LMNB1

Chr 5AD

lamin B1

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

NCBI Gene: 4001 ENSG00000113368 UniProt: P20700 OMIM: 150340

The protein is a B-type lamin that forms part of the nuclear lamina structure. Duplications cause autosomal dominant adult-onset leukodystrophy (ADLD), while other mutations result in autosomal dominant primary microcephaly 26. The pathogenic mechanism involves a dominant-negative effect where mutant protein disrupts normal nuclear envelope function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Microcephaly 26, primary, autosomal dominantMIM #619179

UniProtLeukodystrophy, demyelinating, adult-onset, autosomal dominant, typical

UniProtLeukodystrophy, demyelinating, adult-onset, autosomal dominant, atypical

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · microcephaly 26, primary, autosomal dominant · AD · ClinGen 2026

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.41

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — LMNB1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

1.63Z-score

OE missense 0.74 (0.66–0.82)

229 obs / 309.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.21 (0.11–0.41)

0≤0.351.4

Missense OE?0.74 (0.66–0.82)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 6 / 28.6Missense obs/exp: 229 / 309.5Syn Z: 0.41

Background carrier burden — how many people carry a rare variant somewhere in LMNB1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

693 rare PASS variants

Rare truncating (LoF)

1 in 1,500

52 rare PASS variants

Rare synonymous (reference)

1 in 130

304 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LMNB1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 160	1 in 6,800
South Asian	~43k	1 in 150	≈ 1 in 11,000
Remaining (unassigned)	~30k	1 in 130	1 in 770
European (Finnish)	~27k	1 in 400	1 in 5,300
Admixed American	~22k	1 in 110	1 in 680
African / African American	~21k	1 in 110	≈ 1 in 5,600
East Asian	~20k	1 in 120	none seen
Ashkenazi Jewish	~13k	1 in 370	≈ 1 in 12,000
Middle Eastern	~2,884	1 in 120	≈ 1 in 960

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 8 of 11 coding exons well covered in gnomAD exomes; exons 1, 8, 10 marginal. Genomes: all 11.? see exons ↓