NR2E3

nuclear receptor subfamily 2 group E member 3, the group of Nuclear receptor subfamily 2 group E

Basic information

Region (hg38): 15:71792637-71818259

Links

ENSG00000278570 ∙ NCBI:10002 ∙ OMIM:604485 ∙ HGNC:7974 ∙ Uniprot:Q9Y5X4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa (Supportive), mode of inheritance: AD
• Goldmann-Favre syndrome (Supportive), mode of inheritance: AR
• enhanced S-cone syndrome (Strong), mode of inheritance: AR
• enhanced S-cone syndrome (Strong), mode of inheritance: AR
• retinitis pigmentosa 37 (Strong), mode of inheritance: AD
• enhanced S-cone syndrome (Definitive), mode of inheritance: AR
• retinitis pigmentosa 37 (Definitive), mode of inheritance: AD
• retinitis pigmentosa 37 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Enhanced S-cone syndrome; Retinitis pigmentosa 37	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	13553271; 11071390; 10655056; 15229190; 17564971; 18294254; 20212206; 21364904; 22605927; 22807301

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NR2E3 gene.

• not provided (556 variants)
• Enhanced S-cone syndrome (180 variants)
• Retinitis pigmentosa (61 variants)
• Goldmann-Favre syndrome (48 variants)
• Retinitis Pigmentosa, Recessive (34 variants)
• Enhanced S-cone syndrome;Retinitis pigmentosa 37 (29 variants)
• Retinitis pigmentosa 37 (27 variants)
• Retinal dystrophy (27 variants)
• Inborn genetic diseases (24 variants)
• Retinitis pigmentosa 37;Enhanced S-cone syndrome (15 variants)
• not specified (13 variants)
• NR2E3-Related Disorders (4 variants)
• NR2E3-related condition (3 variants)
• Autosomal recessive retinitis pigmentosa (2 variants)
• Cone-rod dystrophy (2 variants)
• Color vision defect;Visual impairment;Horizontal nystagmus;Retinal dystrophy (1 variants)
• Ocular albinism (1 variants)
• Abnormality of the eye (1 variants)
• Enhanced S-cone syndrome;NR2E3-Related Disorders (1 variants)
• Leber congenital amaurosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NR2E3 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		1	15	149	5	170
missense	9	12	173	7	2	203
nonsense	12	7				19
start loss			3			3
frameshift	29	18	2	1		50
inframe indel	1	2	3			6
splice donor/acceptor (+/-2bp)	2	11	3			16
splice region		1	7	20		28
non coding			32	53	4	89
Total	53	51	231	210	11

Highest pathogenic variant AF is 0.0000526

Variants in NR2E3

This is a list of pathogenic ClinVar variants found in the NR2E3 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-71810534-C-T		Enhanced S-cone syndrome • Retinitis pigmentosa	Likely benign (Jan 13, 2018)
15-71810605-G-A		Retinitis Pigmentosa, Recessive • Enhanced S-cone syndrome	Uncertain significance (Jun 14, 2016)
15-71810605-G-T		Enhanced S-cone syndrome • Retinitis Pigmentosa, Recessive • Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
15-71810697-C-T		Retinitis Pigmentosa, Recessive • Enhanced S-cone syndrome	Uncertain significance (Jun 14, 2016)
15-71810734-C-T		Enhanced S-cone syndrome;Retinitis pigmentosa 37	Uncertain significance (Mar 24, 2017)
15-71810745-T-A			Uncertain significance (Oct 03, 2021)
15-71810745-T-C			Uncertain significance (Aug 27, 2021)
15-71810745-T-G		Enhanced S-cone syndrome	Uncertain significance (Jun 28, 2022)
15-71810748-A-G			Uncertain significance (Sep 27, 2023)
15-71810752-C-T			Uncertain significance (Jun 10, 2022)
15-71810754-G-A			Uncertain significance (Sep 23, 2020)
15-71810766-T-C			Uncertain significance (Nov 13, 2019)
15-71810767-G-A		Retinitis pigmentosa • Enhanced S-cone syndrome	Conflicting classifications of pathogenicity (Dec 03, 2023)
15-71810772-GC-G			Pathogenic (Feb 03, 2022)
15-71810774-T-G			Uncertain significance (Oct 04, 2023)
15-71810778-CA-C			Pathogenic (Nov 17, 2020)
15-71810779-A-G			Likely benign (Apr 06, 2021)
15-71810780-G-T		Enhanced S-cone syndrome	Uncertain significance (Mar 03, 2022)
15-71810782-G-A			Likely benign (Mar 02, 2021)
15-71810788-A-G		Retinitis pigmentosa 37;Enhanced S-cone syndrome	Likely benign (Jan 11, 2024)
15-71810790-C-T		Goldmann-Favre syndrome	Uncertain significance (Aug 13, 2020)
15-71810793-C-T		Goldmann-Favre syndrome • Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 17, 2022)
15-71810794-G-A		Enhanced S-cone syndrome • NR2E3-related disorder	Likely benign (Dec 09, 2023)
15-71810793-C-CAG			Pathogenic (Jul 28, 2021)
15-71810795-C-T			Uncertain significance (Aug 19, 2022)

GnomAD

Source: gnomAD

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Orphan nuclear receptor of retinal photoreceptor cells. Transcriptional factor that is an activator of rod development and repressor of cone development. Binds the promoter region of a number of rod- and cone-specific genes, including rhodopsin, M- and S-opsin and rod-specific phosphodiesterase beta subunit. Enhances rhodopsin expression. Represses M- and S-cone opsin expression. {ECO:0000269|PubMed:15689355, ECO:0000269|PubMed:24069298}.
• Disease: DISEASE: Enhanced S cone syndrome (ESCS) [MIM:268100]: Autosomal recessive retinopathy in which patients have increased sensitivity to blue light; perception of blue light is mediated by what is normally the least populous cone photoreceptor subtype, the S (short wavelength, blue) cones. ESCS is also associated with visual loss, with night blindness occurring from early in life, varying degrees of L (long, red)- and M (middle, green)-cone vision, and retinal degeneration. {ECO:0000269|PubMed:10655056, ECO:0000269|PubMed:11071390, ECO:0000269|PubMed:12963616, ECO:0000269|PubMed:15459973, ECO:0000269|PubMed:16225923, ECO:0000269|PubMed:18294254, ECO:0000269|PubMed:19006237, ECO:0000269|PubMed:24069298}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Retinitis pigmentosa 37 (RP37) [MIM:611131]: 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:17564971, ECO:0000269|PubMed:19006237}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: NHR;Gene expression (Transcription);Generic Transcription Pathway;Nuclear Receptor transcription pathway;RNA Polymerase II Transcription (Consensus)

Recessive Scores

• pRec: 0.523

Haploinsufficiency Scores

• pHI: 0.646

Essentials

• gene_indispensability_pred: E
• gene_indispensability_score: 0.986

Mouse Genome Informatics

• Gene name: Nr2e3
• 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); cellular phenotype

Zebrafish Information Network

• Gene name: nr2e3
• Affected structure: parapineal organ
• Phenotype tag: abnormal
• Phenotype quality: has extra parts of type

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;transcription by RNA polymerase II;transcription initiation from RNA polymerase II promoter;signal transduction;visual perception;phototransduction;negative regulation of cell population proliferation;intracellular receptor signaling pathway;eye photoreceptor cell development;steroid hormone mediated signaling pathway;positive regulation of rhodopsin gene expression;positive regulation of transcription by RNA polymerase II;retina development in camera-type eye
• Cellular component: nucleus;nucleoplasm;transcription factor complex
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription activator activity, RNA polymerase II-specific;steroid hormone receptor activity;nuclear receptor activity;zinc ion binding;sequence-specific DNA binding