RSPO4 (R-spondin 4)

Gene

• Entrez ID: 343637
• Gene name: R-spondin 4
• Gene symbol: RSPO4
• Synonyms: C20orf182, CRISTIN4
• Chromosome: 20
• Chromosome location: 20p13
• Summary: This gene encodes a member of the R-spondin family of proteins that share a common domain organization consisting of a signal peptide, cysteine-rich/furin-like domain, thrombospondin domain and a C-terminal basic region. The encoded protein may be involved in activation of Wnt/beta-catenin signaling pathways. Mutations in this gene are associated with anonychia congenital. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Sep 2009]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs74315420	T>C	Pathogenic	Coding sequence variant, missense variant
rs74315421	A>G	Pathogenic	Coding sequence variant, missense variant
rs74315422	C>T	Pathogenic	Coding sequence variant, missense variant
rs74315423	C>G,T	Pathogenic	Coding sequence variant, missense variant
rs387907026	G>A	Pathogenic	Coding sequence variant, stop gained
rs387907027	G>A	Pathogenic	Coding sequence variant, missense variant
rs387907028	C>G,T	Pathogenic	Coding sequence variant, missense variant
rs768138495	->C	Pathogenic	Coding sequence variant, frameshift variant
rs775644973	C>T	Pathogenic	Splice donor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017214	hsa-miR-335-5p	Microarray	18185580

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005515	Function	Protein binding	IPI	32296183
GO:0005576	Component	Extracellular region	NAS	24431302
GO:0005576	Component	Extracellular region	TAS
GO:0008201	Function	Heparin binding	IEA
GO:0016055	Process	Wnt signaling pathway	IEA
GO:0030177	Process	Positive regulation of Wnt signaling pathway	IDA	29769720
GO:0030177	Process	Positive regulation of Wnt signaling pathway	NAS	24431302
GO:0035878	Process	Nail development	IMP	17805348

Other IDs

• MIM: 610573
• HGNC: 16175
• e!Ensembl: ENSG00000101282

Protein

• UniProt ID: Q2I0M5
• Protein name: R-spondin-4 (Roof plate-specific spondin-4) (hRspo4)
• Protein function: Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors (PubMed:29769720). Upon binding to LGR4-6 (LGR4, LGR5 or LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway (PubMed:21727895, PubMed:21909076).
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF15913	Furin-like_2	35 → 135	Furin-like repeat, cysteine-rich	Domain

• Sequence:

  MRAPLCLLLLVAHAVDMLALNRRKKQVGTGLGGNCTGCIICSEENGCSTCQQRLFLFIRR
  EGIRQYGKCLHDCPPGYFGIRGQEVNRCKKCGATCESCFSQDFCIRCKRQFYLYKGKCLP
  TCPPGTLAHQNTRECQGECELGPWGGWSPCTHNGKTCGSAWGLESRVREAGRAGHEEAAT
  CQVLSESRKCPIQRPCPGERSPGQKKGRKDRRPRKDRKLDRRLDVRPRQPGLQP

• Sequence length: 234

Pathways

KEGG:

Wnt signaling pathway

Reactome:

Regulation of FZD by ubiquitination

Associated diseases

Disease name	Disease term	References
	Alzheimer`s Disease	29274321
	ANONYCHIA
	Anonychia congenita totalis
	NAIL DISORDER, NONSYNDROMIC CONGENITAL, 4	17914448, 17041604