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Symbol LRP4 contributors: mct/npt/pgu - updated : 12-01-2016
HGNC name low density lipoprotein receptor-related protein 4
HGNC id 6696
Corresponding disease
CMS17 myasthenic syndrome, congenital, 17
SOST2 sclerosteosis-2
Location 11p11.2      Physical location : 46.878.268 - 46.940.173
Synonym name multiple epidermal growth factor-like motif 7
Synonym symbol(s) MEGF7, LRP10, KIAA0816
TYPE functioning gene
STRUCTURE 61.66 kb     38 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Physical map
CRY2 11p12-q21.1 cryptochrome 2 (photolyase-like) MAPK8IP1 11p12-p11.2 mitogen-activated protein kinase 8 interacting protein 1 LOC143678 11p11.2 similar to RIKEN cDNA 1700021K07 PEX16 11p11.11 peroxisomal biogenesis factor 16 GYLTL1B 11p11.2 glycosyltransferase-like 1B BHC80 11p11.2 glycosyltransferase-like 1B CREB3L1 11p11.2 cAMP responsive element binding protein 3-like 1 DGKZ 11p11.2 diacylglycerol kinase, zeta 104kDa MDK 11p11.2 midkine (neurite growth-promoting factor 2) CHRM4 11p12-p11.2 cholinergic receptor, muscarinic 4 LOC387765 11 LOC387765 FLJ20294 11p11.2 hypothetical protein FLJ20294 FLJ32675 11p11.2 hypothetical protein FLJ32675 KIAA0652 11p12-q11 hypothetical protein FLJ32675 ARHGAP1 11p12-q12 Rho GTPase activating protein 1 ZNF408 11p11.2 zinc finger protein 408 F2 11p11-q12 coagulation factor II (thrombin) ch-TOG 11p11.2 KIAA0097 gene product LRP4 11p12-p11.2 low density lipoprotein receptor-related protein 4 MGC4707 11p11.2 hypothetical protein MGC4707 ZNF289 11p11.2-p11.12 zinc finger protein 289, ID1 regulated PACSIN3 11p12-p11.2 protein kinase C and casein kinase substrate in neurons 3 DDB2 11p12-p11.2 damage-specific DNA binding protein 2, 48kDa ACP2 11p11.2 acid phosphatase 2, lysosomal NR1H3 11p11.2 nuclear receptor subfamily 1, group H, member 3 MADD 11p11.22-p11.21 MAP-kinase activating death domain MYBPC3 11p11.2 myosin binding protein C, cardiac SPI1 11p12 spleen focus forming virus (SFFV) proviral integration oncogene spi1 SLC39A13 11p11.2 solute carrier family 39 (zinc transporter), member 13 PSMC3 11p13-p12 proteasome (prosome, macropain) 26S subunit, ATPase, 3 RAPSN 11p11.2-p11.1 receptor-associated protein of the synapse, 43kD CUGBP1 11p11 CUG triplet repeat, RNA binding protein 1 KBTBD4 11p11.2 kelch repeat and BTB (POZ) domain containing 4 NDUFS3 11p11.11 NADH dehydrogenase (ubiquinone) Fe-S protein 3, 30kDa (NADH-coenzyme Q reductase) C1QTNF4 11q11 C1q and tumor necrosis factor related protein 4 MTCH2 11p11.2 mitochondrial carrier homolog 2 (C. elegans) FLJ23598 11p11.2 hypothetical protein FLJ23598 FNBP4 11q12.1 formin binding protein 4 NUP160 11q12.1 nucleoporin 160kDa
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
38 - 7998 - 1905 - 2008 18957220
   expressed in (based on citations)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly
Digestiveintestinesmall intestine  moderately
 intestinelarge intestinecolon highly
Endocrinethyroid   predominantly
Hearing/Equilibriumearinnercochlea moderately
Nervousbrainforebraincerebral cortex highly Homo sapiens
 brainlimbic systemhippocampus   Homo sapiens
 brainhindbraincerebellum   Homo sapiens
 nerve   highlyHomo sapiens
Olfactory (smell)olfactory bulb     Homo sapiens
Skeleton      Homo sapiens
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
SystemCellPubmedSpeciesStageRna symbol
Skeletonosteoblast Homo sapiens
cell lineage
cell lines
  • eight LDL-receptor class A domains
  • two calcium binding type EGF-like motif
  • twenty LDL-receptor class B repeats
  • a extracellular beta-propeller structured domain required for the sclerostin facilitator activity
  • an EGF-like motifs
  • a cytoplasmic domain having important signaling and/or anchoring functions in certain tissues but not at neuromuscular synapses
  • conjugated GlycoP
    isoforms Precursor a 17 aa signal peptide of 1.9 kda and a 1888 aa mature peptide of 210.1 kda
    interspecies homolog to rattus Lrp4 (96.4 pc)
    homolog to murine Lrp4 (96.6 pc)
    intraspecies homolog to low density lipoprotein receptor 4 (LDLR)
  • LDLR family
  • CATEGORY receptor membrane
    SUBCELLULAR LOCALIZATION     plasma membrane
    text type II membrane anchored protein
    basic FUNCTION
  • acting as a potential cell surface endocytic receptor which binds and internalizes extracellular ligands for degradation by lysosomes
  • receptor for Agrin, which forms a complex with MUSK, and mediates MUSK activation by Agrin
  • can binds ligands that are structurally akin to AGRN and associates with other receptor tyrosine kinases, like MUSK, in these tissues
  • important for control and modification of Wnt signaling by its antagonistic effect on LRP6-mediated activation of WNT signaling
  • multi-functional receptor implicated in the regulation of several molecular pathways, including Wnt and Bmp signaling
  • specifically facilitates the previously described inhibitory action of sclerostin on WNT1/CTNNB signaling
  • functions as a direct muscle-derived retrograde signal for early steps in presynaptic differentiation
  • acts bi-directionally and coordinates synapse formation by binding Agrin, activating MUSK and stimulating postsynaptic differentiation
  • LRP4 and MUSK act as scaffolds for multiple binding partners, resulting in a complex and dynamic network of interacting proteins that is required for ACHR clustering
    PHYSIOLOGICAL PROCESS endocytosis transport
    a component
  • LRP4 and MUSK can interact and form a complex
    small molecule metal binding, nucleotide,
  • Ca2+
  • protein
  • AGRN receptor
  • sclerostin (SOST) interaction partner (interaction of sclerostin with LRP4 is required to mediate the inhibitory function of sclerostin on bone formation, thus identifying a novel role for LRP4 in bone)
  • AGRN binds LRP4 and stimulates further MUSK phosphorylation, stabilizing nascent synapses
  • cis-acting ligand for MUSK, whereas AGRN functions as an allosteric and paracrine regulator to promote association between LRP4 and MUSK
  • interplay between LRP4 and SOSTDC1 in inhibiting Wnt/CTNNB1 signaling, providing an insight into how modulation of Wnt/CTNNB1 signaling controls cellular processes important for skin placode formation
  • ligand for MUSK, and binding affinity for MUSK is potentiated by agrin, a neuronally derived heparan-sulfate proteoglycan 9)
  • MESD binds to the intracellular form of LRP4 and promotes its glycosylation and cell-surface expression
  • cell & other
    corresponding disease(s) SDTY7 , SOST2 , CMS17
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    associated with bone overgrowth and impaired sclerostin facilitator function
    Variant & Polymorphism
    Candidate gene
    Therapy target
  • polysyndactyly caused by two recessive mutations in the mouse Lrp4 gene
  • syndactyly caused by mutations in the bovine Lrp4 gene
  • Lrp4 mutant mice displayed a delay in placode initiation and changes in distribution and number of mammary precursor cells leading to abnormal morphology, number and position of mammary placodes
  • Lrp4(-/-) mice show a delay in ureteric bud formation that results in unilateral or bilateral kidney agenesis
  • Lrp4 null mutations in mice result in limb development defects and in perinatal death due to a lack of neuromuscular junction formation