NR2E3

Chr 15

nuclear receptor subfamily 2 group E member 3

Also known as: ESCS, ESCS1, PNR, RNR, RP37, rd7

NCBI Gene: 10002 ENSG00000278570 UniProt: Q9Y5X4

This orphan nuclear receptor functions as a transcriptional activator of rod photoreceptor development and repressor of cone development in the retina, directly regulating expression of rhodopsin and cone opsins. Mutations cause enhanced S-cone syndrome and retinitis pigmentosa, inherited in either autosomal recessive or autosomal dominant patterns depending on the specific variant.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This protein is part of a large family of nuclear receptor transcription factors involved in signaling pathways. Nuclear receptors have been shown to regulate pathways involved in embryonic development, as well as in maintenance of proper cell function in adults. Members of this family are characterized by discrete domains that function in DNA and ligand binding. This gene encodes a retinal nuclear receptor that is a ligand-dependent transcription factor. Defects in this gene are a cause of enhanced S cone syndrome. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtEnhanced S-cone syndrome 1

UniProtRetinitis pigmentosa 37

Clinical highlights

Gene–disease validity (ClinGen)

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

LOF

Mechanism· G2P

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GeneReview available — NR2E3

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in NR2E3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 69

589 rare PASS variants

Rare truncating (LoF)

1 in 520

95 rare PASS variants

Rare synonymous (reference)

1 in 150

249 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NR2E3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 74	1 in 480
South Asian	~43k	1 in 64	1 in 730
Remaining (unassigned)	~30k	1 in 61	1 in 540
European (Finnish)	~27k	1 in 180	≈ 1 in 8,200
Admixed American	~22k	1 in 92	1 in 750
African / African American	~21k	1 in 73	1 in 800
East Asian	~20k	1 in 95	1 in 3,100
Ashkenazi Jewish	~13k	1 in 170	≈ 1 in 6,300
Middle Eastern	~2,884	1 in 59	≈ 1 in 820

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 8 coding exons well covered in gnomAD exomes and genomes.? see exons ↓