Incidental Mutation 'IGL03006:Med12'
ID 407567
Institutional Source Australian Phenomics Network (link to record)
Gene Symbol Med12
Ensembl Gene ENSMUSG00000079487
Gene Name mediator complex subunit 12
Synonyms Tnrc11, Mopa, OPA-1, Trap230
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # IGL03006
Quality Score
Status
Chromosome X
Chromosomal Location 100317636-100341071 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to T at 100321684 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Arginine to Tryptophan at position 456 (R456W)
Ref Sequence ENSEMBL: ENSMUSP00000112729 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000087948] [ENSMUST00000087956] [ENSMUST00000117203] [ENSMUST00000117706]
AlphaFold A2AGH6
Predicted Effect probably damaging
Transcript: ENSMUST00000087948
AA Change: R456W

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000085260
Gene: ENSMUSG00000079487
AA Change: R456W

DomainStartEndE-ValueType
Med12 101 161 2.98e-24 SMART
low complexity region 273 282 N/A INTRINSIC
Pfam:Med12-LCEWAV 287 758 1.5e-184 PFAM
low complexity region 1220 1231 N/A INTRINSIC
low complexity region 1245 1267 N/A INTRINSIC
low complexity region 1394 1412 N/A INTRINSIC
low complexity region 1469 1480 N/A INTRINSIC
low complexity region 1732 1774 N/A INTRINSIC
low complexity region 1780 1794 N/A INTRINSIC
Pfam:Med12-PQL 1821 2024 1.2e-79 PFAM
SCOP:d1bg1a1 2056 2129 3e-4 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000087956
AA Change: R456W

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000085269
Gene: ENSMUSG00000079487
AA Change: R456W

DomainStartEndE-ValueType
Med12 101 161 2.98e-24 SMART
low complexity region 273 282 N/A INTRINSIC
Pfam:Med12-LCEWAV 286 758 1.8e-213 PFAM
low complexity region 1220 1231 N/A INTRINSIC
low complexity region 1245 1267 N/A INTRINSIC
low complexity region 1394 1412 N/A INTRINSIC
low complexity region 1469 1480 N/A INTRINSIC
low complexity region 1732 1774 N/A INTRINSIC
low complexity region 1780 1794 N/A INTRINSIC
Pfam:Med12-PQL 1819 1970 1.5e-57 PFAM
Pfam:Med12-PQL 1968 2004 5.7e-18 PFAM
SCOP:d1bg1a1 2035 2108 4e-4 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000117203
AA Change: R456W

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000112729
Gene: ENSMUSG00000079487
AA Change: R456W

DomainStartEndE-ValueType
Med12 101 161 2.98e-24 SMART
low complexity region 273 282 N/A INTRINSIC
Pfam:Med12-LCEWAV 286 758 3.8e-214 PFAM
low complexity region 1220 1231 N/A INTRINSIC
low complexity region 1245 1267 N/A INTRINSIC
low complexity region 1394 1412 N/A INTRINSIC
low complexity region 1469 1480 N/A INTRINSIC
low complexity region 1732 1774 N/A INTRINSIC
low complexity region 1780 1794 N/A INTRINSIC
Pfam:Med12-PQL 1819 2025 1.5e-100 PFAM
SCOP:d1lsha3 2048 2107 4e-4 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000117706
AA Change: R456W

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000112852
Gene: ENSMUSG00000079487
AA Change: R456W

DomainStartEndE-ValueType
Med12 101 161 2.98e-24 SMART
low complexity region 273 282 N/A INTRINSIC
Pfam:Med12-LCEWAV 286 758 3.7e-214 PFAM
low complexity region 1220 1231 N/A INTRINSIC
low complexity region 1245 1267 N/A INTRINSIC
low complexity region 1394 1412 N/A INTRINSIC
low complexity region 1469 1480 N/A INTRINSIC
low complexity region 1732 1774 N/A INTRINSIC
low complexity region 1780 1794 N/A INTRINSIC
Pfam:Med12-PQL 1819 1966 7.5e-63 PFAM
Pfam:Med12-PQL 1964 2000 1.1e-18 PFAM
SCOP:d1lsha3 2023 2082 4e-4 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000156131
Coding Region Coverage
Validation Efficiency
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] 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]
PHENOTYPE: Male chimeras hemizygous for a null allele arrest at E7.5 and lack anterior visceral endoderm. Male chimeras hemizygous for a hypomorphic allele die at E10.5 showing failure of neural crest cell migration and severe defects in neural tube closure, axis elongation, somitogenesis and heart formation. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 44 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700012B07Rik T A 11: 109,718,671 (GRCm39) S21C probably damaging Het
2210408I21Rik T C 13: 77,471,891 (GRCm39) probably null Het
Abcc3 T C 11: 94,259,421 (GRCm39) D340G probably benign Het
Adamts17 G T 7: 66,728,095 (GRCm39) R879L possibly damaging Het
Adissp A C 2: 130,993,634 (GRCm39) D22E probably damaging Het
Cacna1f C A X: 7,493,142 (GRCm39) T1275K probably damaging Het
Csmd2 T A 4: 128,374,558 (GRCm39) probably benign Het
Dll1 C T 17: 15,593,854 (GRCm39) R171Q probably benign Het
Dnm1 T A 2: 32,243,133 (GRCm39) D30V possibly damaging Het
Fam184a G A 10: 53,574,793 (GRCm39) S216L probably damaging Het
Fbxo33 G A 12: 59,251,105 (GRCm39) A470V probably benign Het
Gm6401 C T 14: 41,788,851 (GRCm39) E73K possibly damaging Het
Ighv7-1 A T 12: 113,860,145 (GRCm39) S82R probably damaging Het
Klk1b4 A G 7: 43,861,019 (GRCm39) I221V probably benign Het
Lama3 T C 18: 12,601,425 (GRCm39) probably benign Het
Lrch1 A G 14: 75,051,060 (GRCm39) L359P probably damaging Het
Mapk8ip3 T C 17: 25,120,489 (GRCm39) T882A probably benign Het
Mms22l T C 4: 24,521,253 (GRCm39) S267P probably damaging Het
Mtpap G A 18: 4,375,721 (GRCm39) G34R possibly damaging Het
Nf1 G A 11: 79,436,257 (GRCm39) D1966N probably damaging Het
Nlrp9c G A 7: 26,071,507 (GRCm39) T867I probably damaging Het
Nrap C T 19: 56,335,596 (GRCm39) V941I probably benign Het
Or5k1b T A 16: 58,581,511 (GRCm39) K9N probably benign Het
Pcdh10 A G 3: 45,333,937 (GRCm39) I84V probably damaging Het
Polr3d T A 14: 70,678,603 (GRCm39) probably null Het
Prkar2a G T 9: 108,617,640 (GRCm39) V233L probably benign Het
Prl4a1 T C 13: 28,207,359 (GRCm39) V211A probably damaging Het
Qpct T C 17: 79,378,151 (GRCm39) V107A probably benign Het
Rai1 T C 11: 60,079,031 (GRCm39) S1032P possibly damaging Het
Rims1 G T 1: 22,367,178 (GRCm39) T1113K probably damaging Het
Rxra C T 2: 27,649,657 (GRCm39) T454I probably damaging Het
S100z T C 13: 95,615,127 (GRCm39) I13V probably damaging Het
Scp2 T C 4: 107,948,477 (GRCm39) K167E probably benign Het
Sephs2 A G 7: 126,872,206 (GRCm39) F296L probably benign Het
Setd1b A G 5: 123,286,514 (GRCm39) E520G unknown Het
Slc28a2 G A 2: 122,283,019 (GRCm39) V308M possibly damaging Het
Smarcad1 T A 6: 65,060,873 (GRCm39) I451K probably benign Het
Tarbp1 C T 8: 127,170,881 (GRCm39) D1040N probably damaging Het
Tdrd6 T C 17: 43,936,323 (GRCm39) D1575G probably damaging Het
Tll1 T A 8: 64,527,251 (GRCm39) probably benign Het
Tsks A T 7: 44,600,198 (GRCm39) probably benign Het
Ttc1 A T 11: 43,636,147 (GRCm39) M32K probably benign Het
Txlnb C T 10: 17,714,723 (GRCm39) A385V probably damaging Het
Zc4h2 T C X: 94,687,019 (GRCm39) H98R probably damaging Het
Other mutations in Med12
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00668:Med12 APN X 100,324,792 (GRCm39) missense probably benign 0.02
IGL01122:Med12 APN X 100,325,149 (GRCm39) splice site probably benign
IGL01331:Med12 APN X 100,324,360 (GRCm39) missense possibly damaging 0.82
IGL01636:Med12 APN X 100,318,795 (GRCm39) missense probably damaging 1.00
IGL02121:Med12 APN X 100,331,948 (GRCm39) splice site probably benign
IGL02415:Med12 APN X 100,325,396 (GRCm39) missense probably damaging 1.00
IGL02479:Med12 APN X 100,340,598 (GRCm39) unclassified probably benign
IGL02597:Med12 APN X 100,328,538 (GRCm39) missense probably damaging 1.00
IGL02904:Med12 APN X 100,337,784 (GRCm39) splice site probably null
IGL03002:Med12 APN X 100,339,461 (GRCm39) missense probably benign 0.00
IGL03366:Med12 APN X 100,321,695 (GRCm39) missense probably benign 0.37
R3831:Med12 UTSW X 100,339,498 (GRCm39) missense possibly damaging 0.49
R3833:Med12 UTSW X 100,339,498 (GRCm39) missense possibly damaging 0.49
Z1176:Med12 UTSW X 100,337,179 (GRCm39) missense possibly damaging 0.95
Z1176:Med12 UTSW X 100,324,831 (GRCm39) missense probably damaging 1.00
Posted On 2016-08-02