LMBR1L

Last update 08 May 2025

Basic Info

Synonyms

FLJ10494, KIAA1174, limb development membrane protein 1 like

+ [5]

Introduction

Plays an essential role in lymphocyte development by negatively regulating the canonical Wnt signaling pathway (By similarity). In association with UBAC2 and E3 ubiquitin-protein ligase AMFR, promotes the ubiquitin-mediated degradation of CTNNB1 and Wnt receptors FZD6 and LRP6 (By similarity). LMBR1L stabilizes the beta-catenin destruction complex that is required for regulating CTNNB1 levels (By similarity). Acts as a LCN1 receptor and can mediate its endocytosis (PubMed:11287427, PubMed:12591932, PubMed:23964685).

100 Clinical Results associated with LMBR1L

100 Translational Medicine associated with LMBR1L

0 Patents (Medical) associated with LMBR1L

Literatures (Medical) associated with LMBR1L

01 Jun 2023·PLoS genetics

Autosomal recessive hyposegmentation of granulocytes in Australian Shepherd Dogs indicates a role for LMBR1L in myeloid leukocytes.

Article

Author: Riond, Barbara ; Leeb, Tosso ; Schelling, Claude ; Pieńkowska-Schelling, Aldona ; Christen, Matthias ; Peters, Laureen M ; Reichler, Iris M ; Balogh, Orsolya ; Kipar, Anja ; Suárez Sánchez-Andrade, José ; Jagannathan, Vidhya ; Novacco, Marilisa ; Lourdes Frehner, Bianca

Pelger-Huët anomaly (PHA) in humans is an autosomal dominant hematological phenotype without major clinical consequences. PHA involves a characteristic hyposegmentation of granulocytes (HG). Human PHA is caused by heterozygous loss of function variants in the LBR gene encoding lamin receptor B. Bi-allelic variants and complete deficiency of LBR cause the much more severe Greenberg skeletal dysplasia which is lethal in utero and characterized by massive skeletal malformation and gross fetal hydrops. HG phenotypes have also been described in domestic animals and homology to human PHA has been claimed in the literature. We studied a litter of Australian Shepherd Dogs with four stillborn puppies in which both parents had an HG phenotype. Linkage analysis excluded LBR as responsible gene for the stillborn puppies. We then investigated the HG phenotype in Australian Shepherd Dogs independently of the prenatal lethality. Genome-wide association mapped the HG locus to chromosome 27 and established an autosomal recessive mode of inheritance. Whole genome sequencing identified a splice site variant in LMBR1L, c.191+1G>A, as most likely causal variant for the HG phenotype. The mutant allele abrogates the expression of the longer X2 isoform but does not affect transcripts encoding the shorter X1 isoform of the LMBR1L protein. The homozygous mutant LMBR1L genotype associated with HG is common in Australian Shepherd Dogs and was found in 39 of 300 genotyped dogs (13%). Our results point to a previously unsuspected function of LMBR1L in the myeloid lineage of leukocytes.

15 Mar 2022·Journal of Cell ScienceQ2 · BIOLOGY

LMBR1L regulates the proliferation and migration of endothelial cells through Norrin/β-catenin signaling

Q2 · BIOLOGY

Article

Author: Liu, Wenjing ; Li, Xiao ; Jiang, Xiaoyan ; Li, Shujin ; Yang, Yeming ; Zhu, Xianjun ; Sun, Kuanxiang ; Yang, Mu

ABSTRACTPrecise Norrin and β-catenin (Norrin/β-catenin; encoded by NDP and CTNNB1, respectively) signaling is critical for proper angiogenesis. Dysregulation of this signaling leads to various diseases, of which retinal exudative vitreoretinopathy is the most prevalent. Here, we used a global knockout mouse model to show that limb development membrane protein 1 like (LMBR1L), a transmembrane protein of unknown function in angiogenesis, is essential for retinal vascular development. In vitro experiments revealed that LMBR1L depletion results in aberrant activation of the Norrin/β-catenin signaling pathway via decreased ubiquitylation of FZD4 and increased Norrin co-receptor LRP5 and p-GSK3β-Ser9 expression levels, which cause accumulation of β-catenin. Moreover, inhibition of LMBR1L in human retinal microvascular endothelial cells (HRECs) caused increased proliferation ability and defective cell migration, which might have occurred as a result of upregulated expression levels of the apical junction components. Treatment with p-GSK3β-Ser9 inhibitor AR-A014418 restored the phenotypes in LMBR1L-null HRECs, which further demonstrated the important regulatory role of LMBR1L in the Norrin/β-catenin signaling pathway. Taken together, our data reveal an essential role for LMBR1L in angiogenesis.This article has an associated First Person interview with the first author of the paper.

01 Mar 2022·Human Mutation

Genomic variants reducing expression of two endocytic receptors in 46,XY differences of sex development

Article

Author: Braun, Doreen ; Fabiano, Marietta ; Altmüller, Janine ; Thiele, Holger ; Hornig, Nadine C. ; Betz, Regina C. ; Schweizer, Ulrich ; Holterhus, Paul‐Martin ; Schweikert, Hans‐Udo ; Marko, Hannah L.

Transporter-dependent steroid hormone uptake into target cells was demonstrated in genetically engineered mice and fruit flies. We hypothesized that mutations in such transporters may cause differences in sex development (DSD) in humans. Exome sequencing was performed in 16 genetically unsolved cases of 46,XY DSD selected from an anonymized collection of 708 lines of genital fibroblasts (GF) that were taken from individuals with incomplete virilization. Selection criteria were based on available biochemical characterization of GF compatible with reduced androgen uptake. Two unrelated individuals were identified with mutations in LDL receptor-related protein 2 (LRP2), a gene previously associated with partial sex steroid insensitivity in mice. Like Lrp2^-/- mice, affected individuals had non-descended testes. Western blots on GF confirmed reduced LRP2 expression, and endocytosis of sex hormone-binding globulin was reduced. In three unrelated individuals, two with undescended testes, mutations in another endocytic receptor gene, limb development membrane protein 1 like (LMBR1L), were detected. Two of these individuals had mutations affecting the same codon. In a transfected cell model, mutated LMBR1L showed reduced cell surface expression. Our findings suggest that endocytic androgen uptake in complex with sex hormone-binding globulin is relevant in human. LMBR1L may play a similar role in androgen uptake.

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LMBR1L

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