Incidental Mutation 'R6647:Lats1'
| ID |
526139 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Lats1
|
| Ensembl Gene |
ENSMUSG00000040021 |
| Gene Name |
large tumor suppressor |
| Synonyms |
|
| MMRRC Submission |
044768-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably essential
(E-score: 0.822)
|
| Stock # |
R6647 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Validated
|
| Chromosome |
10 |
| Chromosomal Location |
7556978-7592224 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
G to C
at 7573271 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Methionine to Isoleucine
at position 118
(M118I)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000151533
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000040043]
[ENSMUST00000165952]
[ENSMUST00000217931]
|
| AlphaFold |
Q8BYR2 |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000040043
AA Change: M118I
PolyPhen 2
Score 0.814 (Sensitivity: 0.84; Specificity: 0.93)
|
| SMART Domains |
Protein: ENSMUSP00000041915
Gene: ENSMUSG00000040021
AA Change: M118I
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:UBA
|
101 |
138 |
7.4e-11 |
PFAM |
|
low complexity region
|
228 |
267 |
N/A |
INTRINSIC |
|
low complexity region
|
301 |
314 |
N/A |
INTRINSIC |
|
low complexity region
|
371 |
379 |
N/A |
INTRINSIC |
|
low complexity region
|
433 |
445 |
N/A |
INTRINSIC |
|
low complexity region
|
482 |
493 |
N/A |
INTRINSIC |
|
low complexity region
|
520 |
530 |
N/A |
INTRINSIC |
|
low complexity region
|
554 |
559 |
N/A |
INTRINSIC |
|
S_TKc
|
704 |
1009 |
7.3e-99 |
SMART |
|
S_TK_X
|
1010 |
1081 |
1.2e-2 |
SMART |
|
low complexity region
|
1102 |
1120 |
N/A |
INTRINSIC |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000165952
AA Change: M118I
PolyPhen 2
Score 0.814 (Sensitivity: 0.84; Specificity: 0.93)
|
| SMART Domains |
Protein: ENSMUSP00000132078
Gene: ENSMUSG00000040021
AA Change: M118I
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:UBA
|
101 |
138 |
7.4e-11 |
PFAM |
|
low complexity region
|
228 |
267 |
N/A |
INTRINSIC |
|
low complexity region
|
301 |
314 |
N/A |
INTRINSIC |
|
low complexity region
|
371 |
379 |
N/A |
INTRINSIC |
|
low complexity region
|
433 |
445 |
N/A |
INTRINSIC |
|
low complexity region
|
482 |
493 |
N/A |
INTRINSIC |
|
low complexity region
|
520 |
530 |
N/A |
INTRINSIC |
|
low complexity region
|
554 |
559 |
N/A |
INTRINSIC |
|
S_TKc
|
704 |
1009 |
7.3e-99 |
SMART |
|
S_TK_X
|
1010 |
1081 |
1.2e-2 |
SMART |
|
low complexity region
|
1102 |
1120 |
N/A |
INTRINSIC |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000217931
AA Change: M118I
PolyPhen 2
Score 0.814 (Sensitivity: 0.84; Specificity: 0.93)
|
| Meta Mutation Damage Score |
0.2945 |
| Coding Region Coverage |
- 1x: 99.9%
- 3x: 99.5%
- 10x: 97.4%
- 20x: 91.6%
|
| Validation Efficiency |
98% (53/54) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a putative serine/threonine kinase that localizes to the mitotic apparatus and complexes with cell cycle controller CDC2 kinase in early mitosis. The protein is phosphorylated in a cell-cycle dependent manner, with late prophase phosphorylation remaining through metaphase. The N-terminal region of the protein binds CDC2 to form a complex showing reduced H1 histone kinase activity, indicating a role as a negative regulator of CDC2/cyclin A. In addition, the C-terminal kinase domain binds to its own N-terminal region, suggesting potential negative regulation through interference with complex formation via intramolecular binding. Biochemical and genetic data suggest a role as a tumor suppressor. This is supported by studies in knockout mice showing development of soft-tissue sarcomas, ovarian stromal cell tumors and a high sensitivity to carcinogenic treatments. Two protein-coding transcripts and one non-protein coding transcript have been found for this gene. [provided by RefSeq, Jul 2012]
PHENOTYPE: Homozygotes for a targeted null mutation exhibit high postnatal mortality, lack of mammary development, infertility, pituitary hyperplasia, reduced hormone levels, growth retardation, and susceptibility to sarcomas and ovarian stromal cell tumors. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 56 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Agl |
T |
C |
3: 116,544,060 (GRCm39) |
T1416A |
probably damaging |
Het |
| Atp7b |
A |
G |
8: 22,518,494 (GRCm39) |
S103P |
probably damaging |
Het |
| Ces1h |
A |
C |
8: 94,078,654 (GRCm39) |
*563G |
probably null |
Het |
| Cfap157 |
G |
T |
2: 32,669,086 (GRCm39) |
A339E |
probably benign |
Het |
| Crebbp |
C |
T |
16: 3,937,670 (GRCm39) |
A698T |
possibly damaging |
Het |
| Cyp2b13 |
A |
G |
7: 25,785,324 (GRCm39) |
H231R |
possibly damaging |
Het |
| Ddx31 |
A |
T |
2: 28,765,750 (GRCm39) |
T483S |
probably damaging |
Het |
| Defa25 |
A |
T |
8: 21,575,201 (GRCm39) |
D60V |
possibly damaging |
Het |
| Dnah5 |
G |
A |
15: 28,403,633 (GRCm39) |
A3453T |
probably benign |
Het |
| Dnah6 |
A |
T |
6: 73,115,743 (GRCm39) |
F1500I |
probably damaging |
Het |
| Eprs1 |
C |
T |
1: 185,146,621 (GRCm39) |
A1217V |
probably damaging |
Het |
| Ermp1 |
T |
C |
19: 29,604,335 (GRCm39) |
Y481C |
probably benign |
Het |
| Fmn2 |
T |
A |
1: 174,420,670 (GRCm39) |
N635K |
unknown |
Het |
| Fras1 |
A |
G |
5: 96,883,061 (GRCm39) |
D2531G |
probably damaging |
Het |
| Frat1 |
C |
T |
19: 41,819,264 (GRCm39) |
Q220* |
probably null |
Het |
| Gcc2 |
T |
A |
10: 58,123,103 (GRCm39) |
|
probably null |
Het |
| Gm3285 |
T |
C |
10: 77,698,447 (GRCm39) |
|
probably benign |
Het |
| Gm9857 |
T |
C |
3: 108,847,379 (GRCm39) |
|
probably benign |
Het |
| Grin2b |
C |
A |
6: 135,710,108 (GRCm39) |
W1146L |
probably damaging |
Het |
| Hells |
T |
A |
19: 38,919,948 (GRCm39) |
L33I |
probably benign |
Het |
| Ift81 |
T |
A |
5: 122,748,229 (GRCm39) |
R54* |
probably null |
Het |
| Ints12 |
G |
A |
3: 132,802,639 (GRCm39) |
R41Q |
possibly damaging |
Het |
| Katnal2 |
C |
T |
18: 77,067,733 (GRCm39) |
E403K |
probably benign |
Het |
| Kcnk1 |
A |
G |
8: 126,722,199 (GRCm39) |
M1V |
probably null |
Het |
| Kdm5a |
A |
G |
6: 120,389,422 (GRCm39) |
T950A |
probably benign |
Het |
| Kdr |
G |
A |
5: 76,113,549 (GRCm39) |
A773V |
probably damaging |
Het |
| Mug1 |
A |
G |
6: 121,817,200 (GRCm39) |
I90V |
probably benign |
Het |
| Nid2 |
A |
G |
14: 19,852,484 (GRCm39) |
D1064G |
probably benign |
Het |
| Nkx2-4 |
A |
T |
2: 146,926,187 (GRCm39) |
I225N |
possibly damaging |
Het |
| Nlrp4e |
A |
G |
7: 23,020,740 (GRCm39) |
D409G |
probably benign |
Het |
| Ogfod2 |
G |
C |
5: 124,252,866 (GRCm39) |
R292P |
possibly damaging |
Het |
| Oprk1 |
C |
T |
1: 5,672,507 (GRCm39) |
P215S |
probably damaging |
Het |
| Or5d36 |
A |
T |
2: 87,901,053 (GRCm39) |
F224L |
probably benign |
Het |
| Or6c35 |
T |
A |
10: 129,169,033 (GRCm39) |
C94* |
probably null |
Het |
| Or7g27 |
T |
A |
9: 19,249,925 (GRCm39) |
H56Q |
possibly damaging |
Het |
| Or8g21 |
T |
C |
9: 38,906,210 (GRCm39) |
I174V |
possibly damaging |
Het |
| Pcdhb16 |
A |
G |
18: 37,612,225 (GRCm39) |
K395R |
possibly damaging |
Het |
| Ptprg |
C |
A |
14: 11,962,714 (GRCm38) |
P171T |
probably damaging |
Het |
| Pycard |
T |
C |
7: 127,592,741 (GRCm39) |
T29A |
probably benign |
Het |
| Rap1gap2 |
G |
A |
11: 74,298,754 (GRCm39) |
A452V |
probably benign |
Het |
| Rasgrf1 |
C |
G |
9: 89,892,516 (GRCm39) |
T1072S |
probably benign |
Het |
| Rc3h2 |
G |
A |
2: 37,272,956 (GRCm39) |
R707* |
probably null |
Het |
| Rsf1 |
G |
A |
7: 97,229,117 (GRCm39) |
|
probably benign |
Het |
| Senp7 |
T |
C |
16: 55,993,618 (GRCm39) |
I767T |
probably damaging |
Het |
| Setd7 |
A |
G |
3: 51,450,183 (GRCm39) |
V81A |
probably benign |
Het |
| Shisal2a |
A |
G |
4: 108,225,224 (GRCm39) |
S113P |
probably benign |
Het |
| Shkbp1 |
A |
G |
7: 27,041,800 (GRCm39) |
S685P |
probably benign |
Het |
| Snrnp200 |
A |
G |
2: 127,068,372 (GRCm39) |
E904G |
probably damaging |
Het |
| Spata22 |
T |
A |
11: 73,245,526 (GRCm39) |
|
probably null |
Het |
| Spata31e2 |
T |
A |
1: 26,721,659 (GRCm39) |
N1174Y |
probably damaging |
Het |
| Tas2r138 |
G |
T |
6: 40,589,733 (GRCm39) |
T171K |
possibly damaging |
Het |
| Tor1aip1 |
T |
C |
1: 155,893,999 (GRCm39) |
D77G |
possibly damaging |
Het |
| Vav3 |
A |
T |
3: 109,434,732 (GRCm39) |
H421L |
probably benign |
Het |
| Vmn1r43 |
A |
G |
6: 89,846,841 (GRCm39) |
L215P |
probably damaging |
Het |
| Vmn2r100 |
T |
A |
17: 19,742,785 (GRCm39) |
S386R |
probably benign |
Het |
| Xpa |
T |
A |
4: 46,183,089 (GRCm39) |
R233S |
probably benign |
Het |
|
| Other mutations in Lats1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00234:Lats1
|
APN |
10 |
7,567,330 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL00595:Lats1
|
APN |
10 |
7,578,069 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL00932:Lats1
|
APN |
10 |
7,588,506 (GRCm39) |
missense |
possibly damaging |
0.69 |
|
IGL01019:Lats1
|
APN |
10 |
7,581,435 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01380:Lats1
|
APN |
10 |
7,567,544 (GRCm39) |
missense |
possibly damaging |
0.69 |
|
IGL01965:Lats1
|
APN |
10 |
7,577,470 (GRCm39) |
missense |
probably benign |
0.10 |
|
IGL02027:Lats1
|
APN |
10 |
7,588,712 (GRCm39) |
missense |
probably benign |
|
|
IGL02611:Lats1
|
APN |
10 |
7,581,551 (GRCm39) |
missense |
possibly damaging |
0.91 |
|
IGL02997:Lats1
|
APN |
10 |
7,578,018 (GRCm39) |
missense |
possibly damaging |
0.53 |
|
IGL03107:Lats1
|
APN |
10 |
7,588,510 (GRCm39) |
missense |
probably benign |
0.15 |
|
I1329:Lats1
|
UTSW |
10 |
7,588,566 (GRCm39) |
missense |
probably benign |
0.10 |
|
PIT4378001:Lats1
|
UTSW |
10 |
7,581,369 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0153:Lats1
|
UTSW |
10 |
7,567,339 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0568:Lats1
|
UTSW |
10 |
7,588,292 (GRCm39) |
missense |
possibly damaging |
0.69 |
|
R0581:Lats1
|
UTSW |
10 |
7,578,705 (GRCm39) |
missense |
possibly damaging |
0.67 |
|
R0604:Lats1
|
UTSW |
10 |
7,588,425 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R1681:Lats1
|
UTSW |
10 |
7,581,678 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R1694:Lats1
|
UTSW |
10 |
7,577,709 (GRCm39) |
missense |
probably benign |
0.07 |
|
R1840:Lats1
|
UTSW |
10 |
7,586,703 (GRCm39) |
nonsense |
probably null |
|
|
R1914:Lats1
|
UTSW |
10 |
7,586,221 (GRCm39) |
splice site |
probably benign |
|
|
R2137:Lats1
|
UTSW |
10 |
7,577,611 (GRCm39) |
missense |
possibly damaging |
0.71 |
|
R2317:Lats1
|
UTSW |
10 |
7,567,540 (GRCm39) |
nonsense |
probably null |
|
|
R3863:Lats1
|
UTSW |
10 |
7,581,510 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3864:Lats1
|
UTSW |
10 |
7,581,510 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4597:Lats1
|
UTSW |
10 |
7,567,510 (GRCm39) |
missense |
probably benign |
0.00 |
|
R4657:Lats1
|
UTSW |
10 |
7,581,448 (GRCm39) |
missense |
possibly damaging |
0.82 |
|
R4658:Lats1
|
UTSW |
10 |
7,578,493 (GRCm39) |
missense |
probably benign |
|
|
R4663:Lats1
|
UTSW |
10 |
7,588,347 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4870:Lats1
|
UTSW |
10 |
7,581,549 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5101:Lats1
|
UTSW |
10 |
7,588,348 (GRCm39) |
nonsense |
probably null |
|
|
R5134:Lats1
|
UTSW |
10 |
7,567,575 (GRCm39) |
missense |
probably benign |
0.34 |
|
R5150:Lats1
|
UTSW |
10 |
7,588,415 (GRCm39) |
missense |
probably benign |
|
|
R5546:Lats1
|
UTSW |
10 |
7,581,518 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R5820:Lats1
|
UTSW |
10 |
7,581,672 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6006:Lats1
|
UTSW |
10 |
7,581,359 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6301:Lats1
|
UTSW |
10 |
7,578,871 (GRCm39) |
missense |
probably benign |
0.01 |
|
R6544:Lats1
|
UTSW |
10 |
7,577,434 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R6874:Lats1
|
UTSW |
10 |
7,586,615 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7328:Lats1
|
UTSW |
10 |
7,581,311 (GRCm39) |
missense |
possibly damaging |
0.62 |
|
R7390:Lats1
|
UTSW |
10 |
7,577,859 (GRCm39) |
nonsense |
probably null |
|
|
R7438:Lats1
|
UTSW |
10 |
7,588,706 (GRCm39) |
nonsense |
probably null |
|
|
R7457:Lats1
|
UTSW |
10 |
7,586,655 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7524:Lats1
|
UTSW |
10 |
7,577,742 (GRCm39) |
missense |
possibly damaging |
0.89 |
|
R7593:Lats1
|
UTSW |
10 |
7,577,476 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7736:Lats1
|
UTSW |
10 |
7,578,128 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7884:Lats1
|
UTSW |
10 |
7,573,290 (GRCm39) |
nonsense |
probably null |
|
|
R8166:Lats1
|
UTSW |
10 |
7,577,880 (GRCm39) |
missense |
probably benign |
|
|
R8248:Lats1
|
UTSW |
10 |
7,581,667 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8458:Lats1
|
UTSW |
10 |
7,586,688 (GRCm39) |
nonsense |
probably null |
|
|
R8477:Lats1
|
UTSW |
10 |
7,581,279 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8547:Lats1
|
UTSW |
10 |
7,588,613 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9163:Lats1
|
UTSW |
10 |
7,578,052 (GRCm39) |
missense |
probably benign |
|
|
R9441:Lats1
|
UTSW |
10 |
7,578,681 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R9673:Lats1
|
UTSW |
10 |
7,588,387 (GRCm39) |
missense |
probably benign |
0.29 |
|
RF021:Lats1
|
UTSW |
10 |
7,586,372 (GRCm39) |
missense |
probably damaging |
1.00 |
|
X0026:Lats1
|
UTSW |
10 |
7,586,387 (GRCm39) |
missense |
probably damaging |
1.00 |
|
X0053:Lats1
|
UTSW |
10 |
7,567,373 (GRCm39) |
missense |
probably benign |
0.00 |
|
Z1176:Lats1
|
UTSW |
10 |
7,581,573 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Predicted Primers |
PCR Primer
(F):5'- TAGGACACAGCCAGGTCTCAAC -3'
(R):5'- ATTGAACAAATGCTCAGCAGTG -3'
Sequencing Primer
(F):5'- GGTCTCAACCTTGGCATTCATC -3'
(R):5'- CTAGAATCTGACTTTGGGCCAGGAC -3'
|
| Posted On |
2018-06-22 |
Incidental Mutation