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FLASH GENE
Symbol ROR2 contributors: shn/ - updated : 24-06-2014
HGNC name receptor tyrosine kinase-like orphan receptor 2
HGNC id 10257
Corresponding disease
BDB1 brachydactyly type B
DEL9Q22 chromosome 9q22.3 microdeletion syndrome
RBNS Robinow syndrome
Location 9q22.31      Physical location : 94.484.883 - 94.712.444
Synonym name
  • neurotrophic tyrosine kinase receptor-related 2
  • tyrosine-protein kinase transmembrane receptor ROR2
  • Synonym symbol(s) NTRKR2, BDB, BDB1, MGC163394
    EC.number 2.7.10.1
    DNA
    TYPE functioning gene
    STRUCTURE 227.56 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map ROR2 was localized to 9q22 by radiation hybrid mapping and by FISH cen - D9S1781 - D9S1841 - ROR2 -D9S1803 - D9S197 - qter
    Physical map
    DIRAS2 9q22.32 DIRAS family, GTP-binding RAS-like 2 LOC392367 9 similar to putative taste receptor HTR2 LOC283493 9q22.31 similar to seven transmembrane helix receptor SYK 9q22.1-q22.3 spleen tyrosine kinase AUH 9q22 AU RNA binding protein/enoyl-Coenzyme A hydratase NFIL3 9q22 nuclear factor, interleukin 3 regulated ROR2 9q22.3 receptor tyrosine kinase-like orphan receptor 2 LOC347318 9q22.31 similar to 60S ribosomal protein L21 SPTLC1 9q22.1-q22.2 serine palmitoyltransferase, long chain base subunit 1 LOC389772 9 similar to Osteotesticular phosphatase; protein tyrosine phosphatase, receptor type, V LOC392368 9 similar to KIAA1553 protein LOC138652 9q22.32 similar to bA62C3.1 (similar to testicular serine protease) IARS 9q21 isoleucine-tRNA synthetase C9orf34 9q22.32 chromosome 9 open reading frame 34 OGN 9q22.3 osteoglycin (osteoinductive factor, mimecan) OMD 9p22.3 osteomodulin ASPN 9q22-q31 asporin (LRR class 1) ECM2 9q22.3 extracellular matrix protein 2, female organ and adipocyte specific C9orf12 9q21.33-q22.31 chromosome 9 open reading frame 12 BICD2 9q22.1-q22.3 chromosome 9 open reading frame 12 ANKRD19 9q22.32 ankyrin repeat domain 19 BA526D8.4 9q22.32 KRAB box containing C2H2 type zinc finger bA526D8.4 LOC389773 9 LOC389773 LOC340518 9q22.32 similar to Alox15 protein FGD3 9q22 FGD1 family, member 3 MGC26847 LOC389774 9 LOC389774 MGC11115 9q22.32 hypothetical protein MGC11115 LOC389775 9 LOC389775 NINJ1 9q22.3 ninjurin 1
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 4091 120 943 Ror2 is expressed in chondrocytes of early cartilaginous anlagen in embryos and in chondrocytes of articular cartilage and growth plates in the adult 2000 10700181
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone  highly
    Connectivecartilage  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
     chondrocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal
    Text chondrocytes in all developing cartilage, and mature growth plate, developing nervous system, brain (cortex, caudate putamen, hippocampal neurons during synapse formation)
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an extracellular immunoglobulin-like domain
  • one frizzled-like cysteine rich domain (CRD)
  • a kringle domain
  • a transmembrane and intracellular tyrosine kinase
  • a serine/threonine-rich and proline-rich domains
  • conjugated GlycoP
    HOMOLOGY
    interspecies ortholog to Ror2, Mus musculus
    ortholog to ror2, Danio rerio
    ortholog to Ror2, Rattus norvegicus
    ortholog to ROR2, Pan troglodytes
    Homologene
    FAMILY
  • protein kinase superfamily
  • Ror-family receptor tyrosine kinases
  • ROR subfamily
  • CATEGORY enzyme , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • encodes a receptor-like tyrosine kinase that is particularly important for the chondrocyte lineage
  • may be involved in the early formation of the chondrocytes and may be required for cartilage and growth plate development
  • Ror2 plays essential roles in the development of the heart and in limb/tail formation, in cardiac septal formation and ossification of distal portions of limbs and tails
  • Ror1 and Ror2 are functionally redundant and that they interact genetically in skeletal and cardiac development
  • Ror2 is involved in genital development
  • Ror2 has a role in cartilage formation, chondrocyte differentiation and joint formation
  • play crucial roles in the development of various organs and tissues
  • ROR1, and ROR2, play a key role in WNT-5A-activated signaling pathways leading to synapse formation in the mammalian CNS
  • regulates WNT5A-induced polymerization of Dishevelled (Dvl) and ROR2-mediated regulation of Dvl is independent of the cytoplasmic region of ROR2
  • WNT5A and ROR2 signaling are of substantial importance for BMP2-mediated osteoblastic differentiation
  • ANPEP and ROR2 are cell-surface markers capable of selecting early cardiac mesoderm emerging during embryonic stem cells (hESCs) differentiation
  • signaling through the ROR2 receptor tyrosine kinase promotes invadopodia formation for tumor invasion
  • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS cardiovascular , ossification
    PATHWAY
    metabolism
    signaling
  • WNT5A/ROR2 signaling appears to be involved in BMP2-mediated osteoblast differentiation in a Smad independent pathway
  • a component ROR2/FZD7 receptor complex plays an important role in WNT5a/RAC1/AP-1 pathway by regulating polymerization of DVL2
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • bone morphogenetic protein receptor type Ib (BRIb) with the extracellular CRD domain of ROR2
  • modulates the canonical Wnt signaling in lung epithelial cells through cooperation with FZD2
  • act as a receptor or coreceptor for WNT5A to mediate noncanonical Wnt signaling
  • intracellular interaction partner of WTIP
  • can associate with FZD7 via its extracellular cysteine-rich domain to form a receptor complex that is required for the regulation of Dvl and activation of the AP-1 promoter after WNT5A stimulation
  • binds to WNT5A directly through its Fz-like CRD and may serve as a co-receptor in WNT5A-induced signaling
  • WNT5A-ROR2 signaling might be required for expression of MMP13 gene during the development of the cartilaginous tissue
  • acts autonomously to permit the polarized response of primordial germ cells (PGCs) to KITLG
  • WNT5A potentiates PGC chemotaxis toward secreted KITLG by redistribution of ROR2 within the cell
  • WNT5A activates noncanonical WNT signaling through ROR2
  • TWIST1-binding sequences associated with CHST11, LITAF, ROR2, and SPATA5 also bound the potential TWIST1 cofactor RREB1
  • stimulated by the hyperphosphorylation of DVL3 by CNSK1E, ROR2 has been shown to interact with DVL3
  • ROR2 signaling is required for local upregulation of GFD6 and activation of BMP signaling at the neural plate border
  • IFT20 mediates the ability of ROR2 signaling to induce the invasiveness of the tumors that lack primary cilia
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) BDB1 , DEL9Q22 , RBNS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    hypoxia-inducible factor target in von hippel-Lindau-associated RCC
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    WNT5a-ROR2 signaling can be a target of cancer therapies to prevent cancer cells from undergoing invasion and metastasis
    ANIMAL & CELL MODELS
  • Disruption of mouse Ror2 leads to profound skeletal abnormalities with essentially all endochondrally derived bones foreshortened or misshapen
  • Ror2-deficient mice had cardiac septal defects and skeletal abnormalities, including shorter limbs, vertebrae, and facial structure, with a particular defect in their distal portions and died after birth
  • Ror1/Ror2 double-mutant mice showed skeletal abnormalities including a sternal defect and dysplasia of the symphysis of the pubic bone