CTBP2

Chr 10

C-terminal binding protein 2

NCBI Gene: 1488ENSG00000175029UniProt: P56545

This gene encodes a transcriptional repressor and a synaptic ribbon component essential for specialized synapses, both containing NAD+ binding domains. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, seizures, and visual impairment. The gene shows moderate constraint against loss-of-function variants, suggesting some tolerance to complete gene loss.

ResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.53
Clinical Summary— CTBP2
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Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
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ClinVar Variants
63 unique Pathogenic / Likely Pathogenic· 13 VUS of 147 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
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
1.06Z-score
OE missense 0.88 (0.82–0.95)
581 obs / 657.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.33 (0.21–0.53)
0≤0.351.4
Missense OE0.88 (0.82–0.95)
0≤0.61.4
Synonymous OE1.08
0≤1.21.6
LoF obs/exp: 12 / 36.8Missense obs/exp: 581 / 657.4Syn Z: -1.07
DN
0.6938th %ile
GOF
0.6249th %ile
LOF
0.4233th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

147 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic62
Likely Pathogenic1
VUS13
Likely Benign31
Benign23
62
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
59
0
62
Likely Pathogenic
0
0
1
0
1
VUS
2
5
6
0
13
Likely Benign
2
10
2
17
31
Benign
1
12
1
9
23
Total5306926130

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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients