Incidental Mutation 'R7457:Lats1'
| ID |
578209 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Lats1
|
| Ensembl Gene |
ENSMUSG00000040021 |
| Gene Name |
large tumor suppressor |
| Synonyms |
|
| MMRRC Submission |
045531-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably essential
(E-score: 0.822)
|
| Stock # |
R7457 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Validated
|
| Chromosome |
10 |
| Chromosomal Location |
7556978-7592224 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to A
at 7586655 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Leucine to Histidine
at position 939
(L939H)
|
| 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: L939H
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000041915
Gene: ENSMUSG00000040021
AA Change: L939H
| 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: L939H
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000132078
Gene: ENSMUSG00000040021
AA Change: L939H
| 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: L939H
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| Coding Region Coverage |
- 1x: 100.0%
- 3x: 100.0%
- 10x: 99.7%
- 20x: 99.0%
|
| Validation Efficiency |
100% (61/61) |
| 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: 61 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Adam32 |
A |
T |
8: 25,374,635 (GRCm39) |
H452Q |
probably damaging |
Het |
| Adcy8 |
A |
T |
15: 64,792,529 (GRCm39) |
N142K |
possibly damaging |
Het |
| Alkbh8 |
T |
A |
9: 3,343,056 (GRCm39) |
S57R |
probably damaging |
Het |
| Atp4a |
A |
G |
7: 30,420,192 (GRCm39) |
T780A |
probably benign |
Het |
| Atp9b |
A |
T |
18: 80,960,833 (GRCm39) |
|
probably null |
Het |
| Cdyl2 |
A |
T |
8: 117,305,935 (GRCm39) |
V442E |
probably damaging |
Het |
| Ces2a |
C |
T |
8: 105,464,021 (GRCm39) |
R218C |
possibly damaging |
Het |
| Cfap57 |
A |
T |
4: 118,446,198 (GRCm39) |
V688E |
probably damaging |
Het |
| Clec11a |
T |
C |
7: 43,955,379 (GRCm39) |
T139A |
probably benign |
Het |
| Clstn1 |
A |
T |
4: 149,719,373 (GRCm39) |
T411S |
probably benign |
Het |
| Commd5 |
A |
T |
15: 76,784,824 (GRCm39) |
S74C |
probably damaging |
Het |
| Cyp3a59 |
C |
A |
5: 146,041,560 (GRCm39) |
P368Q |
probably damaging |
Het |
| Dennd4b |
A |
G |
3: 90,176,622 (GRCm39) |
M309V |
probably benign |
Het |
| Dhrs9 |
T |
A |
2: 69,231,611 (GRCm39) |
V257E |
probably benign |
Het |
| Dhx16 |
T |
C |
17: 36,201,952 (GRCm39) |
V993A |
probably damaging |
Het |
| Dok5 |
A |
T |
2: 170,712,735 (GRCm39) |
Q247L |
probably benign |
Het |
| E330034G19Rik |
A |
T |
14: 24,359,582 (GRCm39) |
E331V |
unknown |
Het |
| Efs |
A |
G |
14: 55,157,451 (GRCm39) |
S287P |
probably benign |
Het |
| Fbn1 |
T |
C |
2: 125,193,667 (GRCm39) |
N1384S |
possibly damaging |
Het |
| Flt4 |
A |
G |
11: 49,521,155 (GRCm39) |
E388G |
possibly damaging |
Het |
| Fmn2 |
T |
A |
1: 174,331,303 (GRCm39) |
|
probably null |
Het |
| Fmo4 |
T |
C |
1: 162,621,672 (GRCm39) |
Y513C |
probably benign |
Het |
| Gbp4 |
T |
C |
5: 105,267,419 (GRCm39) |
E500G |
probably damaging |
Het |
| Gm29106 |
T |
C |
1: 118,126,982 (GRCm39) |
S225P |
probably damaging |
Het |
| Gstt2 |
G |
A |
10: 75,668,354 (GRCm39) |
R134W |
probably damaging |
Het |
| Gucy1b2 |
T |
C |
14: 62,630,401 (GRCm39) |
T782A |
probably benign |
Het |
| Gzf1 |
G |
T |
2: 148,532,002 (GRCm39) |
R543L |
probably damaging |
Het |
| H2-Eb2 |
G |
A |
17: 34,553,321 (GRCm39) |
G169E |
probably damaging |
Het |
| Hdhd3 |
T |
A |
4: 62,418,027 (GRCm39) |
R50W |
probably damaging |
Het |
| Hdlbp |
T |
C |
1: 93,355,944 (GRCm39) |
K407E |
probably benign |
Het |
| Isl2 |
A |
G |
9: 55,452,240 (GRCm39) |
T271A |
probably benign |
Het |
| Kbtbd7 |
GTCTCTC |
GTC |
14: 79,665,364 (GRCm39) |
|
probably null |
Het |
| Kdm4b |
T |
A |
17: 56,703,319 (GRCm39) |
N671K |
probably damaging |
Het |
| Map3k1 |
A |
T |
13: 111,892,789 (GRCm39) |
M822K |
probably damaging |
Het |
| Mettl18 |
C |
A |
1: 163,824,330 (GRCm39) |
T217N |
probably damaging |
Het |
| Nav3 |
A |
T |
10: 109,532,189 (GRCm39) |
Y2083* |
probably null |
Het |
| Nckap1l |
T |
C |
15: 103,362,233 (GRCm39) |
|
probably benign |
Het |
| Nkx2-3 |
A |
G |
19: 43,600,986 (GRCm39) |
D16G |
probably damaging |
Het |
| Nlrx1 |
A |
G |
9: 44,167,807 (GRCm39) |
S697P |
probably benign |
Het |
| Or14j4 |
T |
C |
17: 37,921,456 (GRCm39) |
K62R |
possibly damaging |
Het |
| Or1e29 |
G |
C |
11: 73,667,652 (GRCm39) |
S167C |
probably benign |
Het |
| Or4k6 |
A |
T |
14: 50,475,825 (GRCm39) |
N172K |
probably damaging |
Het |
| Or6c75 |
T |
C |
10: 129,337,575 (GRCm39) |
V266A |
probably damaging |
Het |
| Pappa |
A |
T |
4: 65,107,503 (GRCm39) |
D638V |
probably damaging |
Het |
| Pot1a |
T |
C |
6: 25,771,621 (GRCm39) |
D200G |
probably benign |
Het |
| Ptprs |
G |
T |
17: 56,726,502 (GRCm39) |
T1366K |
probably damaging |
Het |
| Sass6 |
A |
T |
3: 116,413,813 (GRCm39) |
R505S |
probably benign |
Het |
| Slc30a6 |
T |
C |
17: 74,714,233 (GRCm39) |
I84T |
probably benign |
Het |
| Sox10 |
A |
T |
15: 79,040,339 (GRCm39) |
F400L |
probably benign |
Het |
| Spata31d1b |
A |
T |
13: 59,864,723 (GRCm39) |
I624F |
probably damaging |
Het |
| Stpg4 |
A |
G |
17: 87,735,006 (GRCm39) |
|
probably null |
Het |
| Tbc1d9 |
G |
T |
8: 83,963,309 (GRCm39) |
K340N |
probably damaging |
Het |
| Tspan12 |
T |
A |
6: 21,772,682 (GRCm39) |
H289L |
probably benign |
Het |
| Ubr1 |
T |
A |
2: 120,748,309 (GRCm39) |
T809S |
probably benign |
Het |
| Vmn1r43 |
C |
T |
6: 89,847,172 (GRCm39) |
V105M |
probably damaging |
Het |
| Vmn1r49 |
A |
G |
6: 90,049,534 (GRCm39) |
V156A |
probably benign |
Het |
| Wnt5a |
A |
G |
14: 28,240,236 (GRCm39) |
|
probably null |
Het |
| Wwp2 |
T |
A |
8: 108,244,592 (GRCm39) |
S255T |
probably benign |
Het |
| Zbtb10 |
A |
G |
3: 9,316,538 (GRCm39) |
T117A |
possibly damaging |
Het |
| Zfp800 |
C |
T |
6: 28,244,228 (GRCm39) |
V246I |
probably benign |
Het |
| Zfp955a |
G |
T |
17: 33,463,025 (GRCm39) |
Y35* |
probably null |
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 |
|
|
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'- CCTGAAGTGCTACTGCGAAC -3'
(R):5'- GTGAATGGAATACTTCTGTCTCAAG -3'
Sequencing Primer
(F):5'- CAGTAGTATTTTAAAGCAGCCAACC -3'
(R):5'- CTGTCTCAAGTGTTTCAGGAAAGAC -3'
|
| Posted On |
2019-10-07 |
Incidental Mutation