Seroatlas · Human Serome Atlas

LRP6

Low-density lipoprotein receptor-related protein 6

Also known as: ADCAD2, LRP6_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: O75581
Gene: LRP6
Ensembl: ENSG00000070018
Chromosome: 12
Canonical length: 1613 aa
Protein class: Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins
Quaternary structure: Homodimer

OverviewNCBI Gene

This gene encodes a member of the low density lipoprotein (LDL) receptor gene family. LDL receptors are transmembrane cell surface proteins involved in receptor-mediated endocytosis of lipoprotein and protein ligands. The protein encoded by this gene functions as a receptor or, with Frizzled, a co-receptor for Wnt and thereby transmits the canonical Wnt/beta-catenin signaling cascade. Through its interaction with the Wnt/beta-catenin signaling cascade this gene plays a role in the regulation of cell differentiation, proliferation, and migration and the development of many cancer types. This protein undergoes gamma-secretase dependent RIP- (regulated intramembrane proteolysis) processing but the precise locations of the cleavage sites have not been determined.[provided by RefSeq, Dec 2009]

Canonical amino-acid sequenceUniProt

1613 residues, UniProt reviewed canonical sequence.

>O75581|LRP6
     1  MGAVLRSLLA CSFCVLLRAA PLLLYANRRD LRLVDATNGK ENATIVVGGL EDAAAVDFVF
    61  SHGLIYWSDV SEEAIKRTEF NKTESVQNVV VSGLLSPDGL ACDWLGEKLY WTDSETNRIE
   121  VSNLDGSLRK VLFWQELDQP RAIALDPSSG FMYWTDWGEV PKIERAGMDG SSRFIIINSE
   181  IYWPNGLTLD YEEQKLYWAD AKLNFIHKSN LDGTNRQAVV KGSLPHPFAL TLFEDILYWT
   241  DWSTHSILAC NKYTGEGLRE IHSDIFSPMD IHAFSQQRQP NATNPCGIDN GGCSHLCLMS
   301  PVKPFYQCAC PTGVKLLENG KTCKDGATEL LLLARRTDLR RISLDTPDFT DIVLQLEDIR
   361  HAIAIDYDPV EGYIYWTDDE VRAIRRSFID GSGSQFVVTA QIAHPDGIAV DWVARNLYWT
   421  DTGTDRIEVT RLNGTMRKIL ISEDLEEPRA IVLDPMVGYM YWTDWGEIPK IERAALDGSD
   481  RVVLVNTSLG WPNGLALDYD EGKIYWGDAK TDKIEVMNTD GTGRRVLVED KIPHIFGFTL
   541  LGDYVYWTDW QRRSIERVHK RSAEREVIID QLPDLMGLKA TNVHRVIGSN PCAEENGGCS
   601  HLCLYRPQGL RCACPIGFEL ISDMKTCIVP EAFLLFSRRA DIRRISLETN NNNVAIPLTG
   661  VKEASALDFD VTDNRIYWTD ISLKTISRAF MNGSALEHVV EFGLDYPEGM AVDWLGKNLY
   721  WADTGTNRIE VSKLDGQHRQ VLVWKDLDSP RALALDPAEG FMYWTEWGGK PKIDRAAMDG
   781  SERTTLVPNV GRANGLTIDY AKRRLYWTDL DTNLIESSNM LGLNREVIAD DLPHPFGLTQ
   841  YQDYIYWTDW SRRSIERANK TSGQNRTIIQ GHLDYVMDIL VFHSSRQSGW NECASSNGHC
   901  SHLCLAVPVG GFVCGCPAHY SLNADNRTCS APTTFLLFSQ KSAINRMVID EQQSPDIILP
   961  IHSLRNVRAI DYDPLDKQLY WIDSRQNMIR KAQEDGSQGF TVVVSSVPSQ NLEIQPYDLS
  1021  IDIYSRYIYW TCEATNVINV TRLDGRSVGV VLKGEQDRPR AVVVNPEKGY MYFTNLQERS
  1081  PKIERAALDG TEREVLFFSG LSKPIALALD SRLGKLFWAD SDLRRIESSD LSGANRIVLE
  1141  DSNILQPVGL TVFENWLYWI DKQQQMIEKI DMTGREGRTK VQARIAQLSD IHAVKELNLQ
  1201  EYRQHPCAQD NGGCSHICLV KGDGTTRCSC PMHLVLLQDE LSCGEPPTCS PQQFTCFTGE
  1261  IDCIPVAWRC DGFTECEDHS DELNCPVCSE SQFQCASGQC IDGALRCNGD ANCQDKSDEK
  1321  NCEVLCLIDQ FRCANGQCIG KHKKCDHNVD CSDKSDELDC YPTEEPAPQA TNTVGSVIGV
  1381  IVTIFVSGTV YFICQRMLCP RMKGDGETMT NDYVVHGPAS VPLGYVPHPS SLSGSLPGMS
  1441  RGKSMISSLS IMGGSSGPPY DRAHVTGASS SSSSSTKGTY FPAILNPPPS PATERSHYTM
  1501  EFGYSSNSPS THRSYSYRPY SYRHFAPPTT PCSTDVCDSD YAPSRRMTSV ATAKGYTSDL
  1561  NYDSEPVPPP PTPRSQYLSA EENYESCPPS PYTERSYSHH LYPPPPSPCT DSS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against LRP6 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Cell surface
Secreted: No
Transmembrane segments: 1
Mean surface accessibility (rSASA): 0.31
Highest tissue expression: 7.8 nTPM

Expression across tissuesHPA

Tissue

placenta: 7.8 nTPM
liver: 7.4 nTPM
parathyroid gland: 5.8 nTPM
salivary gland: 5.2 nTPM
endometrium: 5.1 nTPM
blood vessel: 4.7 nTPM

Single-cell type

choroid plexus epithelial cells: 238 nCPM
distal convoluted tubule cells: 238 nCPM
ependymal cells: 194 nCPM
oligodendrocytes: 186 nCPM
oligodendrocyte progenitor cells: 174 nCPM
loop of henle epithelial cells: 152 nCPM

Immune cell

naive CD4 T-cell: 0.2 nTPM
naive CD8 T-cell: 0.1 nTPM
basophil: 0 nTPM
classical monocyte: 0 nTPM
eosinophil: 0 nTPM
gdT-cell: 0 nTPM

Brain region

choroid plexus: 41 nTPM
basal ganglia: 20 nTPM
white matter: 18 nTPM
hypothalamus: 18 nTPM
thalamus: 18 nTPM
midbrain: 18 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about LRP6.

Disease | AllUniProt

Conditions LRP6 is implicated in, by any mechanism.

Coronary artery disease, autosomal dominant, 2 (ADCAD2) MIM:610947
Tooth agenesis, selective, 7 (STHAG7) MIM:616724
Vitreoretinopathy, exudative 8 (EVR8) MIM:621268

Disease | GeneticClinVar

73 pathogenic / likely-pathogenic of 796 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Disease | ImmuneIEDB

Conditions an epitope on LRP6 was assayed in.

glioblastoma T cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.32
gnomAD pLI: 0.7
gnomAD missense Z: 2.75
DepMap mean gene effect: 0.01
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of LRP6 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads LRP6 as an antibody target. Whether an autoantibody or antibody against LRP6 could matter depends on whether native LRP6 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

LRP6 is annotated at the cell surface, where native LRP6 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label LRP6 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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