Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Orphanet	Ensembl
	HGNC	UniGene	Nucleotide	OMIM		UCSC

Home Page

FLASH GENE

Symbol

MED12

contributors: mct - updated : 09-07-2018

HGNC name	mediator complex subunit 12
HGNC id	11957

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

DNA

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

RNA

TRANSCRIPTS	type	messenger

text	two possible transcription initiation sites without TATA boxes upstream from the putative translation initiation start site

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005120 45 - 6985 NP_005111 230 2117 - 1997 9225980 variant 2 45 - 6966 variant 3 42 - 6383

EXPRESSION

Type	ubiquitous

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Nervous brain hindbrain medulla oblongata   highly   brain forebrain cerebral cortex   highly   brain hindbrain cerebellum   highly   brain forebrain cerebral lobe frontal lobe highly   brain forebrain cerebral lobe occipital lobe highly   brain diencephalon hypothalamus   highly   spinal cord       highly

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, fetal

Text	fetal brain,lung, liver and kidney

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	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

HOMOLOGY

interspecies	ortholog to Med12, Mus musculus
	ortholog to MED12, Pan troglodytes
	homolog to SRB8, Saccharomyces cerevisiae

Homologene

FAMILY

mediator complex subunit 12 family

CATEGORY

regulatory , transcription factor , receptor nuclear

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm
	intracellular,nucleus,nucleoplasm
text	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

PHYSIOLOGICAL PROCESS

development

text	neurogenesis
	transcription co-activator

PATHWAY

metabolism

signaling

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

INTERACTION

DNA

RNA	Homeobox transcription factor nanog Promoter

small molecule

protein	SOX9
	CTNNB1 and GLI3
	HOMEOBOX TRANSCRIPTION FACTOR NANOG; NANOG
	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

REGULATION

Other

under tissue- or developmental-specific control

ASSOCIATED DISORDERS

corresponding disease(s)

FGS1 , LJFS1 , OHDOX

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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)

Susceptibility

Variant & Polymorphism

Candidate gene	for schizophrenia
Marker
Therapy target
	System Type Disorder Pubmed neurology neurodegenerative alzheimer potential therapeutic target in Alzheimer disease

ANIMAL & CELL MODELS

med12-deficient zebrafish embryos showed defects in brain, neural crest, and kidney development and do not survive beyond 1 week after fertilization