CTBP2

Summary

CTBP2 (C-terminal binding protein 2, HGNC:2495) is a protein-coding gene on chromosome 10q26.13, encoding C-terminal-binding protein 2 (P56545). Corepressor targeting diverse transcription regulators. It is a selective cancer dependency (DepMap: 13.7% of cell lines).

This gene produces alternative transcripts encoding two distinct proteins. One protein is a transcriptional repressor, while the other isoform is a major component of specialized synapses known as synaptic ribbons. Both proteins contain a NAD+ binding domain similar to NAD+-dependent 2-hydroxyacid dehydrogenases. A portion of the 3’ untranslated region was used to map this gene to chromosome 21q21.3; however, it was noted that similar loci elsewhere in the genome are likely. Blast analysis shows that this gene is present on chromosome 10. Several transcript variants encoding two different isoforms have been found for this gene.

Source: NCBI Gene 1488 — RefSeq curated summary.

At a glance

• GWAS associations: 25
• Clinical variants (ClinVar): 79 total — 3 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 13.7% of screened cell lines
• Transcription factor: yes — 19 downstream targets (CollecTRI)
• MANE Select transcript: NM_001329

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2495
Approved symbol	CTBP2
Name	C-terminal binding protein 2
Location	10q26.13
Locus type	gene with protein product
Status	Approved
Aliases	ribeye
Ensembl gene	ENSG00000175029
Ensembl biotype	protein_coding
OMIM	602619
Entrez	1488

Gene structure

Transcript identifiers

Ensembl transcripts: 129 — 122 protein_coding, 5 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000309035, ENST00000334808, ENST00000337195, ENST00000395705, ENST00000411419, ENST00000460976, ENST00000467395, ENST00000476817, ENST00000486955, ENST00000493552, ENST00000494626, ENST00000530884, ENST00000530930, ENST00000531469, ENST00000904058, ENST00000904059, ENST00000904060, ENST00000904061, ENST00000904062, ENST00000904063, ENST00000904064, ENST00000904065, ENST00000904066, ENST00000904067, ENST00000904068, ENST00000904069, ENST00000904070, ENST00000904071, ENST00000904072, ENST00000904073, ENST00000904074, ENST00000904075, ENST00000904076, ENST00000904077, ENST00000904078, ENST00000904079, ENST00000904080, ENST00000904081, ENST00000904082, ENST00000904083, ENST00000904084, ENST00000904085, ENST00000904086, ENST00000904087, ENST00000904088, ENST00000904089, ENST00000904090, ENST00000904091, ENST00000904092, ENST00000904093, ENST00000904094, ENST00000904095, ENST00000904096, ENST00000904097, ENST00000904098, ENST00000904099, ENST00000904100, ENST00000904101, ENST00000904102, ENST00000904103, ENST00000904104, ENST00000904105, ENST00000904106, ENST00000904107, ENST00000904108, ENST00000904109, ENST00000904110, ENST00000904111, ENST00000904112, ENST00000904113, ENST00000927613, ENST00000927614, ENST00000927615, ENST00000927616, ENST00000927617, ENST00000927618, ENST00000927619, ENST00000927620, ENST00000927621, ENST00000927622, ENST00000927623, ENST00000927624, ENST00000927625, ENST00000927626, ENST00000927627, ENST00000927628, ENST00000927629, ENST00000927630, ENST00000927631, ENST00000927632, ENST00000927633, ENST00000927634, ENST00000927635, ENST00000927636, ENST00000927637, ENST00000927638, ENST00000927639, ENST00000927640, ENST00000927641, ENST00000927642, ENST00000927643, ENST00000927644, ENST00000966923, ENST00000966924, ENST00000966925, ENST00000966926, ENST00000966927, ENST00000966928, ENST00000966929, ENST00000966930, ENST00000966931, ENST00000966932, ENST00000966933, ENST00000966934, ENST00000966935, ENST00000966936, ENST00000966937, ENST00000966938, ENST00000966939, ENST00000966940, ENST00000966941, ENST00000966942, ENST00000966943, ENST00000966944, ENST00000966945, ENST00000966946, ENST00000966947, ENST00000966948, ENST00000966949

RefSeq mRNA: 9 — MANE Select: NM_001329 NM_001083914, NM_001290214, NM_001290215, NM_001321012, NM_001321013, NM_001321014, NM_001329, NM_001363508, NM_022802

CCDS: CCDS7643, CCDS7644, CCDS86154

Canonical transcript exons

ENST00000337195 — 11 exons

Exon	Start	End
ENSE00001191586	125110990	125111093
ENSE00001191596	124992695	124992812
ENSE00001191602	124993202	124993329
ENSE00001659349	124994469	124994683
ENSE00001883557	125160319	125160563
ENSE00001927348	124984317	124989698
ENSE00003498267	125002960	125003104
ENSE00003563320	125038997	125039155
ENSE00003630689	124993855	124993985
ENSE00003653428	125003338	125003492
ENSE00003716812	124997964	124998170

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.9675 / max 239.8460, expressed in 1753 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
111883	12.6280	1641
111882	4.3662	1600
111880	1.2690	1007
111875	0.8545	483
111879	0.8482	577
111881	0.6968	463
111884	0.5639	323
111876	0.3644	166
111867	0.1261	13
111877	0.1072	28

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	99.10	gold quality
buccal mucosa cell	CL:0002336	98.92	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.80	gold quality
pylorus	UBERON:0001166	98.78	gold quality
cardia of stomach	UBERON:0001162	98.70	gold quality
pigmented layer of retina	UBERON:0001782	98.62	gold quality
retina	UBERON:0000966	98.59	gold quality
renal medulla	UBERON:0000362	98.43	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.42	gold quality
nasal cavity epithelium	UBERON:0005384	98.38	gold quality
caput epididymis	UBERON:0004358	98.34	gold quality
ventricular zone	UBERON:0003053	98.33	gold quality
epithelium of bronchus	UBERON:0002031	98.13	gold quality
bronchial epithelial cell	CL:0002328	98.11	gold quality
cranial nerve II	UBERON:0000941	98.11	gold quality
bronchus	UBERON:0002185	98.10	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.07	gold quality
visceral pleura	UBERON:0002401	98.00	gold quality
choroid plexus epithelium	UBERON:0003911	97.97	gold quality
cauda epididymis	UBERON:0004360	97.96	gold quality
corpus epididymis	UBERON:0004359	97.94	gold quality
embryo	UBERON:0000922	97.93	gold quality
colonic mucosa	UBERON:0000317	97.89	gold quality
trabecular bone tissue	UBERON:0002483	97.86	gold quality
inferior olivary complex	UBERON:0002127	97.73	gold quality
ganglionic eminence	UBERON:0004023	97.61	gold quality
urethra	UBERON:0000057	97.53	gold quality
ileal mucosa	UBERON:0000331	97.49	gold quality
lower lobe of lung	UBERON:0008949	97.37	gold quality
trachea	UBERON:0003126	97.33	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

19 targets.

Target	Regulation
ACHE
AGT	Repression
ATXN1
BBC3	Repression
BIK
BRCA1	Repression
CALCA
CDH1	Repression
CDH17
CDKN2A
CTBP1
FGF3
HP
IL2
KAT2B
NOTCH1
RETN
TIAM1
TNFRSF11A

Upstream regulators (CollecTRI, top): HIPK2, KLF4, MYC, SOX2, SOX6

miRNA regulators (miRDB)

135 targeting CTBP2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-182-5P	99.87	74.03	2589

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 13.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• roles of acetylation in regulating subcellular localization and transcriptional activity of CtBP2. (PMID:16356938)
• analysis of the CtBP2 corepressor complex induced by E1A and modulation of E1A transcriptional activity by CtBP2 (PMID:17023432)
• E1A may gain access to cellular promoters through conservved sequence-dependent interaction with CtBP2. (PMID:17546044)
• PKA 1) induces metabolic changes in the adrenal cortex and 2) phosphorylates CtBP1 and 2 proteins, particularly CtBP1 at T144, resulting in CtBP protein partnering and ACTH-dependent CYP17 transcription (PMID:18184656)
• Data show that loss of CtBP1/2 expression suppresses cell proliferation through a combination of apoptosis, reduction in cell cycle progression, and aberrations in transit through mitosis. (PMID:19506021)
• Study shows that transcription corepressor CtBP2 directly binds acinus, which is regulated by nerve growth factor (NGF), inhibiting its stimulatory effect on cyclin A1, but not cyclin A2, expression in leukemia. (PMID:19668232)
• CtBP2 monomer interacts with a major CtBP-dependent repressor ZEB and HDAC and that the interaction of the two factors with the CtBP2 monomer was mutually exclusive. (PMID:19754958)
• Data suggest that ARF antagonism of CtBP repression of Bik and other BH3-only genes may have a critical role in ARF-induced p53-independent apoptosis and tumor suppression. (PMID:19798104)
• CtBP2 selectively down-regulates Th2 cytokines, therefore it is a potential target for the treatment of allergic diseases. (PMID:20523059)
• CtBP2 proteins are ubiquitously expressed in all lines and tumour samples. (PMID:20964627)
• we demonstrate that it is the interaction of CtBPs with transcriptional regulators and/or chromatin-modifying enzymes in the cell nucleus, rather than their role in Golgi fission, which is critical for the maintenance of mitotic fidelity. (PMID:21057548)
• This study demonstrates that ataxin-1 occupies the promoter region of E-cadherin in vivo and that ataxin-1 activates the promoter in a CtBP2-mediated transcriptional regulation manner. (PMID:21315774)
• Doubly transgenic zebrafish exhibit a startle response and typical swimming behavior, indicating that there is no gross disruption of either hearing or vestibular function useful in the study of ribbon synapse development of the hair cell. (PMID:21334379)
• CtBP1 and CtBP2 promote the oligomerization of truncated APC through binding to the 15 amino acid repeats of truncated APC. (PMID:21665989)
• We propose that CtBP2 is an ovarian cancer oncogene that regulates gene expression program by modulating HDAC activity. (PMID:22945647)
• CtBP2 might contribute to the progression of esophageal squamous cell carcinoma through a negative transcriptional regulation of p16(INK4A). (PMID:23255392)
• Interaction with cyclin H/cyclin-dependent kinase 7 (CCNH/CDK7) stabilizes C-terminal binding protein 2 (CtBP2) and promotes cancer cell migration (PMID:23393140)
• these data demonstrate that CHIP regulates the steady-state level of CtBP2 as an E3 ubiquitin ligase and determines the expression levels of CtBP2 target genes. (PMID:23410750)
• BRCA1 expression is epigenetically repressed in sporadic ovarian cancer cells by overexpression of C-terminal binding protein 2.CtBP2 is an ovarian cancer oncogene. (PMID:23730208)
• CTBP2 is a transcriptional cofactor for RXR-alpha/RAR-alpha. (PMID:23775127)
• E2F7 recruits the co-repressor C-terminal-binding protein (CtBP) and that CtBP2 is essential for E2F7 to repress E2F1 transcription. (PMID:23853115)
• CtBP2 directly targeted stem cell core genes resulting in increased cancer cell stemness and increasing metastatic and tumorigenic potential. (PMID:24012420)
• High CTBP2 expression is associated with prostate cancer. (PMID:24332637)
• Overexpression of CtBP2 is associated with breast carcinoma. (PMID:24522810)
• Crystal structures of human CtBP1 and CtBP2 in complex with 4-Methylthio 2-oxobutyric acid and NAD. (PMID:24657618)
• CtBP2 is over-expressed in prostate cancer.CtBP2 promotes prostate cancer cell proliferation through c-Myc signaling. (PMID:24835310)
• results show how CtBP2 contributes to prostate cancer progression by modulating AR and oncogenic signaling (PMID:25228652)
• Our results indicated that CCNH/CDK7-CtBP2 axis may augment ESCC cell migration, and targeting the interaction of both may provide a novel therapeutic target of esophageal squamous cell carcinoma . (PMID:25820824)
• Releasing the key adipogenic regulator C/EBPalpha from CtBP2 binding. (PMID:25895816)
• Pinin and CtBP1 and CtBP2 are oncotargets that closely interact with each other to regulate transcription and pre-mRNA alternative splicing and promote cell adhesion and other epithelial characteristics of ovarian cancer cells. (PMID:26871283)
• Overall, our findings reveal that CtBP1/2 is essential to promote to human glioma cell growth through maintaining the DNA stability regulated by the MRN/ATR/Chk1/CDK2/HIF-1alpha signaling pathway. (PMID:27699603)
• This Gene-based tests suggest evidence of association with related genes, ZEB2, RND3, MCTP1, CTBP2, and beta EEG (PMID:28040410)
• CtBP2 ameliorated palmitic acid-induced insulin resistance via ROS-dependent JNK pathway. (PMID:28111233)
• CtBP2 may be a potential target to suppress tumorigenesis in neuroblastoma (PMID:28179207)
• this study shows that CtBP2 overexpression promotes tumor cell proliferation and invasion in gastric cancer and is associated with poor prognosis (PMID:28404932)
• these findings provide insight into the role CtBP2 plays in promoting proliferation and migration in breast cancer by the inhibition of p16INK4A. (PMID:28412731)
• CtBP2 is a druggable transforming oncoprotein critical for the evolution of neoplasia driven by Apc mutation. (PMID:28414304)
• High CTBP2 expression is associated with prostate cancer. (PMID:28677795)
• Results indicated that CTBP2 was direct target of miR-338-5p in glioma cells. CTBP2 silencing can rescued the phenotype changes induced by miR-338-5p inhibitor on cell proliferation and invasion in glioma. (PMID:28826173)
• the present study indicated that CtBP2 reduced the susceptibility of ECA109 cells to cisplatin by regulating the expression of apoptosis-related proteins, suggesting that it may be a promising therapeutic target in esophageal squamous cell carcinoma in the future. (PMID:29658564)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	ctbp2a	ENSDARG00000044062
mus_musculus	Ctbp2	ENSMUSG00000030970
rattus_norvegicus	Ctbp2	ENSRNOG00000017326
drosophila_melanogaster	CtBP	FBGN0020496
drosophila_melanogaster	CG9331	FBGN0032889
drosophila_melanogaster	CG1236	FBGN0037370
drosophila_melanogaster	CG31673	FBGN0051673
drosophila_melanogaster	CG31674	FBGN0051674
caenorhabditis_elegans		WBGENE00006424

Paralogs (3): PHGDH (ENSG00000092621), GRHPR (ENSG00000137106), CTBP1 (ENSG00000159692)

Protein

Protein identifiers

C-terminal-binding protein 2 — P56545 (reviewed: P56545)

All UniProt accessions (2): A0A087WYL1, P56545

UniProt curated annotations — full annotation on UniProt →

Function. Corepressor targeting diverse transcription regulators. Functions in brown adipose tissue (BAT) differentiation. Isoform 2 probably acts as a scaffold for specialized synapses.

Subunit / interactions. Can form homodimers or heterodimers of CTBP1 and CTBP2. Interacts with HIPK2 and ZNF217. Interacts with PRDM16; represses white adipose tissue (WAT)-specific genes expression. Interacts with PNN, NRIP1 and WIZ. Interacts with MCRIP1. (Microbial infection) Interacts with human adenovirus 5 E1A protein; this interaction seems to potentiate viral replication.

Subcellular location. Nucleus. Synapse.

Tissue specificity. Ubiquitous. Highest levels in heart, skeletal muscle, and pancreas.

Similarity. Belongs to the D-isomer specific 2-hydroxyacid dehydrogenase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P56545-1	1	yes
P56545-2	2, Ribeye
P56545-3	3

RefSeq proteins (9): NP_001077383, NP_001277143, NP_001277144, NP_001307941, NP_001307942, NP_001307943, NP_001320, NP_001350437, NP_073713 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006139	D-isomer_2_OHA_DH_cat_dom	Domain
IPR006140	D-isomer_DH_NAD-bd	Domain
IPR029753	D-isomer_DH_CS	Conserved_site
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR043322	CtBP	Family
IPR051638	CTBP_dehydrogenase	Family

Pfam: PF00389, PF02826

UniProt features (59 total): helix 16, strand 15, binding site 7, sequence conflict 7, turn 4, active site 3, modified residue 2, splice variant 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9WRI	X-RAY DIFFRACTION	1.85
8ATI	X-RAY DIFFRACTION	2.6
2OME	X-RAY DIFFRACTION	2.8
4LCJ	X-RAY DIFFRACTION	2.86
6WKW	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P56545-F1	83.67	0.74

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 272; 301; 321 (proton donor)

Ligand- & substrate-binding residues (7): 270–272; 296; 321–324; 106; 186–191; 210; 243–249

Post-translational modifications (2): 22, 428

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-4641265	Repression of WNT target genes
R-HSA-5339700	Signaling by TCF7L2 mutants
R-HSA-9764725	Negative Regulation of CDH1 Gene Transcription
R-HSA-9662360	Sensory processing of sound by inner hair cells of the cochlea

MSigDB gene sets: 318 (showing top): GGGACCA_MIR133A_MIR133B, PAX4_01, TGCGCANK_UNKNOWN, GOBP_WHITE_FAT_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_RETINOIC_ACID_RECEPTOR_SIGNALING_PATHWAY, CAGGTCC_MIR492, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, MUELLER_PLURINET, CAGCAGG_MIR370, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, KEGG_PATHWAYS_IN_CANCER, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, GOBP_VIRAL_GENOME_REPLICATION

GO Biological Process (9): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of cell population proliferation (GO:0008285), viral genome replication (GO:0019079), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of retinoic acid receptor signaling pathway (GO:0048386), white fat cell differentiation (GO:0050872), cell differentiation (GO:0030154)

GO Molecular Function (12): transcription coregulator binding (GO:0001221), transcription corepressor binding (GO:0001222), transcription coactivator activity (GO:0003713), transcription corepressor activity (GO:0003714), oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (GO:0016616), protein kinase binding (GO:0019901), identical protein binding (GO:0042802), protein-containing complex binding (GO:0044877), NAD binding (GO:0051287), DNA-binding transcription factor binding (GO:0140297), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription repressor complex (GO:0017053), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Degradation of beta-catenin by the destruction complex	1
Signaling by WNT in cancer	1
Regulation of CDH1 Gene Transcription	1
Sensory processing of sound	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	3
regulation of transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	2
regulation of DNA-templated transcription	2
positive regulation of DNA-templated transcription	2
transcription factor binding	2
transcription coregulator activity	2
binding	2
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
viral process	1
viral life cycle	1
DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
retinoic acid receptor signaling pathway	1
regulation of retinoic acid receptor signaling pathway	1
positive regulation of intracellular signal transduction	1
fat cell differentiation	1
cellular developmental process	1
transcription coregulator binding	1
oxidoreductase activity, acting on CH-OH group of donors	1
kinase binding	1
protein binding	1
adenyl nucleotide binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
transcription regulator complex	1
cell junction	1

Protein interactions and networks

STRING

3578 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTBP2	RBBP8	Q99708	994
CTBP2	CTBP1	Q13363	974
CTBP2	KLF3	P57682	972
CTBP2	KLF8	O95600	951
CTBP2	ZEB1	P37275	939
CTBP2	ZNF217	O75362	938
CTBP2	RCOR1	Q9UKL0	893
CTBP2	OTOF	Q9HC10	874
CTBP2	PRDM16	Q9HAZ2	863
CTBP2	EP300	Q09472	862
CTBP2	HIC1	Q14526	835
CTBP2	HDAC1	Q13547	816
CTBP2	CACNA1F	O60840	815
CTBP2	HDAC2	Q92769	815
CTBP2	NCOR2	Q9Y618	758

IntAct

238 interactions, top by confidence:

A	B	Type	Score
CTBP2	CTBP1	psi-mi:“MI:0915”(physical association)	0.920
FOXP1	FOXP2	psi-mi:“MI:0914”(association)	0.910
CTBP2	LCOR	psi-mi:“MI:0915”(physical association)	0.880
LCOR	CTBP2	psi-mi:“MI:0915”(physical association)	0.880
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
IKZF1	CTBP2	psi-mi:“MI:0915”(physical association)	0.800
CTBP2	IKZF1	psi-mi:“MI:0915”(physical association)	0.800
CTBP1	ZEB2	psi-mi:“MI:0914”(association)	0.800
CTBP1	KDM1A	psi-mi:“MI:0914”(association)	0.790
ZBTB18	CTBP2	psi-mi:“MI:0915”(physical association)	0.790
ZBTB18	CTBP2	psi-mi:“MI:0914”(association)	0.790
TGIF1	CTBP2	psi-mi:“MI:0915”(physical association)	0.740
CTBP2	TGIF1	psi-mi:“MI:0915”(physical association)	0.740
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710

BioGRID (583): CTBP2 (Two-hybrid), FLI1 (Two-hybrid), HOXB5 (Two-hybrid), TGIF1 (Two-hybrid), NOL4 (Two-hybrid), IKZF1 (Two-hybrid), ZBTB18 (Two-hybrid), RAI2 (Two-hybrid), IKZF2 (Two-hybrid), PLCB1 (Two-hybrid), BAZ2B (Two-hybrid), BCAS3 (Two-hybrid), TSHZ3 (Two-hybrid), DMRTB1 (Two-hybrid), ZNF750 (Two-hybrid)

ESM2 similar proteins: A0AV96, A1L1G1, G5EBH0, G5EEN4, O14092, O46036, O88712, P16258, P22059, P25455, P28191, P32232, P36583, P40054, P40510, P56545, P56546, P87228, Q0VCQ1, Q13363, Q20595, Q21029, Q291H5, Q292F9, Q295E6, Q3B7Z2, Q5R5P4, Q5R9H4, Q5XK84, Q5YD48, Q66H68, Q6NNF2, Q7JUR6, Q7K4W1, Q7Q2B7, Q804S5, Q86X55, Q86YT6, Q91WT8, Q91WT9

Diamond homologs: A0A348AXY0, A1RYE4, A4TGN1, A5A6P1, A5GFY8, A6TFG7, A7FPA2, A9R4G6, B1JH01, B1L765, B2K7F1, B2VCD1, B5XMZ4, B6YWH0, C0CMQ8, C5A1V0, D2RJU7, G9EZR6, J7SHB8, O04130, O08651, O27051, O29445, O33116, O43175, O46036, O49485, O58320, O83080, O88712, O94574, P0A545, P17584, P26297, P26298, P30799, P30901, P35136, P43885, P44501

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
CTBP2	“down-regulates quantity by repression”	CDH1	“transcriptional regulation”
STUB1	“down-regulates quantity by destabilization”	CTBP2	ubiquitination
KLF8	“up-regulates activity”	CTBP2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 139 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	5	16.5×	1e-03
Regulation of PTEN gene transcription	8	15.7×	1e-05
Negative Regulation of CDH1 Gene Transcription	10	13.2×	2e-06
Nonhomologous End-Joining (NHEJ)	6	11.1×	1e-03
TP53 Regulates Transcription of DNA Repair Genes	5	10.0×	4e-03
Interaction of NuRD complexes with transcription factors	7	9.8×	8e-04
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	6	9.7×	2e-03
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	6	9.7×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
double-strand break repair	6	9.4×	5e-03
cytoplasmic translation	6	8.6×	6e-03
DNA damage response	12	5.0×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

79 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	7
Likely benign	31
Benign	23

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1696848	NM_001329.4(CTBP2):c.667G>A (p.Val223Met)	Pathogenic
1696849	NM_001329.4(CTBP2):c.545C>T (p.Thr182Met)	Pathogenic
1696855	NM_001329.4(CTBP2):c.349G>A (p.Gly117Ser)	Pathogenic

SpliceAI

4721 predictions. Top by Δscore:

Variant	Effect	Δscore
10:124981703:TTTTA:T	acceptor_loss	1.0000
10:124981704:TTTA:T	acceptor_loss	1.0000
10:124981705:TTA:T	acceptor_loss	1.0000
10:124981706:TA:T	acceptor_loss	1.0000
10:124981707:A:C	acceptor_loss	1.0000
10:124981708:G:GT	acceptor_loss	1.0000
10:124981826:TCAG:T	donor_loss	1.0000
10:124981828:AG:A	donor_loss	1.0000
10:124981829:GGT:G	donor_loss	1.0000
10:124981831:T:A	donor_loss	1.0000
10:124983171:ACAG:A	acceptor_loss	1.0000
10:124983172:C:G	acceptor_gain	1.0000
10:124983173:A:AG	acceptor_gain	1.0000
10:124983173:AGCCT:A	acceptor_gain	1.0000
10:124983174:G:A	acceptor_loss	1.0000
10:124983174:G:GA	acceptor_gain	1.0000
10:124983174:GC:G	acceptor_gain	1.0000
10:124983174:GCCT:G	acceptor_gain	1.0000
10:124983174:GCCTG:G	acceptor_gain	1.0000
10:124983301:CAAG:C	donor_loss	1.0000
10:124983302:AAG:A	donor_loss	1.0000
10:124983305:GT:G	donor_loss	1.0000
10:124983306:T:A	donor_loss	1.0000
10:124983454:TCCA:T	acceptor_loss	1.0000
10:124983456:CAG:C	acceptor_loss	1.0000
10:124983457:A:AG	acceptor_gain	1.0000
10:124983457:A:AT	acceptor_loss	1.0000
10:124983457:AG:A	acceptor_gain	1.0000
10:124983458:G:A	acceptor_loss	1.0000
10:124983458:G:GG	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000038151 (10:125057465 G>A,C), RS1000093476 (10:125109331 C>T), RS1000099236 (10:125024687 C>T), RS1000103745 (10:124993841 G>A), RS1000115541 (10:125161364 C>A,T), RS1000126451 (10:125040900 A>G), RS1000138534 (10:125089956 C>T), RS1000153897 (10:125029964 A>G,T), RS1000169960 (10:125025906 T>C), RS1000199717 (10:125066759 C>A,G,T), RS1000200493 (10:125139957 G>A,C), RS1000211675 (10:124994066 G>A), RS1000215254 (10:125100840 A>G), RS1000225684 (10:125091603 T>A,C), RS1000237100 (10:125161199 T>C)

Disease associations

OMIM: gene MIM:602619 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST000154_3	Prostate cancer	2.000000e-07
GCST002541_81	Menarche (age at onset)	4.000000e-08
GCST002702_23	Height	9.000000e-08
GCST002783_162	Body mass index	2.000000e-06
GCST002783_215	Body mass index	1.000000e-06
GCST006098_5	Vigorous physical activity	3.000000e-10
GCST006630_23	Diastolic blood pressure	6.000000e-10
GCST006730_1	Infant, child and juvenile death in continuous marriage (proportion of children died <15 years)	2.000000e-08
GCST007576_87	Chronotype	2.000000e-09
GCST008129_51	Body mass index	2.000000e-08
GCST009443_6	Age-related cognitive decline (visuospatial skill) (slope of z-scores)	8.000000e-06
GCST010002_228	Refractive error	8.000000e-17
GCST010083_139	Hemoglobin levels	1.000000e-10
GCST010135_48	Oily fish consumption	3.000000e-08
GCST010140_38	Pork consumption	3.000000e-08
GCST010241_327	Apolipoprotein A1 levels	3.000000e-08
GCST010242_264	HDL cholesterol levels	2.000000e-09
GCST010703_273	Brain morphology (MOSTest)	1.000000e-15
GCST010988_454	Adult body size	7.000000e-13
GCST010989_92	Body size at age 10	2.000000e-08
GCST011122_70	Walking pace	8.000000e-09
GCST012442_46	Age-related hearing impairment	2.000000e-26
GCST90002403_232	Red blood cell count	1.000000e-09
GCST90014033_96	Haemorrhoidal disease	4.000000e-08
GCST90020028_782	Hip circumference adjusted for BMI	5.000000e-09

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0004340	body mass index
EFO:0008002	physical activity measurement
EFO:0006336	diastolic blood pressure
EFO:0009437	offspring mortality measurement
EFO:0008328	chronotype measurement
EFO:0007710	cognitive decline measurement
EFO:0004509	hemoglobin measurement
EFO:0008111	diet measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004346	neuroimaging measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0004305	erythrocyte count
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3797016 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs376695472	CTBP2		0.00	0
rs945665113	CTBP2		0.00	0

ChEMBL bioactivities

14 potent at pChembl≥5 of 14 total, top 14 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.77	IC50	170	nM	CHEMBL3799940
6.75	IC50	180	nM	CHEMBL3798669
6.62	IC50	240	nM	CHEMBL3797778
6.52	IC50	300	nM	CHEMBL3800609
6.50	IC50	320	nM	CHEMBL3800006
6.32	IC50	480	nM	CHEMBL3800187
6.14	IC50	720	nM	CHEMBL3799689
6.06	IC50	880	nM	CHEMBL3799251
6.05	IC50	900	nM	CHEMBL3797935
5.93	IC50	1180	nM	MOLIBRESIB
5.67	IC50	2160	nM	CHEMBL3800334
5.13	IC50	7340	nM	CHEMBL3798743
5.12	IC50	7650	nM	CHEMBL3800103
5.06	IC50	8730	nM	CHEMBL3800267

PubChem BioAssay actives

16 with measured affinity, of 46 total; 14 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2Z)-3-(3-chlorophenyl)-2-hydroxyiminopropanoic acid	1298930: Inhibition of recombinant His6-tagged CtBP2 (31 to 384 residues) (unknown origin) dehydrogenase activity expressed in Escherichia coli BL21-Codonplus (DE3)-RIL cells using MTOB as substrate after 15 mins by NADH consumption assay	ic50	0.1700	uM
(2Z)-3-(4-chlorophenyl)-2-hydroxyiminopropanoic acid	1298930: Inhibition of recombinant His6-tagged CtBP2 (31 to 384 residues) (unknown origin) dehydrogenase activity expressed in Escherichia coli BL21-Codonplus (DE3)-RIL cells using MTOB as substrate after 15 mins by NADH consumption assay	ic50	0.1800	uM
(2Z)-2-hydroxyimino-3-phenylpropanoic acid	1298930: Inhibition of recombinant His6-tagged CtBP2 (31 to 384 residues) (unknown origin) dehydrogenase activity expressed in Escherichia coli BL21-Codonplus (DE3)-RIL cells using MTOB as substrate after 15 mins by NADH consumption assay	ic50	0.2400	uM
(2Z)-3-(4-fluorophenyl)-2-hydroxyiminopropanoic acid	1298930: Inhibition of recombinant His6-tagged CtBP2 (31 to 384 residues) (unknown origin) dehydrogenase activity expressed in Escherichia coli BL21-Codonplus (DE3)-RIL cells using MTOB as substrate after 15 mins by NADH consumption assay	ic50	0.3000	uM
(2Z)-2-hydroxyimino-3-(4-methylphenyl)propanoic acid	1298930: Inhibition of recombinant His6-tagged CtBP2 (31 to 384 residues) (unknown origin) dehydrogenase activity expressed in Escherichia coli BL21-Codonplus (DE3)-RIL cells using MTOB as substrate after 15 mins by NADH consumption assay	ic50	0.3200	uM
(2Z)-2-hydroxyimino-3-(3-methylphenyl)propanoic acid	1298930: Inhibition of recombinant His6-tagged CtBP2 (31 to 384 residues) (unknown origin) dehydrogenase activity expressed in Escherichia coli BL21-Codonplus (DE3)-RIL cells using MTOB as substrate after 15 mins by NADH consumption assay	ic50	0.4800	uM
(2Z)-2-hydroxyimino-3-(3-hydroxyphenyl)propanoic acid	1298930: Inhibition of recombinant His6-tagged CtBP2 (31 to 384 residues) (unknown origin) dehydrogenase activity expressed in Escherichia coli BL21-Codonplus (DE3)-RIL cells using MTOB as substrate after 15 mins by NADH consumption assay	ic50	0.7200	uM
(2Z)-2-hydroxyimino-3-(3-methoxyphenyl)propanoic acid	1298930: Inhibition of recombinant His6-tagged CtBP2 (31 to 384 residues) (unknown origin) dehydrogenase activity expressed in Escherichia coli BL21-Codonplus (DE3)-RIL cells using MTOB as substrate after 15 mins by NADH consumption assay	ic50	0.8800	uM
(2Z)-3-(4-cyanophenyl)-2-hydroxyiminopropanoic acid	1298930: Inhibition of recombinant His6-tagged CtBP2 (31 to 384 residues) (unknown origin) dehydrogenase activity expressed in Escherichia coli BL21-Codonplus (DE3)-RIL cells using MTOB as substrate after 15 mins by NADH consumption assay	ic50	0.9000	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178886: Inhibition of CTBP2 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	1.1800	uM
(2Z)-2-hydroxyimino-3-(4-methoxyphenyl)propanoic acid	1298930: Inhibition of recombinant His6-tagged CtBP2 (31 to 384 residues) (unknown origin) dehydrogenase activity expressed in Escherichia coli BL21-Codonplus (DE3)-RIL cells using MTOB as substrate after 15 mins by NADH consumption assay	ic50	2.1600	uM
(2Z)-2-hydroxyimino-3-(4-hydroxyphenyl)propanoic acid	1298930: Inhibition of recombinant His6-tagged CtBP2 (31 to 384 residues) (unknown origin) dehydrogenase activity expressed in Escherichia coli BL21-Codonplus (DE3)-RIL cells using MTOB as substrate after 15 mins by NADH consumption assay	ic50	7.3400	uM
(2Z)-3-(2-chlorophenyl)-2-hydroxyiminopropanoic acid	1298930: Inhibition of recombinant His6-tagged CtBP2 (31 to 384 residues) (unknown origin) dehydrogenase activity expressed in Escherichia coli BL21-Codonplus (DE3)-RIL cells using MTOB as substrate after 15 mins by NADH consumption assay	ic50	7.6500	uM
(2Z)-2-hydroxyimino-3-(2-methylphenyl)propanoic acid	1298930: Inhibition of recombinant His6-tagged CtBP2 (31 to 384 residues) (unknown origin) dehydrogenase activity expressed in Escherichia coli BL21-Codonplus (DE3)-RIL cells using MTOB as substrate after 15 mins by NADH consumption assay	ic50	8.7300	uM

CTD chemical–gene interactions

56 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	7
Valproic Acid	decreases methylation, increases expression, affects expression	5
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression, decreases expression	3
bisphenol A	affects methylation, affects cotreatment, increases methylation, decreases expression	2
sodium arsenite	affects methylation, decreases expression	2
entinostat	affects cotreatment, increases expression	2
Irinotecan	affects cotreatment, affects response to substance, decreases expression	2
Fluorouracil	affects cotreatment, affects response to substance, decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Cyclosporine	increases expression, increases methylation	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	increases expression	1
2-keto-4-methylthiobutyric acid	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Arsenic Trioxide	decreases response to substance	1
Fulvestrant	affects cotreatment, increases methylation	1
Glyphosate	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	affects methylation	1

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3804623	Binding	Inhibition of recombinant His6-tagged CtBP2 (31 to 384 residues) (unknown origin) dehydrogenase activity expressed in Escherichia coli BL21-Codonplus (DE3)-RIL cells using MTOB as substrate after 15 mins by NADH consumption assay	Design, synthesis, and biological evaluation of substrate-competitive inhibitors of C-terminal Binding Protein (CtBP). — Bioorg Med Chem

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A0T8	SEES3-1V human CTBP2, clone1	Embryonic stem cell	Male
CVCL_A0T9	SEES3-1V human CTBP2, clone2	Embryonic stem cell	Male
CVCL_A0U0	SEES3-1V human CTBP2, clone3	Embryonic stem cell	Male
CVCL_D7N3	Ubigene A-549 CTBP2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.