This gene encodes a basic motif-leucine zipper transcription factor of the Maf subfamily. The encoded protein is conserved among vertebrates and is a critical intrinsic regulator of photoceptor development and function. Mutations in this gene have been associated with retinitis pigmentosa and retinal degenerative diseases. [provided by RefSeq, Jul 2008] See more...

Aliases for NRL Gene

Aliases for NRL Gene

  • Neural Retina Leucine Zipper 2 3 5
  • D14S46E 2 3 4
  • Neural Retina-Specific Leucine Zipper Protein 3 4
  • NRL-MAF 2 3
  • RP27 2 3
  • Neural Retinal-Specific Leucine Zipper 3
  • NRL 5

External Ids for NRL Gene

Previous GeneCards Identifiers for NRL Gene

  • GC14M021921
  • GC14M018336
  • GC14M022539
  • GC14M023619
  • GC14M024549
  • GC14M004664

Summaries for NRL Gene

Entrez Gene Summary for NRL Gene

  • This gene encodes a basic motif-leucine zipper transcription factor of the Maf subfamily. The encoded protein is conserved among vertebrates and is a critical intrinsic regulator of photoceptor development and function. Mutations in this gene have been associated with retinitis pigmentosa and retinal degenerative diseases. [provided by RefSeq, Jul 2008]

GeneCards Summary for NRL Gene

NRL (Neural Retina Leucine Zipper) is a Protein Coding gene. Diseases associated with NRL include Retinitis Pigmentosa 27 and Enhanced S-Cone Syndrome. Among its related pathways are Tacrolimus/Cyclosporine Pathway, Pharmacodynamics. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and RNA polymerase II proximal promoter sequence-specific DNA binding. An important paralog of this gene is MAFA.

UniProtKB/Swiss-Prot Summary for NRL Gene

  • Acts as a transcriptional activator which regulates the expression of several rod-specific genes, including RHO and PDE6B (PubMed:21981118). Functions also as a transcriptional coactivator, stimulating transcription mediated by the transcription factor CRX and NR2E3 (PubMed:17335001). Binds in a sequence-specific manner to the rhodopsin promoter (PubMed:17335001).

Gene Wiki entry for NRL Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NRL Gene

Genomics for NRL Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for NRL Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH14J024113 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 250.7 +0.0 13 3.6 SP1 ZNF207 MYC ZNF600 SSRP1 ZNF580 ZMYM3 KLF9 POLR2A CEBPA DCAF11 NRL NONHSAG014521.2 piR-39858-164 NGDN TM9SF1 RNF31 NFATC4 KHNYN IPO4
GH14J024087 Promoter 0.5 EPDnew 261.4 +28.0 28027 0.1 HDAC2 ATF7 NRL DCAF11 CARMIL3 IRF9 IPO4 TM9SF1 TSSK4 PCK2 lnc-NRL-4 CPNE6
GH14J024084 Promoter 0.4 EPDnew 250.3 +30.4 30356 0.1 ZFP91 NRL CARMIL3 PSME2 RNF31 IPO4 TM9SF1 REC8 PCK2 lnc-NRL-4 CPNE6
GH14J024091 Promoter/Enhancer 2.4 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 11.4 +21.4 21363 6.5 BCLAF1 SP1 NCOR1 MYC ZNF600 IKZF1 SSRP1 ZNF592 ZMYM3 KLF9 HSALNG0100088 PCK2 NGDN ACIN1 RNA5SP383 KHNYN RNF31 ENSG00000259321 IPO4 NYNRIN
GH14J024035 Promoter/Enhancer 1.7 Ensembl ENCODE CraniofacialAtlas 11.3 +78.4 78409 2 ZNF654 ZNF600 ZNF580 KLF9 CEBPA ZNF223 ZNF10 ZIC2 ZBTB10 CEBPB HSALNG0100084 piR-35901 piR-51784-002 ACIN1 DHRS4L1 RNA5SP383 KHNYN TM9SF1 C14orf119 AP1G2-AS1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NRL on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NRL

Top Transcription factor binding sites by QIAGEN in the NRL gene promoter:
  • C/EBPbeta
  • COUP
  • COUP-TF
  • COUP-TF1
  • HNF-4alpha1

Genomic Locations for NRL Gene

Latest Assembly
chr14:24,078,662-24,115,010
(GRCh38/hg38)
Size:
36,349 bases
Orientation:
Minus strand

Previous Assembly
chr14:24,547,871-24,584,158
(GRCh37/hg19 by Entrez Gene)
Size:
36,288 bases
Orientation:
Minus strand

chr14:24,549,316-24,584,223
(GRCh37/hg19 by Ensembl)
Size:
34,908 bases
Orientation:
Minus strand

Alternative Locations (GRCh38/hg38)

  • chr14(PATCHES):379,640-415,927 (-)

Genomic View for NRL Gene

Genes around NRL on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NRL Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NRL Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NRL Gene

Proteins for NRL Gene

  • Protein details for NRL Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P54845-NRL_HUMAN
    Recommended name:
    Neural retina-specific leucine zipper protein
    Protein Accession:
    P54845
    Secondary Accessions:
    • A8MX14
    • Q53XD0

    Protein attributes for NRL Gene

    Size:
    237 amino acids
    Molecular mass:
    25940 Da
    Quaternary structure:
    • Interacts with FIZ1; this interaction represses transactivation (By similarity). Interacts (via the leucine-zipper domain) with CRX (PubMed:10887186).

    Alternative splice isoforms for NRL Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NRL Gene

Post-translational modifications for NRL Gene

  • Phosphorylated (PubMed:11477108, PubMed:17335001).
  • Disumoylated at Lys-20. Sumoylation modulates the transcriptional activity of NRL on RHO and NR2E3 promoters, and is required for normal rod differentiation (By similarity).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for NRL Gene

Domains & Families for NRL Gene

Gene Families for NRL Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for NRL Gene

InterPro:
Blocks:
  • Maf transcription factor
  • Maf transcription factor, N-terminal

Suggested Antigen Peptide Sequences for NRL Gene

GenScript: Design optimal peptide antigens:
  • Neural retina-specific leucine zipper protein (NRL_HUMAN)
  • Neural retina-specific leucine zipper protein (Q53XD0_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P54845

UniProtKB/Swiss-Prot:

NRL_HUMAN :
  • The minimal transactivation domain (MTD) is conserved across the MAF family, it may activate transcription by recruiting TBP and associated factors at the promoters of target genes.
  • Belongs to the bZIP family.
Domain:
  • The minimal transactivation domain (MTD) is conserved across the MAF family, it may activate transcription by recruiting TBP and associated factors at the promoters of target genes.
Family:
  • Belongs to the bZIP family.
genes like me logo Genes that share domains with NRL: view

Function for NRL Gene

Molecular function for NRL Gene

UniProtKB/Swiss-Prot Function:
Acts as a transcriptional activator which regulates the expression of several rod-specific genes, including RHO and PDE6B (PubMed:21981118). Functions also as a transcriptional coactivator, stimulating transcription mediated by the transcription factor CRX and NR2E3 (PubMed:17335001). Binds in a sequence-specific manner to the rhodopsin promoter (PubMed:17335001).
GENATLAS Biochemistry:
neural retinal specific transcript,interacting with CRX,regulating the expression of rhodopsin and other retinal genes,small MAF protein family

Phenotypes From GWAS Catalog for NRL Gene

Gene Ontology (GO) - Molecular Function for NRL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IDA 8552602
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ISA --
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific IMP 17335001
GO:0003677 DNA binding TAS 1729696
GO:0003700 DNA-binding transcription factor activity IEA --
genes like me logo Genes that share ontologies with NRL: view
genes like me logo Genes that share phenotypes with NRL: view

Human Phenotype Ontology for NRL Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for NRL Gene

MGI Knock Outs for NRL:
  • Nrl Nrl<tm1.1Jcco>
  • Nrl Nrl<tm1Asw>

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NRL

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for NRL Gene

Localization for NRL Gene

Subcellular locations from UniProtKB/Swiss-Prot for NRL Gene

Cytoplasm. Nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NRL gene
Compartment Confidence
nucleus 5
cytosol 5
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 1
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (3)
  • Cytosol (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for NRL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000785 chromatin ISA --
GO:0005634 nucleus IEA,IDA 11477108
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IEA,IDA 11477108
GO:0005829 cytosol IDA --
genes like me logo Genes that share ontologies with NRL: view

Pathways & Interactions for NRL Gene

genes like me logo Genes that share pathways with NRL: view

Pathways by source for NRL Gene

1 PharmGKB pathway for NRL Gene

SIGNOR curated interactions for NRL Gene

Inactivates:
Is activated by:

Gene Ontology (GO) - Biological Process for NRL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006357 regulation of transcription by RNA polymerase II IBA 21873635
GO:0007275 multicellular organism development IEA --
GO:0007468 regulation of rhodopsin gene expression IEA --
GO:0007601 visual perception TAS,IEA --
genes like me logo Genes that share ontologies with NRL: view

Drugs & Compounds for NRL Gene

(1) Drugs for NRL Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with NRL: view

Transcripts for NRL Gene

mRNA/cDNA for NRL Gene

4 REFSEQ mRNAs :
14 NCBI additional mRNA sequence :
6 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NRL

Alternative Splicing Database (ASD) splice patterns (SP) for NRL Gene

No ASD Table

Relevant External Links for NRL Gene

GeneLoc Exon Structure for
NRL

Expression for NRL Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NRL Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for NRL Gene

This gene is overexpressed in Retina (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for NRL Gene



Protein tissue co-expression partners for NRL Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NRL

SOURCE GeneReport for Unigene cluster for NRL Gene:

Hs.652297

mRNA Expression by UniProt/SwissProt for NRL Gene:

P54845-NRL_HUMAN
Tissue specificity: Expressed in the brain and the retina (PubMed:11477108). Expressed strongly in rod and cone cells (at protein level) (PubMed:11477108).

Evidence on tissue expression from TISSUES for NRL Gene

  • Eye(4.8)
  • Liver(2.6)
  • Kidney(2.3)
  • Nervous system(2.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for NRL Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • immune
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • cerebellum
  • cranial nerve
  • ear
  • eye
  • eyelid
  • face
  • head
  • middle ear
  • nose
  • outer ear
  • skull
Pelvis:
  • penis
  • testicle
General:
  • blood
  • blood vessel
  • peripheral nervous system
  • red blood cell
  • skin
genes like me logo Genes that share expression patterns with NRL: view

Primer products for research

No data available for mRNA differential expression in normal tissues for NRL Gene

Orthologs for NRL Gene

This gene was present in the common ancestor of animals.

Orthologs for NRL Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia NRL 29 30
  • 99.58 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia NRL 29 30
  • 92.69 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia NRL 29 30
  • 92.55 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Nrl 29
  • 86.64 (n)
Mouse
(Mus musculus)
Mammalia Nrl 29 16 30
  • 86.08 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia NRL 30
  • 63 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia NRL 30
  • 50 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia nrl 29
  • 62.81 (n)
African clawed frog
(Xenopus laevis)
Amphibia l-maf-A 29
Zebrafish
(Danio rerio)
Actinopterygii nrl 29 30
  • 66.17 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta tj 30
  • 17 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea maf-1 30
  • 27 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 21 (a)
ManyToMany
Species where no ortholog for NRL was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for NRL Gene

ENSEMBL:
Gene Tree for NRL (if available)
TreeFam:
Gene Tree for NRL (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NRL: view image
Alliance of Genome Resources:
Additional Orthologs for NRL

Paralogs for NRL Gene

Paralogs for NRL Gene

(6) SIMAP similar genes for NRL Gene using alignment to 3 proteins:

  • NRL_HUMAN
  • A8MX14_HUMAN
  • H0YNW2_HUMAN
genes like me logo Genes that share paralogs with NRL: view

Variants for NRL Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NRL Gene

SNP ID Clinical significance and condition Chr 14 pos Variation AA Info Type
1007303 Uncertain Significance: not provided 24,082,724(-) G/T
NM_001354768.3(NRL):c.125C>A (p.Thr42Lys)
MISSENSE_VARIANT,INTRON
1015833 Uncertain Significance: not provided 24,081,334(-) C/T
NM_001354768.3(NRL):c.616G>A (p.Ala206Thr)
MISSENSE
1017251 Uncertain Significance: not provided 24,081,263(-) G/T
NM_001354768.3(NRL):c.687C>A (p.Ser229=)
SYNONYMOUS
1025699 Uncertain Significance: not provided 24,082,514(-) C/A
NM_001354768.3(NRL):c.335G>T (p.Gly112Val)
MISSENSE_VARIANT,INTRON
1030819 Uncertain Significance: Phosphoenolpyruvate carboxykinase deficiency, mitochondrial 24,103,948(-) G/A
NM_004563.4(PCK2):c.1907G>A (p.Arg636His)
MISSENSE_VARIANT,INTRON

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for NRL Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for NRL Gene

Variant ID Type Subtype PubMed ID
nsv1036658 CNV loss 25217958
nsv1052180 CNV loss 25217958
nsv516023 CNV loss 19592680
nsv564057 CNV loss 21841781

Variation tolerance for NRL Gene

Residual Variation Intolerance Score: 52.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.66; 14.03% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NRL Gene

Human Gene Mutation Database (HGMD)
NRL
SNPedia medical, phenotypic, and genealogical associations of SNPs for
NRL
Leiden Open Variation Database (LOVD)
NRL

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NRL Gene

Disorders for NRL Gene

MalaCards: The human disease database

(35) MalaCards diseases for NRL Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards
Search NRL in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

NRL_HUMAN
  • Retinitis pigmentosa 27 (RP27) [MIM:613750]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269 PubMed:10192380, ECO:0000269 PubMed:11385710, ECO:0000269 PubMed:11879142, ECO:0000269 PubMed:15591106, ECO:0000269 PubMed:15994872, ECO:0000269 PubMed:17335001, ECO:0000269 PubMed:21981118, ECO:0000269 PubMed:22334370}. Note=The disease is caused by variants affecting the gene represented in this entry.
  • Retinal degeneration autosomal recessive clumped pigment type (RDCP) [MIM:613750]: A retinopathy characterized by night blindness since early childhood, consistent with a severe reduction in rod function. Color vision is normal although there is a relatively enhanced function of short-wavelength-sensitive cones in the macula. Signs of retinal degeneration and clusters of clumped pigment deposits in the peripheral fundus at the level of the retinal pigment epithelium are present. {ECO:0000269 PubMed:15591106, ECO:0000269 PubMed:17335001}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for NRL

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with NRL: view

No data available for Genatlas for NRL Gene

Publications for NRL Gene

  1. Retinopathy mutations in the bZIP protein NRL alter phosphorylation and transcriptional activity. (PMID: 17335001) Kanda A … Swaroop A (Human mutation 2007) 3 4 22 72
  2. A mutation in NRL is associated with autosomal dominant retinitis pigmentosa. (PMID: 10192380) Bessant DA … Bhattacharya SS (Nature genetics 1999) 2 3 4 72
  3. Association of NR2E3 but not NRL mutations with retinitis pigmentosa in the Chinese population. (PMID: 19933183) Yang Y … Pang CP (Investigative ophthalmology & visual science 2010) 3 22 40
  4. Recessive NRL mutations in patients with clumped pigmentary retinal degeneration and relative preservation of blue cone function. (PMID: 15591106) Nishiguchi KM … Dryja TP (Proceedings of the National Academy of Sciences of the United States of America 2004) 3 4 72
  5. Phenotype of retinitis pigmentosa associated with the Ser50Thr mutation in the NRL gene. (PMID: 12796249) Bessant DA … Bird AC (Archives of ophthalmology (Chicago, Ill. : 1960) 2003) 3 22 72

Products for NRL Gene

Sources for NRL Gene