LRP8

LDL receptor related protein 8, the group of Low density lipoprotein receptors

Basic information

Region (hg38): 1:53242364-53328469

Links

ENSG00000157193 ∙ NCBI:7804 ∙ OMIM:602600 ∙ HGNC:6700 ∙ Uniprot:Q14114 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Tourette syndrome (No Known Disease Relationship), mode of inheritance: Unknown

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LRP8 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LRP8 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				5	6	11
missense			42	6	1	49
nonsense						0
start loss						0
frameshift						0
inframe indel				2		2
splice donor/acceptor (+/-2bp)						0
splice region				1	2	3
non coding				2		2
Total	0	0	42	15	7

Variants in LRP8

This is a list of pathogenic ClinVar variants found in the LRP8 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-53247047-A-G			Likely benign (May 15, 2018)
1-53247055-C-T		Myocardial infarction, susceptibility to, 1	risk factor (Oct 01, 2007)
1-53249403-C-T		not specified	Uncertain significance (Jan 23, 2024)
1-53249426-T-G		not specified	Uncertain significance (Jan 19, 2022)
1-53249496-G-A		not specified	Uncertain significance (Apr 09, 2024)
1-53249502-T-C		not specified	Uncertain significance (Feb 03, 2022)
1-53250719-T-G		not specified	Uncertain significance (Dec 16, 2023)
1-53250747-T-G		not specified	Uncertain significance (Sep 21, 2023)
1-53250793-C-T		not specified	Uncertain significance (Feb 14, 2023)
1-53250809-G-A		not specified	Uncertain significance (Mar 01, 2023)
1-53250819-T-C			Benign (Dec 31, 2019)
1-53252416-G-A			Likely benign (Oct 01, 2023)
1-53255122-G-A		not specified	Uncertain significance (Jan 03, 2024)
1-53255126-C-T		not specified	Uncertain significance (Mar 26, 2024)
1-53255141-C-T		not specified	Uncertain significance (Mar 28, 2024)
1-53257275-G-T		not specified	Uncertain significance (Mar 31, 2024)
1-53257281-G-A		not specified	Likely benign (Dec 11, 2023)
1-53257303-G-T		not specified	Uncertain significance (Sep 17, 2021)
1-53258321-C-T			Benign (Dec 31, 2019)
1-53258354-A-C		not specified	Uncertain significance (Dec 16, 2022)
1-53258422-G-A			Likely benign (Jul 19, 2018)
1-53260511-T-C		not specified	Uncertain significance (Mar 16, 2024)
1-53260565-A-C		not specified	Uncertain significance (Dec 15, 2023)
1-53262190-A-C		not specified	Uncertain significance (Apr 07, 2023)
1-53262192-C-T		not specified	Uncertain significance (May 09, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LRP8	protein_coding	protein_coding	ENST00000306052	19	82526

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000165	125737	0	11	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.52	382	548	0.697	0.0000335	6293
Missense in Polyphen		147	251.17	0.58526		2776
Synonymous	1.45	197	225	0.877	0.0000154	1842
Loss of Function	5.67	5	46.9	0.107	0.00000234	529

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.000123	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000265	0.0000264
Middle Eastern	0.000123	0.000109
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cell surface receptor for Reelin (RELN) and apolipoprotein E (apoE)-containing ligands. LRP8 participates in transmitting the extracellular Reelin signal to intracellular signaling processes, by binding to DAB1 on its cytoplasmic tail. Reelin acts via both the VLDL receptor (VLDLR) and LRP8 to regulate DAB1 tyrosine phosphorylation and microtubule function in neurons. LRP8 has higher affinity for Reelin than VLDLR. LRP8 is thus a key component of the Reelin pathway which governs neuronal layering of the forebrain during embryonic brain development. Binds the endoplasmic reticulum resident receptor-associated protein (RAP). Binds dimers of beta 2-glycoprotein I and may be involved in the suppression of platelet aggregation in the vasculature. Highly expressed in the initial segment of the epididymis, where it affects the functional expression of clusterin and phospholipid hydroperoxide glutathione peroxidase (PHGPx), two proteins required for sperm maturation. May also function as an endocytic receptor. Not required for endocytic uptake of SEPP1 in the kidney which is mediated by LRP2 (By similarity). {ECO:0000250|UniProtKB:Q924X6, ECO:0000269|PubMed:12807892, ECO:0000269|PubMed:12899622, ECO:0000269|PubMed:12950167}.
• Disease: DISEASE: Myocardial infarction 1 (MCI1) [MIM:608446]: A condition defined by the irreversible necrosis of heart muscle secondary to prolonged ischemia. {ECO:0000269|PubMed:17847002}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Signaling by GPCR;Signal Transduction;Metabolism of fat-soluble vitamins;lissencephaly gene (lis1) in neuronal migration and development;Metabolism;Metabolism of vitamins and cofactors;Hemostasis;Retinoid metabolism and transport;G alpha (i) signalling events;Visual phototransduction;Platelet sensitization by LDL;Platelet homeostasis;GPCR downstream signalling;Reelin signaling pathway;Lissencephaly gene (LIS1) in neuronal migration and development (Consensus)

Recessive Scores

• pRec: 0.265

Intolerance Scores

• loftool: 0.0113
• rvis_EVS: -0.88
• rvis_percentile_EVS: 10.5

Haploinsufficiency Scores

• pHI: 0.765
• hipred: Y
• hipred_score: 0.749
• ghis: 0.529

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.681

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Lrp8
• 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system 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); normal phenotype; growth/size/body region phenotype; cellular phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;retinoid metabolic process;proteolysis;lipid metabolic process;endocytosis;receptor-mediated endocytosis;signal transduction;cytokine-mediated signaling pathway;ammon gyrus development;cerebral cortex development;positive regulation of CREB transcription factor activity;reelin-mediated signaling pathway;response to drug;regulation of apoptotic process;regulation of innate immune response;positive regulation of peptidyl-tyrosine phosphorylation;modulation of chemical synaptic transmission;positive regulation of dendritic spine morphogenesis;positive regulation of protein tyrosine kinase activity;cellular response to growth factor stimulus;cellular response to cholesterol;positive regulation of dendrite development
• Cellular component: extracellular region;microtubule associated complex;plasma membrane;caveola;postsynaptic density;membrane;integral component of membrane;axon;dendrite;neuronal cell body;receptor complex
• Molecular function: transmembrane signaling receptor activity;low-density lipoprotein particle receptor activity;calcium ion binding;protein binding;high-density lipoprotein particle binding;kinesin binding;very-low-density lipoprotein particle receptor activity;apolipoprotein binding;reelin receptor activity