Molecular characteristics

The MED12 gene encodes MED12 which is a subunit of the Mediator protein complex that is involved in the interaction between transcription factors and RNA polymerase II.  Mediator can be involved in both repression and activation of transcription.

The following conditions have been found to be caused by distinct MED12 variants (typically missense):

  • FG syndrome is typically due to a recurrent pathogenic p.Arg961Trp missense variant. A p.Gly958Glu pathogenic missense variant in MED12 was reported in a few individuals with features of FG syndrome.
  • A recurrent pathogenic p.Asn1007Ser missense variant in MED12 is the cause of Lujan syndrome.
  • Multiple missense variants (p.Arg1148His, p.Ser1165Pro, p.His1729Asn) have been reported to cause X-linked Ohdo syndrome.
  • Individuals with nonsyndromic intellectual disability distinct from the recognizable syndromes linked to MED12 have been found to be caused by a number of different missense variants (p.Gln1974His, p.Ala1383Thr, p.Arg815Gln, p.Ile1023Val) along with one reported frameshift variant (p.Ser1967GlnfsTer84).