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RSPO1 R-spondin 1 [ Homo sapiens (human) ]

Gene ID: 284654, updated on 5-Mar-2024

Summary

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Official Symbol
RSPO1provided by HGNC
Official Full Name
R-spondin 1provided by HGNC
Primary source
HGNC:HGNC:21679
See related
Ensembl:ENSG00000169218 MIM:609595; AllianceGenome:HGNC:21679
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
RSPO; CRISTIN3
Summary
This gene encodes a secreted activator protein with two cysteine-rich, furin-like domains and one thrombospondin type 1 domain. The encoded protein is a ligand for leucine-rich repeat-containing G-protein coupled receptors (LGR proteins) and positively regulates the Wnt signaling pathway. In mice, the protein induces the rapid onset of crypt cell proliferation and increases intestinal epithelial healing, providing a protective effect against chemotherapy-induced adverse effects. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]
Expression
Biased expression in endometrium (RPKM 16.2), skin (RPKM 2.3) and 5 other tissues See more
Orthologs
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Genomic context

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See RSPO1 in Genome Data Viewer
Location:
1p34.3
Exon count:
8
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (37611350..37634892, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (37476097..37499638, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (38076951..38100564, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:38021148-38022118 Neighboring gene Sharpr-MPRA regulatory region 12224 Neighboring gene ribosomal protein S27 pseudogene 9 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr1:38033816-38035015 Neighboring gene dynein axonemal light intermediate chain 1 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr1:38041731-38042930 Neighboring gene G protein nucleolar 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 770 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 771 Neighboring gene Sharpr-MPRA regulatory region 1638 Neighboring gene Sharpr-MPRA regulatory region 1490 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:38096333-38096846 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:38098855-38099382 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:38099911-38100438 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:38100439-38100965 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:38126219-38126852 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 772 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:38128815-38129348 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:38129349-38129881 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:38132271-38132990 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 773 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 774 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 775 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:38156929-38157439 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:38157440-38157949 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:38157950-38158460 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:38158461-38158969 Neighboring gene AFG2 interacting ribosome maturation factor Neighboring gene cell division cycle associated 8

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. RSPO1-mutated keratinocytes from palmoplantar keratoderma display impaired differentiation, alteration of cell-cell adhesion, EMT-like phenotype and invasiveness properties: implications for squamous cell carcinoma susceptibility in patients with 46XX disorder of sexual development. Dellambra E, et al. Orphanet J Rare Dis, 2022 Jul 19. PMID 35854363, Free PMC Article
  2. The role of R-spondin 1 through activating Wnt/β-catenin in the growth, survival and migration of ovarian cancer cells. Liu Q, et al. Gene, 2019 Mar 20. PMID 30572097
  3. Serum R-Spondin 1 Is a New Surrogate Marker for Obesity and Insulin Resistance. Kang YE, et al. Diabetes Metab J, 2019 Jun. PMID 30398036, Free PMC Article
  4. A Novel Homozygous Missense Mutation in the FU-CRD2 Domain of the R-spondin1 Gene Associated with Familial 46,XX DSD. Naasse Y, et al. Sex Dev, 2017. PMID 29262419
  5. N-Glycosylation of Human R-Spondin 1 Is Required for Efficient Secretion and Stability but Not for Its Heparin Binding Ability. Chang CF, et al. Int J Mol Sci, 2016 Jun 14. PMID 27314333, Free PMC Article

See all (76) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. R-spondin-1 induces Axin degradation via the LRP6-CK1epsilon axis.
    Title: R-spondin-1 induces Axin degradation via the LRP6-CK1ε axis.
  2. Human RSPO1 Mutation Represses Beige Adipocyte Thermogenesis and Contributes to Diet-Induced Adiposity.
    Title: Human RSPO1 Mutation Represses Beige Adipocyte Thermogenesis and Contributes to Diet-Induced Adiposity.
  3. RSPO1-mutated keratinocytes from palmoplantar keratoderma display impaired differentiation, alteration of cell-cell adhesion, EMT-like phenotype and invasiveness properties: implications for squamous cell carcinoma susceptibility in patients with 46XX disorder of sexual development.
    Title: RSPO1-mutated keratinocytes from palmoplantar keratoderma display impaired differentiation, alteration of cell-cell adhesion, EMT-like phenotype and invasiveness properties: implications for squamous cell carcinoma susceptibility in patients with 46XX disorder of sexual development.
  4. Association of WNT7B and RSPO1 with Axial Length in School Children.
    Title: Association of WNT7B and RSPO1 with Axial Length in School Children.
  5. WNT Signaling Driven by R-spondin 1 and LGR6 in High-grade Serous Ovarian Cancer.
    Title: WNT Signaling Driven by R-spondin 1 and LGR6 in High-grade Serous Ovarian Cancer.
  6. This study demonstrated the association between serum levels of RSPO1 and a range of metabolic parameters in humans.
    Title: Serum R-Spondin 1 Is a New Surrogate Marker for Obesity and Insulin Resistance.
  7. R-spondin1/Wnt activated Ascl2 expression dose-dependently in the CD133(+)CD44(+) colorectal cancer population.
    Title: R-spondin1/Wnt-enhanced Ascl2 autoregulation controls the self-renewal of colorectal cancer progenitor cells.
  8. In this study, we aimed at the Wnt signaling characteristic of Cancer stem cells (CSC) and designed a liposomal drug delivery system to target CSCs. Liposomes decorated with RSPO1 on the surface were constructed for specific interactions with the Wnt pathway coreceptor LGR5.
    Title: Selective Targeting and Eradication of LGR5(+) Cancer Stem Cells Using RSPO-Conjugated Doxorubicin Liposomes.
  9. High RSPO1 expression is associated with Gastric Carcinogenesis.
    Title: Divergent Routes toward Wnt and R-spondin Niche Independency during Human Gastric Carcinogenesis.
  10. R-spondin 1 regulates ovarian cancer biological activities via activating Wnt/beta-catenin. This highlights the critical roles of R-spondin 1 in ovarian cancer progression and chemoresistance.
    Title: The role of R-spondin 1 through activating Wnt/β-catenin in the growth, survival and migration of ovarian cancer cells.
Submit: New GeneRIF Correction See all GeneRIFs (40)

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
Palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome
MedGen: C3149931 OMIM: 610644 GeneReviews: Not available
Compare labs

EBI GWAS Catalog

Description
Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error.
EBI GWAS Catalog

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

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Homology

Clone Names

  • FLJ40906

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables G protein-coupled receptor binding IPI
Inferred from Physical Interaction
more info
 PubMed 
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 IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in Wnt signaling pathway IEA
Inferred from Electronic Annotation
more info
  
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 IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of protein phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of receptor internalization IDA
Inferred from Direct Assay
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
  
located_in nucleus IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
R-spondin-1
Names
R-spondin homolog
roof plate-specific spondin-1

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_012239.2 RefSeqGene

    Range
    4928..28470
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001038633.4 → NP_001033722.1  R-spondin-1 isoform 1 precursor

    See identical proteins and their annotated locations for NP_001033722.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1). Both variants 1 and 2 encode the same isoform (1).
    Source sequence(s)
    AK098225, AL513220, DB273983, DQ318235
    Consensus CDS
    CCDS41304.1
    UniProtKB/Swiss-Prot
    A2A420, Q0H8S6, Q14C72, Q2MKA7, Q5T0F2, Q8N7L5
    Related
    ENSP00000383846.1, ENST00000401068.1
    Conserved Domains (2) summary
    pfam15913
    Location:42 → 142
    Furin-like_2; Furin-like repeat, cysteine-rich
    pfam19028
    Location:148 → 203
    TSP1_spondin; Spondin-like TSP1 domain

  2. NM_001242908.2 → NP_001229837.1  R-spondin-1 isoform 1 precursor

    See identical proteins and their annotated locations for NP_001229837.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate exon in the 5' UTR, compared to variant 1. Both variants 1 and 2 encode the same isoform (1).
    Source sequence(s)
    AL513220, DB273983, DQ165084
    Consensus CDS
    CCDS41304.1
    UniProtKB/Swiss-Prot
    A2A420, Q0H8S6, Q14C72, Q2MKA7, Q5T0F2, Q8N7L5
    Related
    ENSP00000348944.2, ENST00000356545.7
    Conserved Domains (2) summary
    pfam15913
    Location:42 → 142
    Furin-like_2; Furin-like repeat, cysteine-rich
    pfam19028
    Location:148 → 203
    TSP1_spondin; Spondin-like TSP1 domain

  3. NM_001242909.2 → NP_001229838.1  R-spondin-1 isoform 2

    See identical proteins and their annotated locations for NP_001229838.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an alternate exon in the 5' UTR and uses an alternate splice site in the 5' region and initiates translation at an alternate upstream start codon, compared to variant 1. The encoded isoform (2) has a distinct N-terminus and is shorter than isoform 1.
    Source sequence(s)
    AK098225, AL513220, DB273983
    Consensus CDS
    CCDS55591.1
    UniProtKB/Swiss-Prot
    Q2MKA7
    Related
    ENSP00000481178.1, ENST00000615459.4
    Conserved Domains (2) summary
    cd00064
    Location:73 → 115
    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:15 → 117
    Furin-like_2; Furin-like repeat, cysteine-rich

  4. NM_001242910.2 → NP_001229839.1  R-spondin-1 isoform 3 precursor

    See identical proteins and their annotated locations for NP_001229839.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks an alternate exon in the 5' UTR and lacks an in-frame exon in the 3' coding region, compared to variant 1. The encoded isoform (3) is shorter than isoform 1.
    Source sequence(s)
    AL513220, DB273983, DQ165085
    Consensus CDS
    CCDS55590.1
    UniProtKB/Swiss-Prot
    Q2MKA7
    Related
    ENSP00000479832.1, ENST00000612451.4
    Conserved Domains (1) summary
    pfam15913
    Location:42 → 143
    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_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    37611350..37634892 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006710583.5 → XP_006710646.1  R-spondin-1 isoform X1

    See identical proteins and their annotated locations for XP_006710646.1

    UniProtKB/Swiss-Prot
    A2A420, Q0H8S6, Q14C72, Q2MKA7, Q5T0F2, Q8N7L5
    Conserved Domains (2) summary
    pfam15913
    Location:42 → 142
    Furin-like_2; Furin-like repeat, cysteine-rich
    pfam19028
    Location:148 → 203
    TSP1_spondin; Spondin-like TSP1 domain

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    37476097..37499638 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054336134.1 → XP_054192109.1  R-spondin-1 isoform X1

    UniProtKB/Swiss-Prot
    A2A420, Q0H8S6, Q14C72, Q2MKA7, Q5T0F2, Q8N7L5

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_173640.1: Suppressed sequence

    Description
    NM_173640.1: This RefSeq was permanently suppressed because there is insufficient support for the transcript and the protein.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q2MKA7.1 GenPept UniProtKB/Swiss-Prot:Q2MKA7

Gene LinkOut

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