Mutagenetix > Incidental Mutation

Incidental Mutation 'R1681:Lats1'

188525

Institutional Source

Beutler Lab

Gene Symbol

Lats1

Ensembl Gene

ENSMUSG00000040021

Gene Name

large tumor suppressor

Synonyms

MMRRC Submission

039717-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.890) question?

Stock #

R1681 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

7681214-7716460 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 7705914 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Threonine at position 821 (M821T)

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: M821T

PolyPhen 2 Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000041915
Gene: ENSMUSG00000040021
AA Change: M821T

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: M821T

PolyPhen 2 Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000132078
Gene: ENSMUSG00000040021
AA Change: M821T

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: M821T

PolyPhen 2 Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.6%
20x: 93.6%

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: 87 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acaca	T	A	11: 84,226,185 (GRCm38)	I247N	probably damaging	Het
Ankle1	G	T	8: 71,407,618 (GRCm38)	S260I	probably benign	Het
Aoc2	T	C	11: 101,325,192 (GRCm38)	S34P	probably benign	Het
Ap1m1	A	C	8: 72,256,122 (GRCm38)	I397L	possibly damaging	Het
Apba1	C	A	19: 23,936,561 (GRCm38)	D649E	probably damaging	Het
Aptx	C	T	4: 40,697,274 (GRCm38)	V25M	probably benign	Het
Arhgef18	G	A	8: 3,439,645 (GRCm38)	G326R	probably damaging	Het
Atm	A	C	9: 53,522,155 (GRCm38)	I265S	possibly damaging	Het
B3galt4	A	T	17: 33,951,213 (GRCm38)	V17E	probably benign	Het
Bcl7a	T	A	5: 123,356,023 (GRCm38)	M86K	possibly damaging	Het
Cela3a	T	A	4: 137,402,684 (GRCm38)		probably null	Het
Cep85	T	A	4: 134,148,728 (GRCm38)	K456*	probably null	Het
Ces1f	C	A	8: 93,275,414 (GRCm38)	A29S	probably benign	Het
Chd9	A	T	8: 90,973,135 (GRCm38)	I598F	probably damaging	Het
Cntln	T	C	4: 84,947,635 (GRCm38)	L176S	probably damaging	Het
Cntn3	A	T	6: 102,170,668 (GRCm38)	N909K	probably damaging	Het
Cntnap5b	T	C	1: 100,076,107 (GRCm38)	S271P	probably damaging	Het
Col6a3	T	A	1: 90,773,502 (GRCm38)	H2564L	unknown	Het
Cyp2b19	C	A	7: 26,763,340 (GRCm38)		probably null	Het
Dapk1	G	T	13: 60,718,464 (GRCm38)		probably null	Het
Dnah7b	T	A	1: 46,324,712 (GRCm38)	Y3497*	probably null	Het
Duoxa2	T	C	2: 122,299,162 (GRCm38)		probably null	Het
Eny2	T	C	15: 44,432,478 (GRCm38)	W42R	probably damaging	Het
Epha3	A	G	16: 63,595,728 (GRCm38)	V635A	probably damaging	Het
Fam167b	G	C	4: 129,578,276 (GRCm38)	Q34E	probably benign	Het
Fam26f	A	G	10: 34,127,900 (GRCm38)	F4L	probably benign	Het
Fancm	T	C	12: 65,105,656 (GRCm38)	M962T	probably benign	Het
Gimap8	T	A	6: 48,656,411 (GRCm38)	I388N	probably benign	Het
Gpaa1	A	G	15: 76,331,453 (GRCm38)	T22A	probably benign	Het
Hoxc11	T	C	15: 102,955,156 (GRCm38)	S211P	possibly damaging	Het
Hsd17b12	T	C	2: 94,033,561 (GRCm38)	N312S	unknown	Het
Idh2	T	G	7: 80,099,158 (GRCm38)	E125A	probably damaging	Het
Igdcc4	A	G	9: 65,128,795 (GRCm38)	Y712C	probably damaging	Het
Kank1	T	C	19: 25,410,304 (GRCm38)	V447A	possibly damaging	Het
Kif1b	T	A	4: 149,195,501 (GRCm38)		probably null	Het
Klc4	A	T	17: 46,636,770 (GRCm38)	D335E	probably damaging	Het
Klhl33	T	A	14: 50,893,077 (GRCm38)	D320V	probably benign	Het
Krt73	A	T	15: 101,802,047 (GRCm38)	M84K	possibly damaging	Het
Kti12	T	A	4: 108,848,858 (GRCm38)	I323N	probably damaging	Het
Kynu	T	C	2: 43,679,825 (GRCm38)	L373P	probably damaging	Het
Lnx1	A	T	5: 74,685,410 (GRCm38)	H126Q	probably benign	Het
Lonrf2	G	A	1: 38,813,276 (GRCm38)	P165S	probably benign	Het
Lrrc4b	T	A	7: 44,461,177 (GRCm38)	Y158N	probably damaging	Het
Lrrc74b	C	A	16: 17,559,753 (GRCm38)	R87L	probably damaging	Het
Meig1	T	C	2: 3,409,274 (GRCm38)	D63G	probably damaging	Het
Mrpl38	G	A	11: 116,138,429 (GRCm38)		probably benign	Het
Naip2	C	T	13: 100,161,860 (GRCm38)	G556D	probably benign	Het
Naip2	T	C	13: 100,161,854 (GRCm38)	E558G	probably benign	Het
Nlrp1a	T	A	11: 71,142,358 (GRCm38)	E3D	unknown	Het
Nphs2	T	A	1: 156,320,898 (GRCm38)	D110E	probably damaging	Het
Nxn	T	A	11: 76,272,464 (GRCm38)	K244N	probably benign	Het
Oas3	A	T	5: 120,769,908 (GRCm38)	F322L	probably benign	Het
Obscn	T	A	11: 59,103,325 (GRCm38)	Y1577F	probably damaging	Het
Olfr1122	G	A	2: 87,388,620 (GRCm38)	R305K	possibly damaging	Het
Olfr911-ps1	T	A	9: 38,524,117 (GRCm38)	N128K	probably benign	Het
Olfr914	G	A	9: 38,606,948 (GRCm38)	G161D	probably damaging	Het
Olfr917	A	G	9: 38,665,320 (GRCm38)	Y175H	probably benign	Het
Olfr924	T	C	9: 38,848,513 (GRCm38)	M133T	probably damaging	Het
Panx1	T	C	9: 15,007,783 (GRCm38)	D260G	probably benign	Het
Pcdhb15	T	C	18: 37,473,813 (GRCm38)	Y33H	probably damaging	Het
Pik3ap1	C	A	19: 41,308,529 (GRCm38)	V461F	probably damaging	Het
Plpp3	G	A	4: 105,208,805 (GRCm38)		probably null	Het
Prtn3	A	T	10: 79,880,541 (GRCm38)	T61S	probably benign	Het
Psen1	T	A	12: 83,724,620 (GRCm38)	Y225N	probably damaging	Het
Rab44	T	A	17: 29,140,124 (GRCm38)	S429T	possibly damaging	Het
Ralgapa1	T	C	12: 55,762,603 (GRCm38)	I462M	probably benign	Het
Rbfox3	T	C	11: 118,505,669 (GRCm38)	N105S	probably damaging	Het
Rbm7	A	C	9: 48,489,721 (GRCm38)	Y236D	possibly damaging	Het
Samhd1	T	C	2: 157,101,732 (GRCm38)	T621A	probably benign	Het
Samt3	C	A	X: 86,046,650 (GRCm38)	D49E	probably benign	Het
Sass6	T	C	3: 116,603,473 (GRCm38)	V26A	possibly damaging	Het
Scn11a	C	T	9: 119,804,412 (GRCm38)	M418I	possibly damaging	Het
Scrib	T	C	15: 76,064,567 (GRCm38)	E480G	probably damaging	Het
Sec24a	T	G	11: 51,695,189 (GRCm38)	T1071P	probably damaging	Het
Siglecg	A	C	7: 43,408,941 (GRCm38)	E84A	probably benign	Het
Slc6a17	C	T	3: 107,474,386 (GRCm38)	V419I	probably damaging	Het
Soga1	T	C	2: 157,030,530 (GRCm38)	T966A	possibly damaging	Het
Ssr2	T	C	3: 88,581,042 (GRCm38)	M75T	possibly damaging	Het
Tbc1d22b	A	G	17: 29,575,177 (GRCm38)	T275A	possibly damaging	Het
Tbx15	T	A	3: 99,351,824 (GRCm38)		probably null	Het
Tll1	A	C	8: 64,085,551 (GRCm38)	L353R	possibly damaging	Het
Tlr4	C	T	4: 66,841,105 (GRCm38)	P712S	probably damaging	Het
Tmem145	T	A	7: 25,314,734 (GRCm38)	F424L	possibly damaging	Het
Tnrc18	T	C	5: 142,773,817 (GRCm38)	K755E	unknown	Het
Trmt44	A	G	5: 35,569,977 (GRCm38)	I298T	probably benign	Het
Vmn1r69	A	G	7: 10,580,252 (GRCm38)	V184A	probably benign	Het
Zfp84	T	C	7: 29,777,400 (GRCm38)	C506R	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
R0568:Lats1	UTSW	10	7,712,528 (GRCm38)	missense	possibly damaging	0.69
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
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'- TTCTGCTCCGAAATCAGGTGGCTC -3'
(R):5'- AGAACCAGCCTATGTCTACTGGTCTC -3'

Sequencing Primer
(F):5'- CCGACAATGAGTGGGTGGTC -3'
(R):5'- GAAGCCACTGTAAATTGTACTGC -3'

Posted On

2014-05-09