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Symbol MED12 contributors: mct - updated : 09-07-2018
HGNC name mediator complex subunit 12
HGNC id 11957
Corresponding disease
FGS1 FG syndrome 1
LJFS1 Lujan-Fryns syndrome 1
OHDOX Ohdo syndrome X-linked
Location Xq13.1      Physical location : 70.338.405 - 70.362.303
Synonym name
  • trinucleotide repeat containing 11 (THR-associated protein, 230kDa subunit)
  • thyroid hormone receptor-associated protein complex 230 kDa component (Trap230)
  • activator-recruited cofactor 240 kDa component (ARC240)
  • mediator of RNA polymerase II transcription, subunit 12 homolog (S. cerevisiae)
  • Trinucleotide repeat-containing gene 11 protein (THR-associated protein, 230 kDa subunit)
  • mediator complex subunit 12
  • OPA-containing protein
  • human opposite paired gene
  • Synonym symbol(s) OKS, FGS1, HOPA, CAGH45, TNRC11, TRAP230, KIAA0192, ARC240
    TYPE like-sequence
    SPECIAL FEATURE overlapping, gene in gene
    text last exon overlapping the putative promoter of NLGN3
    STRUCTURE 23.90 kb     45 Exon(s)
    MAPPING cloned Y linked N status provisional
    Map cen - DXS8107 - DXS8052 - MED12 - DXS8030 - DXS8101 - qter
    TRANSCRIPTS type messenger
    text two possible transcription initiation sites without TATA boxes upstream from the putative translation initiation start site
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    45 - 6985 230 2117 - 1997 9225980
    45 - 6966
    42 - 6383
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrainhindbrainmedulla oblongata highly
     brainforebraincerebral cortex highly
     brainhindbraincerebellum highly
     brainforebraincerebral lobefrontal lobehighly
     brainforebraincerebral lobeoccipital lobehighly
     braindiencephalonhypothalamus highly
     spinal cord   highly
    cell lineage
    cell lines
    at STAGE
    physiological period embryo, fetal
    Text fetal brain,lung, liver and kidney
  • N-terminal nuclear localization signal and N-terminally truncated protein is unable to enter the nucleus due to the lack of identified nuclear localization signal (NLS)
  • a dodecamer repeat
  • two overlapping ligand-dependent nuclear hormone receptor signature recognition motifs
  • a highly glutamine-rich C-terminal region resulting from the CAG repeats
    interspecies ortholog to Med12, Mus musculus
    ortholog to MED12, Pan troglodytes
    homolog to SRB8, Saccharomyces cerevisiae
  • mediator complex subunit 12 family
  • CATEGORY regulatory , transcription factor , receptor nuclear
    SUBCELLULAR LOCALIZATION     intracellular
  • in part cytoplasmic where it negatively regulates TGFBR2 through physical interaction
  • basic FUNCTION
  • involved in the regulated transcription of nearly all RNA polymerase II-dependent genes
  • acts as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and general transcription factors
  • coactivator for nuclear receptors
  • playing a regulatory role in vertebrate neuronal development
  • regulates the homeobox transcription factor NANOG fonctions
  • Med12-Med13-Cdk8-CycC subcomplex may be involved in
  • both positive and negative transcriptional regulation of all RNAPII promoters
  • essential for Nanog signaling and maintenance of ES cell pluripotency
  • Med12 and Nanog function together to regulate Nanog target gene promoters
  • has possible roles in development
  • controls the response to multiple cancer drugs through regulation of TGFBR signaling
  • involved in transcriptional regulation by conveying information from gene-specific regulatory elements to the RNA polymerase II transcription machinery
  • MED12 and KAT6B are chromatin-modifying enzymes implicated in Ohdo syndrome and the development of uterine leiomyomata and other tumors strongly suggests that both genes are functionally related
  • is an essential regulator of hematopoietic stem cell (HSC) homeostasis
  • alterations in MED12-dependent enhancer regulation may control both physiological and malignant hematopoiesis
  • MED12 plays a key role in the regulation of uterine fibroid cell line (HuLM) cell proliferation through the modulation of WNT/CTNNB1, cell cycle-associated, and fibrosis-associated protein expression
  • is an important molecular regulator of tumor dormancy in epithelial ovarian cancer (EOC)
  • CELLULAR PROCESS nucleotide, transcription, regulation
  • neurogenesis
  • transcription co-activator
    Wnt/beta-catenin pathway
    a component
  • subunit of TRAP thyroid hormone receptor-associated protein complex
  • component and a potential therapeutic target in the Wnt/beta-catenin pathway
  • part of CDK8 subcomplex” (containing CDK8, cyclin C, MED12, and MED13), functioning as a simple switch that controls the Mediator–pol II interaction to help regulate transcription initiation and reinitiation events (Knuesel 2009)
  • is a key component of the transcription-regulating Mediator complex
    RNA Homeobox transcription factor nanog Promoter
    small molecule
  • SOX9
  • CTNNB1 and GLI3
  • Med13 (TRAP240)
  • Cdk8 (SRB10)
  • CycC (SRB11)
  • Med12-Med13-Cdk8-CycC subcomplex interact with RNAPII
  • enzymatically active CDK8 is responsible for suppression of GLI3 transactivation activity, and further, MED12 most likely contributes to this suppression through its role as an anchor for CDK8 in Mediator
  • SOX10 functions during terminal differentiation of myelinating glia, at least in part by MED12-dependent recruitment of the Mediator complex
  • CDK8 and its paralog CDK19, in complex with CCNC, MED12 and MED13, are transcriptional regulators that mediate several carcinogenic pathways and the chemotherapy-induced tumor-supporting paracrine network
  • MED12 operates together with PRC1 to silence key developmental genes in pluripotency
  • JMJD6 is found to interact with MED12 in the mediator complex to regulate its recruitment
  • JMJD6 is necessary for MED12 to interact with CARM1, which methylates MED12 at multiple arginine sites and regulates its chromatin binding
  • JMJD6 is necessary for MED12 to interact with CARM1, which methylates MED12 at multiple arginine sites and regulates its chromatin binding
  • MED12 plays an important role in regulating dormancy of EOC (epithelial ovarian cancer) through regulation of EGFR
  • cell & other
    Other under tissue- or developmental-specific control
    corresponding disease(s) FGS1 , LJFS1 , OHDOX
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    in uterine leiomyomas
    tumoral somatic mutation      
    in prostate cancer
    tumoral germinal mutation      
    may likely contribute to chronic lymphocytic leukaemia (CLL) pathogenesis by activating NOTCH signalling
    tumoral somatic mutation      
    in 60p100 of breast fibroadenomas (FAs)
    Variant & Polymorphism
    Candidate gene for schizophrenia
    Therapy target
    potential therapeutic target in Alzheimer disease
  • med12-deficient zebrafish embryos showed defects in brain, neural crest, and kidney development and do not survive beyond 1 week after fertilization