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

Gene ID: 343637, updated on 5-Mar-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
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) 20 NC_000020.11 (958452..1002311, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 20 NC_060944.1 (1005419..1049278, complement)
105.20220307 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
  • 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. Novel missense mutation in the RSPO4 gene in congenital hyponychia and evidence for a polymorphic initiation codon (p.M1I). Khan TN, et al. BMC Med Genet, 2012 Dec 13. PMID 23234511, Free PMC Article
  3. A novel nonsense mutation in RSPO4 gene underlies autosomal recessive congenital anonychia in a Pakistani family. Wasif N, et al. Pediatr Dermatol, 2013 Jan-Feb. PMID 22300369
  4. Congenital hyponychia without RSPO4 mutation. Nakamura M, et al. Acta Derm Venereol, 2008. PMID 18779895
  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
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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 
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 
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
  

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_2023_10

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

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