Alternative titles; symbols
HGNC Approved Gene Symbol: ZNF711
Cytogenetic location: Xq21.1 Genomic coordinates (GRCh38): X:85,243,991-85,273,357 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| Xq21.1 | Intellectual developmental disorder, X-linked 97 | 300803 | X-linked | 3 |
Habeebu et al. (1989) isolated 2 DNA sequences from a human testis cDNA library by screening with a probe containing zinc finger motifs.
Lloyd et al. (1991) noted that the ZNF6 gene is highly conserved across species. Dosage in male and female mice indicated that it is also X-linked in that species. ZFX (314980), ZFY, and ZNF6 may be derived from a common ancestral gene.
Using Southern blot analysis of genomic DNA from somatic cell hybrids containing various complements of autosomes and various deleted X chromosomes, Habeebu et al. (1989) mapped the CMPX1 gene to Xq13-q24. By in situ hybridization, analysis of somatic cell hybrids, and study of males carrying deleted X chromosomes, Lloyd et al. (1991) mapped the CMPX1 (ZNF6) gene to Xq21.1-q21.3. In situ hybridization showed that CMPX1 maps to the boundary between Xq13 and Xq21.
Lloyd et al. (1991) mapped the ZNF6 gene to the region in the proximal long arm of the X chromosome that shows homology to a region of the Y chromosome.
Tarpey et al. (2009) sequenced all exons of the X chromosome in 208 families segregating X-linked intellectual developmental disorder. Two families were identified as having truncating mutations in the ZNF711 gene (314990.0001 and 314990.0002). This form of nonspecific intellectual developmental disorder has been designated XLID97 (300803).
In affected males from 2 unrelated families with XLID97, van der Werf et al. (2017) identified hemizygous mutations in the ZNF711 gene (314990.0003 and 314990.0004). The mutations, which were found by a combination of linkage analysis and whole-exome sequencing, segregated with the disorder in the families. Patient cells showed differential expression of several genes known to be expressed in the brain compared to controls, consistent with the putative function of ZNF711 as a transcription factor.
Habeebu et al. (1989) reported that 5CMP1 maps to 2 distinct loci on chromosome 5, one on 5p14-p13 and the other on 5q12-q13. Habeebu et al. (1989) suggested the symbols TZF1 and TZF2 for the 2 zinc finger loci on chromosome 5 and XF1 for the locus on the X chromosome. The standing nomenclature committee of the Human Gene Mapping Workshops recommended ZNF4, ZNF5, and ZNF6 for these 3 loci, respectively. Scott (2007) stated that there was no supporting evidence for the loci designated ZNF4 and ZNF5.
In a family segregating X-linked intellectual developmental disorder-97 (XLID97; 300803), Tarpey et al. (2009) identified a 2-bp deletion, of TG, at nucleotide 2157 in the ZNF711 gene, resulting in frameshift and premature termination (719fsTer1). The mutation segregated with the phenotype.
In a large family segregating X-linked intellectual developmental disorder-97 (XLID97; 300803), Tarpey et al. (2009) identified a C-to-T transition at nucleotide 1573 of the ZNF711 gene, resulting in premature termination at arginine-525 (R525X). The mutation segregated with the phenotype in affected males.
In 3 affected males from a 4-generation Belgian family (family A) with X-linked intellectual developmental disorder-97 (XLID97; 300803), van der Werf et al. (2017) identified a 1-bp deletion (c.2054del, NM_021998.4) in the last exon of the ZNF711 gene, resulting in a frameshift and premature termination (Phe685SerfsTer7). The mutation, which was found by a combination of linkage analysis and whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in the ExAC database. The mutant transcript was predicted to escape nonsense-mediated mRNA decay.
In 6 affected males from a 3-generation family from the Netherlands (family B) with X-linked intellectual developmental disorder-97 (XLID97; 300803) originally reported by Yntema et al. (1999) as MRX65, van der Werf et al. (2017) identified a c.731T-C transition (c.731T-C, NM_021998.4) in the ZNF711 gene, resulting in an ile244-to-thr (I244T) substitution. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, fell within the previously identified linkage interval and segregated with the disorder in the family. It was not found in the ExAC database.
Habeebu, S. S. M., Gibson, J. E., Affara, N. A., Ferguson-Smith, M. A. Localization of two zinc finger protein genes to (a) two loci on chromosome 5 at 5p13-p14 and 5q12-q13 and to (b) the long arm of the X at Xq13-q21. (Abstract) Cytogenet. Cell Genet. 51: 1009 only, 1989.
Lloyd, S. L., Sargent, C. A., Chalmers, J., Lim, E., Habeebu, S. S. M., Affara, N. A. An X-linked zinc finger gene mapping to Xq21.1-q21.3 closely related to ZFX and ZFY: possible origins from a common ancestral gene. Nucleic Acids Res. 19: 4835-4841, 1991. [PubMed: 1923752] [Full Text: https://doi.org/10.1093/nar/19.18.4835]
Scott, A. F. Personal Communication. Baltimore, Md. 2/7/2007.
Tarpey, P. S., Smith, R., Pleasance, E., Whibley, A., Edkins, S., Hardy, C., O'Meara, S., Latimer, C., Dicks, E., Menzies, A., Stephens, P., Blow, M., and 67 others. A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation. Nature Genet. 41: 535-543, 2009. [PubMed: 19377476] [Full Text: https://doi.org/10.1038/ng.367]
van der Werf, I. M., Van Dijck, A., Reyniers, E., Helsmoortel, C., Kumar, A. A., Kalscheuer, V. M., de Brouwer, A. P. M., Kleefstra, T., van Bokhoven, H., Mortier, G., Janssens, S., Vandeweyer, G., Kooy, R. F. Mutations in two large pedigrees highlight the role of ZNF711 in X-linked intellectual disability. Gene 605: 92-98, 2017. [PubMed: 27993705] [Full Text: https://doi.org/10.1016/j.gene.2016.12.013]
Yntema, H. G., van den Helm, B., Knoers, N. V. A. M., Smits, A. P. T., van Roosmalen, T., Smeets, D. F. C. M., Mariman, E. C. M., van der Burgt, I., van Bokhoven, H., Ropers, H.-H., Kremer, H., Hamel, B. C. J. X-linked mental retardation: evidence for a recent mutation in a five-generation family (MRX65) linked to the pericentromeric region. Am. J. Med. Genet. 85: 305-308, 1999. [PubMed: 10398247] [Full Text: https://doi.org/10.1002/(sici)1096-8628(19990730)85:3<305::aid-ajmg22>3.0.co;2-5]