NRL

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

Basic information

Region (hg38): 14:24078661-24115010

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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinitis pigmentosa 27; Clumped pigmentary retinal degeneration	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	10192380; 11039579; 12796249; 15591106; 17335001

ClinVar

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

• not provided (281 variants)
• Inborn genetic diseases (41 variants)
• Retinitis pigmentosa (37 variants)
• Phosphoenolpyruvate carboxykinase deficiency, mitochondrial (11 variants)
• Retinitis pigmentosa 27 (10 variants)
• Retinal dystrophy (6 variants)
• not specified (4 variants)
• Retinal degeneration, autosomal recessive, clumped pigment type (2 variants)
• PCK2-related condition (1 variants)
• Enhanced S-cone syndrome (1 variants)
• Retinitis Pigmentosa, Dominant (1 variants)
• 6 conditions (1 variants)
• PCK2-related neuropathy (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				29	2	31
missense	4	4	81		1	90
nonsense	1	3				4
start loss			1			1
frameshift	7		6			13
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1		2			3
splice region			2	1		3
non coding	1		119	40	24	184
Total	14	7	210	69	27

Highest pathogenic variant AF is 0.000171

Variants in NRL

This is a list of pathogenic ClinVar variants found in the NRL region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-24080109-A-G		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
14-24080118-C-T		Retinitis pigmentosa	Benign (Jan 13, 2018)
14-24080193-C-T		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
14-24080301-G-A		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
14-24080372-C-T		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
14-24080402-C-G		Retinitis pigmentosa	Benign (Jan 13, 2018)
14-24080423-C-T		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
14-24080456-C-G		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
14-24080458-G-A		Retinitis pigmentosa	Uncertain significance (Mar 02, 2018)
14-24080563-G-T		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
14-24080569-G-A		Retinitis pigmentosa	Benign (Jan 13, 2018)
14-24080678-G-A		Retinitis pigmentosa	Benign (Jan 13, 2018)
14-24080756-T-C		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
14-24080764-G-A		Retinitis pigmentosa	Likely benign (Jan 12, 2018)
14-24080935-T-A		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
14-24080952-AC-A		Retinitis Pigmentosa, Dominant	Uncertain significance (Jun 14, 2016)
14-24081015-C-T		Retinitis pigmentosa	Benign (Jan 13, 2018)
14-24081023-G-T		Retinitis pigmentosa	Likely benign (Jan 13, 2018)
14-24081063-T-A		Retinitis pigmentosa	Benign (Jan 12, 2018)
14-24081123-G-T		Retinitis pigmentosa	Likely benign (Jan 13, 2018)
14-24081128-G-A		Retinitis pigmentosa	Likely benign (Jan 13, 2018)
14-24081180-C-T		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
14-24081237-C-A		Retinitis pigmentosa	Uncertain significance (Apr 01, 2021)
14-24081238-A-G			Uncertain significance (May 01, 2023)
14-24081239-G-A			Likely benign (Aug 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NRL	protein_coding	protein_coding	ENST00000561028	2	34908

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0476	0.865	125720	0	23	125743	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.614	103	122	0.844	0.00000601	1457
Missense in Polyphen		30	42.349	0.70841		554
Synonymous	-0.776	63	55.6	1.13	0.00000269	548
Loss of Function	1.41	3	7.03	0.427	3.87e-7	77

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000210	0.000206
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.000107	0.000105
Middle Eastern	0.00	0.00
South Asian	0.0000981	0.0000980
Other	0.000165	0.000163

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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