Alternative titles; symbols
HGNC Approved Gene Symbol: TSPY1
Cytogenetic location: Yp11.2 Genomic coordinates (GRCh38): Y:9,466,955-9,469,749 (from NCBI)
Y-encoded testis-specific protein is restricted to testicular tissue (Arnemann et al., 1987; Arnemann et al., 1991; Zhang et al., 1992). Multiple TSPY sequences were shown by Manz et al. (1993) to be constitutive parts of DYZ5 repeat units. (The 'Z,' in place of 'S,' in the 'D number' indicates that it refers to repetitive DNA.) Manz et al. (1993) demonstrated microheterogeneity among transcribed and nontranscribed members of the TSPY family. Furthermore, evidence that several splice variants of TSPY transcripts occur was presented.
Schnieders et al. (1996) reported that TSPY gives rise to a pool of heterogeneously composed transcripts, at least 1 of which yields a protein that is a member of a superfamily including the protooncogene SET (600960) and NAP1 (164060), a nucleosome assembly factor. Immunohistologic studies reported by Schnieders et al. (1996) revealed that TSPY is concentrated in the cytoplasm of spermatogonia in normal as well as in pathologic tissue. They further reported that TSPY was found in the early forms of seminomatous testicular tumors. The authors suggested that TSPY function is related to spermatogonial proliferation in a phosphorylation-dependent manner.
Jakubiczka et al. (1993) isolated the bovine homolog of the human TSPY gene. The 2 proteins share 45% sequence identity.
From M. musculus testicular cDNA, Vogel et al. (1998) isolated sequences homologous to human and bovine TSPY and amplified a nearly full-length gene by PCR from mouse genomic DNA. They showed that the gene is present in single copy and apparently nonfunctional.
Lau (1999) discussed the possible role of the TSPY gene in gonadoblastoma (GBY; 424500) and in testicular and prostate cancers.
Schnieders et al. (1996) stated that the TSPY gene cluster is located on proximal chromosome Yp.
Figure 1 of Lau (1999) presented an updated map of genes assigned to the Y chromosome.
Jobling et al. (2007) noted that the Y chromosome reference database sequence (build 36.1) places a single copy of the TSPY gene on chromosome Yp more than 3 Mb telomeric to the major TSPY repeat array. The AMELY (410000), TBL1Y (400033), and PRKY (400008) genes lie within the intervening sequence.
Using a combination of STS deletion mapping, binary marker and Y-short tandem repeat haplotyping, and TSPY copy number estimation, Jobling et al. (2007) identified 4 distinct classes of deletions affecting chromosome Yp in 45 males from 12 different populations. The most common deletion class was found in 41 Y chromosomes (91%) and appeared to be caused by TSPY-mediated recombination that resulted in loss of the AMELY, TBL1Y, and PRKY genes and a reduced TSPY copy number in the TSPY repeat array. The persistence and expansion of deletion lineages, together with phenotypic evidence, suggested that absence of these genes has no major deleterious effects.
Shen et al. (2013) analyzed TSPY1 copy number in 2,272 unrelated Han Chinese men, including 216 b2/b4-deleted patients with severe oligozoospermia, cryptozoospermia, or azoospermia; 326 gr/gr-deleted men with impaired spermatogenesis and 162 gr/gr-deleted controls with normozoospermia; and 870 spermatogenesis-impaired men without AZFc deletions and 698 non-AZFc-deleted controls with normozoospermia. TSPY1 copy number distributions were significantly different among non-AZFc-deleted men with different spermatogenic phenotypes; lower sperm production and an elevated risk of spermatogenic failure were observed in males with fewer than 21 TSPY1 copies and in those with more than 55 copies, compared to men with 21 to 55 copies. Similar results were observed in men with the gr/gr deletion. Shen et al. (2013) concluded that TSPY1 copy number variation (CNV) affects susceptibility to spermatogenic failure by modulating the efficiency of spermatogenesis. The authors suggested that the TSPY1 copy number has a significant quantity effect on the phenotype of the gr/gr deletion.
Guttenbach et al. (1992) demonstrated conservation of DYZ5-homologous sequences on the Y chromosome of primates.
TSPY genes must have been selectively maintained on the mammalian Y chromosome since before the radiation of eutheria, 80 million years ago, as they are found conserved on the Y chromosome in 2 mammalian orders: primate and artiodactyl. Mazeyrat and Mitchell (1998) identified TSPY on the mouse and rat Y chromosome. The gene structure and expression of rat TSPY suggested that it is a functional, testis-specific gene, but the closely related mouse gene, Tspy, has clearly become nonfunctional, producing only low levels of aberrantly spliced transcripts. Thus, TSPY lost its function in the mouse lineage after its divergence from the rat lineage. These observations appeared to support the impression that recombination prevents genetic deterioration in sexual populations because it allows conservation of functional genotypes by removing deleterious mutations. The absence of recombination may have led to the loss of a functional Tspy gene in the mouse.
Arnemann, J., Epplen, J. T., Cooke, H. J., Sauermann, U., Engel, W., Schmidtke, J. A human Y-chromosomal DNA sequence expressed in testicular tissue. Nucleic Acids Res. 15: 8713-8724, 1987. [PubMed: 3479749] [Full Text: https://doi.org/10.1093/nar/15.21.8713]
Arnemann, J., Jakubiczka, S., Thuring, S., Schmidtke, J. Cloning and sequence analysis of a human Y-chromosome-derived, testicular cDNA, TSPY. Genomics 11: 108-114, 1991. [PubMed: 1765369] [Full Text: https://doi.org/10.1016/0888-7543(91)90107-p]
Guttenbach, M., Muller, U., Schmid, M. A human moderately repeated Y-specific DNA sequence is evolutionarily conserved in the Y chromosome of the great apes. Genomics 13: 363-367, 1992. [PubMed: 1612595] [Full Text: https://doi.org/10.1016/0888-7543(92)90254-p]
Jakubiczka, S., Schnieders, F., Schmidtke, J. A bovine homologue of the human TSPY gene. Genomics 17: 732-735, 1993. Note: Erratum: Genomics 19: 198 only, 1994. [PubMed: 8244389] [Full Text: https://doi.org/10.1006/geno.1993.1394]
Jobling, M. A., Lo, I. C. C., Turner, D. J., Bowden, G. R., Lee, A. C., Xue, Y., Carvalho-Silva, D., Hurles, M. E., Adams, S. M., Chang, Y. M., Kraaijenbrink, T., Henke, J., Guanti, G., McKeown, B., van Oorschot, R. A. H., Mitchell, R. J., de Knijff, P., Tyler-Smith, C., Parkin, E. J. Structural variation on the short arm of the human Y chromosome: recurrent multigene deletions encompassing Amelogenin Y. Hum. Molec. Genet. 16: 307-316, 2007. [PubMed: 17189292] [Full Text: https://doi.org/10.1093/hmg/ddl465]
Lau, Y.-F. C. Sex chromosome genetics '99: gonadoblastoma, testicular and prostate cancers, and the TSPY gene. Am. J. Hum. Genet. 64: 921-927, 1999. [PubMed: 10090875] [Full Text: https://doi.org/10.1086/302353]
Manz, E., Schnieders, F., Brechlin, A. M., Schmidtke, J. TSPY-related sequences represent a microheterogeneous gene family organized as constitutive elements in DYZ5 tandem repeat units on the human Y chromosome. Genomics 17: 726-731, 1993. [PubMed: 8244388] [Full Text: https://doi.org/10.1006/geno.1993.1393]
Mazeyrat, S., Mitchell, M. J. Rodent Y chromosome TSPY gene is functional in rat and non-functional in mouse. Hum. Molec. Genet. 7: 557-562, 1998. [PubMed: 9467017] [Full Text: https://doi.org/10.1093/hmg/7.3.557]
Schnieders, F., Dork, T., Arnemann, J., Vogel, T., Werner, M., Schmidtke, J. Testis-specific protein, Y-encoded (TSPY) expression in testicular tissues. Hum. Molec. Genet. 5: 1801-1807, 1996. [PubMed: 8923009] [Full Text: https://doi.org/10.1093/hmg/5.11.1801]
Shen, Y., Yan, Y., Liu, Y., Zhang, S., Yang, D., Zhang, P., Li, L., Wang, Y., Ma, Y., Tao, D., Yang, Y. A significant effect of the TSPY1 copy number on spermatogenesis efficiency and the phenotypic expression of the gr/gr deletion. Hum. Molec. Genet. 22: 1679-1695, 2013. [PubMed: 23307928] [Full Text: https://doi.org/10.1093/hmg/ddt004]
Vogel, T., Boettger-Tong, H., Nanda, I., Dechend, F., Agulnik, A. I., Bishop, C. E., Schmid, M., Schmidtke, J. A murine TSPY. Chromosome Res. 6: 35-40, 1998. Note: Erratum: Chromosome Res. 6: 241 only, 1998. [PubMed: 9510508] [Full Text: https://doi.org/10.1023/a:1009214307764]
Zhang, J. S., Yang-Feng, T. L., Muller, U., Mohandas, T. K., de Jong, P. J., Lau, Y.-F. C. Molecular isolation and characterization of an expressed gene from the human Y-chromosome. Hum. Molec. Genet. 1: 717-726, 1992. [PubMed: 1284595] [Full Text: https://doi.org/10.1093/hmg/1.9.717]