NR2E1

protein-coding

nuclear receptor subfamily 2 group E member 1, the group of Nuclear receptor subfamily 2 group E

Gene summary

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]

Previous symbols:

MANE transcript

NM_003269.5

Inheritance

ClinVar variants

U:30B:4

Top phenotype

NR2E1-related disorder

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr6:108,166,022-108,188,805

External References & Databases

Ensembl (ENSG00000112333)

Transcript & Mutation Effects

hg38 • Region Span ~22.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

microcephalyLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0001149

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NR2E1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 29

NR2E1-related disorderTotal: 6

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003269.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				4 clinvar		4
missense			29 clinvar			29
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	30	4	0	34

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003269.5	RefSeq	NP_003260.1	9	MANE Select
ENST00000368986.9	Ensembl	ENSP00000357982.5	9	MANE Select
NM_001286102.1	RefSeq	NP_001273031.1	9	Standard
ENST00000368983.3	Ensembl	ENSP00000357979.3	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

NHR
Nuclear Receptors
Olfactory bulb development and olfactory learning
Signal Transduction
Gene expression (Transcription)

Biological Process

negative regulation of transcription by RNA polymerase II
behavioral fear response
aggressive behavior
transcription initiation from RNA polymerase II promoter
nervous system development

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription repressor activity, RNA polymerase II-specific
DNA-binding transcription activator activity, RNA polymerase II-specific
steroid hormone receptor activity
protein binding

Cellular Component

nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000368986
Coding exons: 9
Length: 22752
Individuals with no LoFs: 125745
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 125748
p: 0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.60	111	219	0.506	0.0000122	2483
Missense (PolyPhen)		15	57.537	0.2607		712
Synonymous	1.08	76	88.9	0.855	0.00000509	768
Loss of Function	4.06	0	19.2	0.00	9.54e-7	229

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0.00018	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Orphan receptor that binds DNA as a monomer to hormone response elements (HRE) containing an extended core motif half- site sequence 5'-AAGGTCA-3' in which the 5' flanking nucleotides participate in determining receptor specificity (By similarity). May be required to pattern anterior brain differentiation. Involved in the regulation of retinal development and essential for vision. During retinogenesis, regulates PTEN-Cyclin D expression via binding to the promoter region of PTEN and suppressing its activity (By similarity). May be involved in retinoic acid receptor (RAR) regulation in retinal cells. {ECO:0000250}.;

Recessive Scores

pRec: 0.119

Intolerance Scores

LoFtool: 0.0514
RVIS EVS: -0.25
RVIS percentile EVS: 35.42

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.993

Gene Damage Prediction

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