CTBP2

Chr 10

C-terminal binding protein 2

NCBI Gene: 1488ENSG00000175029UniProt: P56545

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. [provided by RefSeq, Feb 2014]

129
ClinVar variants
62
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— CTBP2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
62 Pathogenic / Likely Pathogenic· 13 VUS of 129 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.53LOEUF
pLI 0.001
Z-score 3.79
OE 0.33 (0.21–0.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.06Z-score
OE missense 0.88 (0.82–0.95)
581 obs / 657.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.33 (0.21–0.53)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.82–0.95)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.08
0≤1.21.6
LoF obs/exp: 12 / 36.8Missense obs/exp: 581 / 657.4Syn Z: -1.07

ClinVar Variant Classifications

129 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic61
Likely Pathogenic1
VUS13
Likely Benign31
Benign23
61
Pathogenic
1
Likely Pathogenic
13
VUS
31
Likely Benign
23
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
3
58
0
61
Likely Pathogenic
0
0
1
0
1
VUS
2
5
6
0
13
Likely Benign
1
10
3
17
31
Benign
0
12
2
9
23
Total3307026129

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CTBP2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
CTBP1 and CTBP2 mutations underpinning neurological disorders: a systematic review.
Acosta-Baena N et al.·Neurogenetics
2022Review
The secreted metabolite sensor CtBP2 links metabolism to healthy lifespan.
Sekiya M et al.·Nat Aging
2025
Genetic and functional analyses of CTBP2 in anorexia nervosa and body weight regulation.
Giuranna J et al.·Mol Psychiatry
2025Functional
C-terminal binding protein-2 triggers CYR61-induced metastatic dissemination of osteosarcoma in a non-hypoxic microenvironment.
Di Patria L et al.·J Exp Clin Cancer Res
2025
MECOM is a master repressor of myeloid differentiation through dose control of CEBPA in acute myeloid leukemia.
Pastoors D et al.·Blood
2025
Aldolase B attenuates clear cell renal cell carcinoma progression by inhibiting CtBP2.
Tan M et al.·Front Med
2023
CtBP2 promotes proliferation and reduces drug sensitivity in non-small cell lung cancer via the Wnt/β-catenin pathway.
Wang DP et al.·Neoplasma
2018
CtBP2 is an independent prognostic marker that promotes GLI1 induced epithelial-mesenchymal transition in hepatocellular carcinoma.
Zheng X et al.·Oncotarget
2015
microRNA-133a exerts tumor suppressive role in oral squamous cell carcinoma through the Notch signaling pathway via downregulation of CTBP2.
Liu W et al.·Cancer Gene Ther
2022
MiR-338 suppresses cell proliferation and invasion by targeting CTBP2 in glioma.
Liu DZ et al.·Cancer Biomark
2017
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Prostate CancerProstate Inflammation

Characterization of Microbiological and Genetic Features in Prostate Cancer and Their Association with Disease Stage

ENROLLING BY INVITATION
NCT06505356Phase NAEdgaras BurzinskisStarted 2024-09-01
Prostate biopsy

External Resources

Links to major genomics databases and tools