Alternative titles; symbols
HGNC Approved Gene Symbol: PRDM10
Cytogenetic location: 11q24.3 Genomic coordinates (GRCh38) : 11:129,899,711-130,002,835 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 11q24.3 | ?Birt-Hogg-Dube syndrome 2 | 620459 | Autosomal dominant | 3 |
PRDM10 belongs to a small family of zinc finger transcription factors called positive regulatory domain members (PRDMs). Other PRDMs include BLIMP1 (PRDM1; 603423) and RIZ (PRDM2; 601196) (Siegel et al., 2002).
Nagase et al. (1999) obtained a partial cDNA for PRDM10, which they called KIAA1231, from a fetal brain cDNA library. The deduced amino acid sequence shares homology with human ZNF45 (194554). RT-PCR ELISA of human tissues detected moderate PRDM10 expression in fetal liver and adult brain, kidney, ovary, and spinal cord. Expression was low or undetectable in all other adult and fetal tissues examined. PRDM10 showed moderate expression in all specific brain regions examined.
By PCR screening of a fetal brain cDNA library using probes based on cat Prdm10, Siegel et al. (2002) cloned full-length human PRDM10, which they called tristanin. The deduced 1,023-amino acid human protein contains an N-terminal positive regulatory domain (PRD), followed by 10 Kruppel-type (CCHH) zinc finger motifs. Database analysis suggested the existence of multiple PRDM10 splice variants. Northern and Western blot analyses of mouse and cat brain revealed multiple Prdm10 splice variants and protein isoforms that appeared to be developmentally regulated, with some variants and isoforms upregulated in newborns compared with adults. In addition to brain, Prdm10 protein isoforms were detected in mouse liver, kidney, spleen, and thymus. Immunohistochemical analysis demonstrated punctate expression of Prdm10 throughout the neuron cell body in newborn kittens and mice, but this expression disappeared by adulthood.
Using radiation hybrid analysis, Nagase et al. (1999) mapped the PRDM10 gene to chromosome 11.
Gross (2019) mapped the PRDM10 gene to chromosome 11q24.3 based on an alignment of the PRDM10 sequence (GenBank BC112934) with the genomic sequence (GRCh38).
Siegel et al. (2002) found that a small variant of Prdm10 was upregulated in a cat model of GM2 gangliosidosis (see 272800). Immunohistochemical analysis also showed retention of Prdm10 in nuclei of cortical neurons in diseased, but not healthy, 3-month-old cats. The authors hypothesized that PRDM10 may be involved in dendritogenesis based on its upregulation in developing brain and the gangliosidosis model.
In affected members of a 4-generation Dutch family with Birt-Hogg-Dube syndrome-2 (BHD2; 620459), who had multiple lipomas and fibrofolliculomas as well as renal cell carcinoma and other cancers, van de Beek et al. (2023) identified heterozygosity for a missense mutation in the PRDM10 gene (C677Y; 618319.0001) that segregated fully with disease. Functional analysis identified PRDM10 as an upstream regulator of the tumor suppressor gene folliculin (FLCN; 607273).
In 6 affected members of a 4-generation Dutch family with multiple lipomas and fibrofolliculomas as well as renal cell carcinoma and other cancers (BHD2; 620459), van de Beek et al. (2023) identified heterozygosity for a c.2030G-A transition (c.2030G-A, NM_020228.3) in the PRDM10 gene, resulting in a cys677-to-tyr (C677Y) substitution at a highly conserved residue within the seventh C2H2 zinc finger domain. The variant segregated fully with disease in the family and was found in the gnomAD database (v2.1.1) at an allele frequency of 4.8e-4%. In vitro analysis of HEK293T cells homozygous for C677Y or wildtype PRDM10 showed higher expression of mutant mRNA and protein than wildtype PRDM10, and there was a significant decrease in FLCN (607273) expression in the mutant cells. Western blot analysis confirmed that folliculin protein was almost undetectable in mutant cells. HEK293T cell lines with knockout of FLCN or homozygous for the PRDM10 C677Y mutation displayed similar rates of slower growth compared to wildtype cells. Chromatin immunoprecipitation qPCR demonstrated a marked reduction in FLCN promoter binding with the C677Y mutant compared to wildtype PRDM10. In renal epithelial cells with knockout of FLCN or induced overexpression of the C677Y mutant, analysis of transcriptional effects showed overlap but gene expression patterns were not identical.
Gross, M. B. Personal Communication. Baltimore, Md. 2/7/2019.
Nagase, T., Ishikawa, K., Kikuno, R., Hirosawa, M., Nomura, N., Ohara, O. Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 6: 337-345, 1999. [PubMed: 10574462] [Full Text: https://doi.org/10.1093/dnares/6.5.337]
Siegel, D. A., Huang, M. K., Becker, S. F. Ectopic dendrite initiation: CNS pathogenesis as a model of CNS development. Int. J. Dev. Neurosci. 20: 373-389, 2002. Note: Erratum: Int. J. Dev. Neurosci. 21: 169-170, 2003. [PubMed: 12175877] [Full Text: https://doi.org/10.1016/s0736-5748(02)00055-2]
van de Beek, I., Glykofridis, I. E., Oosterwijk, J. C., van den Akker, P. C., Diercks, G. F. H., Bolling, M. C., Waisfisz, Q., Mensenkamp, A. R., Balk, J. A., Zwart, R., Postma, A. V., Meijers-Heijboer, H. E. J., van Moorselaar, R. J. A., Wolthuis, R. M. F., Houweling, A. C. PRDM10 directs FLCN expression in a novel disorder overlapping with Birt-Hogg-Dube syndrome and familial lipomatosis. Hum. Molec. Genet. 32: 1223-1235, 2023. [PubMed: 36440963] [Full Text: https://doi.org/10.1093/hmg/ddac288]