NCOR2

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

Basic information

Region (hg38): 12:124324414-124567612

Links

ENSG00000196498 ∙ NCBI:9612 ∙ OMIM:600848 ∙ HGNC:7673 ∙ Uniprot:Q9Y618 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NCOR2 gene.

• Inborn genetic diseases (138 variants)
• not provided (28 variants)
• NCOR2-related condition (2 variants)
• not specified (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NCOR2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				15	2	17
missense			140	3	2	145
nonsense						0
start loss						0
frameshift						0
inframe indel					1	1
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding					3	3
Total	0	0	140	18	8

Variants in NCOR2

This is a list of pathogenic ClinVar variants found in the NCOR2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-124325410-T-A		not specified	Uncertain significance (Aug 02, 2021)
12-124325413-C-A		not specified	Uncertain significance (Aug 02, 2021)
12-124325419-G-C		not specified	Uncertain significance (Aug 02, 2021)
12-124325421-G-C		not specified	Uncertain significance (Aug 02, 2021)
12-124325427-T-G		not specified	Uncertain significance (Aug 02, 2021)
12-124325430-T-A		not specified	Uncertain significance (Aug 02, 2021)
12-124325431-G-T		not specified	Uncertain significance (May 08, 2023)
12-124325446-G-A		not specified	Uncertain significance (Oct 18, 2021)
12-124325464-A-G		not specified	Uncertain significance (Jan 23, 2024)
12-124325470-G-A		not specified	Uncertain significance (Dec 13, 2023)
12-124325482-C-T			Benign (Jul 17, 2019)
12-124325499-G-A		not specified	Uncertain significance (Jan 22, 2024)
12-124325500-C-T		not specified	Uncertain significance (Aug 30, 2021)
12-124325514-G-A		not specified	Uncertain significance (Sep 29, 2022)
12-124325537-C-T		NCOR2-related disorder	Likely benign (Sep 16, 2019)
12-124325547-C-T		NCOR2-related disorder	Uncertain significance (Jun 27, 2023)
12-124325588-G-A		NCOR2-related disorder	Likely benign (Mar 01, 2019)
12-124326195-G-A		NCOR2-related disorder	Likely benign (Feb 20, 2019)
12-124326220-C-T		not specified	Uncertain significance (Feb 10, 2022)
12-124326221-G-A		not specified	Uncertain significance (Feb 28, 2024)
12-124326258-C-T		NCOR2-related disorder	Benign (Apr 02, 2019)
12-124326291-C-A		NCOR2-related disorder	Benign (Jul 31, 2019)
12-124326322-G-A		not specified	Uncertain significance (Dec 15, 2022)
12-124326365-C-T		NCOR2-related disorder	Likely benign (Feb 10, 2022)
12-124326366-G-A		NCOR2-related disorder	Likely benign (May 28, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NCOR2	protein_coding	protein_coding	ENST00000405201	47	243175

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	4.66e-10	124789	0	16	124805	0.0000641

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.01	1310	1.53e+3	0.856	0.000108	15933
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000298	0.000287
Ashkenazi Jewish	0.000201	0.000199
East Asian	0.000114	0.000111
Finnish	0.00	0.00
European (Non-Finnish)	0.0000547	0.0000530
Middle Eastern	0.000114	0.000111
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

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}.
• Pathway: Notch signaling pathway - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);NOTCH-Ncore;Androgen receptor signaling pathway;Adipogenesis;Aryl Hydrocarbon Receptor;Notch Signaling Pathway;Notch Signaling Pathway;Notch Signaling Pathway;Developmental Biology;Notch;Disease;Signal Transduction;Gene expression (Transcription);mechanism of gene regulation by peroxisome proliferators via ppara;nuclear receptors coordinate the activities of chromatin remodeling complexes and coactivators to facilitate initiation of transcription in carcinoma cells;mets affect on macrophage differentiation;Generic Transcription Pathway;Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha);Metabolism of lipids;map kinase inactivation of smrt corepressor;HDACs deacetylate histones;RNA Polymerase II Transcription;Chromatin modifying enzymes;Metabolism;Transcriptional regulation of white adipocyte differentiation;Downregulation of SMAD2/3:SMAD4 transcriptional activity;Signaling by NOTCH1;Signaling by NOTCH;AndrogenReceptor;Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer;Signaling events mediated by HDAC Class II;Chromatin organization;RXR and RAR heterodimerization with other nuclear receptor;Notch signaling pathway;Constitutive Signaling by NOTCH1 PEST Domain Mutants;Signaling by NOTCH1 PEST Domain Mutants in Cancer;Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants;Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer;Signaling by NOTCH1 in Cancer;Signaling by TGF-beta Receptor Complex;Signaling by TGF-beta family members;Notch-mediated HES/HEY network;Diseases of signal transduction;Validated nuclear estrogen receptor alpha network;Retinoic acid receptors-mediated signaling;NOTCH1 Intracellular Domain Regulates Transcription;Signaling events mediated by HDAC Class I (Consensus)

Recessive Scores

• pRec: 0.499

Intolerance Scores

• loftool: 0.339
• rvis_EVS: -2.6
• rvis_percentile_EVS: 0.82

Haploinsufficiency Scores

• pHI: 0.884
• hipred: Y
• hipred_score: 0.756
• ghis: 0.629

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.959

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ncor2
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; liver/biliary system phenotype; skeleton phenotype; immune system phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: ncor2
• Affected structure: neutrophil
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• 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;negative regulation of production of miRNAs involved in gene silencing by miRNA
• Cellular component: histone deacetylase complex;nuclear chromatin;nucleus;nucleoplasm;membrane;nuclear matrix;nuclear body;transcriptional repressor complex
• 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;protein binding;nuclear hormone receptor binding;histone deacetylase binding;sequence-specific DNA binding;protein N-terminus binding