Incidental Mutation 'R0568:Lats1'
| ID |
46267 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Lats1
|
| Ensembl Gene |
ENSMUSG00000040021 |
| Gene Name |
large tumor suppressor |
| Synonyms |
|
| MMRRC Submission |
038759-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably essential
(E-score: 0.890)
|
| Stock # |
R0568 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
10 |
| Chromosomal Location |
7681214-7716460 bp(+) (GRCm38) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to T
at 7712528 bp (GRCm38)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Isoleucine to Phenylalanine
at position 970
(I970F)
|
| 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: I970F
PolyPhen 2
Score 0.692 (Sensitivity: 0.86; Specificity: 0.92)
|
| SMART Domains |
Protein: ENSMUSP00000041915
Gene: ENSMUSG00000040021
AA Change: I970F
| 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: I970F
PolyPhen 2
Score 0.692 (Sensitivity: 0.86; Specificity: 0.92)
|
| SMART Domains |
Protein: ENSMUSP00000132078
Gene: ENSMUSG00000040021
AA Change: I970F
| 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: I970F
PolyPhen 2
Score 0.692 (Sensitivity: 0.86; Specificity: 0.92)
|
| Meta Mutation Damage Score |
0.3068 |
| Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.4%
- 10x: 96.5%
- 20x: 93.4%
|
| Validation Efficiency |
100% (38/38) |
| 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: 37 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Acnat1 |
G |
A |
4: 49,451,003 (GRCm38) |
T36I |
possibly damaging |
Het |
| Adamts20 |
T |
C |
15: 94,291,713 (GRCm38) |
|
probably benign |
Het |
| Adamtsl1 |
T |
C |
4: 86,418,552 (GRCm38) |
L1558S |
probably damaging |
Het |
| Ap3b2 |
A |
G |
7: 81,464,629 (GRCm38) |
|
probably null |
Het |
| Bag2 |
T |
C |
1: 33,746,978 (GRCm38) |
M88V |
probably benign |
Het |
| Brms1l |
A |
G |
12: 55,861,388 (GRCm38) |
|
probably null |
Het |
| C8b |
A |
G |
4: 104,793,380 (GRCm38) |
I462V |
probably benign |
Het |
| Cfap410 |
C |
T |
10: 77,983,038 (GRCm38) |
T181I |
possibly damaging |
Het |
| Cfap410 |
A |
T |
10: 77,984,547 (GRCm38) |
*250C |
probably null |
Het |
| Cnpy4 |
A |
G |
5: 138,192,577 (GRCm38) |
E167G |
probably damaging |
Het |
| Copa |
T |
C |
1: 172,112,137 (GRCm38) |
V624A |
possibly damaging |
Het |
| Gm4553 |
G |
T |
7: 142,165,620 (GRCm38) |
P24T |
unknown |
Het |
| Gna12 |
A |
G |
5: 140,760,883 (GRCm38) |
V269A |
possibly damaging |
Het |
| Gtf2ird2 |
G |
T |
5: 134,211,242 (GRCm38) |
E302* |
probably null |
Het |
| Hmcn2 |
C |
A |
2: 31,415,236 (GRCm38) |
S3140R |
probably benign |
Het |
| Hspa4 |
A |
G |
11: 53,262,876 (GRCm38) |
|
probably benign |
Het |
| Hspbp1 |
A |
T |
7: 4,684,432 (GRCm38) |
L60* |
probably null |
Het |
| Lipo3 |
T |
C |
19: 33,582,042 (GRCm38) |
|
probably benign |
Het |
| Lrrc3 |
T |
A |
10: 77,901,585 (GRCm38) |
R6W |
probably damaging |
Het |
| Lxn |
C |
T |
3: 67,461,002 (GRCm38) |
A143T |
probably damaging |
Het |
| Mga |
T |
C |
2: 119,935,422 (GRCm38) |
I1390T |
probably damaging |
Het |
| Ncapg2 |
T |
A |
12: 116,423,215 (GRCm38) |
I286N |
probably damaging |
Het |
| Or4c107 |
T |
A |
2: 88,959,043 (GRCm38) |
Y192* |
probably null |
Het |
| Pitpnm2 |
A |
G |
5: 124,140,517 (GRCm38) |
|
probably benign |
Het |
| Plxna2 |
T |
C |
1: 194,751,386 (GRCm38) |
V581A |
probably benign |
Het |
| Polr3d |
A |
T |
14: 70,439,519 (GRCm38) |
H378Q |
possibly damaging |
Het |
| Ptpn13 |
T |
C |
5: 103,489,765 (GRCm38) |
V173A |
probably damaging |
Het |
| Rbpms2 |
ACTGCTGCTGCTGCTGC |
ACTGCTGCTGCTGCTGCTGC |
9: 65,651,666 (GRCm38) |
|
probably benign |
Het |
| Smc4 |
T |
C |
3: 69,022,461 (GRCm38) |
|
probably null |
Het |
| Snrnp40 |
C |
G |
4: 130,378,043 (GRCm38) |
|
probably null |
Het |
| Syngr3 |
C |
T |
17: 24,686,581 (GRCm38) |
A140T |
probably benign |
Het |
| Tent2 |
A |
G |
13: 93,154,992 (GRCm38) |
S381P |
probably benign |
Het |
| Tprn |
T |
C |
2: 25,264,321 (GRCm38) |
V545A |
probably damaging |
Het |
| Trim66 |
T |
C |
7: 109,460,695 (GRCm38) |
H828R |
probably benign |
Het |
| Ugt2b5 |
G |
A |
5: 87,137,365 (GRCm38) |
|
probably benign |
Het |
| Vps9d1 |
A |
G |
8: 123,246,748 (GRCm38) |
V432A |
probably damaging |
Het |
| Zswim9 |
A |
T |
7: 13,261,026 (GRCm38) |
D401E |
probably damaging |
Het |
|
| Other mutations in Lats1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00234:Lats1
|
APN |
10 |
7,691,566 (GRCm38) |
missense |
probably damaging |
0.99 |
|
IGL00595:Lats1
|
APN |
10 |
7,702,305 (GRCm38) |
missense |
probably benign |
0.00 |
|
IGL00932:Lats1
|
APN |
10 |
7,712,742 (GRCm38) |
missense |
possibly damaging |
0.69 |
|
IGL01019:Lats1
|
APN |
10 |
7,705,671 (GRCm38) |
missense |
probably damaging |
1.00 |
|
IGL01380:Lats1
|
APN |
10 |
7,691,780 (GRCm38) |
missense |
possibly damaging |
0.69 |
|
IGL01965:Lats1
|
APN |
10 |
7,701,706 (GRCm38) |
missense |
probably benign |
0.10 |
|
IGL02027:Lats1
|
APN |
10 |
7,712,948 (GRCm38) |
missense |
probably benign |
|
|
IGL02611:Lats1
|
APN |
10 |
7,705,787 (GRCm38) |
missense |
possibly damaging |
0.91 |
|
IGL02997:Lats1
|
APN |
10 |
7,702,254 (GRCm38) |
missense |
possibly damaging |
0.53 |
|
IGL03107:Lats1
|
APN |
10 |
7,712,746 (GRCm38) |
missense |
probably benign |
0.15 |
|
I1329:Lats1
|
UTSW |
10 |
7,712,802 (GRCm38) |
missense |
probably benign |
0.10 |
|
PIT4378001:Lats1
|
UTSW |
10 |
7,705,605 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R0153:Lats1
|
UTSW |
10 |
7,691,575 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R0581:Lats1
|
UTSW |
10 |
7,702,941 (GRCm38) |
missense |
possibly damaging |
0.67 |
|
R0604:Lats1
|
UTSW |
10 |
7,712,661 (GRCm38) |
missense |
probably damaging |
0.96 |
|
R1681:Lats1
|
UTSW |
10 |
7,705,914 (GRCm38) |
missense |
probably damaging |
0.99 |
|
R1694:Lats1
|
UTSW |
10 |
7,701,945 (GRCm38) |
missense |
probably benign |
0.07 |
|
R1840:Lats1
|
UTSW |
10 |
7,710,939 (GRCm38) |
nonsense |
probably null |
|
|
R1914:Lats1
|
UTSW |
10 |
7,710,457 (GRCm38) |
splice site |
probably benign |
|
|
R2137:Lats1
|
UTSW |
10 |
7,701,847 (GRCm38) |
missense |
possibly damaging |
0.71 |
|
R2317:Lats1
|
UTSW |
10 |
7,691,776 (GRCm38) |
nonsense |
probably null |
|
|
R3863:Lats1
|
UTSW |
10 |
7,705,746 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R3864:Lats1
|
UTSW |
10 |
7,705,746 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R4597:Lats1
|
UTSW |
10 |
7,691,746 (GRCm38) |
missense |
probably benign |
0.00 |
|
R4657:Lats1
|
UTSW |
10 |
7,705,684 (GRCm38) |
missense |
possibly damaging |
0.82 |
|
R4658:Lats1
|
UTSW |
10 |
7,702,729 (GRCm38) |
missense |
probably benign |
|
|
R4663:Lats1
|
UTSW |
10 |
7,712,583 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R4870:Lats1
|
UTSW |
10 |
7,705,785 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R5101:Lats1
|
UTSW |
10 |
7,712,584 (GRCm38) |
nonsense |
probably null |
|
|
R5134:Lats1
|
UTSW |
10 |
7,691,811 (GRCm38) |
missense |
probably benign |
0.34 |
|
R5150:Lats1
|
UTSW |
10 |
7,712,651 (GRCm38) |
missense |
probably benign |
|
|
R5546:Lats1
|
UTSW |
10 |
7,705,754 (GRCm38) |
missense |
probably damaging |
0.99 |
|
R5820:Lats1
|
UTSW |
10 |
7,705,908 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R6006:Lats1
|
UTSW |
10 |
7,705,595 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R6301:Lats1
|
UTSW |
10 |
7,703,107 (GRCm38) |
missense |
probably benign |
0.01 |
|
R6544:Lats1
|
UTSW |
10 |
7,701,670 (GRCm38) |
missense |
possibly damaging |
0.94 |
|
R6647:Lats1
|
UTSW |
10 |
7,697,507 (GRCm38) |
missense |
possibly damaging |
0.81 |
|
R6874:Lats1
|
UTSW |
10 |
7,710,851 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R7328:Lats1
|
UTSW |
10 |
7,705,547 (GRCm38) |
missense |
possibly damaging |
0.62 |
|
R7390:Lats1
|
UTSW |
10 |
7,702,095 (GRCm38) |
nonsense |
probably null |
|
|
R7438:Lats1
|
UTSW |
10 |
7,712,942 (GRCm38) |
nonsense |
probably null |
|
|
R7457:Lats1
|
UTSW |
10 |
7,710,891 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R7524:Lats1
|
UTSW |
10 |
7,701,978 (GRCm38) |
missense |
possibly damaging |
0.89 |
|
R7593:Lats1
|
UTSW |
10 |
7,701,712 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R7736:Lats1
|
UTSW |
10 |
7,702,364 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R7884:Lats1
|
UTSW |
10 |
7,697,526 (GRCm38) |
nonsense |
probably null |
|
|
R8166:Lats1
|
UTSW |
10 |
7,702,116 (GRCm38) |
missense |
probably benign |
|
|
R8248:Lats1
|
UTSW |
10 |
7,705,903 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R8458:Lats1
|
UTSW |
10 |
7,710,924 (GRCm38) |
nonsense |
probably null |
|
|
R8477:Lats1
|
UTSW |
10 |
7,705,515 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R8547:Lats1
|
UTSW |
10 |
7,712,849 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R9163:Lats1
|
UTSW |
10 |
7,702,288 (GRCm38) |
missense |
probably benign |
|
|
R9441:Lats1
|
UTSW |
10 |
7,702,917 (GRCm38) |
missense |
probably damaging |
0.96 |
|
R9673:Lats1
|
UTSW |
10 |
7,712,623 (GRCm38) |
missense |
probably benign |
0.29 |
|
RF021:Lats1
|
UTSW |
10 |
7,710,608 (GRCm38) |
missense |
probably damaging |
1.00 |
|
X0026:Lats1
|
UTSW |
10 |
7,710,623 (GRCm38) |
missense |
probably damaging |
1.00 |
|
X0053:Lats1
|
UTSW |
10 |
7,691,609 (GRCm38) |
missense |
probably benign |
0.00 |
|
Z1176:Lats1
|
UTSW |
10 |
7,705,809 (GRCm38) |
missense |
probably damaging |
1.00 |
|
| Predicted Primers |
PCR Primer
(F):5'- ACCTTACTGTGACTCTTCTCACGGG -3'
(R):5'- TGCCATCGCTCCACAATTTATCAGG -3'
Sequencing Primer
(F):5'- TTCTCACGGGGAGAGGAC -3'
(R):5'- TTTATCAGGATCAACAGGGTCG -3'
|
| Posted On |
2013-06-11 |
Incidental Mutation