CTBP2: C-Terminal Binding Protein 2 - Transcriptional Corepressor and Key Regulator of Development and Disease
Comprehensive genomic and functional analysis of CTBP2, a dual-function transcriptional corepressor involved in cancer, neurodevelopment, and metabolic disorders.
Gene Information Card
| Symbol | CTBP2 |
|---|---|
| Full Name | C-terminal binding protein 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 10q26.13 |
| NCBI Gene ID | 1488 ncbi.nlm.nih.gov/gene/1488 |
| Ensembl ID | ENSG00000175029 |
| UniProt ID | P56545 |
| OMIM ID | 602619 |
| HGNC ID | 2495 |
| Aliases | CtBP2, HsT18368, RIBEYE |
Description
CTBP2 (C-terminal binding protein 2) encodes a transcriptional corepressor that interacts with C-terminal binding motifs of various transcription factors, including E1A and ZEB1. It functions as a homodimer and regulates gene expression by recruiting histone deacetylases and methyltransferases. CTBP2 also has a retina-specific isoform (RIBEYE) that is a structural component of synaptic ribbons. The gene is involved in development, apoptosis, cell cycle control, and its dysregulation is linked to cancer, neurodevelopmental disorders, and metabolic diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | CTBP2 overexpression promotes epithelial-mesenchymal transition (EMT) via repression of E-cadherin, enhancing invasion and metastasis. | PMID: 23431129; COSMIC |
| Breast cancer | CTBP2 upregulation correlates with poor prognosis; it represses pro-apoptotic genes and enhances cell survival. | PMID: 25636834; COSMIC |
| Huntington disease | CTBP2 interacts with mutant huntingtin protein, contributing to transcriptional dysregulation and neuronal toxicity. | PMID: 12086634; OMIM #602619 |
| Intellectual disability | De novo CTBP2 missense variants identified in patients with developmental delay and intellectual disability. | PMID: 28135719; ClinVar |
| Retinal dystrophy | RIBEYE isoform mutations affect synaptic ribbon structure, leading to visual impairment. | PMID: 20096349; OMIM #602619 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Retina | 18.3 | High |
| Heart | 8.2 | Low |
| Liver | 6.1 | Low |
| Kidney | 7.4 | Low |
| Testis | 15.1 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.2 | Embryonic kidney; high CTBP2 expression |
| HeLa | 11.8 | Cervical carcinoma; moderate expression |
| MCF7 | 9.5 | Breast cancer; moderate expression |
| HCT116 | 16.7 | Colorectal carcinoma; high expression |
| SH-SY5Y | 13.0 | Neuroblastoma; high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339Trp) | Missense | <0.01% | Loss of transcriptional repression activity; associated with intellectual disability |
| c.1246G>A (p.Gly416Arg) | Missense | <0.01% | Altered dimerization; linked to neurodevelopmental delay |
| c.1570_1572del (p.Lys524del) | In-frame deletion | <0.01% | RIBEYE isoform; retinal dystrophy |
| c.1742A>G (p.Tyr581Cys) | Missense | <0.01% | Reduced binding to E1A; potential gain-of-function in cancer |
Mutation functional classification
Loss of Function (LOF)
Missense variants (e.g., p.Arg339Trp) impair transcriptional repression and are associated with neurodevelopmental disorders.
Gain of Function (GOF)
Overexpression or mutations that enhance CTBP2 stability or dimerization may promote oncogenic EMT and metastasis.
Dominant Negative (DN)
Dimerization-defective mutants (e.g., p.Gly416Arg) can interfere with wild-type CTBP2 function, leading to dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Epithelial-mesenchymal transition (EMT) - CTBP2 represses CDH1 (E-cadherin) via ZEB1 interaction
• Wnt/β-catenin signaling - CTBP2 modulates TCF/LEF transcription
• Apoptosis - CTBP2 represses pro-apoptotic genes (e.g.
• BAX
• BIK)
• Notch signaling - CTBP2 interacts with CSL/RBP-Jκ to repress Notch target genes
Protein Summary
CTBP2 encodes a 445-amino acid (canonical) or 1,058-amino acid (RIBEYE isoform) protein. The canonical CTBP2 is a nuclear transcriptional corepressor that forms homodimers and binds to PXDLS motifs in transcription factors. It recruits chromatin-modifying enzymes (HDACs, G9a) to silence target genes. The RIBEYE isoform is specific to retinal synaptic ribbons and contains a unique N-terminal domain. CTBP2 is widely expressed, with highest levels in brain, retina, and testis. Its dysregulation contributes to cancer progression, neurodevelopmental disorders, and retinal degeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CTBP2 Knockout HEK293 Cell Line | EDJ-KQ289 | Human | 1488 | Details Get a Quote |
| CTBP2 Knockout A-549 Cell Line | EDJ-KQ18400 | Human | 1488 | Details Get a Quote |
| CTBP2 Knockout HCT 116 Cell Line | EDJ-KQ18401 | Human | 1488 | Details Get a Quote |
| CTBP2 Knockout HeLa Cell Line | EDJ-KQ18402 | Human | 1488 | Details Get a Quote |
