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

ENSG00000123384 ∙ NCBI:4035 ∙ OMIM:107770 ∙ HGNC:6692 ∙ Uniprot:Q07954 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the LRP1 gene.

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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				77	38	115
missense			195	18	7	220
nonsense			1			1
start loss						0
frameshift				1		1
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region				13	5	18
non coding				6	42	48
Total	0	1	196	102	87

Variants in LRP1

This is a list of pathogenic ClinVar variants found in the LRP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-57128978-C-T		not specified	Uncertain significance (Jul 20, 2021)
12-57129034-G-A		LRP1-related disorder	Likely benign (May 23, 2019)
12-57138168-C-T			Benign (Jun 20, 2021)
12-57138528-G-A		not specified	Uncertain significance (Oct 03, 2022)
12-57138528-G-C		not specified	Uncertain significance (Oct 27, 2023)
12-57138551-C-T		not specified	Uncertain significance (Aug 10, 2021)
12-57138557-G-A		not specified	Uncertain significance (Apr 25, 2023)
12-57138565-C-T			Likely benign (Dec 01, 2022)
12-57138780-G-A			Benign (Jun 20, 2021)
12-57141129-G-A			Benign (Jun 19, 2021)
12-57141394-C-A			Likely benign (Aug 01, 2018)
12-57141483-C-T		Keratosis pilaris • LRP1-related disorder • not specified	Benign (May 04, 2022)
12-57143756-A-C		not specified	Uncertain significance (Apr 19, 2024)
12-57144994-C-T		LRP1-related disorder	Likely benign (Jun 17, 2019)
12-57145012-A-G			Benign (Mar 29, 2018)
12-57145066-G-A			Benign (Oct 28, 2017)
12-57145071-C-T		not specified	Uncertain significance (Dec 27, 2023)
12-57145284-C-T		not specified	Uncertain significance (Apr 07, 2023)
12-57145299-C-T		LRP1-related disorder	Benign (Mar 27, 2019)
12-57145319-C-G		Developmental dysplasia of the hip 3	Pathogenic (Jan 26, 2024)
12-57145334-C-A		not specified	Uncertain significance (Apr 23, 2024)
12-57145362-C-T		not specified	Uncertain significance (Sep 01, 2021)
12-57145365-A-G		not specified	Uncertain significance (Mar 04, 2024)
12-57145373-G-A		not specified	Uncertain significance (Jun 17, 2024)
12-57145411-G-A			Benign (Dec 31, 2019)

GnomAD

Source: gnomAD

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: dbNSFP

• 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