Alternative titles; symbols
HGNC Approved Gene Symbol: ZPBP
Cytogenetic location: 7p12.2 Genomic coordinates (GRCh38) : 7:49,840,654-50,093,246 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 7p12.2 | ?Spermatogenic failure 66 | 619799 | Autosomal recessive | 3 |
ZPBP is one of several proteins that are thought to participate in secondary binding between acrosome-reacted sperm and the egg-specific extracellular matrix, the zona pellucida (McLeskey et al., 1998).
Katoh and Katoh (2003) determined that the deduced 351-amino acid ZPBP protein has no N-terminal signal peptide, but contains an N-terminal transmembrane domain and a long extracellular domain of almost 300 amino acids. The extracellular domain shares 38.1% identity with a homologous domain within ZPBP2 (608499), including 15 conserved Cys residues. Analysis of EST databases indicated that ZPBP mRNA was coexpressed with ZPBP2 mRNA in testis, germ cell tumor, and brain medulla.
By immunohistochemistry, Oud et al. (2020) demonstrated localization of ZPBP to the acrosome in human spermatids.
Katoh and Katoh (2003) stated that the ZPBP gene maps to chromosome 7p12. Other genes at this locus include ZNFN1A1 (603023), GRB10 (601523), and EGFR (131550). Comparative genomics revealed that this locus is paralogous to the locus on chromosome 17q that contains ZPBP2.
Yu et al. (2009) noted that ZPBP, which they called IAM38, is the most abundant protein of the inner acrosomal membrane extracellular coat of mammalian spermatozoa and remains in the membrane after the acrosome reaction. By Northern blot and immunocytochemical analyses of mouse, rat, and bull testis, Yu et al. (2009) studied the origin and assembly of Iam38 during spermiogenesis. They found that Iam38 originated in the acrosome granule and redistributed to the acrosomal membrane during acrosome formation. Iam38 localized on the extracellular side of both the inner and outer acrosomal membrane during the cap phase of acrosomal development, supporting a role for Iam38 in acrosomal compaction. The authors noted that failure in compaction in Iam38 -/- mice (see ANIMAL MODEL) coincided with the time that Iam38 is normally distributed along the inner acrosome membrane, suggesting that Iam38 may be involved in creating a lattice that brings the sides of the vesicle together.
In a Moroccan man with infertility due to globozoospermia (SPGF66; 619799), Oud et al. (2020) identified homozygosity for a nonsense mutation in the ZPBP gene (Q311X; 608498.0001). The mutation segregated with disease in the family and was not found in public variant databases.
Lin et al. (2007) disrupted Zpbp1 or Zpbp2 in mice. Loss of Zpbp1 resulted in male sterility with abnormal round-headed sperm morphology and no forward sperm motility. Ultrastructural analysis demonstrated that absence of Zpbp1 prevented proper acrosome compaction, leading to acrosome fragmentation and disruption of Sertoli-spermatid junctions. Males lacking Zpbp2 were subfertile, with aberrant acrosomal membrane invaginations, and they produced dysmorphic sperm with reduced ability to penetrate zona pellucida. Phylogenetic analysis suggested that the 2 paralogous ZPBP genes coevolved to play cooperative roles during spermiogenesis. Lin et al. (2007) concluded that both ZPBP proteins play an early structural role during spermiogenesis.
In a Moroccan man (GL-11) with infertility due to globozoospermia (SPGF66; 619799), Oud et al. (2020) identified homozygosity for a c.931C-T transition (c.931C-T, NM_007009.2) in the ZPBP gene, resulting in a gln311-to-ter (Q311X) substitution predicted to result in a truncated protein lacking the last 40 amino acids of the conserved SP38 domain. The variant was located in a 24-Mb region of homozygosity on chromosome 7. The proband's mother and 2 fertile brothers were heterozygous for the mutation, which was not found in the gnomAD database. DNA was unavailable from the proband's 2 infertile brothers or his father.
Katoh, M., Katoh, M. Identification and characterization of human ZPBP-like gene in silico. Int. J. Molec. Med. 12: 399-404, 2003. [PubMed: 12883658]
Lin, Y.-N., Roy, A., Yan, W., Burns, K. H., Matzuk, M. M. Loss of zona pellucida proteins in the acrosomal matrix disrupts acrosome biogenesis and sperm morphogenesis. Molec. Cell. Biol. 27: 6794-6805, 2007. Note: Erratum: Molec. Cell. Biol. 28: 2495 only, 2008. [PubMed: 17664285] [Full Text: https://doi.org/10.1128/MCB.01029-07]
McLeskey, S. B., Dowds, C., Carballada, R., White, R. R., Saling, P. M. Molecules involved in mammalian sperm-egg interaction. Int. Rev. Cytol. 177: 57-113, 1998. [PubMed: 9378618] [Full Text: https://doi.org/10.1016/s0074-7696(08)62231-7]
Oud, M. S., Okutman, O., Hendricks, L. A. J., de Vries, P. F., Houston, B. J., Vissers, L. E. L. M., O'Bryan, M. K., Ramos, L., Chemes, H. E., Viville, S., Veltman, J. A. Exome sequencing reveals novel causes as well as new candidate genes for human globozoospermia. Hum. Reprod. 35: 240-252, 2020. [PubMed: 31985809] [Full Text: https://doi.org/10.1093/humrep/dez246]
Yu, Y., Vanhorne, J., Oko, R. The origin and assembly of a zona pellucida binding protein, IAM38, during spermiogenesis. Microsc. Res. Tech. 72: 558-565, 2009. [PubMed: 19204925] [Full Text: https://doi.org/10.1002/jemt.20696]