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FLASH GENE

Symbol

ROR2

contributors: shn/ - updated : 24-06-2018

HGNC name	receptor tyrosine kinase-like orphan receptor 2
HGNC id	10257

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004560 9 - 4091 NP_004551 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)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone     highly Connective cartilage     highly

cells

System Cell Pubmed Species Stage Rna 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
	may act as a tumor suppressor in endometrioid endometrial cancer, similar to its role in colorectal cancer
	ROR1/ROR2 are essential for the progression of myofibroblast differentiation and for the adaptive remodeling of the heart in response to pressure overload

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   hypoxia-inducible factor target in von hippel-Lindau-associated RCC

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer     WNT5a-ROR2 signaling can be a target of cancer therapies to prevent cancer cells from undergoing invasion and metastasis cancer brain glioma/neuroblstoma ROR1 and ROR2 could serve as novel targets for immunotherapy in neuroblastoma cancer reproductive ovary targeting both ROR1 and ROR2 may be a powerful approach to treating ovarian cancer

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