Incidental Mutation 'R7554:Map3k4'
| ID |
584647 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Map3k4
|
| Ensembl Gene |
ENSMUSG00000014426 |
| Gene Name |
mitogen-activated protein kinase kinase kinase 4 |
| Synonyms |
T-associated sex reversal, D17Rp17, D17Rp17e, Mekk4, Tas, RP17, MAPKKK4, MTK1 |
| MMRRC Submission |
045651-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably essential
(E-score: 0.953)
|
| Stock # |
R7554 (G1)
|
| Quality Score |
172.009 |
|
Status
|
Not validated
|
| Chromosome |
17 |
| Chromosomal Location |
12446508-12537683 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to A
at 12451300 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Lysine to Methionine
at position 1531
(K1531M)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000086459
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000089058]
|
| AlphaFold |
O08648 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000089058
AA Change: K1531M
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000086459
Gene: ENSMUSG00000014426
AA Change: K1531M
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
8 |
21 |
N/A |
INTRINSIC |
|
low complexity region
|
27 |
43 |
N/A |
INTRINSIC |
|
low complexity region
|
215 |
235 |
N/A |
INTRINSIC |
|
low complexity region
|
432 |
462 |
N/A |
INTRINSIC |
|
low complexity region
|
1177 |
1191 |
N/A |
INTRINSIC |
|
S_TKc
|
1332 |
1590 |
1.41e-91 |
SMART |
|
| Coding Region Coverage |
- 1x: 100.0%
- 3x: 99.9%
- 10x: 99.7%
- 20x: 99.0%
|
| Validation Efficiency |
|
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The central core of each mitogen-activated protein kinase (MAPK) pathway is a conserved cascade of 3 protein kinases: an activated MAPK kinase kinase (MAPKKK) phosphorylates and activates a specific MAPK kinase (MAPKK), which then activates a specific MAPK. While the ERK MAPKs are activated by mitogenic stimulation, the CSBP2 and JNK MAPKs are activated by environmental stresses such as osmotic shock, UV irradiation, wound stress, and inflammatory factors. This gene encodes a MAPKKK, the MEKK4 protein, also called MTK1. This protein contains a protein kinase catalytic domain at the C terminus. The N-terminal nonkinase domain may contain a regulatory domain. Expression of MEKK4 in mammalian cells activated the CSBP2 and JNK MAPK pathways, but not the ERK pathway. In vitro kinase studies indicated that recombinant MEKK4 can specifically phosphorylate and activate PRKMK6 and SERK1, MAPKKs that activate CSBP2 and JNK, respectively but cannot phosphorylate PRKMK1, an MAPKK that activates ERKs. MEKK4 is a major mediator of environmental stresses that activate the CSBP2 MAPK pathway, and a minor mediator of the JNK pathway. Several alternatively spliced transcripts encoding distinct isoforms have been described. [provided by RefSeq, May 2014]
PHENOTYPE: Homozygous null mice exhibit some perinatal lethality and survivors appear smaller. On certain genetic backgrounds, heterozygous X/Y mice may develop as phenotypic females or hermaphrodites. The sex-reversal phenotype is dependent on a combination of strain-specific autosomal and Y-linked alleles. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 70 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 5031439G07Rik |
A |
T |
15: 84,839,686 (GRCm39) |
F185I |
probably damaging |
Het |
| Abi3bp |
T |
A |
16: 56,438,575 (GRCm39) |
|
probably null |
Het |
| Acot5 |
T |
A |
12: 84,120,254 (GRCm39) |
L203H |
probably damaging |
Het |
| Alad |
C |
T |
4: 62,430,023 (GRCm39) |
|
probably null |
Het |
| Alkbh5 |
C |
T |
11: 60,429,415 (GRCm39) |
T56I |
probably benign |
Het |
| Apbb1ip |
G |
A |
2: 22,713,558 (GRCm39) |
D138N |
unknown |
Het |
| BC049715 |
T |
G |
6: 136,817,295 (GRCm39) |
S178R |
probably damaging |
Het |
| C1rb |
C |
A |
6: 124,557,365 (GRCm39) |
H501N |
probably damaging |
Het |
| Celsr3 |
A |
T |
9: 108,718,408 (GRCm39) |
M2327L |
probably benign |
Het |
| Cers4 |
G |
A |
8: 4,565,718 (GRCm39) |
V55I |
probably benign |
Het |
| Cngb3 |
A |
T |
4: 19,461,753 (GRCm39) |
K545* |
probably null |
Het |
| Crb1 |
C |
T |
1: 139,265,019 (GRCm39) |
C133Y |
probably damaging |
Het |
| Cryba4 |
C |
T |
5: 112,398,969 (GRCm39) |
R25Q |
probably damaging |
Het |
| Cyp7b1 |
C |
T |
3: 18,151,610 (GRCm39) |
G201D |
probably benign |
Het |
| Dcun1d2 |
A |
T |
8: 13,331,077 (GRCm39) |
C18S |
probably benign |
Het |
| Ddx39b |
A |
T |
17: 35,466,006 (GRCm39) |
I176F |
probably benign |
Het |
| Dnah7a |
A |
G |
1: 53,567,857 (GRCm39) |
I1913T |
possibly damaging |
Het |
| Eif2ak1 |
T |
C |
5: 143,816,296 (GRCm39) |
I198T |
probably damaging |
Het |
| Esp34 |
G |
A |
17: 38,866,782 (GRCm39) |
M75I |
probably benign |
Het |
| Fam98a |
G |
T |
17: 75,854,670 (GRCm39) |
C46* |
probably null |
Het |
| Fanci |
A |
T |
7: 79,062,500 (GRCm39) |
N342I |
probably damaging |
Het |
| Fat1 |
A |
T |
8: 45,490,202 (GRCm39) |
I3705F |
possibly damaging |
Het |
| Fbxw7 |
T |
A |
3: 84,883,620 (GRCm39) |
V598D |
|
Het |
| Gas2l2 |
G |
A |
11: 83,315,236 (GRCm39) |
Q306* |
probably null |
Het |
| Gbp10 |
G |
A |
5: 105,384,015 (GRCm39) |
|
probably benign |
Het |
| Gigyf2 |
T |
A |
1: 87,335,292 (GRCm39) |
S378T |
unknown |
Het |
| Hao1 |
C |
T |
2: 134,372,538 (GRCm39) |
V157M |
possibly damaging |
Het |
| Hdlbp |
C |
T |
1: 93,365,031 (GRCm39) |
V79M |
probably damaging |
Het |
| Htt |
G |
A |
5: 35,022,084 (GRCm39) |
R1676H |
probably damaging |
Het |
| Ift56 |
T |
A |
6: 38,362,435 (GRCm39) |
L70Q |
probably null |
Het |
| Klhl11 |
A |
G |
11: 100,354,774 (GRCm39) |
V349A |
probably benign |
Het |
| Lama2 |
T |
C |
10: 27,031,492 (GRCm39) |
E1522G |
probably damaging |
Het |
| Mapk15 |
A |
G |
15: 75,867,745 (GRCm39) |
Y120C |
possibly damaging |
Het |
| Mapt |
C |
A |
11: 104,189,528 (GRCm39) |
P182Q |
probably benign |
Het |
| Mgat4d |
A |
C |
8: 84,082,402 (GRCm39) |
K117N |
probably benign |
Het |
| Mid1 |
G |
T |
X: 168,769,010 (GRCm39) |
S468I |
possibly damaging |
Het |
| Mmp8 |
T |
C |
9: 7,563,112 (GRCm39) |
L225P |
probably damaging |
Het |
| Mrps31 |
A |
G |
8: 22,911,445 (GRCm39) |
K229R |
possibly damaging |
Het |
| Muc5b |
A |
T |
7: 141,412,513 (GRCm39) |
T1820S |
unknown |
Het |
| Myof |
T |
C |
19: 37,942,958 (GRCm39) |
T707A |
probably benign |
Het |
| Nckap5l |
A |
T |
15: 99,327,261 (GRCm39) |
S143T |
probably benign |
Het |
| Notch3 |
A |
G |
17: 32,341,345 (GRCm39) |
S2136P |
probably benign |
Het |
| Nphp3 |
A |
T |
9: 103,919,270 (GRCm39) |
D1306V |
probably damaging |
Het |
| Or10ag56 |
T |
A |
2: 87,139,349 (GRCm39) |
M92K |
probably damaging |
Het |
| Or1e1b-ps1 |
C |
T |
11: 73,845,630 (GRCm39) |
T38I |
probably damaging |
Het |
| Or2at1 |
T |
A |
7: 99,417,210 (GRCm39) |
N280K |
possibly damaging |
Het |
| Or52n1 |
T |
C |
7: 104,383,074 (GRCm39) |
I166V |
probably benign |
Het |
| Or56b1 |
T |
C |
7: 104,285,733 (GRCm39) |
M284T |
probably benign |
Het |
| Or5k15 |
T |
C |
16: 58,709,769 (GRCm39) |
I271M |
probably benign |
Het |
| Pabpc4l |
T |
A |
3: 46,401,549 (GRCm39) |
T32S |
probably benign |
Het |
| Pcdhb10 |
A |
C |
18: 37,544,935 (GRCm39) |
T4P |
probably benign |
Het |
| Pkhd1l1 |
A |
G |
15: 44,358,866 (GRCm39) |
I358M |
probably damaging |
Het |
| Plekhg1 |
A |
G |
10: 3,913,647 (GRCm39) |
E1178G |
|
Het |
| Prkcd |
A |
T |
14: 30,331,220 (GRCm39) |
Y52N |
probably damaging |
Het |
| Rasa3 |
G |
A |
8: 13,645,390 (GRCm39) |
T183M |
probably damaging |
Het |
| Rbm26 |
G |
T |
14: 105,398,029 (GRCm39) |
A31D |
unknown |
Het |
| Scara3 |
T |
C |
14: 66,158,299 (GRCm39) |
T570A |
possibly damaging |
Het |
| Sec24d |
T |
A |
3: 123,149,423 (GRCm39) |
V810D |
probably damaging |
Het |
| Sgcz |
A |
T |
8: 38,030,426 (GRCm39) |
|
probably null |
Het |
| Stt3b |
A |
G |
9: 115,109,477 (GRCm39) |
|
probably null |
Het |
| Synpo |
G |
T |
18: 60,736,405 (GRCm39) |
Q514K |
probably benign |
Het |
| Tagln2 |
G |
T |
1: 172,333,411 (GRCm39) |
K88N |
probably damaging |
Het |
| Tcaf1 |
T |
A |
6: 42,654,388 (GRCm39) |
K601N |
probably benign |
Het |
| Tent4a |
G |
T |
13: 69,648,191 (GRCm39) |
H734Q |
probably damaging |
Het |
| Tprn |
T |
C |
2: 25,153,811 (GRCm39) |
F371S |
probably damaging |
Het |
| Ttn |
A |
T |
2: 76,671,652 (GRCm39) |
V11304E |
unknown |
Het |
| Ttn |
C |
T |
2: 76,706,207 (GRCm39) |
W9171* |
probably null |
Het |
| Vmn2r50 |
A |
T |
7: 9,784,066 (GRCm39) |
M136K |
probably null |
Het |
| Zfp518b |
G |
A |
5: 38,830,415 (GRCm39) |
P530L |
probably damaging |
Het |
| Zfp941 |
C |
A |
7: 140,391,970 (GRCm39) |
S463I |
possibly damaging |
Het |
|
| Other mutations in Map3k4 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL01065:Map3k4
|
APN |
17 |
12,451,877 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01124:Map3k4
|
APN |
17 |
12,474,087 (GRCm39) |
missense |
probably benign |
0.01 |
|
IGL01125:Map3k4
|
APN |
17 |
12,490,849 (GRCm39) |
missense |
probably damaging |
0.96 |
|
IGL01585:Map3k4
|
APN |
17 |
12,467,846 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02194:Map3k4
|
APN |
17 |
12,482,815 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02194:Map3k4
|
APN |
17 |
12,467,882 (GRCm39) |
missense |
probably benign |
0.30 |
|
IGL02292:Map3k4
|
APN |
17 |
12,454,045 (GRCm39) |
missense |
possibly damaging |
0.77 |
|
IGL02326:Map3k4
|
APN |
17 |
12,467,897 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02388:Map3k4
|
APN |
17 |
12,490,497 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL02621:Map3k4
|
APN |
17 |
12,482,900 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02668:Map3k4
|
APN |
17 |
12,454,840 (GRCm39) |
missense |
possibly damaging |
0.85 |
|
IGL02850:Map3k4
|
APN |
17 |
12,490,801 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02939:Map3k4
|
APN |
17 |
12,491,036 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL03148:Map3k4
|
APN |
17 |
12,457,045 (GRCm39) |
missense |
probably benign |
0.01 |
|
IGL03238:Map3k4
|
APN |
17 |
12,490,045 (GRCm39) |
missense |
probably benign |
0.10 |
|
ANU74:Map3k4
|
UTSW |
17 |
12,451,863 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0012:Map3k4
|
UTSW |
17 |
12,457,076 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0012:Map3k4
|
UTSW |
17 |
12,457,076 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0128:Map3k4
|
UTSW |
17 |
12,466,950 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R0183:Map3k4
|
UTSW |
17 |
12,454,015 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0309:Map3k4
|
UTSW |
17 |
12,489,902 (GRCm39) |
frame shift |
probably null |
|
|
R0355:Map3k4
|
UTSW |
17 |
12,473,058 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0367:Map3k4
|
UTSW |
17 |
12,476,928 (GRCm39) |
splice site |
probably benign |
|
|
R1103:Map3k4
|
UTSW |
17 |
12,455,950 (GRCm39) |
splice site |
probably null |
|
|
R1446:Map3k4
|
UTSW |
17 |
12,475,681 (GRCm39) |
nonsense |
probably null |
|
|
R1542:Map3k4
|
UTSW |
17 |
12,454,793 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R1713:Map3k4
|
UTSW |
17 |
12,468,458 (GRCm39) |
missense |
probably benign |
0.39 |
|
R1777:Map3k4
|
UTSW |
17 |
12,490,617 (GRCm39) |
missense |
possibly damaging |
0.82 |
|
R1797:Map3k4
|
UTSW |
17 |
12,482,906 (GRCm39) |
missense |
probably benign |
0.30 |
|
R1997:Map3k4
|
UTSW |
17 |
12,473,882 (GRCm39) |
critical splice donor site |
probably null |
|
|
R2042:Map3k4
|
UTSW |
17 |
12,496,870 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R2878:Map3k4
|
UTSW |
17 |
12,482,954 (GRCm39) |
missense |
probably benign |
0.00 |
|
R2939:Map3k4
|
UTSW |
17 |
12,480,157 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R2940:Map3k4
|
UTSW |
17 |
12,480,157 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R3405:Map3k4
|
UTSW |
17 |
12,475,668 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3930:Map3k4
|
UTSW |
17 |
12,454,880 (GRCm39) |
missense |
possibly damaging |
0.83 |
|
R4291:Map3k4
|
UTSW |
17 |
12,474,147 (GRCm39) |
missense |
probably benign |
0.08 |
|
R4410:Map3k4
|
UTSW |
17 |
12,467,885 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4632:Map3k4
|
UTSW |
17 |
12,451,391 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4641:Map3k4
|
UTSW |
17 |
12,482,932 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4726:Map3k4
|
UTSW |
17 |
12,451,851 (GRCm39) |
missense |
possibly damaging |
0.89 |
|
R4730:Map3k4
|
UTSW |
17 |
12,467,861 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R4832:Map3k4
|
UTSW |
17 |
12,490,667 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4896:Map3k4
|
UTSW |
17 |
12,490,906 (GRCm39) |
missense |
possibly damaging |
0.65 |
|
R4934:Map3k4
|
UTSW |
17 |
12,490,787 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4971:Map3k4
|
UTSW |
17 |
12,468,382 (GRCm39) |
critical splice donor site |
probably null |
|
|
R4980:Map3k4
|
UTSW |
17 |
12,490,958 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5211:Map3k4
|
UTSW |
17 |
12,451,321 (GRCm39) |
missense |
possibly damaging |
0.88 |
|
R5337:Map3k4
|
UTSW |
17 |
12,490,497 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R5356:Map3k4
|
UTSW |
17 |
12,466,195 (GRCm39) |
missense |
possibly damaging |
0.87 |
|
R5550:Map3k4
|
UTSW |
17 |
12,462,445 (GRCm39) |
nonsense |
probably null |
|
|
R5824:Map3k4
|
UTSW |
17 |
12,448,526 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5890:Map3k4
|
UTSW |
17 |
12,490,303 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6285:Map3k4
|
UTSW |
17 |
12,482,945 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6380:Map3k4
|
UTSW |
17 |
12,490,954 (GRCm39) |
missense |
possibly damaging |
0.56 |
|
R6383:Map3k4
|
UTSW |
17 |
12,468,470 (GRCm39) |
missense |
possibly damaging |
0.82 |
|
R6571:Map3k4
|
UTSW |
17 |
12,461,579 (GRCm39) |
missense |
possibly damaging |
0.80 |
|
R6584:Map3k4
|
UTSW |
17 |
12,479,378 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6616:Map3k4
|
UTSW |
17 |
12,490,231 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6644:Map3k4
|
UTSW |
17 |
12,451,297 (GRCm39) |
critical splice donor site |
probably null |
|
|
R6909:Map3k4
|
UTSW |
17 |
12,489,872 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6947:Map3k4
|
UTSW |
17 |
12,479,456 (GRCm39) |
nonsense |
probably null |
|
|
R6970:Map3k4
|
UTSW |
17 |
12,467,803 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7120:Map3k4
|
UTSW |
17 |
12,490,354 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7253:Map3k4
|
UTSW |
17 |
12,490,955 (GRCm39) |
missense |
probably benign |
0.00 |
|
R7267:Map3k4
|
UTSW |
17 |
12,490,536 (GRCm39) |
nonsense |
probably null |
|
|
R7322:Map3k4
|
UTSW |
17 |
12,489,833 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7522:Map3k4
|
UTSW |
17 |
12,480,219 (GRCm39) |
missense |
probably benign |
0.39 |
|
R7554:Map3k4
|
UTSW |
17 |
12,451,301 (GRCm39) |
nonsense |
probably null |
|
|
R7681:Map3k4
|
UTSW |
17 |
12,537,430 (GRCm39) |
missense |
unknown |
|
|
R7734:Map3k4
|
UTSW |
17 |
12,482,998 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7842:Map3k4
|
UTSW |
17 |
12,490,030 (GRCm39) |
missense |
possibly damaging |
0.54 |
|
R8013:Map3k4
|
UTSW |
17 |
12,489,918 (GRCm39) |
nonsense |
probably null |
|
|
R8014:Map3k4
|
UTSW |
17 |
12,489,918 (GRCm39) |
nonsense |
probably null |
|
|
R8235:Map3k4
|
UTSW |
17 |
12,458,968 (GRCm39) |
splice site |
probably null |
|
|
R8294:Map3k4
|
UTSW |
17 |
12,537,500 (GRCm39) |
missense |
unknown |
|
|
R8528:Map3k4
|
UTSW |
17 |
12,451,821 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8858:Map3k4
|
UTSW |
17 |
12,490,759 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8924:Map3k4
|
UTSW |
17 |
12,490,433 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9063:Map3k4
|
UTSW |
17 |
12,482,878 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9224:Map3k4
|
UTSW |
17 |
12,456,973 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R9446:Map3k4
|
UTSW |
17 |
12,451,375 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9486:Map3k4
|
UTSW |
17 |
12,489,860 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9488:Map3k4
|
UTSW |
17 |
12,489,860 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9591:Map3k4
|
UTSW |
17 |
12,454,795 (GRCm39) |
missense |
possibly damaging |
0.91 |
|
R9617:Map3k4
|
UTSW |
17 |
12,476,871 (GRCm39) |
missense |
possibly damaging |
0.67 |
|
R9722:Map3k4
|
UTSW |
17 |
12,490,523 (GRCm39) |
missense |
probably benign |
0.01 |
|
X0067:Map3k4
|
UTSW |
17 |
12,482,981 (GRCm39) |
missense |
probably benign |
0.03 |
|
Z1177:Map3k4
|
UTSW |
17 |
12,490,584 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Predicted Primers |
PCR Primer
(F):5'- AAAGCTCTCCCACACTCTGG -3'
(R):5'- ACATTTGCTGCCTGTACCTG -3'
Sequencing Primer
(F):5'- GGACCCGTCAAATAGACTGTCTTG -3'
(R):5'- GGAGTAACAACATATTGCTTGGTGC -3'
|
| Posted On |
2019-10-17 |
Incidental Mutation