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Gene Review

GPR64  -  G protein-coupled receptor 64

Homo sapiens

Synonyms: EDDM6, G-protein coupled receptor 64, HE6, He6, Human epididymis-specific protein 6, ...
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Disease relevance of GPR64


High impact information on GPR64

  • A nearly full-length cDNA clone (HE6) encoding the entire sequence of the hatching enzyme was isolated from a prehatching blastula lambda gt11 cDNA library [3].
  • HE6 is specifically expressed within the efferent ductules and the initial segment of the epididymis, ductal systems involved in spermatozoon maturation [1].
  • The fertility phenotype of HE6 knockout mice identifies this receptor as a potential nonsteroidal, nontesticular target for future male contraceptives and identifies an in vivo function for a member of this unusual gene family [1].
  • However, the precise function of HE6, together with its potential ligand(s), and signal transduction pathways have remained largely unknown [4].
  • Clues to the function of HE6 within the epithelium of male excurrent ducts may come from its co-localisation with the apical actin cytoskeleton and from the down-regulation in "knockout" male mice of various proteins specific to the initial segment [4].

Biological context of GPR64

  • The human HE6 gene was assigned to the X chromosome in a region, which is syntenic to the mouse [5].
  • A novel gene product, HE6, showing homology to the seven transmembrane-domain (Tm7) receptor superfamily, has been cloned by differential screening from a human epididymal cDNA library [6].
  • In conceptual terms, HE6 wears two hats: an unusually long extracellular region characteristic of cell adhesion proteins, and an intracellular region with binding affinity to G protein [7].

Anatomical context of GPR64

  • HE6 (GPR64) is a highly conserved, tissue-specific heptahelical receptor of the human epididymis [4].
  • HE6, a two-subunit heptahelical receptor associated with apical membranes of efferent and epididymal duct epithelia [5].

Other interactions of GPR64

  • This method identified six human epididymal cDNAs, named HE1-HE6, which are derived from abundant epididymal mRNAs [8].

Analytical, diagnostic and therapeutic context of GPR64

  • Sequence analysis of this PAC clone did not reveal other known genes: neither the RYRI gene, nor the HE6 gene, nor other human Xp22 genes were identified [2].
  • This study with HE6 exemplifies how targets for male contraception have to be validated before drug development can start [9].


  1. Targeted deletion of the epididymal receptor HE6 results in fluid dysregulation and male infertility. Davies, B., Baumann, C., Kirchhoff, C., Ivell, R., Nubbemeyer, R., Habenicht, U.F., Theuring, F., Gottwald, U. Mol. Cell. Biol. (2004) [Pubmed]
  2. Analysis of the spermine synthase gene region in Fugu rubripes, Tetraodon fluviatilis, and Danio rerio. Boeddrich, A., Burgtorf, C., Roest Crollius, H., Hennig, S., Bernot, A., Clark, M., Reinhardt, R., Lehrach, H., Francis, F. Genomics (1999) [Pubmed]
  3. Early expression of a collagenase-like hatching enzyme gene in the sea urchin embryo. Lepage, T., Gache, C. EMBO J. (1990) [Pubmed]
  4. Role of epididymal receptor HE6 in the regulation of sperm microenvironment. Kirchhoff, C., Obermann, H., Behnen, M., Davies, B. Mol. Cell. Endocrinol. (2006) [Pubmed]
  5. HE6, a two-subunit heptahelical receptor associated with apical membranes of efferent and epididymal duct epithelia. Obermann, H., Samalecos, A., Osterhoff, C., Schröder, B., Heller, R., Kirchhoff, C. Mol. Reprod. Dev. (2003) [Pubmed]
  6. Cloning of a human epididymis-specific mRNA, HE6, encoding a novel member of the seven transmembrane-domain receptor superfamily. Osterhoff, C., Ivell, R., Kirchhoff, C. DNA Cell Biol. (1997) [Pubmed]
  7. Epididymal G protein-coupled receptor (GPCR): two hats and a two-piece suit tailored at the GPS motif. Kierszenbaum, A.L. Mol. Reprod. Dev. (2003) [Pubmed]
  8. Function of human epididymal proteins in sperm maturation. Kirchhoff, C., Osterhoff, C., Pera, I., Schröter, S. Andrologia (1998) [Pubmed]
  9. New approaches for male fertility control: HE6 as an example of a putative target. Gottwald, U., Davies, B., Fritsch, M., Habenicht, U.F. Mol. Cell. Endocrinol. (2006) [Pubmed]
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