LMNB2

Chr 19ARAD

lamin B2

Also known as: EPM9, LAMB2, LMN2, MCPH27

NCBI Gene: 84823ENSG00000176619UniProt: Q03252

This gene encodes a B type nuclear lamin. The nuclear lamina consists of a two-dimensional matrix of proteins located next to the inner nuclear membrane. The lamin family of proteins make up the matrix and are highly conserved in evolution. During mitosis, the lamina matrix is reversibly disassembled as the lamin proteins are phosphorylated. Lamin proteins are thought to be involved in nuclear stability, chromatin structure and gene expression. Vertebrate lamins consist of two types, A and B. Mutations in this gene are associated with acquired partial lipodystrophy. [provided by RefSeq, May 2012]

Primary Disease Associations & Inheritance

?Epilepsy, progressive myoclonic, 9MIM #616540
AR
{Lipodystrophy, partial, acquired, susceptibility to}MIM #608709
AD
Microcephaly 27, primary, autosomal dominantMIM #619180
AD
UniProtPartial acquired lipodystrophy
408
ClinVar variants
12
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— LMNB2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 210 VUS of 408 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.10LOEUF
pLI 1.000
Z-score 4.95
OE 0.00 (0.00–0.10)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

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.
0.66Z-score
OE missense 0.91 (0.83–0.99)
359 obs / 395.9 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.0.00 (0.00–0.10)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.83–0.99)
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.1.05
0≤1.21.6
LoF obs/exp: 0 / 28.5Missense obs/exp: 359 / 395.9Syn Z: -0.47

ClinVar Variant Classifications

408 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic1
VUS210
Likely Benign162
Benign16
Conflicting8
11
Pathogenic
1
Likely Pathogenic
210
VUS
162
Likely Benign
16
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
9
0
11
Likely Pathogenic
0
0
1
0
1
VUS
1
188
21
0
210
Likely Benign
0
13
68
81
162
Benign
0
3
11
2
16
Conflicting
—8
Total220511083408

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.

Gene2Phenotype Curations

LMNB2-related primary microcephaly

strong
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
LAMIN B2; LMNB2
MIM #150341 · *

?Epilepsy, progressive myoclonic, 9

MIM #616540

Molecular basis of disorder known

Autosomal recessive

{Lipodystrophy, partial, acquired, susceptibility to}

MIM #608709

Molecular basis of disorder known

Autosomal dominant

Microcephaly 27, primary, autosomal dominant

MIM #619180

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Homozygous loss of function variant in LMNB2 gene causes major brain malformation and perinatal death.
Desgrouas C et al.·J Med Genet
2025Case report
[Primary lipodystrophies].
Capeau J et al.·Ann Endocrinol (Paris)
2007
A novel missense variant in the LMNB2 gene causes progressive myoclonus epilepsy.
Soleimanipour F et al.·Acta Neurol Belg
2022
LMNB2 promotes the progression of colorectal cancer by silencing p21 expression.
Dong CH et al.·Cell Death Dis
2021
The Fall of the Armor: Lamin Dysregulation and a Wide Network of Laminopathies.
Ray H et al.·Subcell Biochem
2025Review
"Laminopathies": a wide spectrum of human diseases.
Worman HJ et al.·Exp Cell Res
2007Review
A Lamin Family-Based Signature Predicts Prognosis and Immunotherapy Response in Hepatocellular Carcinoma.
Yang Y et al.·J Immunol Res
2022
Lamin B2 promotes the progression of triple negative breast cancer via mediating cell proliferation and apoptosis.
Zhao CC et al.·Biosci Rep
2021
Mutation of the nuclear lamin gene LMNB2 in progressive myoclonus epilepsy with early ataxia.
Damiano JA et al.·Hum Mol Genet
2015
Clinical Characteristics of Patients With Acquired Partial Lipodystrophy: A Multicenter Retrospective Study.
Magno S et al.·J Clin Endocrinol Metab
2024Cohort
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools