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    GPRC6A G protein-coupled receptor class C group 6 member A [ Homo sapiens (human) ]

    Gene ID: 222545, updated on 9-Dec-2024

    Summary

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    Official Symbol
    GPRC6Aprovided by HGNC
    Official Full Name
    G protein-coupled receptor class C group 6 member Aprovided by HGNC
    Primary source
    HGNC:HGNC:18510
    See related
    Ensembl:ENSG00000173612 MIM:613572; AllianceGenome:HGNC:18510
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    GPCR; bA86F4.3
    Summary
    Members of family C of the G protein-coupled receptor (GPCR) superfamily, such as GPRC6A, are characterized by an evolutionarily conserved amino acid-sensing motif linked to an intramembranous 7-transmembrane loop region. Several members of GPCR family C, including GPRC6A, also have a long N-terminal domain (summary by Pi et al., 2005 [PubMed 16199532]).[supplied by OMIM, Nov 2010]
    Expression
    Low expression observed in reference dataset See more
    Orthologs
    mouse all
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    Genomic context

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    See GPRC6A in Genome Data Viewer
    Location:
    6q22.1
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (116792085..116829240, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (117975811..118012987, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (117113248..117150246, complement)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_88226 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:117085903-117086417 Neighboring gene uncharacterized LOC105377963 Neighboring gene family with sequence similarity 162 member B Neighboring gene RFX6 promoter region Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr6:117198416-117199374 Neighboring gene RFX6 prostate cancer risk allelic enhancer Neighboring gene regulatory factor X6 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr6:117246147-117247346 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25000 Neighboring gene ribosomal protein S29 pseudogene 13

    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. Analysis of GPRC6A variants in different pancreatitis etiologies. Kaune T, et al. Pancreatology, 2020 Oct. PMID 32859544
    2. rs2274911 polymorphism in GPRC6A associated with serum E2 and PSA in a Southern Chinese male population. Qi N, et al. Gene, 2020 Dec 30. PMID 32827681
    3. SHBG141-161 Domain-Peptide Stimulates GPRC6A-Mediated Response in Leydig and β-Langerhans cell lines. De Toni L, et al. Sci Rep, 2019 Dec 19. PMID 31857654, Free PMC Article
    4. Human GPRC6A Mediates Testosterone-Induced Mitogen-Activated Protein Kinases and mTORC1 Signaling in Prostate Cancer Cells. Ye R, et al. Mol Pharmacol, 2019 May. PMID 30894404, Free PMC Article
    5. CRISPR/Cas9 targeting of GPRC6A suppresses prostate cancer tumorigenesis in a human xenograft model. Ye R, et al. J Exp Clin Cancer Res, 2017 Jun 28. PMID 28659174, Free PMC Article

    See all (35) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. RS 2247911 polymorphism of GPRC6A gene and serum undercarboxylated-osteocalcin are associated with testis function.
      Title: RS 2247911 polymorphism of GPRC6A gene and serum undercarboxylated-osteocalcin are associated with testis function.
    2. Explaining Divergent Observations Regarding Osteocalcin/GPRC6A Endocrine Signaling.
      Title: Explaining Divergent Observations Regarding Osteocalcin/GPRC6A Endocrine Signaling.
    3. Analysis of GPRC6A variants in different pancreatitis etiologies.
      Title: Analysis of GPRC6A variants in different pancreatitis etiologies.
    4. Humanized GPRC6A(KGKY) is a gain-of-function polymorphism in mice.
      Title: Humanized GPRC6A(KGKY) is a gain-of-function polymorphism in mice.
    5. SHBG141-161 Domain-Peptide Stimulates GPRC6A-Mediated Response in Leydig and beta-Langerhans cell lines.
      Title: SHBG141-161 Domain-Peptide Stimulates GPRC6A-Mediated Response in Leydig and β-Langerhans cell lines.
    6. rs2274911 polymorphism in GPRC6A associated with serum E2 and PSA in a Southern Chinese male population.
      Title: rs2274911 polymorphism in GPRC6A associated with serum E2 and PSA in a Southern Chinese male population.
    7. Human GPRC6A is required for mediating the effects of testosterone on cell proliferation and autophagy.
      Title: Human GPRC6A Mediates Testosterone-Induced Mitogen-Activated Protein Kinases and mTORC1 Signaling in Prostate Cancer Cells.
    8. The G protein-coupled receptor family C group 6 member A (GPRC6A) and zinc transporter member 9 (ZIP9) have also been portrayed as mARs, related to the extranuclear action of androgens.
      Title: Membrane androgen receptors (OXER1, GPRC6A AND ZIP9) in prostate and breast cancer: A comparative study of their expression.
    9. If the regulatory functions of GPRC6A identified in mice translate to humans, and polymorphisms in GPRC6A are found to predict racial disparities in human diseases, GPRC6A may be a new gene target to predict, prevent, and treat MetS, PCa, and other disorders impacted by GPRC6A.
      Title: GPRC6A: Jack of all metabolism (or master of none).
    10. Human GPRC6A is a functional osteocalcin and testosterone sensing receptor that promotes prostate cancer progression.
      Title: CRISPR/Cas9 targeting of GPRC6A suppresses prostate cancer tumorigenesis in a human xenograft model.
    Submit: New GeneRIF Correction See all GeneRIFs (28)

    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

    EBI GWAS Catalog

    Description
    Genome-wide association study identifies five new susceptibility loci for prostate cancer in the Japanese population.
    EBI GWAS Catalog
    Meta-analysis of genome-wide association studies in >80 000 subjects identifies multiple loci for C-reactive protein levels.
    EBI GWAS Catalog

    Variation

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    See Variation Viewer (GRCh37.p13)

    Pathways from PubChem

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    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables G protein-coupled receptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables G protein-coupled receptor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Process Evidence Code Pubs
    involved_in G protein-coupled receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in calcium-mediated signaling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of testosterone biosynthetic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in response to amino acid IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cell surface IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    G-protein coupled receptor family C group 6 member A
    Names
    G protein-coupled receptor, family C, group 6, member A
    G-protein coupled receptor GPCR33
    predicted with SOSUI analysis
    seven transmembrane helix receptor

    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.

    mRNA and Protein(s)

    1. NM_001286354.1 → NP_001273283.1  G-protein coupled receptor family C group 6 member A isoform 2 precursor

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the central coding region, compared to variant 1, resulting in an isoform (2) that is shorter than isoform 1.
      Source sequence(s)
      AF502962, AY435126, BG191110, DY319308
      Consensus CDS
      CCDS69185.1
      UniProtKB/Swiss-Prot
      Q5T6X5
      Related
      ENSP00000433465.1, ENST00000530250.1
      Conserved Domains (4) summary
      pfam00003
      Location:432 → 661
      7tm_3; 7 transmembrane sweet-taste receptor of 3 GCPR
      pfam01094
      Location:75 → 302
      ANF_receptor; Receptor family ligand binding region
      pfam07562
      Location:344 → 396
      NCD3G; Nine Cysteines Domain of family 3 GPCR
      cl10011
      Location:37 → 331
      Periplasmic_Binding_Protein_Type_1; Type 1 periplasmic binding fold superfamily

    2. NM_001286355.1 → NP_001273284.1  G-protein coupled receptor family C group 6 member A isoform 3 precursor

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) lacks an alternate in-frame exon in the central coding region, compared to variant 1, resulting in an isoform (3) that is shorter than isoform 1.
      Source sequence(s)
      AF502962, AW771483, AY435127, BG191110, DY319308
      Consensus CDS
      CCDS69184.1
      UniProtKB/Swiss-Prot
      Q5T6X5
      Related
      ENSP00000357537.3, ENST00000368549.7
      Conserved Domains (4) summary
      pfam00003
      Location:536 → 765
      7tm_3; 7 transmembrane sweet-taste receptor of 3 GCPR
      pfam01094
      Location:75 → 344
      ANF_receptor; Receptor family ligand binding region
      pfam07562
      Location:448 → 500
      NCD3G; Nine Cysteines Domain of family 3 GPCR
      cl10011
      Location:37 → 445
      Periplasmic_Binding_Protein_Type_1; Type 1 periplasmic binding fold superfamily

    3. NM_148963.4 → NP_683766.2  G-protein coupled receptor family C group 6 member A isoform 1 precursor

      See identical proteins and their annotated locations for NP_683766.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AL354716
      Consensus CDS
      CCDS5112.1
      UniProtKB/Swiss-Prot
      Q5T6X5, Q6JK43, Q6JK44, Q8NGU8, Q8NHZ9, Q8TDT6
      Related
      ENSP00000309493.4, ENST00000310357.8
      Conserved Domains (4) summary
      cd06361
      Location:37 → 506
      PBP1_GPC6A_like; Ligand-binding domain of the promiscuous L-alpha-amino acid receptor GPRC6A which is a broad-spectrum amino acid-sensing receptor
      pfam00003
      Location:607 → 836
      7tm_3; 7 transmembrane sweet-taste receptor of 3 GCPR
      pfam01094
      Location:75 → 482
      ANF_receptor; Receptor family ligand binding region
      pfam07562
      Location:519 → 571
      NCD3G; Nine Cysteines Domain of family 3 GPCR

    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_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      116792085..116829240 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017010475.2 → XP_016865964.1  G-protein coupled receptor family C group 6 member A isoform X1

    2. XM_017010476.2 → XP_016865965.1  G-protein coupled receptor family C group 6 member A isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      117975811..118012987 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054354644.1 → XP_054210619.1  G-protein coupled receptor family C group 6 member A isoform X1

    2. XM_054354645.1 → XP_054210620.1  G-protein coupled receptor family C group 6 member A isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q5T6X5.1 GenPept UniProtKB/Swiss-Prot:Q5T6X5

    Gene LinkOut

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

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