NR2C1

protein-coding

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

Gene summary

This gene encodes a nuclear hormone receptor characterized by a highly conserved DNA binding domain (DBD), a variable hinge region, and a carboxy-terminal ligand binding domain (LBD) that is typical for all members of the steroid/thyroid hormone receptor superfamily. This protein also belongs to a large family of ligand-inducible transcription factors that regulate gene expression by binding to specific DNA sequences within promoters of target genes. Multiple alternatively spliced transcript variants have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

Previous symbols:

MANE transcript

NM_003297.4

Inheritance

—

ClinVar variants

P:1U:74B:5

Top phenotype

Flexion contracture

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr12:95,020,229-95,073,628

External References & Databases

Ensembl (ENSG00000120798)

Transcript & Mutation Effects

hg38 • Region Span ~53.4 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 NR2C1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 67

not providedTotal: 1

Flexion contractureTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003297.4. 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			2 clinvar	2 clinvar		4
missense			65 clinvar	3 clinvar		68
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)		1 clinvar	7 clinvar			8
Total	0	1	74	5	0	80

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 67 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003297.4	RefSeq	NP_003288.2	13	MANE Select
ENST00000333003.10	Ensembl	ENSP00000333275.4	13	MANE Select
NM_001032287.3	RefSeq	NP_001027458.1	11	Standard
NM_001127362.2	RefSeq	NP_001120834.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

NHR
Gene expression (Transcription)
Generic Transcription Pathway
Nuclear Receptor transcription pathway
RNA Polymerase II Transcription

Biological Process

negative regulation of transcription by RNA polymerase II
transcription initiation from RNA polymerase II promoter
steroid hormone mediated signaling pathway
positive regulation of retinoic acid receptor signaling pathway

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription repressor activity, RNA polymerase II-specific
DNA binding
steroid hormone receptor activity

Cellular Component

nucleoplasm
PML body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000333003
Coding exons: 13
Length: 53475
Individuals with no LoFs: 125732
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 125748
p: 0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.16	256	314	0.816	0.0000152	3965
Missense (PolyPhen)		91	145.01	0.62753		1825
Synonymous	1.62	88	110	0.803	0.00000568	1113
Loss of Function	4.34	7	34.5	0.203	0.00000198	403

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.000059	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000071	0.000053	rare
South Asian	0.00015	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Orphan nuclear receptor. Binds the IR7 element in the promoter of its own gene in an autoregulatory negative feedback mechanism. Primarily repressor of a broad range of genes. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences. Together with NR2C2, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription. Also activator of OCT4 gene expression. May be involved in stem cell proliferation and differentiation. Mediator of retinoic acid- regulated preadipocyte proliferation. {ECO:0000269|PubMed:12093804, ECO:0000269|PubMed:17010934}.;

Recessive Scores

pRec: 0.144

Intolerance Scores

LoFtool: 0.0729
RVIS EVS: -0.51
RVIS percentile EVS: 21.41

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.989

Gene Damage Prediction

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