NCOR2

protein-coding

nuclear receptor corepressor 2, the group of Myb/SANT domain containing|NCoR/SMRT transcriptional repression complex subunits

Gene summary

This gene encodes a nuclear receptor co-repressor that mediates transcriptional silencing of certain target genes. The encoded protein is a member of a family of thyroid hormone- and retinoic acid receptor-associated co-repressors. This protein acts as part of a multisubunit complex which includes histone deacetylases to modify chromatin structure that prevents basal transcriptional activity of target genes. Aberrant expression of this gene is associated with certain cancers. Alternate splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Apr 2011]

MANE transcript

NM_006312.6

Inheritance

—

ClinVar variants

P:1U:528B:100

Top phenotype

NCOR2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr12:124,324,415-124,567,612

External References & Databases

Ensembl (ENSG00000196498)

Transcript & Mutation Effects

hg38 • Region Span ~243.2 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 NCOR2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 497

NCOR2-related disorderTotal: 85

not providedTotal: 28

Multiple myelomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006312.6. 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			9 clinvar	62 clinvar	14 clinvar	85
missense		1 clinvar	496 clinvar	16 clinvar	8 clinvar	521
nonsense			6 clinvar			6
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			15 clinvar			15
Total	0	1	528	78	22	629

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006312.6	RefSeq	NP_006303.4	47	MANE Select
ENST00000405201.6	Ensembl	ENSP00000384018.1	47	MANE Select
NM_001077261.4	RefSeq	NP_001070729.2	46	Standard
NM_001206654.2	RefSeq	NP_001193583.1	46	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ncor2	Danio rerio	Structure: neutrophil Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

ncor2

Danio rerio

Structure: neutrophil

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Notch signaling pathway - Homo sapiens (human)
Epstein-Barr virus infection - Homo sapiens (human)
NOTCH-Ncore
Androgen receptor signaling pathway
Adipogenesis

Biological Process

negative regulation of transcription by RNA polymerase II
regulation of lipid metabolic process
negative regulation of transcription, DNA-templated
negative regulation of androgen receptor signaling pathway
regulation of cellular ketone metabolic process by negative regulation of transcription from RNA polymerase II promoter

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
RNA polymerase II regulatory region DNA binding
chromatin binding
transcription corepressor activity
Notch binding

Cellular Component

histone deacetylase complex
nuclear chromatin
nucleus
nucleoplasm
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000405201
Coding exons: 47
Length: 243175
Individuals with no LoFs: 124789
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 124805
p: 0.0000641

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.01	1310	1.53e+3	0.856	0.000108	15933
Missense (PolyPhen)		492	544.69	0.90327		5692
Synonymous	-1.47	734	685	1.07	0.0000550	5182
Loss of Function	8.62	11	108	0.102	0.00000561	1274

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00027	0.00026	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000055	0.000053	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional corepressor (PubMed:20812024). Mediates the transcriptional repression activity of some nuclear receptors by promoting chromatin condensation, thus preventing access of the basal transcription. Isoform 1 and isoform 4 have different affinities for different nuclear receptors. Involved in the regulation BCL6-dependent of the germinal center (GC) reactions, mainly through the control of the GC B-cells proliferation and survival. Recruited by ZBTB7A to the androgen response elements/ARE on target genes, negatively regulates androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). {ECO:0000269|PubMed:18212045, ECO:0000269|PubMed:20812024, ECO:0000269|PubMed:23911289}.;

Recessive Scores

pRec: 0.499

Intolerance Scores

LoFtool: 0.339
RVIS EVS: -2.6
RVIS percentile EVS: 0.82

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.959

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High