CBLN2
Chr 18cerebellin 2 precursor
The CBLN2 protein acts as a synaptic organizer that is essential for long-term maintenance of excitatory synapses, functioning in trans-synaptic complexes with neurexins and GRID1 to regulate NMDA and AMPA receptor activity at hippocampal synapses. Mutations in CBLN2 cause neurodevelopmental disorders with intellectual disability and seizures, inherited in an autosomal recessive pattern. The gene shows relatively low constraint to loss-of-function variation (pLI 0.12, LOEUF 1.17).
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
CBLN2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools