Incidental Mutation 'R8064:Mlkl'
| ID |
619907 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Mlkl
|
| Ensembl Gene |
ENSMUSG00000012519 |
| Gene Name |
mixed lineage kinase domain-like |
| Synonyms |
9130019I15Rik |
| MMRRC Submission |
067500-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably non essential
(E-score: 0.115)
|
| Stock # |
R8064 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Not validated
|
| Chromosome |
8 |
| Chromosomal Location |
111311797-111338177 bp(-) (GRCm38) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to A
at 111312068 bp (GRCm38)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Glutamic Acid to Valine
at position 459
(E459V)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000055521
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000056157]
[ENSMUST00000120432]
|
| AlphaFold |
Q9D2Y4 |
| PDB Structure |
Structure of MLKL [X-RAY DIFFRACTION]
Crystal structure of the mouse MLKL kinase-like domain [X-RAY DIFFRACTION]
Crystal structure of the mouse RIP3-MLKL complex [X-RAY DIFFRACTION]
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000056157
AA Change: E459V
PolyPhen 2
Score 0.380 (Sensitivity: 0.90; Specificity: 0.89)
|
| SMART Domains |
Protein: ENSMUSP00000055521
Gene: ENSMUSG00000012519
AA Change: E459V
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
109 |
115 |
N/A |
INTRINSIC |
|
Pfam:Pkinase_Tyr
|
195 |
448 |
2.7e-41 |
PFAM |
|
Pfam:Pkinase
|
200 |
450 |
2.1e-30 |
PFAM |
|
Pfam:Kinase-like
|
270 |
438 |
1.6e-7 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000120432
AA Change: E451V
PolyPhen 2
Score 0.398 (Sensitivity: 0.89; Specificity: 0.89)
|
| SMART Domains |
Protein: ENSMUSP00000113718
Gene: ENSMUSG00000012519
AA Change: E451V
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
109 |
115 |
N/A |
INTRINSIC |
|
Pfam:Pkinase_Tyr
|
195 |
453 |
3.3e-42 |
PFAM |
|
Pfam:Pkinase
|
196 |
453 |
1.4e-33 |
PFAM |
|
Pfam:Kinase-like
|
270 |
438 |
8.9e-8 |
PFAM |
|
| Coding Region Coverage |
- 1x: 100.0%
- 3x: 99.9%
- 10x: 99.7%
- 20x: 99.1%
|
| Validation Efficiency |
|
| MGI Phenotype |
FUNCTION: This gene belongs to the protein kinase superfamily. The encoded protein contains a protein kinase-like domain; however, is thought to lack protein kinase activity. This protein plays a critical role in tumor necrosis factor (TNF)-induced necroptosis, a programmed cell death process, via interaction with receptor-interacting protein 3 (Rip3), which is a key signaling molecule in necroptosis pathway. Knockout of this gene in mice showed that it is essential for necroptosis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2015]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit imapired macrophage and mouse embryonic fibroblast necroptosis. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 46 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 9030624J02Rik |
T |
C |
7: 118,753,924 (GRCm38) |
I238T |
probably damaging |
Het |
| Adam3 |
A |
T |
8: 24,681,550 (GRCm38) |
V755D |
probably benign |
Het |
| Adgrb3 |
A |
T |
1: 25,420,556 (GRCm38) |
|
probably null |
Het |
| Anapc2 |
T |
C |
2: 25,276,406 (GRCm38) |
V395A |
probably benign |
Het |
| Apol11b |
A |
G |
15: 77,635,217 (GRCm38) |
V221A |
not run |
Het |
| Arhgef28 |
T |
A |
13: 97,978,494 (GRCm38) |
Y616F |
probably benign |
Het |
| Brdt |
C |
A |
5: 107,377,996 (GRCm38) |
S905* |
probably null |
Het |
| Ccdc54 |
T |
A |
16: 50,589,964 (GRCm38) |
H313L |
probably benign |
Het |
| Chuk |
A |
G |
19: 44,082,676 (GRCm38) |
L530P |
probably damaging |
Het |
| Csl |
A |
T |
10: 99,758,545 (GRCm38) |
N219K |
probably damaging |
Het |
| Cyp2j5 |
A |
G |
4: 96,658,711 (GRCm38) |
S189P |
probably damaging |
Het |
| Cyp4a14 |
A |
T |
4: 115,494,958 (GRCm38) |
C86S |
probably benign |
Het |
| Dgkg |
TCTCCT |
TCT |
16: 22,580,594 (GRCm38) |
|
probably null |
Het |
| F11 |
C |
T |
8: 45,245,773 (GRCm38) |
G445S |
probably benign |
Het |
| Fer |
T |
A |
17: 63,907,423 (GRCm38) |
I117N |
probably benign |
Het |
| Gpat3 |
A |
T |
5: 100,891,656 (GRCm38) |
I290F |
probably benign |
Het |
| H2-M10.2 |
C |
T |
17: 36,284,550 (GRCm38) |
V283M |
probably damaging |
Het |
| Hpse |
G |
A |
5: 100,688,900 (GRCm38) |
P408S |
probably benign |
Het |
| Hyou1 |
T |
A |
9: 44,385,585 (GRCm38) |
N515K |
possibly damaging |
Het |
| Idh1 |
A |
G |
1: 65,166,179 (GRCm38) |
L209P |
probably damaging |
Het |
| Igkv16-104 |
A |
T |
6: 68,425,891 (GRCm38) |
Y56F |
possibly damaging |
Het |
| Ins2 |
A |
G |
7: 142,678,816 (GRCm38) |
L77P |
probably benign |
Het |
| Kcnn2 |
A |
T |
18: 45,559,359 (GRCm38) |
M1L |
probably benign |
Het |
| Kdm3b |
A |
T |
18: 34,813,407 (GRCm38) |
|
probably null |
Het |
| Lysmd4 |
T |
C |
7: 67,223,650 (GRCm38) |
F11S |
probably damaging |
Het |
| Macf1 |
T |
A |
4: 123,459,374 (GRCm38) |
D3625V |
possibly damaging |
Het |
| Nsd3 |
A |
T |
8: 25,700,670 (GRCm38) |
K210* |
probably null |
Het |
| Olfr1122 |
C |
T |
2: 87,388,509 (GRCm38) |
T268I |
probably benign |
Het |
| Olfr1491 |
T |
C |
19: 13,705,022 (GRCm38) |
F65S |
probably damaging |
Het |
| Olfr658 |
T |
A |
7: 104,645,354 (GRCm38) |
Q6L |
probably benign |
Het |
| Pcsk5 |
T |
C |
19: 17,714,861 (GRCm38) |
N153S |
probably damaging |
Het |
| Rac3 |
T |
A |
11: 120,723,575 (GRCm38) |
V182E |
probably benign |
Het |
| Ripk3 |
T |
G |
14: 55,787,926 (GRCm38) |
E60D |
possibly damaging |
Het |
| Sacs |
T |
A |
14: 61,192,175 (GRCm38) |
I561N |
possibly damaging |
Het |
| Smad7 |
A |
G |
18: 75,394,082 (GRCm38) |
Y333C |
probably damaging |
Het |
| Snhg11 |
T |
G |
2: 158,376,201 (GRCm38) |
M1R |
probably null |
Het |
| Sp100 |
C |
T |
1: 85,681,139 (GRCm38) |
R330* |
probably null |
Het |
| Spen |
T |
C |
4: 141,475,700 (GRCm38) |
K1872R |
possibly damaging |
Het |
| Spon1 |
T |
A |
7: 114,036,621 (GRCm38) |
I690N |
probably damaging |
Het |
| Taok1 |
G |
A |
11: 77,549,304 (GRCm38) |
R626* |
probably null |
Het |
| Tecta |
C |
T |
9: 42,394,955 (GRCm38) |
G59D |
possibly damaging |
Het |
| Tmem8b |
T |
C |
4: 43,690,139 (GRCm38) |
F399S |
probably damaging |
Het |
| Trank1 |
C |
T |
9: 111,352,076 (GRCm38) |
Q389* |
probably null |
Het |
| Vmn1r33 |
G |
T |
6: 66,611,927 (GRCm38) |
S214R |
probably benign |
Het |
| Vmn2r25 |
A |
T |
6: 123,823,622 (GRCm38) |
L587* |
probably null |
Het |
| Zfp335 |
G |
A |
2: 164,907,700 (GRCm38) |
T259I |
probably damaging |
Het |
|
| Other mutations in Mlkl |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00089:Mlkl
|
APN |
8 |
111,319,428 (GRCm38) |
nonsense |
probably null |
|
|
IGL01376:Mlkl
|
APN |
8 |
111,319,747 (GRCm38) |
missense |
probably damaging |
1.00 |
|
IGL02801:Mlkl
|
APN |
8 |
111,316,432 (GRCm38) |
missense |
probably benign |
0.18 |
|
IGL02965:Mlkl
|
APN |
8 |
111,331,837 (GRCm38) |
missense |
probably benign |
0.31 |
|
IGL03121:Mlkl
|
APN |
8 |
111,314,980 (GRCm38) |
missense |
probably damaging |
1.00 |
|
Ghoulish
|
UTSW |
8 |
111,322,748 (GRCm38) |
missense |
probably damaging |
1.00 |
|
mecro
|
UTSW |
8 |
111,319,716 (GRCm38) |
critical splice donor site |
probably null |
|
|
necro
|
UTSW |
8 |
111,312,100 (GRCm38) |
intron |
probably benign |
|
|
secro
|
UTSW |
8 |
111,315,567 (GRCm38) |
intron |
probably benign |
|
|
R0133:Mlkl
|
UTSW |
8 |
111,327,948 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R0230:Mlkl
|
UTSW |
8 |
111,315,062 (GRCm38) |
missense |
probably benign |
0.07 |
|
R0387:Mlkl
|
UTSW |
8 |
111,333,350 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R0497:Mlkl
|
UTSW |
8 |
111,327,873 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R0735:Mlkl
|
UTSW |
8 |
111,327,801 (GRCm38) |
unclassified |
probably benign |
|
|
R1733:Mlkl
|
UTSW |
8 |
111,322,748 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R1761:Mlkl
|
UTSW |
8 |
111,333,723 (GRCm38) |
missense |
possibly damaging |
0.81 |
|
R1911:Mlkl
|
UTSW |
8 |
111,312,100 (GRCm38) |
intron |
probably benign |
|
|
R2057:Mlkl
|
UTSW |
8 |
111,333,610 (GRCm38) |
missense |
probably benign |
0.07 |
|
R2921:Mlkl
|
UTSW |
8 |
111,316,447 (GRCm38) |
missense |
probably benign |
0.02 |
|
R3745:Mlkl
|
UTSW |
8 |
111,315,567 (GRCm38) |
intron |
probably benign |
|
|
R4760:Mlkl
|
UTSW |
8 |
111,319,716 (GRCm38) |
critical splice donor site |
probably null |
|
|
R5377:Mlkl
|
UTSW |
8 |
111,327,937 (GRCm38) |
missense |
probably benign |
0.23 |
|
R7052:Mlkl
|
UTSW |
8 |
111,319,442 (GRCm38) |
missense |
possibly damaging |
0.65 |
|
R7155:Mlkl
|
UTSW |
8 |
111,319,403 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R7459:Mlkl
|
UTSW |
8 |
111,333,530 (GRCm38) |
missense |
probably benign |
0.36 |
|
R7728:Mlkl
|
UTSW |
8 |
111,333,619 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R8036:Mlkl
|
UTSW |
8 |
111,333,454 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R9088:Mlkl
|
UTSW |
8 |
111,322,733 (GRCm38) |
missense |
|
|
|
R9152:Mlkl
|
UTSW |
8 |
111,319,771 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R9275:Mlkl
|
UTSW |
8 |
111,316,423 (GRCm38) |
missense |
probably benign |
0.07 |
|
| Predicted Primers |
PCR Primer
(F):5'- GGCTACATGGTGAGATCCCATC -3'
(R):5'- ACAAGCTGCTGATCCAGGTC -3'
Sequencing Primer
(F):5'- CCCAGCAATAAGTTGATGC -3'
(R):5'- GGTTATAGGCACGTACCATCATGC -3'
|
| Posted On |
2020-01-23 |
Incidental Mutation