S100B
Chr 21S100 calcium binding protein B
Also known as: NEF, S100, S100-B, S100beta
S100B encodes a small calcium- and zinc-binding protein highly expressed in astrocytes that acts as a neurotrophic factor promoting astrocytosis and axonal proliferation. Mutations cause autosomal dominant epileptic encephalopathy with variable age of onset, primarily affecting the central nervous system. The gene shows low constraint to loss-of-function variation (pLI 0.04, LOEUF 1.73), and comprehensive clinical information is available in GeneReviews.
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
123 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | — | — | — | — | 82 |
Likely Pathogenic | — | — | — | — | 8 |
VUS | — | — | — | — | 28 |
Likely Benign | — | — | — | — | 1 |
Benign | — | — | — | — | 3 |
| Total | — | 122 | |||
Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
S100B · 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
Precision Medicine in the Treatment of Epilepsy
RECRUITINGBiomarkers in the Etiology of Idiopathic Intracranial Hypertension
RECRUITINGExternal Resources
Links to major genomics databases and tools