RSPO4

Protein identityUniProt · HPA

UniProt accession

Q2I0M5

Gene

RSPO4

Ensembl

ENSG00000101282

Chromosome

20

Canonical length

234 aa

Protein class

Disease related genes, Human disease related genes, Predicted secreted proteins

Secretome location

Secreted in other tissues

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

234 residues, UniProt reviewed canonical sequence.

>Q2I0M5|RSPO4
     1  MRAPLCLLLL VAHAVDMLAL NRRKKQVGTG LGGNCTGCII CSEENGCSTC QQRLFLFIRR
    61  EGIRQYGKCL HDCPPGYFGI RGQEVNRCKK CGATCESCFS QDFCIRCKRQ FYLYKGKCLP
   121  TCPPGTLAHQ NTRECQGECE LGPWGGWSPC THNGKTCGSA WGLESRVREA GRAGHEEAAT
   181  CQVLSESRKC PIQRPCPGER SPGQKKGRKD RRPRKDRKLD RRLDVRPRQP GLQP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against RSPO4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.49

Highest tissue expression

12 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about RSPO4.

Disease | AllUniProt

Conditions RSPO4 is implicated in, by any mechanism.

• Nail disorder, non-syndromic congenital, 4 (NDNC4) MIM:206800

Disease | GeneticClinVar

12 pathogenic / likely-pathogenic of 88 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Nonsyndromic congenital nail disorder 4
• Inborn genetic diseases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.59

gnomAD pLI

0

gnomAD missense Z

-0.47

DepMap mean gene effect

0.05

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• nail development
• positive regulation of canonical Wnt signaling pathway
• positive regulation of Wnt signaling pathway
• Wnt signaling pathway

Molecular functions

• heparin binding
• signaling receptor binding

Cellular components

• extracellular region
• extracellular space

Protein domainsUniProt · Pfam · InterPro

• Thrombospondin type-1 (TSP1) repeat
• Furin-like repeat
• Growth factor receptor cysteine-rich domain superfamily
• R-spondin, Fu-CRD domain
• R-spondin domain-containing protein
• Furin-like repeat, cysteine-rich

KeywordsUniProt

• Disulfide bond
• Glycoprotein
• Heparin-binding
• Phosphoprotein
• Secreted
• Sensory transduction
• Signal
• Wnt signaling pathway

InteractionsUniProt · HPA

Protein binding partners of RSPO4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• LGR4
• LGR5
• LGR6