GeneBe

NRL

neural retina leucine zipper, the group of Basic leucine zipper proteins

Basic information

Region (hg38): 14:24078662-24115010

Links

ENSG00000129535 ∙ NCBI:4901 ∙ OMIM:162080 ∙ HGNC:8002 ∙ Uniprot:P54845 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • retinitis pigmentosa (Supportive), mode of inheritance: AD
  • retinitis pigmentosa 27 (Strong), mode of inheritance: AR
  • retinitis pigmentosa 27 (Strong), mode of inheritance: AD
  • retinitis pigmentosa 27 (Definitive), mode of inheritance: AD
  • retinitis pigmentosa 27 (Definitive), mode of inheritance: AR
  • enhanced S-cone syndrome (Definitive), mode of inheritance: AR
  • retinitis pigmentosa 27 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Retinitis pigmentosa 27; Clumped pigmentary retinal degenerationAD/ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingOphthalmologic10192380; 11039579; 12796249; 15591106; 17335001

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NRL gene.

  • not_provided (394 variants)
  • not_specified (104 variants)
  • Inborn_genetic_diseases (24 variants)
  • PCK2-related_disorder (22 variants)
  • Retinal_dystrophy (22 variants)
  • Retinitis_pigmentosa (17 variants)
  • Retinitis_pigmentosa_27 (16 variants)
  • Phosphoenolpyruvate_carboxykinase_deficiency,_mitochondrial (14 variants)
  • NRL-related_disorder (4 variants)
  • ENHANCED_S-CONE_SYNDROME_2 (4 variants)
  • Phosphoenolpyruvate_carboxykinase_(GTP)_deficiency (2 variants)
  • Elevated_circulating_hepatic_transaminase_concentration (1 variants)
  • Albinism (1 variants)
  • Slow_decrease_in_visual_acuity (1 variants)
  • Abnormality_of_metabolism/homeostasis (1 variants)
  • PCK2-related_neuropathy (1 variants)
  • Enhanced_S-cone_syndrome (1 variants)
  • Foveal_hypoplasia (1 variants)
  • Choroidal_neovascularization (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NRL gene is commonly pathogenic or not. These statistics are base on transcript: NM_001354768.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
2
clinvar
37
clinvar
3
clinvar
 43
missense
3
clinvar
10
clinvar
112
clinvar
2
clinvar
1
clinvar
 128
nonsense
3
clinvar
4
clinvar
1
clinvar
 8
start loss
0
frameshift
9
clinvar
4
clinvar
5
clinvar
 18
splice donor/acceptor (+/-2bp)
1
clinvar
1
clinvar
 2
Total 16 19 121 39 4

Highest pathogenic variant AF is 0.00011017

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
NRLprotein_codingprotein_codingENST00000561028 234908
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.04760.8651257200231257430.0000915
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.6141031220.8440.000006011457
Missense in Polyphen3042.3490.70841554
Synonymous-0.7766355.61.130.00000269548
Loss of Function1.4137.030.4273.87e-777

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0002100.000206
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.00004630.0000462
European (Non-Finnish)0.0001070.000105
Middle Eastern0.000.00
South Asian0.00009810.0000980
Other0.0001650.000163

dbNSFP

Source: dbNSFP

Function
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). {ECO:0000269|PubMed:17335001, ECO:0000269|PubMed:21981118}.;
Disease
DISEASE: 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 mutations affecting the gene represented in this entry.; DISEASE: 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 mutations affecting the gene represented in this entry.;
Pathway
Tacrolimus/Cyclosporine Pathway, Pharmacodynamics (Consensus)

Recessive Scores

pRec
0.422

Haploinsufficiency Scores

pHI
0.864
hipred
N
hipred_score
0.297
ghis
0.594

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
H
gene_indispensability_pred
E
gene_indispensability_score
0.801

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Nrl
Phenotype
behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); pigmentation phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); homeostasis/metabolism phenotype;

Gene ontology

Biological process
transcription by RNA polymerase II;regulation of rhodopsin gene expression;visual perception;positive regulation of rhodopsin gene expression;positive regulation of transcription by RNA polymerase II;retinal rod cell development;response to stimulus
Cellular component
nucleus;nucleoplasm;cytoplasm;cytosol
Molecular function
RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;transcription coactivator activity;protein binding;leucine zipper domain binding;sequence-specific DNA binding;promoter-specific chromatin binding