LMNB2
Chr 19ARADlamin B2
Also known as: EPM9, LAMB2, LMN2, MCPH27
This gene encodes lamin B2, an intermediate filament protein that forms the nuclear lamina meshwork on the inner nuclear membrane and plays essential roles in nuclear envelope structure, chromatin organization, and gene expression. Mutations cause autosomal dominant primary microcephaly with early onset, progressive myoclonic epilepsy, and contribute to acquired partial lipodystrophy susceptibility. The gene is highly constrained against loss-of-function variants (pLI 0.999, LOEUF 0.104), indicating that complete loss of function is poorly tolerated.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). 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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
500 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 1 | 0 | 2 | 0 | 3 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 4 | 209 | 18 | 0 | 231 |
Likely Benign | 0 | 14 | 76 | 116 | 206 |
Benign | 0 | 2 | 39 | 1 | 42 |
Conflicting | — | 10 | |||
| Total | 5 | 225 | 135 | 117 | 492 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
LMNB2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
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