LBR

Chr 1ADAR

lamin B receptor

Also known as: C14SR, DHCR14B, LMN2R, PHA, PHASK, TDRD18

NCBI Gene: 3930 ENSG00000143815 UniProt: Q14739 OMIM: 600024

This protein catalyzes a key step in cholesterol biosynthesis by reducing lanosterol and also anchors the nuclear lamina and heterochromatin to the inner nuclear membrane. Mutations cause a spectrum of disorders including severe Greenberg skeletal dysplasia, Pelger-Huet anomaly (a benign neutrophil nuclear morphology variant), and rhizomelic skeletal dysplasia, with inheritance patterns that are both autosomal recessive and autosomal dominant depending on the specific condition. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.422), reflecting the range from benign to severe phenotypes associated with different mutation types.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene belongs to the ERG4/ERG24 family. It localized in the nuclear envelope inner membrane and anchors the lamina and the heterochromatin to the membrane. It may mediate interaction between chromatin and lamin B. Mutations of this gene has been associated with autosomal recessive HEM/Greenberg skeletal dysplasia. Alternative splicing occurs at this locus and two transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismAD/ARLOEUF 0.424 OMIM phenotypes

Clinical Summary— LBR

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Gene-Disease Validity (ClinGen)

Greenberg dysplasia · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.42LOEUF

pLI 0.181

Z-score 4.29

OE 0.24 (0.14–0.42)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.29Z-score

OE missense 0.96 (0.87–1.05)

337 obs / 352.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.24 (0.14–0.42)

0≤0.351.4

Missense OE?0.96 (0.87–1.05)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 9 / 37.2Missense obs/exp: 337 / 352.3Syn Z: 1.19

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveLBR-related hydrops-ectopic calcification-moth-eaten skeletal dysplasiaLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6746th %ile

GOF

0.5856th %ile

LOF

0.3356th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

DNThe fibroblast specific abnormalities observed suggest that this particular LBR mutation might have dominant negative deleterious effects in a tissue specific fashion, possibly through the perturbation of the interactions or stability of the nuclear envelope protein network.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

References