Incidental Mutation 'R3831:Med12'
| ID |
274031 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Med12
|
| Ensembl Gene |
ENSMUSG00000079487 |
| Gene Name |
mediator complex subunit 12 |
| Synonyms |
Tnrc11, Mopa, OPA-1, Trap230 |
| MMRRC Submission |
040777-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R3831 (G1)
|
| Quality Score |
222 |
|
Status
|
Not validated
|
| Chromosome |
X |
| Chromosomal Location |
100317636-100341071 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
C to A
at 100339498 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Proline to Glutamine
at position 2037
(P2037Q)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000112729
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000065858]
[ENSMUST00000087948]
[ENSMUST00000087956]
[ENSMUST00000117203]
[ENSMUST00000117706]
[ENSMUST00000118111]
[ENSMUST00000151528]
[ENSMUST00000130555]
|
| AlphaFold |
A2AGH6 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000065858
|
| SMART Domains |
Protein: ENSMUSP00000066304
Gene: ENSMUSG00000031302
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:COesterase
|
16 |
601 |
2.3e-194 |
PFAM |
|
Pfam:Abhydrolase_3
|
180 |
342 |
1.7e-7 |
PFAM |
|
transmembrane domain
|
685 |
707 |
N/A |
INTRINSIC |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000087948
AA Change: P2037Q
PolyPhen 2
Score 0.491 (Sensitivity: 0.88; Specificity: 0.90)
|
| SMART Domains |
Protein: ENSMUSP00000085260
Gene: ENSMUSG00000079487
AA Change: P2037Q
| Domain | Start | End | E-Value | Type |
|---|
|
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 benign
Transcript: ENSMUST00000087956
AA Change: P2016Q
PolyPhen 2
Score 0.425 (Sensitivity: 0.89; Specificity: 0.90)
|
| SMART Domains |
Protein: ENSMUSP00000085269
Gene: ENSMUSG00000079487
AA Change: P2016Q
| Domain | Start | End | E-Value | Type |
|---|
|
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 |
noncoding transcript
Transcript: ENSMUST00000113671
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000117203
AA Change: P2037Q
PolyPhen 2
Score 0.491 (Sensitivity: 0.88; Specificity: 0.90)
|
| SMART Domains |
Protein: ENSMUSP00000112729
Gene: ENSMUSG00000079487
AA Change: P2037Q
| Domain | Start | End | E-Value | Type |
|---|
|
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 benign
Transcript: ENSMUST00000117706
AA Change: P2012Q
PolyPhen 2
Score 0.006 (Sensitivity: 0.97; Specificity: 0.75)
|
| SMART Domains |
Protein: ENSMUSP00000112852
Gene: ENSMUSG00000079487
AA Change: P2012Q
| Domain | Start | End | E-Value | Type |
|---|
|
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 |
probably benign
Transcript: ENSMUST00000118111
|
| SMART Domains |
Protein: ENSMUSP00000113863
Gene: ENSMUSG00000031302
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:COesterase
|
3 |
487 |
3.6e-161 |
PFAM |
|
Pfam:Abhydrolase_3
|
66 |
232 |
2.4e-7 |
PFAM |
|
transmembrane domain
|
571 |
593 |
N/A |
INTRINSIC |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000132269
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000148846
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000147443
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000137664
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000151528
|
| SMART Domains |
Protein: ENSMUSP00000123283
Gene: ENSMUSG00000031302
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:COesterase
|
16 |
621 |
3.4e-207 |
PFAM |
|
Pfam:Abhydrolase_3
|
200 |
363 |
1.2e-6 |
PFAM |
|
transmembrane domain
|
705 |
727 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000130555
|
| SMART Domains |
Protein: ENSMUSP00000122213
Gene: ENSMUSG00000031302
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:COesterase
|
16 |
510 |
4.6e-179 |
PFAM |
|
Pfam:Abhydrolase_3
|
160 |
323 |
1.5e-7 |
PFAM |
|
| Meta Mutation Damage Score |
0.0732 |
| Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.7%
- 10x: 97.7%
- 20x: 96.2%
|
| 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: 54 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 4930563M21Rik |
T |
C |
9: 55,880,992 (GRCm39) |
T527A |
unknown |
Het |
| Bcat1 |
T |
A |
6: 144,955,834 (GRCm39) |
D349V |
probably damaging |
Het |
| Cacna1c |
A |
G |
6: 118,581,424 (GRCm39) |
S1727P |
probably benign |
Het |
| Cacnb2 |
A |
T |
2: 14,986,236 (GRCm39) |
I338F |
probably damaging |
Het |
| Cemip2 |
T |
G |
19: 21,825,315 (GRCm39) |
S1204R |
probably damaging |
Het |
| Cibar2 |
T |
A |
8: 120,901,633 (GRCm39) |
Y24F |
probably damaging |
Het |
| Cyb5d2 |
G |
T |
11: 72,686,349 (GRCm39) |
S80R |
possibly damaging |
Het |
| Cyfip2 |
T |
C |
11: 46,152,333 (GRCm39) |
D485G |
probably benign |
Het |
| Cyp27b1 |
G |
T |
10: 126,886,929 (GRCm39) |
V382L |
probably damaging |
Het |
| Dpp9 |
A |
T |
17: 56,506,113 (GRCm39) |
F429I |
possibly damaging |
Het |
| Frmd4b |
T |
A |
6: 97,389,486 (GRCm39) |
K73* |
probably null |
Het |
| Hao1 |
A |
T |
2: 134,364,925 (GRCm39) |
V234D |
probably damaging |
Het |
| Hkdc1 |
T |
C |
10: 62,235,991 (GRCm39) |
Y517C |
probably benign |
Het |
| Iglv2 |
A |
T |
16: 19,079,593 (GRCm39) |
M1K |
probably null |
Het |
| Inpp5j |
T |
C |
11: 3,450,229 (GRCm39) |
D228G |
probably damaging |
Het |
| Itih5 |
A |
G |
2: 10,256,081 (GRCm39) |
D849G |
possibly damaging |
Het |
| Itpkb |
T |
C |
1: 180,161,260 (GRCm39) |
V462A |
probably benign |
Het |
| Kif26b |
GAAA |
GAA |
1: 178,744,181 (GRCm39) |
|
probably null |
Het |
| Kremen1 |
G |
GGGC |
11: 5,151,794 (GRCm39) |
|
probably benign |
Het |
| Lzic |
G |
C |
4: 149,573,185 (GRCm39) |
E112D |
probably null |
Het |
| Mageh1 |
A |
T |
X: 151,820,004 (GRCm39) |
W111R |
probably damaging |
Het |
| Mapk7 |
A |
G |
11: 61,380,680 (GRCm39) |
S641P |
possibly damaging |
Het |
| Mapt |
A |
T |
11: 104,177,961 (GRCm39) |
Q38L |
possibly damaging |
Het |
| Med22 |
A |
G |
2: 26,800,379 (GRCm39) |
S17P |
probably damaging |
Het |
| Melk |
C |
A |
4: 44,345,021 (GRCm39) |
Q384K |
probably benign |
Het |
| Morc2b |
C |
T |
17: 33,356,233 (GRCm39) |
S513N |
probably benign |
Het |
| Nap1l3 |
A |
G |
X: 121,305,995 (GRCm39) |
V241A |
possibly damaging |
Het |
| Or2t45 |
T |
A |
11: 58,669,571 (GRCm39) |
|
probably null |
Het |
| Or56a4 |
A |
G |
7: 104,806,589 (GRCm39) |
F100S |
probably damaging |
Het |
| Or9e1 |
T |
G |
11: 58,732,686 (GRCm39) |
F249V |
probably damaging |
Het |
| Pdgfd |
T |
C |
9: 6,359,762 (GRCm39) |
S278P |
probably damaging |
Het |
| Pgc |
C |
A |
17: 48,040,236 (GRCm39) |
F93L |
probably null |
Het |
| Phf14 |
A |
G |
6: 11,933,873 (GRCm39) |
|
probably null |
Het |
| Pja2 |
T |
C |
17: 64,616,397 (GRCm39) |
D166G |
probably benign |
Het |
| Rgs5 |
A |
G |
1: 169,504,470 (GRCm39) |
Y40C |
probably benign |
Het |
| Rsad1 |
A |
G |
11: 94,434,130 (GRCm39) |
V366A |
probably benign |
Het |
| S100a10 |
T |
C |
3: 93,471,680 (GRCm39) |
V88A |
probably damaging |
Het |
| Scarf1 |
T |
C |
11: 75,406,078 (GRCm39) |
C121R |
probably damaging |
Het |
| Scn7a |
A |
G |
2: 66,528,028 (GRCm39) |
S821P |
probably damaging |
Het |
| Sco1 |
T |
C |
11: 66,944,605 (GRCm39) |
V76A |
probably damaging |
Het |
| Selp |
T |
A |
1: 163,959,849 (GRCm39) |
C368* |
probably null |
Het |
| Sema3e |
T |
A |
5: 14,276,496 (GRCm39) |
C294S |
probably damaging |
Het |
| Slit3 |
A |
T |
11: 35,579,509 (GRCm39) |
S1229C |
probably null |
Het |
| Smarca5 |
A |
T |
8: 81,455,123 (GRCm39) |
N199K |
probably damaging |
Het |
| Sorbs2 |
A |
T |
8: 46,248,132 (GRCm39) |
D442V |
probably damaging |
Het |
| Specc1 |
T |
A |
11: 62,008,793 (GRCm39) |
I183N |
probably damaging |
Het |
| Tcerg1 |
G |
T |
18: 42,701,554 (GRCm39) |
R872L |
probably damaging |
Het |
| Tekt1 |
T |
C |
11: 72,245,645 (GRCm39) |
N170S |
probably benign |
Het |
| Thsd1 |
T |
G |
8: 22,733,132 (GRCm39) |
S60A |
possibly damaging |
Het |
| Usp24 |
T |
C |
4: 106,219,209 (GRCm39) |
|
probably null |
Het |
| Usp28 |
A |
G |
9: 48,946,938 (GRCm39) |
T505A |
probably benign |
Het |
| Zcchc17 |
T |
C |
4: 130,232,317 (GRCm39) |
D62G |
probably benign |
Het |
| Zfp445 |
T |
G |
9: 122,681,541 (GRCm39) |
E800A |
probably damaging |
Het |
| Zranb1 |
C |
T |
7: 132,584,505 (GRCm39) |
A591V |
probably damaging |
Het |
|
| Other mutations in Med12 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH 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 |
|
IGL03006:Med12
|
APN |
X |
100,321,684 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL03366:Med12
|
APN |
X |
100,321,695 (GRCm39) |
missense |
probably benign |
0.37 |
|
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 |
|
| Predicted Primers |
PCR Primer
(F):5'- CTCCTCTCATTAGTGCCAAGACG -3'
(R):5'- TCTGACACAATCCCATGGCC -3'
Sequencing Primer
(F):5'- CATTAGTGCCAAGACGAATGAATAC -3'
(R):5'- ATGGCCTTACCCGTAGCATCTG -3'
|
| Posted On |
2015-04-02 |
Incidental Mutation