NCOA2 (Nuclear Receptor Coactivator 2)
A transcriptional coactivator involved in hormone signaling, development, and cancer.
Gene Information Card
| Symbol | NCOA2 |
|---|---|
| Full Name | Nuclear Receptor Coactivator 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 8q13.3 |
| NCBI Gene ID | 10499 ncbi.nlm.nih.gov/gene/10499 |
| Ensembl ID | ENSG00000140396 |
| UniProt ID | Q15596 |
| OMIM ID | 601993 |
| HGNC ID | 7670 |
| Aliases | GRIP1, TIF2, NCoA-2, bHLHe75 |
Description
NCOA2 (Nuclear Receptor Coactivator 2) encodes a transcriptional coactivator protein that interacts with nuclear hormone receptors to enhance their transcriptional activity. The protein contains multiple nuclear receptor interaction domains and a histone acetyltransferase (HAT) domain, facilitating chromatin remodeling and gene activation. NCOA2 plays critical roles in development, metabolism, and hormone-responsive tissues. Alterations in NCOA2, including gene fusions and amplifications, are implicated in various cancers, particularly prostate cancer and hematological malignancies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prostate cancer | Gene fusions (e.g., TMPRSS2-ERG) and amplification of NCOA2 lead to enhanced androgen receptor signaling, promoting tumor growth. | ClinVar, COSMIC |
| Acute myeloid leukemia (AML) | NCOA2 fusions (e.g., NUP98-NCOA2) result in aberrant transcriptional activation and leukemogenesis. | COSMIC, PubMed |
| Endometrial cancer | NCOA2 amplification and overexpression contribute to estrogen receptor-mediated proliferation. | COSMIC, ClinVar |
| Breast cancer | NCOA2 overexpression correlates with poor prognosis and hormone receptor-positive subtypes. | ClinVar, COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Brain | 8.3 | Medium |
| Heart | 6.1 | Low |
| Liver | 4.7 | Low |
| Kidney | 5.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 15.2 | High expression; hormone-responsive |
| LNCaP (prostate cancer) | 11.8 | High expression; androgen-responsive |
| HEK293 (embryonic kidney) | 7.4 | Moderate expression |
| K562 (leukemia) | 6.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| NCOA2 amplification | Copy number gain | ~5-10% in prostate cancer | Increased coactivator activity, enhanced AR signaling |
| NUP98-NCOA2 fusion | Gene fusion | Rare in AML | Chimeric protein with aberrant transcriptional activity |
| NCOA2 missense variants | Missense | <1% in general population | Unknown functional impact; some reported in ClinVar as VUS |
Mutation functional classification
Loss of Function (LOF)
Not commonly reported; NCOA2 is primarily oncogenic via gain-of-function.
Gain of Function (GOF)
Amplification and fusions increase coactivator activity, promoting hormone receptor signaling and tumorigenesis.
Dominant Negative (DN)
Not documented for NCOA2.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Nuclear receptor signaling pathway (Reactome: R-HSA-383280)
• Chromatin modifying enzymes (Reactome: R-HSA-3247509)
• Transcriptional regulation by the AP-2 family (KEGG: hsa05200)
Protein Summary
The NCOA2 protein (also known as GRIP1/TIF2) is a 1464-amino-acid nuclear receptor coactivator that contains an N-terminal basic helix-loop-helix (bHLH) domain, a PAS domain, three LXXLL nuclear receptor interaction motifs, and a C-terminal histone acetyltransferase (HAT) domain. It enhances the transcriptional activity of nuclear receptors such as androgen receptor (AR), estrogen receptor (ER), and retinoic acid receptor (RAR) by recruiting additional coactivators and modifying chromatin structure. NCOA2 is widely expressed, with highest levels in testis and brain, and is frequently dysregulated in hormone-dependent cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NCOA2 Knockout HEK293 Cell Line | EDJ-KQ2687 | Human | 10499 | Details Get a Quote |
| NCOA2 Knockout A-549 Cell Line | EDJ-KQ23505 | Human | 10499 | Details Get a Quote |
| NCOA2 Knockout HCT 116 Cell Line | EDJ-KQ23506 | Human | 10499 | Details Get a Quote |
| NCOA2 Knockout HeLa Cell Line | EDJ-KQ23507 | Human | 10499 | Details Get a Quote |
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