LMNB1

Chr 5

lamin B1

Also known as: ADLD, LMN, LMN2, LMNB, MCPH26

NCBI Gene: 4001ENSG00000113368UniProt: P20700

This gene encodes one of the two B-type lamin proteins and is a component of the nuclear lamina. A duplication of this gene is associated with autosomal dominant adult-onset leukodystrophy (ADLD). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

Primary Disease Associations & Inheritance

UniProtLeukodystrophy, demyelinating, adult-onset, autosomal dominant, typical
UniProtLeukodystrophy, demyelinating, adult-onset, autosomal dominant, atypical
UniProtMicrocephaly 26, primary, autosomal dominant
341
ClinVar variants
35
Pathogenic / LP
0.55
pLI score
0
Active trials
Clinical Summary— LMNB1
🧬
Gene-Disease Validity (ClinGen)
microcephaly 26, primary, autosomal dominant · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.55) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
35 Pathogenic / Likely Pathogenic· 182 VUS of 341 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.41LOEUF
pLI 0.555
Z-score 3.92
OE 0.21 (0.11–0.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.63Z-score
OE missense 0.74 (0.66–0.82)
229 obs / 309.5 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.0.21 (0.11–0.41)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.66–0.82)
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.0.95
0≤1.21.6
LoF obs/exp: 6 / 28.6Missense obs/exp: 229 / 309.5Syn Z: 0.41

ClinVar Variant Classifications

341 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic2
VUS182
Likely Benign66
Benign42
Conflicting16
33
Pathogenic
2
Likely Pathogenic
182
VUS
66
Likely Benign
42
Benign
16
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
4
27
0
33
Likely Pathogenic
1
1
0
0
2
VUS
6
143
31
2
182
Likely Benign
1
10
22
33
66
Benign
0
3
28
11
42
Conflicting
—16
Total1016110846341

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

LMNB1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

LMNB1-related developmental disorder

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

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — LMNB1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Unmasking Transcriptional Heterogeneity in Senescent Cells.
Hernandez-Segura A et al.·Curr Biol
2017
Structural Variants at the LMNB1 Locus: Deciphering Pathomechanisms in Autosomal Dominant Adult-Onset Demyelinating Leukodystrophy.
Dimartino P et al.·Ann Neurol
2024Functional
LMNB1-related autosomal-dominant leukodystrophy: Clinical and radiological course.
Finnsson J et al.·Ann Neurol
2015
An oligodendrocyte silencer element underlies the pathogenic impact of lamin B1 structural variants.
Nmezi B et al.·Nat Commun
2025
LMNB1 deletion in ovarian cancer inhibits the proliferation and metastasis of tumor cells through PI3K/Akt pathway.
Dong J et al.·Exp Cell Res
2023
Cell-Surface LAMP1 is a Senescence Marker in Aging and Idiopathic Pulmonary Fibrosis.
Meca-Laguna G et al.·Aging Cell
2025
LMNB1/CDKN1A Signaling Regulates the Cell Cycle and Promotes Hepatocellular Carcinoma Progression.
Gao D et al.·Curr Cancer Drug Targets
2025
Impact of Nuclear Peripheral Chromatin Lamin LMNB1 Gene in the Proliferation and Migration of Glioma Cells.
Shi XC et al.·Neurochem Res
2024
Mangiferin protects mesenchymal stem cells against DNA damage and cellular aging via SIRT1 activation.
Lim GM et al.·Mech Ageing Dev
2025
The synergistic effect of c-Myb hyperactivation and Pu.1 deficiency induces Pelger-Huët anomaly and promotes sAML.
Xu S et al.·Proc Natl Acad Sci U S A
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Zinc finger protein Zfp335 is required for T cell homeostatic proliferation through regulating Lmnb1.
Yang B et al.·Cell Biosci
2025🔓 Open Access
Mendelian Randomization Combined with Experimental Validation Identifies Prognostic Genes LMNB1 and PLXNB2 in the Immune Response in Multiple Myeloma.
Zhang X et al.·Recent Pat Anticancer Drug Discov
2025
Clinical Practice Guidelines for the Diagnosis, Management, and Surveillance of LMNB1-Related Autosomal Dominant Leukodystrophy.
Dhamija R et al.·Neurol Genet
2025🔓 Open Access
LMNB1 and LMNB2 as Prognostic Risk Factors in Hepatocellular Carcinoma: Therapeutic Potential of GSK461364 via Downregulation of LMNB1 and LMNB2 Expression.
Yong H et al.·Recent Pat Anticancer Drug Discov
2025
LMNB1 regulates breast cancer cell senescence and migration through PPAR signaling pathway.
Meng S et al.·Discov Oncol
2025🔓 Open Access
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