proteins and R-loops at genomic regulatory elements, suggesting additional functions in coordinating transcription with RNA processing during photoreceptor maturation 5. In the absence of functional NRL, photoreceptor precursor cells adopt a default developmental pathway, differentiating into S-cone-like cells rather than rods, demonstrating NRL's critical role in rod identity specification 1. Mutations in NRL are associated with retinitis pigmentosa 27 and autosomal recessive retinal degeneration, highlighting its clinical significance in inherited retinal diseases 4.

Sources cited
1
NRL is required for rod photoreceptor specification; NRL-deficient cells default to S-cone-like differentiation
PMID: 33400844
2
NRL acts as transcriptional activator regulating rod-specific genes RHO and PDE6B
PMID: 21981118
3
CRX and NRL form protein complexes in live cells that synergistically activate rod gene expression
PMID: 35484285
4
NRL encodes bZIP transcription factor with retina-specific expression; genomic structure and location at 14q11.2; mutations associated with retinal degeneration
PMID: 9344665
5
NRL interacts with multiple RNA-binding proteins and R-loops, coordinating transcription with RNA processing in photoreceptors
PMID: 40047526
Disease Associationsβ“˜2
Retinal degeneration autosomal recessive clumped pigment typeUniProt
Retinitis pigmentosa 27UniProt
Pathogenic Variants33
NM_001354768.3(NRL):c.223dup (p.Leu75fs)Pathogenic
not provided|Retinitis pigmentosa 27|Enhanced S-cone syndrome 2
β˜…β˜…β˜†β˜†2025β†’ Residue 75
NM_001354768.3(NRL):c.91C>T (p.Arg31Ter)Pathogenic
Enhanced S-cone syndrome|not provided|Retinitis pigmentosa 27
β˜…β˜…β˜†β˜†2024β†’ Residue 31
NM_001354768.3(NRL):c.151C>T (p.Pro51Ser)Pathogenic
not provided|Retinitis pigmentosa 27
β˜…β˜…β˜†β˜†2024β†’ Residue 51
NM_001354768.3(NRL):c.152C>T (p.Pro51Leu)Pathogenic
not provided|Retinal dystrophy|Retinitis pigmentosa 27
β˜…β˜…β˜†β˜†2023β†’ Residue 51
NM_001354768.3(NRL):c.149C>T (p.Ser50Leu)Pathogenic
not provided|Retinal dystrophy
β˜…β˜…β˜†β˜†2023β†’ Residue 50
NM_001354768.3(NRL):c.339C>G (p.Tyr113Ter)Pathogenic
Retinitis pigmentosa 27|not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 113
NM_001354768.3(NRL):c.148T>C (p.Ser50Pro)Pathogenic
not provided|Retinal dystrophy
β˜…β˜…β˜†β˜†2022β†’ Residue 50
NM_001354768.3(NRL):c.516C>A (p.Tyr172Ter)Pathogenic
Retinal dystrophy|not provided
β˜…β˜…β˜†β˜†2021β†’ Residue 172
NM_001354768.3(NRL):c.589C>T (p.Gln197Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 197
NM_001354768.3(NRL):c.67del (p.Glu22_Val23insTer)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 22
NM_001354768.3(NRL):c.147_149del (p.Ser50del)Likely pathogenic
Retinitis pigmentosa 27
β˜…β˜†β˜†β˜†2025β†’ Residue 50
NM_001354768.3(NRL):c.152C>G (p.Pro51Arg)Likely pathogenic
Retinitis pigmentosa 27
β˜…β˜†β˜†β˜†2025β†’ Residue 51
NM_001354768.3(NRL):c.235C>T (p.Gln79Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 79
NM_001354768.3(NRL):c.452_459dup (p.Arg154fs)Likely pathogenic
Retinal dystrophy|Enhanced S-cone syndrome 2
β˜…β˜†β˜†β˜†2024β†’ Residue 154
NM_001354768.3(NRL):c.146C>T (p.Pro49Leu)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 49
NM_001354768.3(NRL):c.604C>A (p.Arg202=)Likely pathogenic
Retinal dystrophy
β˜…β˜†β˜†β˜†2023β†’ Residue 202
NM_001354768.3(NRL):c.371A>C (p.Gln124Pro)Likely pathogenic
Retinal dystrophy
β˜…β˜†β˜†β˜†2023β†’ Residue 124
NM_001354768.3(NRL):c.459_477dup (p.Leu160fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 160
NM_001354768.3(NRL):c.479T>C (p.Leu160Pro)Likely pathogenic
not provided|Enhanced S-cone syndrome 2
β˜…β˜†β˜†β˜†2023β†’ Residue 160
NM_001354768.3(NRL):c.381+1G>APathogenic
not provided
β˜…β˜†β˜†β˜†2023
View on ClinVar β†—
Related Genes
GNAT1Protein interaction99%RHOProtein interaction94%CRXProtein interaction89%FIZ1Protein interaction89%RPE65Protein interaction88%EYSProtein interaction86%
Tissue Expression

No tissue expression data available for this gene.

Gene Interaction Network
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NRLGNAT1RHOCRXFIZ1RPE65EYS
PROTEIN STRUCTURE
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AlphaFoldAI-predicted Β· UniProt P54845
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.92LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.52 [1.09–1.92]
RankingsWhere NRL stands among ~20K protein-coding genes
  • #8,990of 20,598
    Most Researched49
  • #1,734of 5,498
    Most Pathogenic Variants33
  • #17,377of 17,882
    Most Constrained (LOEUF)1.92
Genes detectedNRL
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Interaction of human CRX and NRL in live HEK293T cells measured using fluorescence resonance energy transfer (FRET).
PMID: 35484285
Sci Rep Β· 2022
1.00
2
NRL
PMID: 33400844
Stem Cells Β· 2021
0.90
3
The latex story.
PMID: 24925405
Chem Immunol Allergy Β· 2014
0.80
4
Safety, Tolerability, and Pharmacokinetics of NRL-1049, a Rho-Associated Kinase Inhibitor, in Healthy Volunteers: A Phase 1, First-in-Human, Single-Ascending Dose, Randomized, Placebo-Controlled Trial.
PMID: 40627117
CNS Drugs Β· 2025
0.70
5
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.
PMID: 9344665
Genomics Β· 1997
0.60