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Aliases for RSPO4 Gene

Aliases for RSPO4 Gene

  • R-Spondin 4 2 3 5
  • Roof Plate-Specific Spondin-4 3 4
  • R-Spondin Family, Member 4 2 3
  • C20orf182 3 4
  • HRspo4 3 4
  • Chromosome 20 Open Reading Frame 182 2
  • R-Spondin-4 3
  • CRISTIN4 3

External Ids for RSPO4 Gene

Previous HGNC Symbols for RSPO4 Gene

  • C20orf182

Previous GeneCards Identifiers for RSPO4 Gene

  • GC20M000890

Summaries for RSPO4 Gene

Entrez Gene Summary for RSPO4 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]

GeneCards Summary for RSPO4 Gene

RSPO4 (R-Spondin 4) is a Protein Coding gene. Diseases associated with RSPO4 include Nail Disorder, Nonsyndromic Congenital, 4 and Nail Disease. Among its related pathways are Signaling by GPCR and Wnt Signaling Pathways: beta-Catenin-dependent Wnt Signaling. Gene Ontology (GO) annotations related to this gene include heparin binding and G-protein coupled receptor binding. An important paralog of this gene is RSPO2.

UniProtKB/Swiss-Prot for RSPO4 Gene

  • Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors. 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.

Additional gene information for RSPO4 Gene

No data available for CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for RSPO4 Gene

Genomics for RSPO4 Gene

GeneHancer (GH) Regulatory Elements for RSPO4 Gene

Promoters and enhancers for RSPO4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH20I001003 Promoter 0.7 EPDnew 550.8 0.0 -47 0.1 ZNF335 ZBTB26 EZH2 GC20M001001 PIR43351 RSPO4 GC20M000980 GC20M000981
GH20I001002 Enhancer 0.4 ENCODE 550.8 -0.2 -199 0 ZNF335 ZBTB26 EZH2 GC20M001001 PIR43351 RSPO4 GC20M000980 GC20M000981
GH20I000840 Promoter/Enhancer 2.1 EPDnew FANTOM5 Ensembl ENCODE 10.2 +157.7 157664 7.5 ELF3 SIN3A ZNF335 GLIS2 ELK1 RCOR1 EGR2 SP3 CEBPB ZHX2 FAM110A PIR36894 ANGPT4 RSPO4 RPS10P5 GC20M000847 PIR34196
GH20I000766 Promoter/Enhancer 1.5 EPDnew Ensembl ENCODE 11 +233.5 233534 3.5 ATF1 KLF17 ZBTB40 RAD21 ETS1 ZNF143 FOS ATF7 CREM THAP11 SLC52A3 RSPO4 ANGPT4 GC20P000743
GH20I000775 Enhancer 0.7 Ensembl ENCODE 11 +226.4 226398 1.1 MAZ LEF1 POLR2A PRDM10 DPF2 KLF4 ZKSCAN1 SLC52A3 RSPO4 ANGPT4 C20orf96 GC20P000743
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around RSPO4 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the RSPO4 gene promoter:

Genomic Locations for RSPO4 Gene

Genomic Locations for RSPO4 Gene
chr20:958,452-1,002,284
(GRCh38/hg38)
Size:
43,833 bases
Orientation:
Minus strand
chr20:939,095-982,907
(GRCh37/hg19)

Genomic View for RSPO4 Gene

Genes around RSPO4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RSPO4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RSPO4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RSPO4 Gene

Proteins for RSPO4 Gene

  • Protein details for RSPO4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q2I0M5-RSPO4_HUMAN
    Recommended name:
    R-spondin-4
    Protein Accession:
    Q2I0M5
    Secondary Accessions:
    • A2A2I6
    • Q9UGB2

    Protein attributes for RSPO4 Gene

    Size:
    234 amino acids
    Molecular mass:
    26171 Da
    Quaternary structure:
    • Binds heparin (By similarity). Interacts with LGR4, LGR5 and LGR6.
    Miscellaneous:
    • Upon injection into mice, it induces rapid onset of crypt cell proliferation involving beta-catenin stabilization. It also displays efficacy in a model of chemotherapy-induced intestinal mucositis (PubMed:16357527).

    Alternative splice isoforms for RSPO4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RSPO4 Gene

Post-translational modifications for RSPO4 Gene

  • Tyr-112 may be phosphorylated; however as this position is probably extracellular, the vivo relevance is not proven.
  • Glycosylation at posLast=3434

Other Protein References for RSPO4 Gene

No data available for DME Specific Peptides for RSPO4 Gene

Domains & Families for RSPO4 Gene

Gene Families for RSPO4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted secreted proteins

Protein Domains for RSPO4 Gene

Suggested Antigen Peptide Sequences for RSPO4 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q2I0M5

UniProtKB/Swiss-Prot:

RSPO4_HUMAN :
  • The FU repeat is required for activation and stabilization of beta-catenin.
  • Belongs to the R-spondin family.
Domain:
  • The FU repeat is required for activation and stabilization of beta-catenin.
Family:
  • Belongs to the R-spondin family.
genes like me logo Genes that share domains with RSPO4: view

Function for RSPO4 Gene

Molecular function for RSPO4 Gene

UniProtKB/Swiss-Prot Function:
Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors. 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.

Phenotypes From GWAS Catalog for RSPO4 Gene

Gene Ontology (GO) - Molecular Function for RSPO4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0008201 heparin binding IEA --
genes like me logo Genes that share ontologies with RSPO4: view
genes like me logo Genes that share phenotypes with RSPO4: view

Human Phenotype Ontology for RSPO4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

miRNA for RSPO4 Gene

miRTarBase miRNAs that target RSPO4

Inhibitory RNA Products

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for RSPO4 Gene

Localization for RSPO4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for RSPO4 Gene

Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for RSPO4 gene
Compartment Confidence
extracellular 5
plasma membrane 1
mitochondrion 1
endoplasmic reticulum 1
cytosol 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for RSPO4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
genes like me logo Genes that share ontologies with RSPO4: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for RSPO4 Gene

Pathways & Interactions for RSPO4 Gene

genes like me logo Genes that share pathways with RSPO4: view

Gene Ontology (GO) - Biological Process for RSPO4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016055 Wnt signaling pathway IEA --
GO:0030177 positive regulation of Wnt signaling pathway NAS 24431302
GO:0035878 nail development IMP 17805348
GO:0050896 response to stimulus IEA --
genes like me logo Genes that share ontologies with RSPO4: view

No data available for SIGNOR curated interactions for RSPO4 Gene

Drugs & Compounds for RSPO4 Gene

No Compound Related Data Available

Transcripts for RSPO4 Gene

mRNA/cDNA for RSPO4 Gene

(3) REFSEQ mRNAs :
(2) Additional mRNA sequences :
(21) Selected AceView cDNA sequences:
(2) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for RSPO4 Gene

R-spondin 4:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Alternative Splicing Database (ASD) splice patterns (SP) for RSPO4 Gene

No ASD Table

Relevant External Links for RSPO4 Gene

GeneLoc Exon Structure for
RSPO4
ECgene alternative splicing isoforms for
RSPO4

Expression for RSPO4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for RSPO4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for RSPO4 Gene

This gene is overexpressed in Lung (x6.6), Brain - Hypothalamus (x5.4), and Brain - Putamen (basal ganglia) (x4.6).

NURSA nuclear receptor signaling pathways regulating expression of RSPO4 Gene:

RSPO4

SOURCE GeneReport for Unigene cluster for RSPO4 Gene:

Hs.444980

Phenotype-based relationships between genes and organs from Gene ORGANizer for RSPO4 Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • integumentary
  • skeleton
Organs:
Pelvis:
  • pelvis
Limb:
  • digit
  • femur
  • finger
  • foot
  • hand
  • hip
  • lower limb
  • nail
  • thigh
  • toe
  • upper limb
General:
  • skin
genes like me logo Genes that share expression patterns with RSPO4: view

Primer Products

No data available for Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Evidence on tissue expression from TISSUES for RSPO4 Gene

Orthologs for RSPO4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for RSPO4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia RSPO4 33 34
  • 96.7 (n)
dog
(Canis familiaris)
Mammalia RSPO4 33 34
  • 89.32 (n)
cow
(Bos Taurus)
Mammalia RSPO4 33 34
  • 88.3 (n)
rat
(Rattus norvegicus)
Mammalia Rspo4 33
  • 81.87 (n)
mouse
(Mus musculus)
Mammalia Rspo4 33 16 34
  • 81.14 (n)
oppossum
(Monodelphis domestica)
Mammalia RSPO4 34
  • 69 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia RSPO4 34
  • 41 (a)
OneToOne
chicken
(Gallus gallus)
Aves RSPO4 33 34
  • 68.12 (n)
lizard
(Anolis carolinensis)
Reptilia RSPO4 34
  • 58 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii LOC570865 33
  • 56.06 (n)
rspo4 34
  • 39 (a)
OneToOne
Species where no ortholog for RSPO4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for RSPO4 Gene

ENSEMBL:
Gene Tree for RSPO4 (if available)
TreeFam:
Gene Tree for RSPO4 (if available)

Paralogs for RSPO4 Gene

Paralogs for RSPO4 Gene

(3) SIMAP similar genes for RSPO4 Gene using alignment to 1 proteins:

genes like me logo Genes that share paralogs with RSPO4: view

Variants for RSPO4 Gene

Sequence variations from dbSNP and Humsavar for RSPO4 Gene

SNP ID Clin Chr 20 pos Variation AA Info Type
rs387907026 pathogenic, Anonychia 967,282(-) G/A coding_sequence_variant, stop_gained
rs387907027 pathogenic, Anonychia 968,028(-) G/A coding_sequence_variant, missense_variant
rs387907028 pathogenic, Anonychia 968,019(-) C/G/T coding_sequence_variant, missense_variant
rs74315420 pathogenic, Anonychia, Nail disorder, non-syndromic congenital, 4 (NDNC4) [MIM:206800] 968,024(-) T/C coding_sequence_variant, missense_variant
rs74315421 pathogenic, Anonychia, Nail disorder, non-syndromic congenital, 4 (NDNC4) [MIM:206800] 967,264(-) A/G coding_sequence_variant, missense_variant

Structural Variations from Database of Genomic Variants (DGV) for RSPO4 Gene

Variant ID Type Subtype PubMed ID
esv2668964 CNV deletion 23128226
esv2722039 CNV deletion 23290073
esv2722041 CNV deletion 23290073
esv2722042 CNV deletion 23290073
esv2722043 CNV deletion 23290073
esv2722044 CNV deletion 23290073
esv274959 CNV loss 21479260
esv3575346 CNV gain 25503493
esv3575347 CNV gain 25503493
esv3575348 CNV gain 25503493
esv3644952 CNV gain 21293372
esv3644966 CNV gain 21293372
esv3644968 CNV loss 21293372
nsv1055853 CNV gain 25217958
nsv1067403 CNV gain 25217958
nsv520121 CNV loss 19592680
nsv525407 CNV loss 19592680

Variation tolerance for RSPO4 Gene

Residual Variation Intolerance Score: 79.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.54; 55.77% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for RSPO4 Gene

Human Gene Mutation Database (HGMD)
RSPO4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
RSPO4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RSPO4 Gene

Disorders for RSPO4 Gene

MalaCards: The human disease database

(2) MalaCards diseases for RSPO4 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, and DISEASES

Disorder Aliases PubMed IDs
nail disorder, nonsyndromic congenital, 4
  • ndnc4
nail disease
  • abnormality of the nail
- elite association - COSMIC cancer census association via MalaCards
Search RSPO4 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

RSPO4_HUMAN
  • Nail disorder, non-syndromic congenital, 4 (NDNC4) [MIM:206800]: A nail disorder characterized by congenital anonychia or its milder phenotypic variant hyponychia. Anonychia/hyponychia is the absence or severe hypoplasia of all fingernails and toenails without significant bone anomalies. {ECO:0000269 PubMed:17041604}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for RSPO4

genes like me logo Genes that share disorders with RSPO4: view

No data available for Genatlas for RSPO4 Gene

Publications for RSPO4 Gene

  1. RSPO4 is the major gene in autosomal-recessive anonychia and mutations cluster in the furin-like cysteine-rich domains of the Wnt signaling ligand R-spondin 4. (PMID: 17914448) Brüchle NO … Bergmann C (The Journal of investigative dermatology 2008) 3 22 58
  2. R-Spondin proteins: a novel link to beta-catenin activation. (PMID: 16357527) Kim KA … Funk WD (Cell cycle (Georgetown, Tex.) 2006) 3 4 58
  3. The gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signaling, is mutated in inherited anonychia. (PMID: 17041604) Blaydon DC … Kelsell DP (Nature genetics 2006) 3 4 58
  4. Mutations in the gene encoding the Wnt-signaling component R-spondin 4 (RSPO4) cause autosomal recessive anonychia. (PMID: 17186469) Bergmann C … Zerres K (American journal of human genetics 2006) 3 22 58
  5. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4 58

Products for RSPO4 Gene

Sources for RSPO4 Gene

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