Alternative titles; symbols
HGNC Approved Gene Symbol: MED20
Cytogenetic location: 6p21.1 Genomic coordinates (GRCh38) : 6:41,905,354-41,921,139 (from NCBI)
MED20 is a subunit of the Mediator complex, a multiprotein coactivator of RNA transcription that interacts with DNA-bound transcriptional activators, RNA polymerase II (see 180660), and general initiation factors (Sato et al., 2003).
By sequencing peptides from a protein coimmunoprecipitated with SRB7 (MED21; 603800) from HeLa cell nuclear extracts, followed by database analysis, Xiao et al. (1999) identified MED20, which they called TRFP. The deduced 209-amino acid protein shares 44% amino identity with Drosophila Trfp. TRFP had an apparent molecular mass of 28 kD by SDS-PAGE.
Xiao et al. (1999) identified TRFP as a component of an RNA polymerase II-SRB complex. The TRFP-containing complex could substitute for core RNA polymerase II in driving basal transcription from a minimal promoter.
By coexpression of epitope-tagged Mediator subunits, Sato et al. (2003) found that TRFP appeared to bridge an interaction between the Mediator subunits MED29 (612914) and p28b (MED18; 612384).
Hartz (2009) mapped the MED20 gene to chromosome 6p21.1 based on an alignment of the MED20 sequence (GenBank AF097725) with the genomic sequence (build 36.1).
For discussion of a possible role of variation in the MED20 gene in a neurodegenerative disorder characterized by infantile-onset basal ganglia degeneration and brain atrophy, see 612915.0001.
This variant is classified as a variant of unknown significance because its contribution to infantile-onset basal ganglia degeneration and brain atrophy has not been confirmed.
In 2 affected sisters from a consanguineous Austrian family with infantile-onset basal ganglia degeneration and brain atrophy, Vodopiutz et al. (2015) identified a homozygous c.341G-C transversion in the MED20 gene, resulting in a gly114-to-ala (G114A) substitution at a highly conserved residue in a beta-strand within the head domain of the Mediator complex. The mutation, which was found by a combination of homozygosity mapping and exome sequencing, was confirmed by Sanger sequencing and segregated with the disorder in the family. It was not present in public sequence variant databases, 300 healthy controls, or 60 in-house exomes. Functional studies of the variant were not performed. The patients had a progressive neurodegenerative disorder characterized by severely delayed psychomotor development, spasticity, and dystonia. One patient had progressive microcephaly during childhood. Brain imaging of both patients showed parenchymal and cerebellar atrophy and T2-weighted hyperintensities in the basal ganglia. No MED20 mutations were found in 6 additional unrelated patients with a similar disorder.
Hartz, P. A. Personal Communication. Baltimore, Md. 7/16/2009.
Sato, S., Tomomori-Sato, C., Banks, C. A. S., Parmely, T. J., Sorokina, I., Brower, C. S., Conaway, R. C., Conaway, J. W. A mammalian homolog of Drosophila melanogaster transcriptional coactivator Intersex is a subunit of the mammalian Mediator complex. J. Biol. Chem. 278: 49671-49674, 2003. [PubMed: 14576168] [Full Text: https://doi.org/10.1074/jbc.C300444200]
Vodopiutz, J., Schmook, M. T., Konstantopoulou, V., Plecko, B., Greber-Platzer, S., Creus, M., Seidl, R., Janecke, A. R. MED20 mutation associated with infantile basal ganglia degeneration and brain atrophy. Europ. J. Pediat. 174: 113-118, 2015. [PubMed: 25446406] [Full Text: https://doi.org/10.1007/s00431-014-2463-7]
Xiao, H., Tao, Y., Roeder, R. G. The human homologue of Drosophila TRF-proximal protein is associated with an RNA polymerase II-SRB complex. J. Biol. Chem. 274: 3937-3940, 1999. [PubMed: 9933582] [Full Text: https://doi.org/10.1074/jbc.274.7.3937]