Seroatlas · Human Serome Atlas

MED12

Mediator of RNA polymerase II transcription subunit 12

Also known as: ARC240, CAGH45, FGS1, HOPA, KIAA0192, Kto, MED12_HUMAN, OKS, OPA1, TNRC11, TRAP230

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q93074
Gene: MED12
Ensembl: ENSG00000184634
Chromosome: X
Canonical length: 2177 aa
Protein class: Cancer-related genes, Disease related genes, Human disease related genes, Predicted intracellular proteins
Subcellular location: Nucleoplasm

OverviewNCBI Gene

The initiation of transcription is controlled in part by a large protein assembly known as the preinitiation complex. A component of this preinitiation complex is a 1.2 MDa protein aggregate called Mediator. This Mediator component binds with a CDK8 subcomplex which contains the protein encoded by this gene, mediator complex subunit 12 (MED12), along with MED13, CDK8 kinase, and cyclin C. The CDK8 subcomplex modulates Mediator-polymerase II interactions and thereby regulates transcription initiation and reinitation rates. The MED12 protein is essential for activating CDK8 kinase. Defects in this gene cause X-linked Opitz-Kaveggia syndrome, also known as FG syndrome, and Lujan-Fryns syndrome. [provided by RefSeq, Aug 2009]

Canonical amino-acid sequenceUniProt

2177 residues, UniProt reviewed canonical sequence.

>Q93074|MED12
     1  MAAFGILSYE HRPLKRPRLG PPDVYPQDPK QKEDELTALN VKQGFNNQPA VSGDEHGSAK
    61  NVSFNPAKIS SNFSSIIAEK LRCNTLPDTG RRKPQVNQKD NFWLVTARSQ SAINTWFTDL
   121  AGTKPLTQLA KKVPIFSKKE EVFGYLAKYT VPVMRAAWLI KMTCAYYAAI SETKVKKRHV
   181  DPFMEWTQII TKYLWEQLQK MAEYYRPGPA GSGGCGSTIG PLPHDVEVAI RQWDYTEKLA
   241  MFMFQDGMLD RHEFLTWVLE CFEKIRPGED ELLKLLLPLL LRYSGEFVQS AYLSRRLAYF
   301  CTRRLALQLD GVSSHSSHVI SAQSTSTLPT TPAPQPPTSS TPSTPFSDLL MCPQHRPLVF
   361  GLSCILQTIL LCCPSALVWH YSLTDSRIKT GSPLDHLPIA PSNLPMPEGN SAFTQQVRAK
   421  LREIEQQIKE RGQAVEVRWS FDKCQEATAG FTIGRVLHTL EVLDSHSFER SDFSNSLDSL
   481  CNRIFGLGPS KDGHEISSDD DAVVSLLCEW AVSCKRSGRH RAMVVAKLLE KRQAEIEAER
   541  CGESEAADEK GSIASGSLSA PSAPIFQDVL LQFLDTQAPM LTDPRSESER VEFFNLVLLF
   601  CELIRHDVFS HNMYTCTLIS RGDLAFGAPG PRPPSPFDDP ADDPEHKEAE GSSSSKLEDP
   661  GLSESMDIDP SSSVLFEDME KPDFSLFSPT MPCEGKGSPS PEKPDVEKEV KPPPKEKIEG
   721  TLGVLYDQPR HVQYATHFPI PQEESCSHEC NQRLVVLFGV GKQRDDARHA IKKITKDILK
   781  VLNRKGTAET DQLAPIVPLN PGDLTFLGGE DGQKRRRNRP EAFPTAEDIF AKFQHLSHYD
   841  QHQVTAQVSR NVLEQITSFA LGMSYHLPLV QHVQFIFDLM EYSLSISGLI DFAIQLLNEL
   901  SVVEAELLLK SSDLVGSYTT SLCLCIVAVL RHYHACLILN QDQMAQVFEG LCGVVKHGMN
   961  RSDGSSAERC ILAYLYDLYT SCSHLKNKFG ELFSDFCSKV KNTIYCNVEP SESNMRWAPE
  1021  FMIDTLENPA AHTFTYTGLG KSLSENPANR YSFVCNALMH VCVGHHDPDR VNDIAILCAE
  1081  LTGYCKSLSA EWLGVLKALC CSSNNGTCGF NDLLCNVDVS DLSFHDSLAT FVAILIARQC
  1141  LLLEDLIRCA AIPSLLNAAC SEQDSEPGAR LTCRILLHLF KTPQLNPCQS DGNKPTVGIR
  1201  SSCDRHLLAA SQNRIVDGAV FAVLKAVFVL GDAELKGSGF TVTGGTEELP EEEGGGGSGG
  1261  RRQGGRNISV ETASLDVYAK YVLRSICQQE WVGERCLKSL CEDSNDLQDP VLSSAQAQRL
  1321  MQLICYPHRL LDNEDGENPQ RQRIKRILQN LDQWTMRQSS LELQLMIKQT PNNEMNSLLE
  1381  NIAKATIEVF QQSAETGSSS GSTASNMPSS SKTKPVLSSL ERSGVWLVAP LIAKLPTSVQ
  1441  GHVLKAAGEE LEKGQHLGSS SRKERDRQKQ KSMSLLSQQP FLSLVLTCLK GQDEQREGLL
  1501  TSLYSQVHQI VNNWRDDQYL DDCKPKQLMH EALKLRLNLV GGMFDTVQRS TQQTTEWAML
  1561  LLEIIISGTV DMQSNNELFT TVLDMLSVLI NGTLAADMSS ISQGSMEENK RAYMNLAKKL
  1621  QKELGERQSD SLEKVRQLLP LPKQTRDVIT CEPQGSLIDT KGNKIAGFDS IFKKEGLQVS
  1681  TKQKISPWDL FEGLKPSAPL SWGWFGTVRV DRRVARGEEQ QRLLLYHTHL RPRPRAYYLE
  1741  PLPLPPEDEE PPAPTLLEPE KKAPEPPKTD KPGAAPPSTE ERKKKSTKGK KRSQPATKTE
  1801  DYGMGPGRSG PYGVTVPPDL LHHPNPGSIT HLNYRQGSIG LYTQNQPLPA GGPRVDPYRP
  1861  VRLPMQKLPT RPTYPGVLPT TMTGVMGLEP SSYKTSVYRQ QQPAVPQGQR LRQQLQQSQG
  1921  MLGQSSVHQM TPSSSYGLQT SQGYTPYVSH VGLQQHTGPA GTMVPPSYSS QPYQSTHPST
  1981  NPTLVDPTRH LQQRPSGYVH QQAPTYGHGL TSTQRFSHQT LQQTPMISTM TPMSAQGVQA
  2041  GVRSTAILPE QQQQQQQQQQ QQQQQQQQQQ QQQQQQYHIR QQQQQQILRQ QQQQQQQQQQ
  2101  QQQQQQQQQQ QQQQQHQQQQ QQQAAPPQPQ PQSQPQFQRQ GLQQTQQQQQ TAALVRQLQQ
  2161  QLSNTQPQPS TNIFGRY

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MED12 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Intracellular
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.41
Highest tissue expression: 14 nTPM

Expression across tissuesHPA

Tissue

thymus: 14 nTPM
ovary: 13 nTPM
parathyroid gland: 11 nTPM
placenta: 11 nTPM
adrenal gland: 11 nTPM
spleen: 11 nTPM

Single-cell type

neutrophils: 55 nCPM
syncytiotrophoblasts: 33 nCPM
cytotrophoblasts: 28 nCPM
sertoli cells: 27 nCPM
neutrophil progenitors: 25 nCPM
erythrocyte progenitors: 24 nCPM

Immune cell

T-reg: 3 nTPM
gdT-cell: 2.3 nTPM
plasmacytoid DC: 2.3 nTPM
memory CD8 T-cell: 2.1 nTPM
MAIT T-cell: 2 nTPM
naive CD8 T-cell: 1.8 nTPM

Brain region

cerebral cortex: 13 nTPM
medulla oblongata: 12 nTPM
pons: 12 nTPM
midbrain: 12 nTPM
cerebellum: 12 nTPM
spinal cord: 12 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MED12.

Disease | AllUniProt

Conditions MED12 is implicated in, by any mechanism.

Opitz-Kaveggia syndrome (OKS) MIM:305450
Intellectual developmental disorder, X-linked, syndromic, Lujan-Fryns type (MRXSLF) MIM:309520
Ohdo syndrome, X-linked (OHDOX) MIM:300895
Hardikar syndrome (HDKR) MIM:301068

Disease | GeneticClinVar

91 pathogenic / likely-pathogenic of 2,545 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

FG syndrome 1
Blepharophimosis - intellectual disability syndrome, MKB type
Cholestasis-pigmentary retinopathy-cleft palate syndrome
FG syndrome
MED12-Related Disorders

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.07
gnomAD pLI: 1
gnomAD missense Z: 6.58
DepMap mean gene effect: -0.53
DepMap dependency class: common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of MED12 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads MED12 as an antibody target. Whether an autoantibody or antibody against MED12 could matter depends on whether native MED12 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

MED12 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label MED12 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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