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GPR65 G protein-coupled receptor 65 [ Homo sapiens (human) ]

Gene ID: 8477, updated on 12-Jun-2025
Official Symbol
GPR65provided by HGNC
Official Full Name
G protein-coupled receptor 65provided by HGNC
Primary source
HGNC:HGNC:4517
See related
Ensembl:ENSG00000140030 MIM:604620; AllianceGenome:HGNC:4517
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
TDAG8; hTDAG8
Summary
Enables G protein-coupled receptor activity. Involved in adenylate cyclase-activating G protein-coupled receptor signaling pathway; cellular response to acidic pH; and positive regulation of stress fiber assembly. Is active in early endosome membrane; late endosome membrane; and plasma membrane. [provided by Alliance of Genome Resources, Jun 2025]
Expression
Broad expression in appendix (RPKM 6.3), bone marrow (RPKM 5.3) and 18 other tissues See more
Orthologs
mouse all
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See GPR65 in Genome Data Viewer
Location:
14q31.3
Exon count:
2
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (88005135..88014811)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (82225763..82235439)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (88471479..88481155)

Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene galactosylceramidase Neighboring gene uncharacterized LOC124903355 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_38584 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_38590 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5988 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:88459339-88459839 Neighboring gene RNA, U6 small nuclear 835, pseudogene Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_38639 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8834 Neighboring gene long intergenic non-protein coding RNA 1147 Neighboring gene NANOG hESC enhancer GRCh37_chr14:88503612-88504113 Neighboring gene HIF1A stabilizing long noncoding RNA Neighboring gene uncharacterized LOC107984699

Go to nucleotide: Graphics FASTA GenBank

  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

Related articles in PubMed

  1. IBD-associated G protein-coupled receptor 65 variant compromises signalling and impairs key functions involved in inflammation. Mercier V, et al. Cell Signal, 2022 May. PMID 35218908, Free PMC Article
  2. Genetic polymorphisms of G protein-coupled receptor 65 gene are associated with ankylosing spondylitis in a Chinese Han population: A case-control study. Yuan Y, et al. Hum Immunol, 2019 Feb. PMID 30529363
  3. The impact of the rs8005161 polymorphism on G protein-coupled receptor GPR65 (TDAG8) pH-associated activation in intestinal inflammation. Tcymbarevich IV, et al. BMC Gastroenterol, 2019 Jan 7. PMID 30616622, Free PMC Article
  4. Overexpression of G-protein-coupled receptors 65 in glioblastoma predicts poor patient prognosis. Wang HX, et al. Clin Neurol Neurosurg, 2018 Jan. PMID 29223793
  5. Contextual tumor suppressor function of T cell death-associated gene 8 (TDAG8) in hematological malignancies. Justus CR, et al. J Transl Med, 2017 Oct 10. PMID 29017562, Free PMC Article

See all (47) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. The proton-sensing receptors TDAG8 and GPR4 are differentially expressed in human and mouse oligodendrocytes: Exploring their role in neuroinflammation and multiple sclerosis.
    Title: The proton-sensing receptors TDAG8 and GPR4 are differentially expressed in human and mouse oligodendrocytes: Exploring their role in neuroinflammation and multiple sclerosis.
  2. Targeting GPR65 alleviates hepatic inflammation and fibrosis by suppressing the JNK and NF-kappaB pathways.
    Title: Targeting GPR65 alleviates hepatic inflammation and fibrosis by suppressing the JNK and NF-κB pathways.
  3. Intestinal epithelial pH-sensing receptor GPR65 maintains mucosal homeostasis via regulating antimicrobial defense and restrains gut inflammation in inflammatory bowel disease.
    Title: Intestinal epithelial pH-sensing receptor GPR65 maintains mucosal homeostasis via regulating antimicrobial defense and restrains gut inflammation in inflammatory bowel disease.
  4. GPR65 inhibits human trophoblast cell adhesion through upregulation of MYLK and downregulation of fibronectin via cAMP-ERK signaling in a low pH environment.
    Title: GPR65 inhibits human trophoblast cell adhesion through upregulation of MYLK and downregulation of fibronectin via cAMP-ERK signaling in a low pH environment.
  5. MicroRNAs combined with the TLR4/TDAG8 mRNAs and proinflammatory cytokines are biomarkers for the rapid diagnosis of sepsis.
    Title: MicroRNAs combined with the TLR4/TDAG8 mRNAs and proinflammatory cytokines are biomarkers for the rapid diagnosis of sepsis.
  6. IBD-associated G protein-coupled receptor 65 variant compromises signalling and impairs key functions involved in inflammation.
    Title: IBD-associated G protein-coupled receptor 65 variant compromises signalling and impairs key functions involved in inflammation.
  7. GPR65 promotes intestinal mucosal Th1 and Th17 cell differentiation and gut inflammation through downregulating NUAK2.
    Title: GPR65 promotes intestinal mucosal Th1 and Th17 cell differentiation and gut inflammation through downregulating NUAK2.
  8. Multilocus evaluation of genetic predictors of multiple sclerosis.
    Title: Multilocus evaluation of genetic predictors of multiple sclerosis.
  9. Carbon dioxide inhibits UVB-induced inflammatory response by activating the proton-sensing receptor, GPR65, in human keratinocytes.
    Title: Carbon dioxide inhibits UVB-induced inflammatory response by activating the proton-sensing receptor, GPR65, in human keratinocytes.
  10. The evolution and mechanism of GPCR proton sensing.
    Title: The evolution and mechanism of GPCR proton sensing.
Submit: New GeneRIF Correction See all GeneRIFs (30)

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
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.
EBI GWAS Catalog
Genome-wide genetic and transcriptomic investigation of variation in antibody response to dietary antigens.
EBI GWAS Catalog
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.
EBI GWAS Catalog
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
EBI GWAS Catalog

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Products Interactant Other Gene Complex Source Pubs Description

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 IDA
Inferred from Direct Assay
more info
 PubMed 
enables G protein-coupled receptor activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in G protein-coupled receptor signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in G protein-coupled receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in adenylate cyclase-activating G protein-coupled receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
acts_upstream_of_or_within adenylate cyclase-activating G protein-coupled receptor signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in adenylate cyclase-activating G protein-coupled receptor signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to acidic pH IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in immune response TAS
Traceable Author Statement
more info
 PubMed 
involved_in positive regulation of T-helper cell differentiation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of interleukin-22 production ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of stress fiber assembly IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in response to acidic pH IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in signal transduction IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
is_active_in early endosome membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in early endosome membrane IEA
Inferred from Electronic Annotation
more info
  
located_in endosome IEA
Inferred from Electronic Annotation
more info
  
is_active_in late endosome membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in late endosome membrane IEA
Inferred from Electronic Annotation
more info
  
located_in membrane IEA
Inferred from Electronic Annotation
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane IEA
Inferred from Electronic Annotation
more info
  
located_in plasma membrane TAS
Traceable Author Statement
more info
 PubMed 
Preferred Names
psychosine receptor
Names
T-cell death-associated gene 8 protein

NEW Try the new Transcript table

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_003608.4 → NP_003599.2  psychosine receptor

    See identical proteins and their annotated locations for NP_003599.2

    Status: VALIDATED

    Source sequence(s)
    AL157955
    Consensus CDS
    CCDS9879.1
    UniProtKB/Swiss-Prot
    O75819, Q8IYL9
    UniProtKB/TrEMBL
    B2R9I6, B5B0C2
    Related
    ENSP00000267549.3, ENST00000267549.5
    Conserved Domains (1) summary
    cd15365
    Location:15 → 301
    7tmA_GPR65_TDAG8; proton-sensing G protein-coupled receptor 65, member of the class A family of seven-transmembrane G protein-coupled receptors

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_000014.9 Reference GRCh38.p14 Primary Assembly

    Range
    88005135..88014811
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060938.1 Alternate T2T-CHM13v2.0

    Range
    82225763..82235439
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q8IYL9.1 GenPept UniProtKB/Swiss-Prot:Q8IYL9

Gene LinkOut

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

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