LBR

Chr 1ADAR

lamin B receptor

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

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 0.424 OMIM phenotypes
Clinical SummaryLBR
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Gene-Disease Validity (ClinGen)
Greenberg dysplasia · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
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ClinVar Variants
41 unique Pathogenic / Likely Pathogenic· 242 VUS of 499 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.42LOEUF
pLI 0.181
Z-score 4.29
OE 0.24 (0.140.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.29Z-score
OE missense 0.96 (0.871.05)
337 obs / 352.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.24 (0.140.42)
00.351.4
Missense OE0.96 (0.871.05)
00.61.4
Synonymous OE0.87
01.21.6
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

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

DN
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.PMID:20522425

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

499 submitted variants in ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic8
VUS242
Likely Benign125
Benign36
Conflicting36
33
Pathogenic
8
Likely Pathogenic
242
VUS
125
Likely Benign
36
Benign
36
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
3
21
0
33
Likely Pathogenic
4
4
0
0
8
VUS
2
207
31
2
242
Likely Benign
0
10
56
59
125
Benign
0
1
31
4
36
Conflicting
36
Total1522513965480

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

View in ClinVar →

Protein Context — Lollipop Plot

LBR · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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