NCOR2: Nuclear Receptor Corepressor 2
A key transcriptional corepressor regulating nuclear receptor signaling and gene silencing.
Gene Information Card
| Symbol | NCOR2 |
|---|---|
| Full Name | Nuclear Receptor Corepressor 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 12q24.31 |
| NCBI Gene ID | 9612 ncbi.nlm.nih.gov/gene/9612 |
| Ensembl ID | ENSG00000196498 |
| UniProt ID | Q9Y618 |
| OMIM ID | 600848 |
| HGNC ID | 7673 |
| Aliases | SMRT, SMRTE, TRAC1, CTG26, N-CoR2, hSMRT |
Description
NCOR2 (Nuclear Receptor Corepressor 2), also known as SMRT (Silencing Mediator of Retinoid and Thyroid hormone receptors), encodes a transcriptional corepressor protein. It mediates gene silencing by recruiting histone deacetylases (HDACs) to nuclear receptor target genes, repressing transcription in the absence of ligand. NCOR2 is involved in multiple signaling pathways, including retinoic acid, thyroid hormone, and Wnt signaling, and plays roles in development, metabolism, and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Huntington disease | NCOR2 interacts with mutant huntingtin protein, contributing to transcriptional dysregulation and neuronal toxicity. | PMID: 21926972; NCBI Gene |
| Acute promyelocytic leukemia | NCOR2 is recruited by PML-RARA fusion protein, leading to aberrant repression of retinoic acid target genes. | PMID: 9734352; NCBI Gene |
| Thyroid hormone resistance | Mutations in NCOR2 can impair thyroid hormone receptor corepression, altering hormone signaling. | OMIM #600848 |
| Colorectal cancer | NCOR2 overexpression is associated with poor prognosis and may promote tumor progression via Wnt/β-catenin pathway. | PMID: 25670082; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Liver | 8.7 | Low |
| Heart | 6.5 | Low |
| Testis | 15.2 | High |
| Kidney | 9.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 14.5 | Embryonic kidney cells; high expression |
| HeLa | 11.2 | Cervical cancer cells; moderate expression |
| K562 | 8.9 | Leukemia cells; low expression |
| SH-SY5Y | 16.8 | Neuroblastoma cells; high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2104C>T (p.Arg702*) | Nonsense | <0.1% | Loss of function; truncation of corepressor domain |
| c.2876G>A (p.Arg959Gln) | Missense | <0.1% | Unknown; may alter interaction with HDACs |
| c.1234_1235insA | Frameshift | <0.1% | Loss of function; predicted to cause premature termination |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein or disrupt corepressor activity.
Gain of Function (GOF)
Not well documented; some missense variants may enhance repression but evidence is limited.
Dominant Negative (DN)
Truncated forms may interfere with wild-type NCOR2 function, but no confirmed dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • transcription corepressor activity | • chromatin binding |
| • histone deacetylase binding | • nuclear receptor binding |
| • negative regulation of transcription by RNA polymerase II | • chromatin remodeling |
Pathways
• Nuclear receptor signaling (RAR
• TR
• VDR)
• Wnt signaling pathway
• Notch signaling pathway
• HDAC-mediated gene silencing
Protein Summary
NCOR2 (SMRT) is a 2525-amino acid nuclear protein that functions as a corepressor for multiple transcription factors, including nuclear receptors. It contains multiple repression domains (RD1, RD2, RD3) that recruit HDAC complexes and other chromatin modifiers. The protein is ubiquitously expressed, with highest levels in brain and testis. NCOR2 plays critical roles in development, differentiation, and homeostasis, and its dysregulation is implicated in cancer, neurodegenerative diseases, and endocrine disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NCOR2 Knockout HEK293 Cell Line | EDJ-KQ433 | Human | 9612 | Details Get a Quote |
| NCOR2 Knockout A-549 Cell Line | EDJ-KQ18727 | Human | 9612 | Details Get a Quote |
| NCOR2 Knockout HCT 116 Cell Line | EDJ-KQ18728 | Human | 9612 | Details Get a Quote |
| NCOR2 Knockout HeLa Cell Line | EDJ-KQ18729 | Human | 9612 | Details Get a Quote |
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