Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders
Moldiag Diseases Genes Support Contact

Low density lipoprotein receptor-related protein 2

Mutations in LRP2 gene cause autosomal recessive Donnai-Barrow syndrome (DBS) and facio-oculoacoustico-renal syndrome (FOAR).

Protein Structure

Megalin, the product of the LRP2 gene, belongs to the LDL receptor family. I consists of a huge extracellular domain (4398 amino acids), a single transmembrane segment, and a short cytoplsmatic tail (209). The extracellular domain contains 36 cysteine-rich complement-type repeats in four clusters, 16 growth factor repeats separated by 8 YWTD spacers, and a single epidermal growth factor-like repeat. The intracellular domain contains 2 endocytic motifs (NPXY), 1 NPXY-like motif (NQNY), 1 SH3 domain, 1 PDZ domain, and phosphorylation sites.

Genetests:

Clinic Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25 days
Specimen type genomic DNA
Clinic Method Genomic sequencing of the entire coding region
Turnaround 25 days
Specimen type genomic DNA

Related Diseases:

Donnai-Barrow syndrome
LRP2

References:

1.

Chatelet F et al. (1986) Ultrastructural localization by monoclonal antibodies of brush border antigens expressed by glomeruli. II. Extrarenal distribution.

external link
2.

Saito A et al. (2010) Molecular mechanisms of receptor-mediated endocytosis in the renal proximal tubular epithelium.

external link
3.

Kantarci S et al. (2007) Mutations in LRP2, which encodes the multiligand receptor megalin, cause Donnai-Barrow and facio-oculo-acoustico-renal syndromes.

external link
4.

Caruso-Neves C et al. (2006) PKB and megalin determine the survival or death of renal proximal tubule cells.

external link
5.

Naccache SN et al. (2006) Binding of internalized receptors to the PDZ domain of GIPC/synectin recruits myosin VI to endocytic vesicles.

external link
6.

Hammes A et al. (2005) Role of endocytosis in cellular uptake of sex steroids.

external link
7.

Tramontano A et al. (2004) Conformation and glycosylation of a megalin fragment correlate with nephritogenicity in Heymann nephritis.

external link
8.

Nagai M et al. (2003) The adaptor protein ARH escorts megalin to and through endosomes.

external link
9.

Chassaing N et al. (2003) Donnai-Barrow syndrome: four additional patients.

external link
10.

Nykjaer A et al. (2001) Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3).

external link
11.

Schmitz C et al. (2002) Megalin deficiency offers protection from renal aminoglycoside accumulation.

external link
12.

Leheste JR et al. (1999) Megalin knockout mice as an animal model of low molecular weight proteinuria.

external link
13.

Marinò M et al. (1999) Serum antibodies against megalin (GP330) in patients with autoimmune thyroiditis.

external link
14.

Nykjaer A et al. (1999) An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3.

external link
15.

Willnow TE et al. (1996) Defective forebrain development in mice lacking gp330/megalin.

external link
16.

Raychowdhury R et al. (1989) Autoimmune target in Heymann nephritis is a glycoprotein with homology to the LDL receptor.

external link
17.

Kerjaschki D et al. (1983) Immunocytochemical localization of the Heymann nephritis antigen (GP330) in glomerular epithelial cells of normal Lewis rats.

external link
18.

Moestrup SK et al. (1995) Evidence that epithelial glycoprotein 330/megalin mediates uptake of polybasic drugs.

external link
19.

Farquhar MG et al. (1995) The Heymann nephritis antigenic complex: megalin (gp330) and RAP.

external link
20.

Chowdhary BP et al. (1995) In situ hybridization mapping of a 500-kDa calcium-sensing protein gene (LRP2) to human chromosome region 2q31>q32.1 and porcine chromosome region 15q22>q24.

external link
21.

None (1995) The unfolding story of megalin (gp330): now recognized as a drug receptor.

external link
22.

Kounnas MZ et al. (1995) Identification of glycoprotein 330 as an endocytic receptor for apolipoprotein J/clusterin.

external link
23.

Saito A et al. (1994) Complete cloning and sequencing of rat gp330/"megalin," a distinctive member of the low density lipoprotein receptor gene family.

external link
24.

Korenberg JR et al. (1994) Chromosomal localization of human genes for the LDL receptor family member glycoprotein 330 (LRP2) and its associated protein RAP (LRPAP1).

external link
25.

Donnai D et al. (1993) Diaphragmatic hernia, exomphalos, absent corpus callosum, hypertelorism, myopia, and sensorineural deafness: a newly recognized autosomal recessive disorder?

external link
26.

Hjälm G et al. (1996) Cloning and sequencing of human gp330, a Ca(2+)-binding receptor with potential intracellular signaling properties.

external link
27.

Devriendt K et al. (1998) Proteinuria in a patient with the diaphragmatic hernia-hypertelorism-myopia-deafness syndrome: further evidence that the facio-oculo-acoustico-renal syndrome represents the same entity.

external link
28.

OMIM.ORG article

Omim 600073 external link
29.

NCBI article

NCBI 4036 external link
30.

Orphanet article

Orphanet ID 159747 external link
31.

Wikipedia article

Wikipedia EN (LRP2) external link
Update: Aug. 14, 2020
Copyright © 2005-2020 by Center for Nephrology and Metabolic Disorders, Dr. Mato Nagel, MD
Albert-Schweitzer-Ring 32, D-02943 Weißwasser, Germany, Tel.: +49-3576-287922, Fax: +49-3576-287944
Sitemap | Webmail | Disclaimer | Privacy Issues