NR2C2

protein-coding

nuclear receptor subfamily 2 group C member 2, the group of Nuclear receptor subfamily 2 group C

Gene summary

This gene encodes a protein that belongs to the nuclear hormone receptor family. Members of this family act as ligand-activated transcription factors and function in many biological processes such as development, cellular differentiation and homeostasis. The activated receptor/ligand complex is translocated to the nucleus where it binds to hormone response elements of target genes. The protein encoded by this gene plays a role in protecting cells from oxidative stress and damage induced by ionizing radiation. The lack of a similar gene in mouse results in growth retardation, severe spinal curvature, subfertility, premature aging, and prostatic intraepithelial neoplasia (PIN) development. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2014]

Previous symbols:

MANE transcript

NM_001291694.2

Inheritance

—

ClinVar variants

U:36B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr3:14,947,583-15,053,600

External References & Databases

Ensembl (ENSG00000177463)

Transcript & Mutation Effects

hg38 • Region Span ~106.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NR2C2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 30

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001291694.2. 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			3 clinvar	1 clinvar	1 clinvar	5
missense			29 clinvar			29
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	36	1	1	38

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 65 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001291694.2	RefSeq	NP_001278623.1	13	MANE Select
ENST00000425241.6	Ensembl	ENSP00000388387.1	13	MANE Select
NM_003298.5	RefSeq	NP_003289.2	14	Standard
ENST00000323373.10	Ensembl	ENSP00000320447.6	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

NHR
Androgen receptor signaling pathway
Nuclear Receptors
Hypothesized Pathways in Pathogenesis of Cardiovascular Disease
EMT transition in Colorectal Cancer

Biological Process

regulation of transcription, DNA-templated
transcription initiation from RNA polymerase II promoter
spermatogenesis
nervous system development
cell differentiation

Molecular Function

RNA polymerase II regulatory region sequence-specific DNA binding
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 transcription factor activity

Cellular Component

nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000323373
Coding exons: 14
Length: 106017
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125740
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.18	195	366	0.532	0.0000215	4040
Missense (PolyPhen)		17	100.98	0.16835		1073
Synonymous	-0.523	141	133	1.06	0.00000765	1203
Loss of Function	4.61	2	28.6	0.0698	0.00000130	345

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Orphan nuclear receptor that can act as a repressor or activator of transcription. An important repressor of nuclear receptor signaling pathways such as retinoic acid receptor, retinoid X, vitamin D3 receptor, thyroid hormone receptor and estrogen receptor pathways. May regulate gene expression during the late phase of spermatogenesis. Together with NR2C1, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription including that of GATA1. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences. Plays a fundamental role in early embryonic development and embryonic stem cells. Required for normal spermatogenesis and cerebellum development. Appears to be important for neurodevelopmentally regulated behavior (By similarity). Activates transcriptional activity of LHCG. Antagonist of PPARA-mediated transactivation. {ECO:0000250, ECO:0000269|PubMed:10347174, ECO:0000269|PubMed:10644740, ECO:0000269|PubMed:17974920, ECO:0000269|PubMed:7779113, ECO:0000269|PubMed:9556573}.;

Recessive Scores

pRec: 0.184

Intolerance Scores

LoFtool: 0.0630
RVIS EVS: -0.89
RVIS percentile EVS: 10.37

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

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