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GeneE
25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CTBP2
C-terminal binding protein 2
Chromosome 10 · 10q26.13
NCBI Gene: 1488Ensembl: ENSG00000175029.18HGNC: HGNC:2495UniProt: P56545
247PubMed Papers
20Diseases
0Drugs
3Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneTranscription Factor
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleusprotein kinase bindingprotein-containing complex bindingpositive regulation of transcription by RNA polymerase IIhearing lossSensorineural hearing impairmentPulmonary artery atresiaage-related hearing impairment
✦AI Summary

CTBP2 (C-terminal binding protein 2) is a multifunctional transcriptional coregulator and metabolite-sensing protein with distinct roles in development, metabolism, and disease. As a transcriptional coregulator, CTBP2 functions as a scaffold protein that interacts with other transcription factors through its PLDLS motif domain 1. CTBP2 forms complexes with other proteins to regulate gene expression; notably, the CTBP2-PCIF1 complex catalyzes m6Am modification of mRNA, suppressing translation of tumor suppressors like TET2 in head and neck squamous cell carcinoma 2. The CTBP2/RIBEYE locus produces tissue-specific isoforms: CTBP2 is expressed in retinal progenitors and GABAergic amacrine cells, while RIBEYE is localized to ribbon synapses in photoreceptor and bipolar cells 3. CTBP2 also functions as a secreted metabolite sensor via exosomes that links cellular metabolism to longevity; exosomal CTBP2 extends lifespan in aged mice through AMPK activation 4. Pathologically, CTBP2 is upregulated in high-grade gliomas and correlates with poor prognosis 5, while CTBP2 mutations are implicated in neurological disorders and body weight regulation 67. These findings establish CTBP2 as a pleiotropic regulator integrating transcriptional control, metabolic homeostasis, and neurodevelopmental functions.

Sources cited
1
CTBP2-PCIF1 complex catalyzes m6Am modification of mRNA and suppresses TET2 tumor suppressor translation in head and neck squamous cell carcinoma
PMID: 37643007
2
CTBP1/2 are transcriptional coregulators involved in neurodevelopment; CTBP1 mutations cause intellectual disability and cerebellar abnormalities
PMID: 36331689
3
CTBP2 polymorphisms influence lipid profiles in association with brown adipose tissue development regulation
PMID: 37313181
4
CTBP2 expression is significantly upregulated in high-grade gliomas and associated with poor disease-specific survival
PMID: 27698809
5
CTBP2 functions as a secreted metabolite sensor via exosomes that extends lifespan and improves healthspan through AMPK activation
PMID: 41062862
6
CTBP2 and RIBEYE are isoforms from the same locus with distinct expression patterns: CTBP2 in retinal progenitors and GABAergic cells; RIBEYE in ribbon synapses
PMID: 35095414
7
CTBP2 interaction with oncogenic transcription factors like EVI1 via PLDLS motif is essential for leukemic transformation in 3q26/MECOM rearranged AML
PMID: 38748792
8
CTBP2/RIBEYE variants are associated with anorexia nervosa and severe obesity, suggesting roles in body weight regulation
PMID: 39511451
Disease Associationsⓘ20
hearing lossOpen Targets
0.51Moderate
Sensorineural hearing impairmentOpen Targets
0.48Moderate
Pulmonary artery atresiaOpen Targets
0.47Moderate
age-related hearing impairmentOpen Targets
0.45Moderate
prostate carcinomaOpen Targets
0.40Moderate
goutOpen Targets
0.35Weak
disorder of earOpen Targets
0.32Weak
sensorineural hearing lossOpen Targets
0.32Weak
atrial fibrillationOpen Targets
0.32Weak
connective tissue diseaseOpen Targets
0.32Weak
spinal cord injuryOpen Targets
0.32Weak
poisoningOpen Targets
0.32Weak
COVID-19Open Targets
0.31Weak
Abnormality of refractionOpen Targets
0.31Weak
respiratory tract infectious disorderOpen Targets
0.30Weak
refractive errorOpen Targets
0.29Weak
cholelithiasisOpen Targets
0.29Weak
Peyronie diseaseOpen Targets
0.28Weak
pericarditisOpen Targets
0.27Weak
Abnormality of limbsOpen Targets
0.25Weak
Pathogenic Variants3
NM_001329.4(CTBP2):c.667G>A (p.Val223Met)Pathogenic
Pulmonary artery atresia
☆☆☆☆→ Residue 223
NM_001329.4(CTBP2):c.545C>T (p.Thr182Met)Pathogenic
Pulmonary artery atresia
☆☆☆☆→ Residue 182
NM_001329.4(CTBP2):c.349G>A (p.Gly117Ser)Pathogenic
Pulmonary artery atresia
☆☆☆☆→ Residue 117
View on ClinVar ↗
Related Genes
CDKN2AProtein interaction100%EP300Protein interaction100%HDAC2Protein interaction100%KDM1AProtein interaction100%ZNF217Protein interaction100%RBBP8Protein interaction100%
Tissue Expression6 tissues
Ovary
100%
Lung
78%
Brain
53%
Heart
50%
Bone Marrow
39%
Liver
14%
Gene Interaction Network
Click a node to explore
CTBP2CDKN2AEP300HDAC2KDM1AZNF217RBBP8
PROTEIN STRUCTURE
Preparing viewer…
PDB8ATI · 2.60 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.52Moderately Constrained
pLIⓘ
0.82Intermediate
Observed/Expected LoF0.38 [0.28–0.52]
RankingsWhere CTBP2 stands among ~20K protein-coding genes
  • #1,562of 20,598
    Most Researched247 · top 10%
  • #3,922of 5,498
    Most Pathogenic Variants3
  • #3,230of 17,882
    Most Constrained (LOEUF)0.52 · top quartile
Genes detectedCTBP2
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
The CTBP2-PCIF1 complex regulates m6Am modification of mRNA in head and neck squamous cell carcinoma.
PMID: 37643007
J Clin Invest · 2023
1.00
2
CTBP1 and CTBP2 mutations underpinning neurological disorders: a systematic review.
PMID: 36331689
Neurogenetics · 2022
0.90
3
Association of PRDM16 rs12409277 and CtBP2 rs1561589 gene polymorphisms with lipid profile of adolescents.
PMID: 37313181
Arch Med Sci · 2023
0.80
4
Expression and prognostic significance of CTBP2 in human gliomas.
PMID: 27698809
Oncol Lett · 2016
0.70
5
C-terminal binding protein-2 triggers CYR61-induced metastatic dissemination of osteosarcoma in a non-hypoxic microenvironment.
PMID: 40038783
J Exp Clin Cancer Res · 2025
0.64