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FLASH GENE

Symbol

RSPO2

contributors: mct/npt/pgu - updated : 26-08-2019

HGNC name	R-spondin 2 homolog (Xenopus laevis)
HGNC id	28583

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	8q23.1      Physical location : 108.911.544 - 109.095.913
Synonym name	Roof plate-specific spondin-2
Synonym symbol(s)	MGC43342, CRISTIN2, MGC35555

DNA

TYPE	functioning gene
STRUCTURE	184.37 kb     6 Exon(s)

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_178565 6 - 3149 isoform 1 - 243 - 2011 21160497 Rspo2-2F - - - - - - 2011 21160497 derivative containing only the two furin-like domains having potent activity and synergized strongly with WNT3A in a beta-catenin reporter assay (Li 2009) NM_001282863 5 - 2777 NP_001269792 - 179 - 2011 21160497 NM_001317942 5 - 2498 NP_001304871 - 176 - 2011 21160497

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 Hearing/Equilibrium ear inner cochlea     Homo sapiens Fetal Nervous brain         Reproductive male system testis

cells

System Cell Pubmed Species Stage Rna symbol Hearing / Equilibrium cochlea cell Homo sapiens Fetal

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

HOMOLOGY

Homologene

FAMILY

R-spondin family

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,nucleus

basic FUNCTION	functioning in a positive feedback loop to stimulate the Wnt/beta-catenin cascade
	having essential roles in vertebrate development and its ligand-type activities overlap substantially with those of the canonical Wnt ligands in that both RSPO and canonical Wnt signaling result in the activation of beta-catenin
	required for normal laryngeal-tracheal, lung and limb morphogenesis
	modulate the Wnt pathway by a common mechanism and coexpression with specific Wnt ligands and DKK1 may determine their biological specificity
	may regulates midfacial, limb, and lung morphogenesis during development through the Wnt/CTNNB signaling
	RSPO1, RSPO2, RSPO3, RSPO4 can stimulate the proliferation of intestinal crypt stem cells, through enhancement of Wnt/CTNNB signaling
	mesenchyme-derived factor that plays critical roles in regulating first branchial arch (BA1) patterning and morphogenesis through ectodermal-mesenchymal interaction and a novel genetic factor for cleft palate
	in cochlea is required to limit the number of outer hair cells to three rows and for optimal arrangement of peripheral nerve fibers
	may promote hepatic stellate cells (HSCs) activation by enhancing the canonical Wnt pathway
	activates WNT/CTNNB1 signaling to reduce COL2A1 and SOX9 and to facilitate differentiation of proliferating chondrocytes into hypertrophic chondrocytes in growth cartilage
	secreted agonist of canonical WNT-CTNNB signaling

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	potentiate Wnt/CTNNB signaling by actually functioning as ligands of LGR4 and LGR5
	each of the four R-spondins, secreted Wnt pathway agonists, can bind to LGR4, LGR5 and LGR6 (Pubmed 21727895)
	LGR4 acted as a key receptor for RSPO2 to promote osteogenesis
	RSPO2 and its receptor LGR5 are WNT-dependent and agrin-independent regulators of acetylcholine receptor (ACHR) clustering at the neuromuscular junction (NMJ)
	inhibited expression of genes encoding early chondrocyte differentiation markers by activating WNT-CTNNB1 signaling
	RSPO2, serves as a direct antagonistic ligand to RNF43 and ZNRF3, which together constitute a master switch that governs limb specification
	TBX4, TBX5 are both upstream regulators of FGF10 and RSPO2, which drive the outgrowth of all four limb buds
	LGR6 had a close interaction with RSPO1, RSPO2, RSPO3, and RSPO4
	RSPO2 is a context-specific regulator of TCF3 phosphorylation and Wnt signaling

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in human colorectal cancers (CRCs) due to promoter hypermethylation

Susceptibility

to ossification of the posterior longitudinal ligament of the spine (OPLL)

Variant & Polymorphism SNP	SNP (rs374810) in the RSPO2 promoter causes deceased binding of C/EBPB, which leads to decreased RSPO2 expression, decreased Wnt-CTNNB1 signal, and eventually OPLL

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	CLP with mild facial skeletal defects in Rspo2(-/-) mice which also exhibited distal limb loss and lung hypoplasia, and died immediately after birth with respiratory failure; apparent reduction of Wnt/Ctnnb1 signaling activity at the branchial arch and the apical ectodermal ridge in Rspo2(-/-)mice
	in Rspo2(-/-) mouse, loss of Rspo2 results in an additional single row of outer hair cells and disruption of peripheral innervation pattern
	mice lacking a functional Rspo2 gene exhibit craniofacial abnormalities such as mandibular hypoplasia, maxillary and mandibular skeletal deformation, and cleft palate