Mutagenetix > Incidental Mutation

Incidental Mutation 'R3863:Lats1'

276430

Institutional Source

Beutler Lab

Gene Symbol

Lats1

Ensembl Gene

ENSMUSG00000040021

Gene Name

large tumor suppressor

Synonyms

Accession Numbers

Essential gene?

Probably essential (E-score: 0.847) question?

Stock #

R3863 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

7556978-7592224 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 7581510 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 765 (V765A)

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: V765A

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000041915
Gene: ENSMUSG00000040021
AA Change: V765A

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: V765A

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000132078
Gene: ENSMUSG00000040021
AA Change: V765A

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: V765A

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

Coding Region Coverage

1x: 99.2%
3x: 98.7%
10x: 97.5%
20x: 95.8%

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: 23 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aldh18a1	A	T	19: 40,539,758 (GRCm39)	I739N	probably damaging	Het
Arfgef1	CAGAG	CAG	1: 10,212,811 (GRCm39)		probably null	Het
Ccdc85a	T	A	11: 28,527,335 (GRCm39)		probably null	Het
D430041D05Rik	T	C	2: 104,044,522 (GRCm39)	I825M	possibly damaging	Het
Evi2	T	A	11: 79,406,472 (GRCm39)	I368F	probably benign	Het
Greb1	G	A	12: 16,752,421 (GRCm39)	R974W	probably damaging	Het
Ighv1-7	A	G	12: 114,502,266 (GRCm39)	I67T	probably damaging	Het
Kcnd2	C	G	6: 21,217,262 (GRCm39)	S322*	probably null	Het
Lrrd1	G	A	5: 3,901,248 (GRCm39)	V518I	probably benign	Het
Ltbp3	G	A	19: 5,804,050 (GRCm39)	R854Q	probably benign	Het
Marchf11	C	T	15: 26,387,952 (GRCm39)	A269V	probably damaging	Het
Mep1b	A	G	18: 21,217,226 (GRCm39)	N115S	possibly damaging	Het
N4bp1	T	C	8: 87,587,055 (GRCm39)	T628A	probably benign	Het
Nuak1	C	T	10: 84,213,951 (GRCm39)		probably null	Het
Obscn	T	C	11: 59,022,472 (GRCm39)	R758G	possibly damaging	Het
Parp8	A	G	13: 117,031,303 (GRCm39)	S470P	probably benign	Het
Pcdhb3	A	G	18: 37,436,329 (GRCm39)	E765G	probably damaging	Het
Rbm26	G	T	14: 105,358,504 (GRCm39)	Q912K	probably damaging	Het
Sgcz	T	C	8: 37,990,565 (GRCm39)	I263V	probably benign	Het
Slc15a1	C	T	14: 121,722,269 (GRCm39)	V211I	probably benign	Het
Slc4a4	T	C	5: 89,283,507 (GRCm39)	F442S	possibly damaging	Het
Sorcs2	G	T	5: 36,555,007 (GRCm39)	S128*	probably null	Het
Vmn1r173	T	A	7: 23,401,977 (GRCm39)	F71I	probably 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
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'- GATGCTTTGCCAGAAAGAGTC -3'
(R):5'- GGCCATCACGGTCAATCAAAATG -3'

Sequencing Primer
(F):5'- TCGTCTTAAAAGGGCTAAAATGGAC -3'
(R):5'- CACGGTCAATCAAAATGTTATCAGG -3'

Posted On

2015-04-06