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    RSPO4 R-spondin 4 [ Homo sapiens (human) ]

    Gene ID: 343637, updated on 2-Nov-2024

    Summary

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    Official Symbol
    RSPO4provided by HGNC
    Official Full Name
    R-spondin 4provided by HGNC
    Primary source
    HGNC:HGNC:16175
    See related
    Ensembl:ENSG00000101282 MIM:610573; AllianceGenome:HGNC:16175
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    CRISTIN4; C20orf182
    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]
    Expression
    Biased expression in lung (RPKM 1.4), testis (RPKM 0.6) and 7 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See RSPO4 in Genome Data Viewer
    Location:
    20p13
    Exon count:
    5
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 20 NC_000020.11 (958452..1002311, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 20 NC_060944.1 (1005419..1049278, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 20 NC_000020.10 (939095..982954, complement)

    Chromosome 20 - NC_000020.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124904854 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:853162-853662 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:853663-854163 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17448 Neighboring gene MPRA-validated peak4114 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:865931-866430 Neighboring gene angiopoietin 4 Neighboring gene uncharacterized LOC105372492 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:925889-926498 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:932465-932965 Neighboring gene H3K27ac hESC enhancer GRCh37_chr20:952527-953244 Neighboring gene Sharpr-MPRA regulatory region 1111 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17449 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12586 Neighboring gene NANOG hESC enhancer GRCh37_chr20:1067234-1067735 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17450 Neighboring gene uncharacterized LOC105372493 Neighboring gene H3K27ac hESC enhancer GRCh37_chr20:1098996-1099638 Neighboring gene proteasome inhibitor subunit 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:1141197-1141698 Neighboring gene actin gamma 1 pseudogene 3

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. RSPO4 is a potential risk gene of stages III-IV, grade C periodontitis through effects on innate immune response and oral barrier integrity. Chopra A, et al. J Clin Periodontol, 2023 Apr. PMID 36507580
    2. Mutations in the gene encoding the Wnt-signaling component R-spondin 4 (RSPO4) cause autosomal recessive anonychia. Bergmann C, et al. Am J Hum Genet, 2006 Dec. PMID 17186469, Free PMC Article
    3. The Wnt signalling ligand RSPO4, causing inherited anonychia, is not mutated in a patient with congenital nail hypoplasia/aplasia with underlying skeletal defects. Seitz CS, et al. Br J Dermatol, 2007 Oct. PMID 17596144
    4. 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. Brüchle NO, et al. J Invest Dermatol, 2008 Apr. PMID 17914448
    5. A novel missense mutation in RSPO4 gene underlies autosomal recessive congenital anonychia in a consanguineous Pakistani family. Chishti MS, et al. Br J Dermatol, 2008 Mar. PMID 18070203

    See all (23) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. RSPO4 is a potential risk gene of stages III-IV, grade C periodontitis through effects on innate immune response and oral barrier integrity.
      Title: RSPO4 is a potential risk gene of stages III-IV, grade C periodontitis through effects on innate immune response and oral barrier integrity.
    2. Single-cell RNA sequencing of human nail unit defines RSPO4 onychofibroblasts and SPINK6 nail epithelium.
      Title: Single-cell RNA sequencing of human nail unit defines RSPO4 onychofibroblasts and SPINK6 nail epithelium.
    3. A novel nonsense mutation in RSPO4 gene involves in the development of anonychia congenita.
      Title: A novel nonsense mutation in RSPO4 gene underlies autosomal recessive congenital anonychia in a Pakistani family.
    4. c.3G>A mutation is not sufficient to cause the congenital hyponychia and could be considered a polymorphism.
      Title: Novel missense mutation in the RSPO4 gene in congenital hyponychia and evidence for a polymorphic initiation codon (p.M1I).
    5. identification of a missense mutation c.199G > C (p.Gly67Arg) in the RSPO4 gene in a large consanguineous Pakistani family with an autosomal recessive form of anonychia
      Title: A novel missense mutation in RSPO4 gene underlies autosomal recessive congenital anonychia in a consanguineous Pakistani family.
    6. These findings expand our understanding of the role of RSPO4 in nail development and disease.
      Title: Mutations in R-spondin 4 (RSPO4) underlie inherited anonychia.
    7. The previously unknown mutations c.190C>T (p.Arg64Cys) in exon 2 and c.301C>T (p.Gln101X) in exon 3 were identified in RSPO4, thereby corroborating R-spondin 4 as the major protein in autosomal-recessive anonychia.
      Title: 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.
    8. RSPO4 has a crucial role in nail morphogenesis.
      Title: The gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signaling, is mutated in inherited anonychia.
    Submit: New GeneRIF Correction

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Anonychia
    MedGen: C0265998 OMIM: 206800 GeneReviews: Not available
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ16018

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables heparin binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables signaling receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in Wnt signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within nail development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of Wnt signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of Wnt signaling pathway NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in positive regulation of canonical Wnt signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in extracellular region NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    R-spondin-4
    Names
    R-spondin family, member 4
    hRspo4
    roof plate-specific spondin-4

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_013043.1 RefSeqGene

      Range
      4954..48813
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001029871.4 → NP_001025042.2  R-spondin-4 isoform 1 precursor

      See identical proteins and their annotated locations for NP_001025042.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AK122609, AL050325, BQ185331
      Consensus CDS
      CCDS42846.1
      UniProtKB/Swiss-Prot
      A2A2I6, Q2I0M5, Q9UGB2
      Related
      ENSP00000217260.4, ENST00000217260.9
      Conserved Domains (2) summary
      cd00064
      Location:90 → 136
      FU; Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.
      pfam15913
      Location:35 → 138
      Furin-like_2; Furin-like repeat, cysteine-rich

    2. NM_001040007.3 → NP_001035096.1  R-spondin-4 isoform 2 precursor

      See identical proteins and their annotated locations for NP_001035096.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an in-frame exon in the coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
      Source sequence(s)
      AL050325, BQ185331, DQ355152
      Consensus CDS
      CCDS42845.1
      UniProtKB/Swiss-Prot
      Q2I0M5
      Related
      ENSP00000383475.2, ENST00000400634.2
      Conserved Domains (2) summary
      cd00064
      Location:90 → 136
      FU; Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.
      pfam15913
      Location:35 → 137
      Furin-like_2; Furin-like repeat, cysteine-rich

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000020.11 Reference GRCh38.p14 Primary Assembly

      Range
      958452..1002311 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017027839.2 → XP_016883328.1  R-spondin-4 isoform X1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060944.1 Alternate T2T-CHM13v2.0

      Range
      1005419..1049278 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054323406.1 → XP_054179381.1  R-spondin-4 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q2I0M5.2 GenPept UniProtKB/Swiss-Prot:Q2I0M5

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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