LRP4

Protein identityUniProt · HPA

UniProt accession

O75096

Gene

LRP4

Ensembl

ENSG00000134569

Chromosome

11

Canonical length

1905 aa

Protein class

Disease related genes, Human disease related genes, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters

Subcellular location

Nucleoplasm,Mitochondria

Quaternary structure

Homooligomer

OverviewNCBI Gene

This gene encodes a member of the low-density lipoprotein receptor-related protein family. The encoded protein may be a regulator of Wnt signaling. Mutations in this gene are associated with Cenani-Lenz syndrome. [provided by RefSeq, May 2010]

Canonical amino-acid sequenceUniProt

1905 residues, UniProt reviewed canonical sequence.

>O75096|LRP4
     1  MRRQWGALLL GALLCAHGLA SSPECACGRS HFTCAVSALG ECTCIPAQWQ CDGDNDCGDH
    61  SDEDGCILPT CSPLDFHCDN GKCIRRSWVC DGDNDCEDDS DEQDCPPREC EEDEFPCQNG
   121  YCIRSLWHCD GDNDCGDNSD EQCDMRKCSD KEFRCSDGSC IAEHWYCDGD TDCKDGSDEE
   181  NCPSAVPAPP CNLEEFQCAY GRCILDIYHC DGDDDCGDWS DESDCSSHQP CRSGEFMCDS
   241  GLCINAGWRC DGDADCDDQS DERNCTTSMC TAEQFRCHSG RCVRLSWRCD GEDDCADNSD
   301  EENCENTGSP QCALDQFLCW NGRCIGQRKL CNGVNDCGDN SDESPQQNCR PRTGEENCNV
   361  NNGGCAQKCQ MVRGAVQCTC HTGYRLTEDG HTCQDVNECA EEGYCSQGCT NSEGAFQCWC
   421  ETGYELRPDR RSCKALGPEP VLLFANRIDI RQVLPHRSEY TLLLNNLENA IALDFHHRRE
   481  LVFWSDVTLD RILRANLNGS NVEEVVSTGL ESPGGLAVDW VHDKLYWTDS GTSRIEVANL
   541  DGAHRKVLLW QNLEKPRAIA LHPMEGTIYW TDWGNTPRIE ASSMDGSGRR IIADTHLFWP
   601  NGLTIDYAGR RMYWVDAKHH VIERANLDGS HRKAVISQGL PHPFAITVFE DSLYWTDWHT
   661  KSINSANKFT GKNQEIIRNK LHFPMDIHTL HPQRQPAGKN RCGDNNGGCT HLCLPSGQNY
   721  TCACPTGFRK ISSHACAQSL DKFLLFARRM DIRRISFDTE DLSDDVIPLA DVRSAVALDW
   781  DSRDDHVYWT DVSTDTISRA KWDGTGQEVV VDTSLESPAG LAIDWVTNKL YWTDAGTDRI
   841  EVANTDGSMR TVLIWENLDR PRDIVVEPMG GYMYWTDWGA SPKIERAGMD ASGRQVIISS
   901  NLTWPNGLAI DYGSQRLYWA DAGMKTIEFA GLDGSKRKVL IGSQLPHPFG LTLYGERIYW
   961  TDWQTKSIQS ADRLTGLDRE TLQENLENLM DIHVFHRRRP PVSTPCAMEN GGCSHLCLRS
  1021  PNPSGFSCTC PTGINLLSDG KTCSPGMNSF LIFARRIDIR MVSLDIPYFA DVVVPINITM
  1081  KNTIAIGVDP QEGKVYWSDS TLHRISRANL DGSQHEDIIT TGLQTTDGLA VDAIGRKVYW
  1141  TDTGTNRIEV GNLDGSMRKV LVWQNLDSPR AIVLYHEMGF MYWTDWGENA KLERSGMDGS
  1201  DRAVLINNNL GWPNGLTVDK ASSQLLWADA HTERIEAADL NGANRHTLVS PVQHPYGLTL
  1261  LDSYIYWTDW QTRSIHRADK GTGSNVILVR SNLPGLMDMQ AVDRAQPLGF NKCGSRNGGC
  1321  SHLCLPRPSG FSCACPTGIQ LKGDGKTCDP SPETYLLFSS RGSIRRISLD TSDHTDVHVP
  1381  VPELNNVISL DYDSVDGKVY YTDVFLDVIR RADLNGSNME TVIGRGLKTT DGLAVDWVAR
  1441  NLYWTDTGRN TIEASRLDGS CRKVLINNSL DEPRAIAVFP RKGYLFWTDW GHIAKIERAN
  1501  LDGSERKVLI NTDLGWPNGL TLDYDTRRIY WVDAHLDRIE SADLNGKLRQ VLVSHVSHPF
  1561  ALTQQDRWIY WTDWQTKSIQ RVDKYSGRNK ETVLANVEGL MDIIVVSPQR QTGTNACGVN
  1621  NGGCTHLCFA RASDFVCACP DEPDSRPCSL VPGLVPPAPR ATGMSEKSPV LPNTPPTTLY
  1681  SSTTRTRTSL EEVEGRCSER DARLGLCARS NDAVPAAPGE GLHISYAIGG LLSILLILVV
  1741  IAALMLYRHK KSKFTDPGMG NLTYSNPSYR TSTQEVKIEA IPKPAMYNQL CYKKEGGPDH
  1801  NYTKEKIKIV EGICLLSGDD AEWDDLKQLR SSRGGLLRDH VCMKTDTVSI QASSGSLDDT
  1861  ETEQLLQEEQ SECSSVHTAA TPERRGSLPD TGWKHERKLS SESQV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against LRP4 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

30 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about LRP4.

Disease | AllUniProt

Conditions LRP4 is implicated in, by any mechanism.

• Cenani-Lenz syndactyly syndrome (CLSS) MIM:212780
• Sclerosteosis 2 (SOST2) MIM:614305
• Myasthenic syndrome, congenital, 17 (CMS17) MIM:616304

Disease | GeneticClinVar

49 pathogenic / likely-pathogenic of 1,543 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Cenani-Lenz syndactyly syndrome
• Congenital myasthenic syndrome 17
• Sclerosteosis 2
• LRP4-related disorder
• Isolated hand syndactyly

Disease | AutoantibodyPubMed

Conditions in which antibodies against LRP4 are reported. Each links to that disease's full target list.

• Myasthenia Gravis 53
• Thymoma 3

Showing 2 of 3 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for LRP4 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)

0.42

gnomAD pLI

0

gnomAD missense Z

3.06

DepMap mean gene effect

-0.16

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• amyloid-beta clearance by cellular catabolic process
• dendrite morphogenesis
• dorsal/ventral pattern formation
• embryonic digit morphogenesis
• endocytosis
• enzyme-linked receptor protein signaling pathway
• generation of neurons
• hair follicle development
• kidney development
• limb development
• negative regulation of axonogenesis
• negative regulation of canonical Wnt signaling pathway
• negative regulation of ossification
• odontogenesis of dentin-containing tooth
• positive regulation of Rac protein signal transduction
• positive regulation of skeletal muscle acetylcholine-gated channel clustering
• postsynaptic membrane assembly
• presynaptic membrane assembly
• proximal/distal pattern formation
• Rac protein signal transduction
• regulation of postsynapse assembly
• skeletal muscle acetylcholine-gated channel clustering
• synapse organization
• synaptic assembly at neuromuscular junction
• Wnt signaling pathway
• positive regulation of presynaptic membrane organization

Molecular functions

• apolipoprotein binding
• calcium ion binding
• coreceptor activity
• protein homodimerization activity
• receptor tyrosine kinase binding
• scaffold protein binding

Cellular components

• cell surface
• dendrite
• neuromuscular junction
• neuronal cell body
• plasma membrane
• plasma membrane raft
• postsynaptic density
• synaptic membrane

Protein domainsUniProt · Pfam · InterPro

• LDLR class B repeat
• EGF-like domain
• EGF-like calcium-binding domain
• Low-density lipoprotein (LDL) receptor class A repeat
• Growth factor receptor cysteine-rich domain superfamily
• Six-bladed beta-propeller, TolB-like
• EGF-like calcium-binding, conserved site
• Low-density lipoprotein (LDL) receptor class A, conserved site
• Complement Clr-like EGF domain
• LDL receptor-like superfamily
• Low-density lipoprotein receptor-related
• Low-density lipoprotein receptor domain class A
• Low-density lipoprotein receptor repeat class B
• Complement Clr-like EGF-like
• Coagulation Factor Xa inhibitory site

KeywordsUniProt

• Calcium
• Cell membrane
• Congenital myasthenic syndrome
• Developmental protein
• Differentiation
• Disulfide bond
• EGF-like domain
• Endocytosis
• Glycoprotein
• Membrane
• Receptor
• Repeat
• Signal
• Transmembrane
• Transmembrane helix
• Wnt signaling pathway

InteractionsUniProt · HPA

Protein binding partners of LRP4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MESD
• MUSK
• SOST