HGNC Approved Gene Symbol: ZNF81
Cytogenetic location: Xp11.23 Genomic coordinates (GRCh38): X:47,836,902-47,925,627 (from NCBI)
Marino et al. (1993) isolated a novel zinc finger protein gene (ZNF81) from an X chromosome-specific library. The pattern of segregation in human-hamster somatic cell hybrids with various deletions established that the gene resides within the Xp22.1-p11 region.
Knight et al. (1994) confirmed the assignment to Xp22.11-p11.23 in a region occupied also by ZNF21 (314993) and ZNF41 (314995) by demonstrating that they were located in the same YAC contig spanning approximately 1.5 Mb of DNA. The ELK1 gene (311040) was shown to be linked to the PFC gene (300383), which had previously been shown to be in a cluster with ARAF1 (311010), SYN1 (313440), and TIMP (305370); all 5 genes were contained within a distance of 120 kb. ZNF21 and ZNF81 lay 150 kb distal to the chromosomal breakpoint associated with synovial sarcoma (312820).
Kleefstra et al. (2004) characterized the breakpoints of a de novo translocation, t(X;9)(p11.23;q34.3), in a female patient with severe mental retardation and found that the translocation disrupted the ZNF81 gene. Mutation analysis in more than 300 families and patients with nonspecific X-linked mental retardation revealed a ser179-to-asn substitution (314998.0001) in ZNF81 in family MRX45 (300498), reported by Hamel et al. (1999), that fully segregated with the phenotype.
This variant, previously designated MENTAL RETARDATION, X-LINKED 45, has been reclassified based on a review of the ExAC database by Hamosh (2017).
In affected members of family MRX45 (300498) reported by Hamel et al. (1999), Kleefstra et al. (2004) identified a 536G-A transition in the ZNF81 gene, resulting in a ser179-to-asn (S179N) substitution. The mutation segregated with the disorder in the family and was not detected in 451 X chromosomes of controls.
The S179N variant was found in 4 males and in 8 of 81,134 alleles in the ExAC database (February 22, 2017), suggesting that it is not pathogenic (Hamosh, 2017).
Hamel, B. C. J., Smits, A. P. T., van den Helm, B., Smeets, D. F. C. M., Knoers, N. V. A. M., van Roosmalen, T., Thoonen, G. H. J., Assman-Hulsmans, C. F. C. H., Ropers, H.-H., Mariman, E. C. M., Kremer, H. Four families (MRX43, MRX44, MRX45, MRX52) with nonspecific X-linked mental retardation: clinical and psychometric data and results of linkage analysis. Am. J. Med. Genet. 85: 290-304, 1999. [PubMed: 10398246]
Hamosh, A. Personal Communication. Baltimore, Md. February 22, 2017.
Kleefstra, T., Yntema, H. G., Oudakker, A. R., Banning, M. J. G., Kalscheuer, V. M., Chelly, J., Moraine, C., Ropers, H.-H., Fryns, J.-P., Janssen, I. M., Sistermans, E. A., Nillesen, W. N., de Vries, L. B. A., Hamel, B. C. J., van Bokhoven, H. Zinc finger 81 (ZNF81) mutations associated with X-linked mental retardation. (Letter) J. Med. Genet. 41: 394-399, 2004. [PubMed: 15121780] [Full Text: https://doi.org/10.1136/jmg.2003.016972]
Knight, J. C., Grimaldi, G., Thiesen, H.-J., Bech-Hansen, N. T., Fletcher, C. D. M., Coleman, M. P. Clustered organization of Kruppel zinc-finger genes at Xp11.23, flanking a translocation breakpoint at OATL1: a physical map with locus assignments for ZNF21, ZNF41, ZNF81, and ELK1. Genomics 21: 180-187, 1994. [PubMed: 8088786] [Full Text: https://doi.org/10.1006/geno.1994.1240]
Marino, M., Archidiacono, N., Franze, A., Rosati, M., Rocchi, M., Ballabio, A., Grimaldi, G. A novel X-linked member of the human zinc finger protein gene family: isolation, mapping, and expression. Mammalian Genome 4: 252-257, 1993. [PubMed: 8507979] [Full Text: https://doi.org/10.1007/BF00417431]