LBR

Cilia effects upon perturbation of LBR

Ciliogenesis screen results (6 screens)

• Kim2016: No effect
• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-3.41) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: Joubert Candidate / Ciliogenesis Defect (robust z=-2.29, ciliated=20.1%) PMID:26595381
• Pusapati et al. 2018 (CRISPR) [CRISPR]: Positive Regulator (Hh signaling, neg_rank=97, lfc=-3.43) PMID:30270045
• Elliott et al. 2025 (CRISPRa) [CRISPRa]: Disassembly Trigger (casTLE Effect=-3.71) PMID:41160700

Phenotypes

Mouse phenotype:

spermatogenesis defect; decreased bone mineral density; decreased locomotor activity; abnormal skin morphology; alopecia; abnormal coat/ hair morphology; germ cell defect; dysplasia; abnormal digit morphology; enlarged lymph nodes; decreased grip strength; decreased mean corpuscular hemoglobin; decreased exploration in new environment; developmental dysplasia; increased neutrophil cell number; decreased bone mineral content; abnormal forelimb morphology; abnormal hindlimb morphology; decreased prepulse inhibition; decreased body length; abnormal bone structure; abnormal tail morphology; impaired pupillary reflex; small testis; short tibia; decreased lymphocyte cell number; decreased circulating alkaline phosphatase level; increased monocyte cell number; preweaning lethality; incomplete penetrance; small seminal vesicle; abnormal cranium morphology

Mouse ciliopathy phenotype:

hydrocephalus

Ciliopathy associations

• Spondylometaphyseal Dysplasia

Subcellular localization

cilia associated gene, nuclear membrane, nucleoli fibrillar center

Functional category

• Signaling (Hedgehog, GPCRs, ion channels)

Function

An individual with ATD associated with compound heterozygosity for two missense mutations in LBR, encoding the lamin B receptor identified. The phenotype thus appears to be allelic with Greenberg dysplasia, a lethal skeletal disorder resulting from disruption of the sterol reductase activity of the protein. Our results suggest a new link between LBR and cilia, and we speculate that disruption of sterol modification of key signaling proteins, including sonic hedgehog, that are essential for cilia function and for normal skeletal development is the underlying basis for the phenotype (PMID: 29068549). LBR mutations causing a mild bone dysplasia, we suggest that a peripheral blood smear to assess for Pelger-Huet anomaly be done as a screening test in an individual with an undelineated metaphyseal or spondylometaphyseal dysplasia (PMID: 25348816).