Incidental Mutation 'R0604:Lats1'
| ID |
55594 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Lats1
|
| Ensembl Gene |
ENSMUSG00000040021 |
| Gene Name |
large tumor suppressor |
| Synonyms |
|
| MMRRC Submission |
038793-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably essential
(E-score: 0.822)
|
| Stock # |
R0604 (G1)
|
| Quality Score |
200 |
|
Status
|
Not validated
|
| Chromosome |
10 |
| Chromosomal Location |
7556978-7592224 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to A
at 7588425 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Phenylalanine to Tyrosine
at position 1014
(F1014Y)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000151533
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000040043]
[ENSMUST00000165952]
[ENSMUST00000217931]
|
| AlphaFold |
Q8BYR2 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000040043
AA Change: F1014Y
PolyPhen 2
Score 0.959 (Sensitivity: 0.78; Specificity: 0.95)
|
| SMART Domains |
Protein: ENSMUSP00000041915
Gene: ENSMUSG00000040021
AA Change: F1014Y
| 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: F1014Y
PolyPhen 2
Score 0.959 (Sensitivity: 0.78; Specificity: 0.95)
|
| SMART Domains |
Protein: ENSMUSP00000132078
Gene: ENSMUSG00000040021
AA Change: F1014Y
| 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: F1014Y
PolyPhen 2
Score 0.959 (Sensitivity: 0.78; Specificity: 0.95)
|
| Coding Region Coverage |
- 1x: 99.4%
- 3x: 98.8%
- 10x: 97.4%
- 20x: 94.8%
|
| 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: 32 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Acap1 |
T |
C |
11: 69,775,451 (GRCm39) |
E302G |
probably benign |
Het |
| Acsbg3 |
T |
A |
17: 57,192,169 (GRCm39) |
Y577* |
probably null |
Het |
| Adrb2 |
G |
A |
18: 62,311,586 (GRCm39) |
T413I |
possibly damaging |
Het |
| Aqr |
T |
C |
2: 113,961,085 (GRCm39) |
K725R |
probably benign |
Het |
| Braf |
A |
G |
6: 39,600,631 (GRCm39) |
I662T |
probably damaging |
Het |
| Ccdc178 |
A |
G |
18: 22,200,500 (GRCm39) |
S435P |
probably benign |
Het |
| Chd9 |
A |
G |
8: 91,763,170 (GRCm39) |
M2332V |
possibly damaging |
Het |
| Clgn |
T |
C |
8: 84,150,823 (GRCm39) |
V496A |
probably benign |
Het |
| Dnah17 |
A |
C |
11: 118,012,297 (GRCm39) |
S193R |
probably benign |
Het |
| Dntt |
A |
G |
19: 41,041,588 (GRCm39) |
E424G |
probably benign |
Het |
| Fam149a |
A |
G |
8: 45,798,045 (GRCm39) |
L492P |
probably damaging |
Het |
| Fetub |
T |
C |
16: 22,754,410 (GRCm39) |
Y126H |
possibly damaging |
Het |
| Fgfr3 |
A |
T |
5: 33,890,126 (GRCm39) |
Y96F |
probably damaging |
Het |
| Gm4952 |
A |
G |
19: 12,602,036 (GRCm39) |
E148G |
probably benign |
Het |
| Gucy2g |
T |
A |
19: 55,191,519 (GRCm39) |
L977F |
probably benign |
Het |
| Il1r1 |
T |
C |
1: 40,321,406 (GRCm39) |
V6A |
probably benign |
Het |
| Itsn2 |
C |
A |
12: 4,708,189 (GRCm39) |
Q832K |
probably benign |
Het |
| Mcc |
G |
A |
18: 44,606,823 (GRCm39) |
A536V |
probably damaging |
Het |
| Mtrf1 |
T |
C |
14: 79,653,327 (GRCm39) |
V334A |
possibly damaging |
Het |
| Or1j21 |
T |
A |
2: 36,684,119 (GRCm39) |
Y290* |
probably null |
Het |
| Or2t46 |
T |
A |
11: 58,472,174 (GRCm39) |
M168K |
probably damaging |
Het |
| Or2z8 |
C |
T |
8: 72,812,244 (GRCm39) |
T240M |
probably damaging |
Het |
| Or4p18 |
T |
C |
2: 88,232,727 (GRCm39) |
T184A |
probably benign |
Het |
| Pard6g |
A |
G |
18: 80,160,423 (GRCm39) |
S179G |
probably damaging |
Het |
| Pierce1 |
C |
A |
2: 28,356,103 (GRCm39) |
R60L |
possibly damaging |
Het |
| Polr3a |
G |
A |
14: 24,534,232 (GRCm39) |
P91L |
probably damaging |
Het |
| Psg27 |
A |
T |
7: 18,290,997 (GRCm39) |
V402D |
probably damaging |
Het |
| Rttn |
A |
G |
18: 88,995,882 (GRCm39) |
I222V |
probably damaging |
Het |
| Sp9 |
T |
A |
2: 73,103,982 (GRCm39) |
S179T |
probably benign |
Het |
| Tbc1d8 |
T |
A |
1: 39,444,407 (GRCm39) |
H184L |
probably damaging |
Het |
| Vmn1r69 |
A |
G |
7: 10,314,581 (GRCm39) |
V50A |
probably benign |
Het |
| Vmn2r58 |
A |
G |
7: 41,510,000 (GRCm39) |
F526L |
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 |
|
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 |
|
|
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'- AGTACCCGGCAGATCATTTAGAAAACC -3'
(R):5'- CAGACTGTTGTTCTGAGCCCTGTG -3'
Sequencing Primer
(F):5'- GTACAAAACCTGGGAAATTACTGTG -3'
(R):5'- TCTGAGCCCTGTGAATGAATG -3'
|
| Posted On |
2013-07-11 |
Incidental Mutation