Incidental Mutation 'R9441:Lats1'
| ID |
713652 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Lats1
|
| Ensembl Gene |
ENSMUSG00000040021 |
| Gene Name |
large tumor suppressor |
| Synonyms |
|
| MMRRC Submission |
|
| Accession Numbers |
|
| Essential gene? |
Probably essential
(E-score: 0.847)
|
| Stock # |
R9441 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Not validated
|
| Chromosome |
10 |
| Chromosomal Location |
7556978-7592224 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
G to T
at 7578681 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Glycine to Tryptophan
at position 602
(G602W)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000132078
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000040043]
[ENSMUST00000165952]
[ENSMUST00000217931]
|
| AlphaFold |
Q8BYR2 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000040043
AA Change: G602W
PolyPhen 2
Score 0.962 (Sensitivity: 0.78; Specificity: 0.95)
|
| SMART Domains |
Protein: ENSMUSP00000041915
Gene: ENSMUSG00000040021
AA Change: G602W
| 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 |
probably damaging
Transcript: ENSMUST00000165952
AA Change: G602W
PolyPhen 2
Score 0.962 (Sensitivity: 0.78; Specificity: 0.95)
|
| SMART Domains |
Protein: ENSMUSP00000132078
Gene: ENSMUSG00000040021
AA Change: G602W
| 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 |
probably damaging
Transcript: ENSMUST00000217931
AA Change: G602W
PolyPhen 2
Score 0.962 (Sensitivity: 0.78; Specificity: 0.95)
|
| Coding Region Coverage |
- 1x: 100.0%
- 3x: 99.9%
- 10x: 99.4%
- 20x: 98.0%
|
| Validation Efficiency |
|
| 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 |
|---|
| 4930563M21Rik |
C |
A |
9: 55,917,776 (GRCm39) |
G20V |
unknown |
Het |
| Adam22 |
T |
C |
5: 8,161,974 (GRCm39) |
T733A |
possibly damaging |
Het |
| Adam28 |
T |
A |
14: 68,874,943 (GRCm39) |
N245Y |
probably damaging |
Het |
| Aldh9a1 |
C |
G |
1: 167,177,919 (GRCm39) |
R39G |
probably benign |
Het |
| Armc3 |
A |
C |
2: 19,253,426 (GRCm39) |
E189A |
possibly damaging |
Het |
| Atg9a |
C |
T |
1: 75,163,086 (GRCm39) |
C338Y |
possibly damaging |
Het |
| Card6 |
TTGGGAGGACTGTGGATGAGAGGGCTTAGCATGGGAGGACTGTGGATGAGAGGGCTTAGCATGGGAGGACTGTGGATGAGAGGGCTTAGCATGGGAGGACTGCGGATGAGAGGGCTTAGCATGGGAGGACTG |
TTGGGAGGACTGTGGATGAGAGGGCTTAGCATGGGAGGACTGTGGATGAGAGGGCTTAGCATGGGAGGACTGCGGATGAGAGGGCTTAGCATGGGAGGACTG |
15: 5,128,173 (GRCm39) |
|
probably benign |
Het |
| Cars1 |
G |
A |
7: 143,123,185 (GRCm39) |
T560I |
probably benign |
Het |
| Casp8ap2 |
A |
G |
4: 32,645,873 (GRCm39) |
K1649E |
probably benign |
Het |
| Ccdc88b |
T |
C |
19: 6,833,213 (GRCm39) |
E278G |
probably damaging |
Het |
| Cd84 |
G |
A |
1: 171,713,994 (GRCm39) |
|
probably null |
Het |
| Ces2g |
G |
T |
8: 105,690,623 (GRCm39) |
A135S |
possibly damaging |
Het |
| Cfh |
T |
C |
1: 140,030,149 (GRCm39) |
D926G |
probably benign |
Het |
| Chrm2 |
A |
G |
6: 36,500,955 (GRCm39) |
T271A |
probably benign |
Het |
| Col6a3 |
G |
T |
1: 90,705,249 (GRCm39) |
Y2824* |
probably null |
Het |
| Cth |
T |
A |
3: 157,616,575 (GRCm39) |
R196S |
probably damaging |
Het |
| Cyp2g1 |
T |
C |
7: 26,514,060 (GRCm39) |
M222T |
possibly damaging |
Het |
| Depdc5 |
T |
A |
5: 33,095,042 (GRCm39) |
M773K |
probably benign |
Het |
| Dmbx1 |
G |
A |
4: 115,780,884 (GRCm39) |
P39L |
probably damaging |
Het |
| Dst |
G |
C |
1: 34,238,432 (GRCm39) |
W1697C |
probably damaging |
Het |
| Eno1 |
C |
T |
4: 150,321,208 (GRCm39) |
|
probably benign |
Het |
| Erc2 |
G |
T |
14: 27,802,114 (GRCm39) |
V761L |
possibly damaging |
Het |
| Frem1 |
A |
T |
4: 82,924,083 (GRCm39) |
I292N |
probably damaging |
Het |
| Ftdc2 |
G |
A |
16: 58,458,884 (GRCm39) |
|
probably benign |
Het |
| Hip1 |
G |
T |
5: 135,460,571 (GRCm39) |
L530M |
possibly damaging |
Het |
| Kcna2 |
A |
G |
3: 107,012,268 (GRCm39) |
Q283R |
probably benign |
Het |
| Kndc1 |
G |
A |
7: 139,501,392 (GRCm39) |
D894N |
probably damaging |
Het |
| Lgals12 |
A |
G |
19: 7,581,356 (GRCm39) |
L117P |
probably damaging |
Het |
| Mfsd4b1 |
A |
T |
10: 39,878,680 (GRCm39) |
L406I |
possibly damaging |
Het |
| Msln |
A |
T |
17: 25,969,731 (GRCm39) |
M333K |
probably benign |
Het |
| Mup2 |
A |
G |
4: 60,139,740 (GRCm39) |
V16A |
probably benign |
Het |
| Mybpc2 |
T |
C |
7: 44,166,330 (GRCm39) |
E220G |
probably null |
Het |
| Myh6 |
A |
G |
14: 55,197,771 (GRCm39) |
Y456H |
probably benign |
Het |
| Nlrp1a |
A |
G |
11: 71,013,934 (GRCm39) |
S439P |
probably damaging |
Het |
| Nyap1 |
T |
C |
5: 137,733,194 (GRCm39) |
E613G |
probably benign |
Het |
| Or10b1 |
G |
A |
10: 78,355,609 (GRCm39) |
V56M |
probably benign |
Het |
| Parp8 |
C |
T |
13: 117,029,562 (GRCm39) |
V554M |
probably damaging |
Het |
| Phpt1 |
A |
T |
2: 25,464,750 (GRCm39) |
D34E |
probably benign |
Het |
| Ppip5k2 |
G |
A |
1: 97,672,921 (GRCm39) |
S463L |
probably benign |
Het |
| Prss28 |
A |
G |
17: 25,530,215 (GRCm39) |
Q173R |
probably benign |
Het |
| Rtel1 |
T |
A |
2: 180,988,860 (GRCm39) |
W441R |
possibly damaging |
Het |
| Serbp1 |
T |
C |
6: 67,244,025 (GRCm39) |
|
probably benign |
Het |
| Skint5 |
T |
C |
4: 113,347,848 (GRCm39) |
K1319E |
unknown |
Het |
| Slc35a4 |
G |
A |
18: 36,816,111 (GRCm39) |
G314S |
probably damaging |
Het |
| Slc8a1 |
A |
G |
17: 81,956,498 (GRCm39) |
I180T |
probably damaging |
Het |
| Spire1 |
G |
A |
18: 67,652,462 (GRCm39) |
P205L |
probably benign |
Het |
| Tat |
G |
T |
8: 110,720,547 (GRCm39) |
G168W |
probably damaging |
Het |
| Thap1 |
CAGCATCTGCTCGGAGCA |
CAGCA |
8: 26,650,884 (GRCm39) |
|
probably null |
Het |
| Trh |
C |
T |
6: 92,219,939 (GRCm39) |
G126R |
probably benign |
Het |
| Ugcg |
G |
A |
4: 59,207,843 (GRCm39) |
G61R |
probably damaging |
Het |
| Uggt1 |
T |
C |
1: 36,260,306 (GRCm39) |
T170A |
probably benign |
Het |
| Unc5b |
G |
A |
10: 60,608,028 (GRCm39) |
P702S |
probably damaging |
Het |
| Usp8 |
A |
G |
2: 126,562,073 (GRCm39) |
D89G |
possibly damaging |
Het |
| Vmn2r1 |
T |
A |
3: 64,012,674 (GRCm39) |
I845K |
probably damaging |
Het |
| Vnn3 |
A |
G |
10: 23,740,498 (GRCm39) |
N267S |
possibly damaging |
Het |
| Xkr9 |
A |
G |
1: 13,771,587 (GRCm39) |
R368G |
possibly damaging |
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 |
|
R6647:Lats1
|
UTSW |
10 |
7,573,271 (GRCm39) |
missense |
possibly damaging |
0.81 |
|
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 |
|
|
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'- ACCTGTTGCTGAAGCTCCAAG -3'
(R):5'- TGAGAAAGTTTAAAGCTTTACCCGC -3'
Sequencing Primer
(F):5'- GCTCCAAGCTATCAAGGTCC -3'
(R):5'- TGCTTCTTCCGATGCAGACG -3'
|
| Posted On |
2022-06-15 |
Incidental Mutation