LRP1
LDL receptor related protein 1, the group of CD molecules|Low density lipoprotein receptors|MicroRNA protein coding host genes
Basic information
Region (hg38): 12:57128483-57213361
Previous symbols: [ "APR", "A2MR" ]
Links
Phenotypes
GenCC
Source:
- schizophrenia (Limited), mode of inheritance: Unknown
- keratosis follicularis spinulosa decalvans (Supportive), mode of inheritance: AD
- atrophoderma vermiculata (Supportive), mode of inheritance: AR
- keratosis pilaris atrophicans (Limited), mode of inheritance: Unknown
- developmental dysplasia of the hip 3 (Limited), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Developmental dysplasia of the hip 3; Schizophrenia; Keratosis pilaris atrophicans | AD/AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Musculoskeletal; Neurologic | 21743468; 26142438; 36067312 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (411 variants)
- not_provided (128 variants)
- LRP1-related_disorder (62 variants)
- Developmental_dysplasia_of_the_hip_3 (7 variants)
- Keratosis_pilaris_atrophicans (5 variants)
- Ventricular_septal_defect (2 variants)
- Tricuspid_atresia (2 variants)
- Variant_of_unknown_significance (1 variants)
- Global_developmental_delay (1 variants)
- Keratosis_pilaris (1 variants)
- Prostate_cancer (1 variants)
- Neuromuscular_disease (1 variants)
- Atrophoderma_vermiculatum (1 variants)
- Developmental_disorder (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the LRP1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002332.3. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 83 | 30 | 114 | |||
| missense | 419 | 25 | 452 | |||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 4 | 1 | 421 | 109 | 34 |
Highest pathogenic variant AF is 0.0000701201
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| LRP1 | protein_coding | protein_coding | ENST00000243077 | 89 | 84859 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 7.45e-35 | 125735 | 0 | 13 | 125748 | 0.0000517 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 8.25 | 1692 | 2.95e+3 | 0.573 | 0.000209 | 30166 |
| Missense in Polyphen | 547 | 1378.5 | 0.39682 | 14033 | ||
| Synonymous | 2.22 | 1104 | 1.20e+3 | 0.918 | 0.0000908 | 8584 |
| Loss of Function | 14.1 | 8 | 247 | 0.0324 | 0.0000134 | 2549 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000615 | 0.0000615 |
| Ashkenazi Jewish | 0.000200 | 0.000198 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.0000465 | 0.0000462 |
| European (Non-Finnish) | 0.0000444 | 0.0000439 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.0000654 | 0.0000653 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Endocytic receptor involved in endocytosis and in phagocytosis of apoptotic cells. Required for early embryonic development. Involved in cellular lipid homeostasis. Involved in the plasma clearance of chylomicron remnants and activated LRPAP1 (alpha 2-macroglobulin), as well as the local metabolism of complexes between plasminogen activators and their endogenous inhibitors. May modulate cellular events, such as APP metabolism, kinase-dependent intracellular signaling, neuronal calcium signaling as well as neurotransmission (PubMed:11907044, PubMed:12888553, PubMed:12713657). Acts as an alpha-2- macroglobulin receptor (PubMed:26142438). {ECO:0000269|PubMed:11907044, ECO:0000269|PubMed:12713657, ECO:0000269|PubMed:12888553, ECO:0000269|PubMed:26142438}.;
- Disease
- DISEASE: Keratosis pilaris atrophicans (KPA) [MIM:604093]: A group of rare genodermatoses characterized by keratotic follicular papules, variable degrees of inflammation, and secondary atrophic scarring. Most cases are associated with an atopic diathesis and keratosis pilaris on the extensor extremities. KPA is comprised of three distinct clinical subtypes: keratosis pilaris atrophicans faciei, atrophoderma vermiculatum, and keratosis follicularis spinulosa decalvans. Affected individuals may present with features overlapping the 3 subtypes. {ECO:0000269|PubMed:26142438}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Alzheimer,s disease - Homo sapiens (human);Malaria - Homo sapiens (human);Cholesterol metabolism - Homo sapiens (human);Statin Pathway, Pharmacodynamics;miR-targeted genes in epithelium - TarBase;miR-targeted genes in muscle cell - TarBase;Alzheimers Disease;Regulation of Wnt-B-catenin Signaling by Small Molecule Compounds;Statin Pathway;Signaling by GPCR;Signal Transduction;Metabolism of fat-soluble vitamins;Vesicle-mediated transport;Metabolism;Metabolism of vitamins and cofactors;Retinoid metabolism and transport;G alpha (i) signalling events;Visual phototransduction;Wnt;Scavenging of heme from plasma;Binding and Uptake of Ligands by Scavenger Receptors;GPCR downstream signalling;amb2 Integrin signaling;Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling;PDGFR-beta signaling pathway
(Consensus)
Recessive Scores
- pRec
- 0.766
Intolerance Scores
- loftool
- 0.00262
- rvis_EVS
- -7.28
- rvis_percentile_EVS
- 0.02
Haploinsufficiency Scores
- pHI
- 0.654
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.619
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.745
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Lrp1
- Phenotype
- reproductive system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); embryo phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); muscle phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype;
Zebrafish Information Network
- Gene name
- lrp1aa
- Affected structure
- vasculature
- Phenotype tag
- abnormal
- Phenotype quality
- morphology
Gene ontology
- Biological process
- retinoid metabolic process;astrocyte activation involved in immune response;lipid metabolic process;receptor-mediated endocytosis;phagocytosis;protein kinase C-activating G protein-coupled receptor signaling pathway;aging;cell population proliferation;regulation of extracellular matrix disassembly;positive regulation of cholesterol efflux;positive regulation of cell death;negative regulation of neuron projection development;negative regulation of smooth muscle cell migration;cerebral cortex development;negative regulation of Wnt signaling pathway;receptor internalization;positive regulation of protein binding;positive regulation of lipid transport;regulation of cholesterol transport;regulation of phospholipase A2 activity;regulation of actin cytoskeleton organization;aorta morphogenesis;lipoprotein metabolic process;lipoprotein transport;apoptotic cell clearance;negative regulation of neuron apoptotic process;transcytosis;positive regulation of protein catabolic process;positive regulation of endocytosis;positive regulation of protein transport;regulation of protein metabolic process;amyloid-beta clearance;positive regulation of amyloid-beta clearance;positive regulation of protein localization to plasma membrane;cellular response to amyloid-beta;positive regulation of lysosomal protein catabolic process;negative regulation of platelet-derived growth factor receptor-beta signaling pathway
- Cellular component
- nucleus;lysosomal membrane;early endosome;plasma membrane;integral component of plasma membrane;clathrin-coated pit;focal adhesion;membrane;basolateral plasma membrane;clathrin-coated vesicle;dendrite;endocytic vesicle membrane;neuronal cell body;receptor complex;plasma membrane protein complex
- Molecular function
- amyloid-beta binding;protease binding;RNA binding;low-density lipoprotein particle receptor activity;scavenger receptor activity;calcium ion binding;protein binding;alpha-2 macroglobulin receptor activity;apolipoprotein receptor activity;clathrin heavy chain binding;apolipoprotein binding;signaling receptor activity;lipoprotein transporter activity;heparan sulfate proteoglycan binding;protein-containing complex binding;lipoprotein particle receptor binding