Seroatlas · Human Serome Atlas

LRP5

Low-density lipoprotein receptor-related protein 5

Also known as: BMND1, EVR1, EVR4, HBM, LR3, LRP5_HUMAN, LRP7, OPPG, OPS, OPTA1, VBCH2

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

Protein identityUniProt · HPA

UniProt accession: O75197
Gene: LRP5
Ensembl: ENSG00000162337
Chromosome: 11
Canonical length: 1615 aa
Protein class: Disease related genes, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins
Quaternary structure: Homodimer

OverviewNCBI Gene

This gene encodes a transmembrane low-density lipoprotein receptor that binds and internalizes ligands in the process of receptor-mediated endocytosis. This protein also acts as a co-receptor with Frizzled protein family members for transducing signals by Wnt proteins and was originally cloned on the basis of its association with type 1 diabetes mellitus in humans. This protein plays a key role in skeletal homeostasis and many bone density related diseases are caused by mutations in this gene. Mutations in this gene also cause familial exudative vitreoretinopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

Canonical amino-acid sequenceUniProt

1615 residues, UniProt reviewed canonical sequence.

>O75197|LRP5
     1  MEAAPPGPPW PLLLLLLLLL ALCGCPAPAA ASPLLLFANR RDVRLVDAGG VKLESTIVVS
    61  GLEDAAAVDF QFSKGAVYWT DVSEEAIKQT YLNQTGAAVQ NVVISGLVSP DGLACDWVGK
   121  KLYWTDSETN RIEVANLNGT SRKVLFWQDL DQPRAIALDP AHGYMYWTDW GETPRIERAG
   181  MDGSTRKIIV DSDIYWPNGL TIDLEEQKLY WADAKLSFIH RANLDGSFRQ KVVEGSLTHP
   241  FALTLSGDTL YWTDWQTRSI HACNKRTGGK RKEILSALYS PMDIQVLSQE RQPFFHTRCE
   301  EDNGGCSHLC LLSPSEPFYT CACPTGVQLQ DNGRTCKAGA EEVLLLARRT DLRRISLDTP
   361  DFTDIVLQVD DIRHAIAIDY DPLEGYVYWT DDEVRAIRRA YLDGSGAQTL VNTEINDPDG
   421  IAVDWVARNL YWTDTGTDRI EVTRLNGTSR KILVSEDLDE PRAIALHPVM GLMYWTDWGE
   481  NPKIECANLD GQERRVLVNA SLGWPNGLAL DLQEGKLYWG DAKTDKIEVI NVDGTKRRTL
   541  LEDKLPHIFG FTLLGDFIYW TDWQRRSIER VHKVKASRDV IIDQLPDLMG LKAVNVAKVV
   601  GTNPCADRNG GCSHLCFFTP HATRCGCPIG LELLSDMKTC IVPEAFLVFT SRAAIHRISL
   661  ETNNNDVAIP LTGVKEASAL DFDVSNNHIY WTDVSLKTIS RAFMNGSSVE HVVEFGLDYP
   721  EGMAVDWMGK NLYWADTGTN RIEVARLDGQ FRQVLVWRDL DNPRSLALDP TKGYIYWTEW
   781  GGKPRIVRAF MDGTNCMTLV DKVGRANDLT IDYADQRLYW TDLDTNMIES SNMLGQERVV
   841  IADDLPHPFG LTQYSDYIYW TDWNLHSIER ADKTSGRNRT LIQGHLDFVM DILVFHSSRQ
   901  DGLNDCMHNN GQCGQLCLAI PGGHRCGCAS HYTLDPSSRN CSPPTTFLLF SQKSAISRMI
   961  PDDQHSPDLI LPLHGLRNVK AIDYDPLDKF IYWVDGRQNI KRAKDDGTQP FVLTSLSQGQ
  1021  NPDRQPHDLS IDIYSRTLFW TCEATNTINV HRLSGEAMGV VLRGDRDKPR AIVVNAERGY
  1081  LYFTNMQDRA AKIERAALDG TEREVLFTTG LIRPVALVVD NTLGKLFWVD ADLKRIESCD
  1141  LSGANRLTLE DANIVQPLGL TILGKHLYWI DRQQQMIERV EKTTGDKRTR IQGRVAHLTG
  1201  IHAVEEVSLE EFSAHPCARD NGGCSHICIA KGDGTPRCSC PVHLVLLQNL LTCGEPPTCS
  1261  PDQFACATGE IDCIPGAWRC DGFPECDDQS DEEGCPVCSA AQFPCARGQC VDLRLRCDGE
  1321  ADCQDRSDEA DCDAICLPNQ FRCASGQCVL IKQQCDSFPD CIDGSDELMC EITKPPSDDS
  1381  PAHSSAIGPV IGIILSLFVM GGVYFVCQRV VCQRYAGANG PFPHEYVSGT PHVPLNFIAP
  1441  GGSQHGPFTG IACGKSMMSS VSLMGGRGGV PLYDRNHVTG ASSSSSSSTK ATLYPPILNP
  1501  PPSPATDPSL YNMDMFYSSN IPATARPYRP YIIRGMAPPT TPCSTDVCDS DYSASRWKAS
  1561  KYYLDLNSDS DPYPPPPTPH SQYLSAEDSC PPSPATERSY FHLFPPPPSP CTDSS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against LRP5 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: Intracellular
Secreted: No
Transmembrane segments: 1
Mean surface accessibility (rSASA): 0.31
Highest tissue expression: 122 nTPM

Expression across tissuesHPA

Tissue

liver: 122 nTPM
salivary gland: 69 nTPM
blood vessel: 50 nTPM
small intestine: 42 nTPM
duodenum: 41 nTPM
choroid plexus: 39 nTPM

Single-cell type

cytotrophoblasts: 136 nCPM
tuft cells: 127 nCPM
salivary acinar cells: 118 nCPM
proximal tubule cells: 105 nCPM
lymphatic endothelial cells: 101 nCPM
enterocytes: 101 nCPM

Immune cell

plasmacytoid DC: 0.5 nTPM
NK-cell: 0.1 nTPM
basophil: 0 nTPM
classical monocyte: 0 nTPM
eosinophil: 0 nTPM
gdT-cell: 0 nTPM

Brain region

choroid plexus: 91 nTPM
medulla oblongata: 19 nTPM
midbrain: 18 nTPM
basal ganglia: 16 nTPM
cerebellum: 15 nTPM
white matter: 14 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about LRP5.

Disease | AllUniProt

Conditions LRP5 is implicated in, by any mechanism.

Vitreoretinopathy, exudative 1 (EVR1) MIM:133780
Vitreoretinopathy, exudative 4 (EVR4) MIM:601813
Osteoporosis (OSTEOP) MIM:166710
Osteoporosis-pseudoglioma syndrome (OPPG) MIM:259770
High bone mass trait (HBM) MIM:601884
Endosteal hyperostosis, Worth type (WENHY) MIM:144750
Osteopetrosis, autosomal dominant 1 (OPTA1) MIM:607634
Van Buchem disease 2 (VBCH2) MIM:607636
Polycystic liver disease 4 with or without kidney cysts (PCLD4) MIM:617875

Disease | GeneticClinVar

217 pathogenic / likely-pathogenic of 2,487 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Osteoporosis with pseudoglioma
Exudative vitreoretinopathy 4
Retinal dystrophy
6 conditions
LRP5-related disorder

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): 0.34
gnomAD pLI: 0.51
gnomAD missense Z: 1.67
DepMap mean gene effect: -0.16
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% 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 LRP5 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 LRP5 as an antibody target. Whether an autoantibody or antibody against LRP5 could matter depends on whether native LRP5 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

LRP5 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label LRP5 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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