NR2E1

Chr 6

nuclear receptor subfamily 2 group E member 1

Also known as: TLL, TLX, XTLL

NCBI Gene: 7101ENSG00000112333UniProt: Q9Y466

The protein encoded by this gene is an orphan receptor involved in retinal development. The encoded protein also regulates adult neural stem cell proliferation and may be involved in control of aggressive behavior. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

61
ClinVar variants
18
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— NR2E1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
18 Pathogenic / Likely Pathogenic· 37 VUS of 61 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.16LOEUF
pLI 0.999
Z-score 4.06
OE 0.00 (0.00–0.16)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.60Z-score
OE missense 0.51 (0.43–0.59)
111 obs / 219.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.16)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.51 (0.43–0.59)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.85
0≤1.21.6
LoF obs/exp: 0 / 19.2Missense obs/exp: 111 / 219.2Syn Z: 1.08

ClinVar Variant Classifications

61 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
VUS37
Likely Benign5
Benign1
18
Pathogenic
37
VUS
5
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
0
0
0
0
0
VUS
0
29
8
0
37
Likely Benign
0
0
0
5
5
Benign
0
0
1
0
1
Total02927561

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NR2E1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Co-activator candidate interactions for orphan nuclear receptor NR2E1.
Corso-Díaz X et al.·BMC Genomics
2016
Retina restored and brain abnormalities ameliorated by single-copy knock-in of human NR2E1 in null mice.
Schmouth JF et al.·Mol Cell Biol
2012
Absence of NR2E1 mutations in patients with aniridia.
Corso-Díaz X et al.·Mol Vis
2012Cohort
Bioinformatics-Led Identification of Potential Biomarkers and Inflammatory Infiltrates in Burn Injury.
Niu Z et al.·J Burn Care Res
2023
Minireview: role of orphan nuclear receptors in cancer and potential as drug targets.
Safe S et al.·Mol Endocrinol
2014Review
Absence of mutations in NR2E1 and SNX3 in five patients with MMEP (microcephaly, microphthalmia, ectrodactyly, and prognathism) and related phenotypes.
Kumar RA et al.·BMC Med Genet
2007Case report
Differential dimerization of variants linked to enhanced S-cone sensitivity syndrome (ESCS) located in the NR2E3 ligand-binding domain.
von Alpen D et al.·Hum Mutat
2015
Localization of the mouse kidney disease (kd) gene to a YAC/BAC contig on Chromosome 10.
Dell KM et al.·Mamm Genome
2000Functional
Modelling human regulatory variation in mouse: finding the function in genome-wide association studies and whole-genome sequencing.
Schmouth JF et al.·PLoS Genet
2012Review
Differential expression and methylation of brain developmental genes define location-specific subsets of pilocytic astrocytoma.
Lambert SR et al.·Acta Neuropathol
2013
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Polymorphism of g.462C>G in the NR2E1/PstI gene and its relationship with Japanese Quail (Coturnix japonica) economic traits.
Putra WPB et al.·Open Vet J
2025🔓 Open Access
Functional studies on methylation of the promoter region of the NR2E1 gene regulating adipocytes in beef cattle.
Feng L et al.·BMC Genomics
2025🔓 Open AccessFunctional
Increased nuclear receptor subfamily 2, group E, member 1 (NR2E1) concentrations of PBMCs are associated with chronic inflammation in overweight/obesity.
He M et al.·Heliyon
2024🔓 Open Access
Lack of Nr2e1 expression in hepatocytes impaired cell survival and aggravated palmitate-induced oxidative stress.
Xiong Q et al.·Adv Med Sci
2024
A NR2E1-interacting peptide of LSD1 inhibits the proliferation of brain tumour initiating cells.
Hu R et al.·Cell Prolif
2023🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools