|Institutional Source||Beutler Lab|
|Gene Name||low density lipoprotein receptor-related protein 2|
|Synonyms||Gp330, D230004K18Rik, b2b1625.2Clo, Megalin|
|Is this an essential gene?||Essential (E-score: 1.000)|
|Stock #||R0391 (G1)|
|Chromosomal Location||69424340-69586065 bp(-) (GRCm38)|
|Type of Mutation||missense|
|DNA Base Change (assembly)||T to A at 69456858 bp|
|Amino Acid Change||Aspartic acid to Valine at position 3745 (D3745V)|
|Ref Sequence||ENSEMBL: ENSMUSP00000079752 (fasta)|
|Gene Model||predicted gene model for transcript(s): [ENSMUST00000080953]|
|Predicted Effect||probably damaging
AA Change: D3745V
PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)
AA Change: D3745V
|Meta Mutation Damage Score||0.6467|
|Coding Region Coverage||
|Validation Efficiency||97% (97/100)|
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene, low density lipoprotein-related protein 2 (LRP2) or megalin, is a multi-ligand endocytic receptor that is expressed in many different tissues but primarily in absorptive epithilial tissues such as the kidney. This glycoprotein has a large amino-terminal extracellular domain, a single transmembrane domain, and a short carboxy-terminal cytoplasmic tail. The extracellular ligand-binding-domains bind diverse macromolecules including albumin, apolipoproteins B and E, and lipoprotein lipase. The LRP2 protein is critical for the reuptake of numerous ligands, including lipoproteins, sterols, vitamin-binding proteins, and hormones. This protein also has a role in cell-signaling; extracellular ligands include parathyroid horomones and the morphogen sonic hedgehog while cytosolic ligands include MAP kinase scaffold proteins and JNK interacting proteins. Recycling of this membrane receptor is regulated by phosphorylation of its cytoplasmic domain. Mutations in this gene cause Donnai-Barrow syndrome (DBS) and facio-oculoacoustico-renal syndrome (FOAR).[provided by RefSeq, Aug 2009]
PHENOTYPE: Homozygotes for a targeted null mutation exhibit lung and kidney epithelial defects, impaired B12 uptake, reduced proliferation of the neuroepithelium resulting in lack of olfactory bulbs, forebrain fusions, ventricular defects, and perinatal lethality. [provided by MGI curators]
|Allele List at MGI|
|Other mutations in this stock||
|Other mutations in Lrp2||
(F):5'- GCCAAGGCTGAGGACTTCTGAAAC -3'
(R):5'- ACTCTATCAACATGAGACGGGGACC -3'
(F):5'- gtgtgtgtgtgtAACATACCAAAG -3'
(R):5'- GGACCCTAGTTTACGAAGTCTTGAC -3'