Mutagenetix > Incidental Mutation

Incidental Mutation 'R6154:Tnk1'

489462

Institutional Source

Beutler Lab

Gene Symbol

Tnk1

Ensembl Gene

ENSMUSG00000001583

Gene Name

tyrosine kinase, non-receptor, 1

Synonyms

Tnk1b, Tnk1a, Kos1

MMRRC Submission

044301-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R6154 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

69741831-69749556 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 69747780 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Isoleucine at position 41 (V41I)

Ref Sequence

ENSEMBL: ENSMUSP00000118490 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000001626] [ENSMUST00000108626] [ENSMUST00000108628] [ENSMUST00000108633] [ENSMUST00000125571] [ENSMUST00000156507]

AlphaFold

Q99ML2

Predicted Effect

probably damaging
Transcript: ENSMUST00000001626
AA Change: V41I

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000001626
Gene: ENSMUSG00000001583
AA Change: V41I

Domain	Start	End	E-Value	Type
low complexity region	6	15	N/A	INTRINSIC
Blast:TyrKc	43	80	1e-5	BLAST
TyrKc	116	378	1.2e-108	SMART
SH3	384	440	4.11e-1	SMART
low complexity region	504	517	N/A	INTRINSIC
low complexity region	528	544	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000108626
AA Change: V41I

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000104266
Gene: ENSMUSG00000001583
AA Change: V41I

Domain	Start	End	E-Value	Type
low complexity region	6	15	N/A	INTRINSIC
Blast:TyrKc	43	80	6e-6	BLAST
TyrKc	116	378	1.2e-108	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000108628
AA Change: V41I

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000104268
Gene: ENSMUSG00000001583
AA Change: V41I

Domain	Start	End	E-Value	Type
low complexity region	6	15	N/A	INTRINSIC
Blast:TyrKc	43	80	1e-5	BLAST
TyrKc	116	378	1.2e-108	SMART
SH3	384	445	6.1e-1	SMART
low complexity region	509	522	N/A	INTRINSIC
low complexity region	533	549	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000108633

SMART Domains

Protein: ENSMUSP00000104273
Gene: ENSMUSG00000019461

Domain	Start	End	E-Value	Type
low complexity region	6	28	N/A	INTRINSIC
low complexity region	32	49	N/A	INTRINSIC
Pfam:Scramblase	63	285	1.7e-88	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000125571
AA Change: V41I

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000118490
Gene: ENSMUSG00000001583
AA Change: V41I

Domain	Start	End	E-Value	Type
low complexity region	6	15	N/A	INTRINSIC
Blast:TyrKc	43	72	2e-6	BLAST
Pfam:Pkinase	116	268	3.3e-21	PFAM
Pfam:Pkinase_Tyr	116	268	1.9e-37	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000156507

SMART Domains

Protein: ENSMUSP00000120585
Gene: ENSMUSG00000001583

Domain	Start	End	E-Value	Type
Pfam:Pkinase_Tyr	1	76	8.4e-17	PFAM
Pfam:Pkinase	1	97	1.2e-6	PFAM
low complexity region	127	140	N/A	INTRINSIC
low complexity region	151	167	N/A	INTRINSIC

Meta Mutation Damage Score

0.2303

Coding Region Coverage

1x: 99.9%
3x: 99.6%
10x: 98.1%
20x: 94.8%

Validation Efficiency

97% (70/72)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene belongs to the tyrosine protein kinase family. Tyrosine protein kinases are important regulators of intracellular signal transduction pathways, mediating cellular proliferation, survival, and development. This gene is highly expressed in fetal tissues and at lower levels in few adult tissues, thus may function in signaling pathways utilized broadly during fetal development, and more selectively in adult tissues. It plays a negative regulatory role in the Ras-Raf1-MAPK pathway, and knockout mice have been shown to develop spontaneous tumors, suggesting a role as a tumor suppressor gene. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]
PHENOTYPE: Mice either heterozygous or homozygous for a knock-out allele develop spontaneous tumors, including lymphomas and carcinomas, at high rates. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 72 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acss3	T	G	10: 106,959,210 (GRCm39)	I79L	probably benign	Het
Adam6a	C	T	12: 113,509,292 (GRCm39)	T555I	probably benign	Het
Adap1	A	G	5: 139,293,531 (GRCm39)	V60A	possibly damaging	Het
Afg3l2	G	T	18: 67,554,329 (GRCm39)	L458M	probably damaging	Het
Angpt1	T	C	15: 42,387,051 (GRCm39)	E101G	probably damaging	Het
Asxl2	T	C	12: 3,546,593 (GRCm39)	V459A	possibly damaging	Het
Cabs1	C	T	5: 88,127,613 (GRCm39)	T88I	possibly damaging	Het
Camta2	G	A	11: 70,569,211 (GRCm39)	A578V	probably damaging	Het
Cdc16	A	G	8: 13,818,609 (GRCm39)	N316D	possibly damaging	Het
Chrm3	T	A	13: 9,928,476 (GRCm39)	M187L	possibly damaging	Het
Clcn4	T	C	7: 7,294,481 (GRCm39)	T367A	probably benign	Het
Clcn7	T	C	17: 25,376,928 (GRCm39)	S654P	probably damaging	Het
Col6a3	T	A	1: 90,701,387 (GRCm39)	T2510S	unknown	Het
Crisp4	T	C	1: 18,193,012 (GRCm39)	E192G	possibly damaging	Het
Dmbt1	T	A	7: 130,711,370 (GRCm39)		probably null	Het
Dnah5	T	G	15: 28,204,177 (GRCm39)	L18R	probably benign	Het
Dnah9	T	G	11: 65,746,164 (GRCm39)	D3983A	probably benign	Het
Dock5	C	A	14: 68,097,361 (GRCm39)	V71L	probably benign	Het
Dync1h1	T	C	12: 110,584,427 (GRCm39)	V610A	probably damaging	Het
Dynlrb2	A	G	8: 117,242,428 (GRCm39)	Y86C	probably benign	Het
Ep400	T	C	5: 110,903,799 (GRCm39)	I267V	probably damaging	Het
Gaa	A	G	11: 119,169,178 (GRCm39)	Y575C	probably damaging	Het
Gm8094	T	A	14: 42,934,020 (GRCm39)	D24V	probably benign	Het
Grina	T	C	15: 76,133,087 (GRCm39)	I244T	possibly damaging	Het
Haus6	A	G	4: 86,501,993 (GRCm39)	L626P	possibly damaging	Het
Hexd	A	T	11: 121,112,097 (GRCm39)	H439L	probably benign	Het
Ifna12	A	T	4: 88,521,531 (GRCm39)	C5*	probably null	Het
Igf2bp2	G	T	16: 21,894,843 (GRCm39)	S300*	probably null	Het
Ighv6-5	T	C	12: 114,380,362 (GRCm39)	R71G	probably benign	Het
Lrrc37	A	G	11: 103,504,969 (GRCm39)	V2333A	probably benign	Het
Lrrn4cl	T	C	19: 8,829,252 (GRCm39)	S77P	probably damaging	Het
Mast4	A	G	13: 102,923,929 (GRCm39)	L302P	probably damaging	Het
Mink1	T	C	11: 70,500,927 (GRCm39)	V831A	possibly damaging	Het
Mme	T	A	3: 63,207,674 (GRCm39)	I40N	probably damaging	Het
Myh2	A	G	11: 67,077,438 (GRCm39)	T858A	probably benign	Het
Ncbp3	T	A	11: 72,940,700 (GRCm39)	Y67N	probably damaging	Het
Nedd1	T	A	10: 92,534,104 (GRCm39)	I349F	possibly damaging	Het
Nek11	A	T	9: 105,200,368 (GRCm39)	*81K	probably null	Het
Nrip1	A	G	16: 76,090,718 (GRCm39)	Y280H	probably damaging	Het
Obsl1	T	C	1: 75,476,788 (GRCm39)	D722G	probably benign	Het
Or10ag55-ps1	T	G	2: 87,139,902 (GRCm39)	S256R	probably benign	Het
Or2m12	A	T	16: 19,105,181 (GRCm39)	I104K	probably damaging	Het
Or4c29	A	G	2: 88,740,734 (GRCm39)	M1T	probably null	Het
Or5i1	A	G	2: 87,613,100 (GRCm39)	D72G	possibly damaging	Het
Or6c7	C	T	10: 129,323,545 (GRCm39)	T222I	probably damaging	Het
Pcdhb6	A	G	18: 37,467,966 (GRCm39)	I296V	probably benign	Het
Pcnx2	G	T	8: 126,489,552 (GRCm39)	L1681M	probably damaging	Het
Pdlim5	T	C	3: 141,983,674 (GRCm39)	R360G	possibly damaging	Het
Peli2	C	T	14: 48,488,051 (GRCm39)	Q81*	probably null	Het
Pitpnb	C	T	5: 111,486,263 (GRCm39)	Q56*	probably null	Het
Ppp1r3a	A	G	6: 14,754,603 (GRCm39)	S215P	possibly damaging	Het
Prrt3	A	G	6: 113,471,989 (GRCm39)	Y728H	probably damaging	Het
Rsf1	A	AAGGCGACGG	7: 97,229,111 (GRCm39)		probably null	Het
Rsf1	GCG	GCGACGGCGACG	7: 97,229,114 (GRCm39)		probably benign	Het
Sbno1	T	C	5: 124,516,542 (GRCm39)	H1277R	possibly damaging	Het
Siglecg	C	A	7: 43,061,441 (GRCm39)	N481K	possibly damaging	Het
Sirt6	C	T	10: 81,462,339 (GRCm39)	G20D	probably damaging	Het
Sit1	C	A	4: 43,482,981 (GRCm39)	R89S	probably benign	Het
Slc7a12	A	G	3: 14,546,094 (GRCm39)	R80G	probably damaging	Het
Smok3c	T	A	5: 138,062,747 (GRCm39)	M78K	probably benign	Het
Stk10	T	A	11: 32,553,654 (GRCm39)		probably null	Het
Tada2b	A	G	5: 36,634,008 (GRCm39)	V190A	probably damaging	Het
Tpr	T	A	1: 150,299,567 (GRCm39)	V1146E	probably benign	Het
Trappc9	T	C	15: 72,929,930 (GRCm39)	D142G	probably benign	Het
Trpm3	T	C	19: 22,965,178 (GRCm39)	Y1558H	probably damaging	Het
Unc5c	C	A	3: 141,383,914 (GRCm39)	S97R	probably damaging	Het
Vmn1r172	T	C	7: 23,359,583 (GRCm39)	I156T	probably damaging	Het
Vmn2r51	A	T	7: 9,821,921 (GRCm39)	M588K	possibly damaging	Het
Vps26a	T	G	10: 62,304,119 (GRCm39)	E117D	probably damaging	Het
Zfp451	A	T	1: 33,842,627 (GRCm39)		probably benign	Het
Zfp534	C	A	4: 147,759,145 (GRCm39)	R508I	probably benign	Het
Zp3r	C	T	1: 130,526,642 (GRCm39)	C187Y	probably damaging	Het

Other mutations in Tnk1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01445:Tnk1	APN	11	69,746,731 (GRCm39)	unclassified	probably benign
IGL02668:Tnk1	APN	11	69,747,749 (GRCm39)	missense	probably damaging	1.00
R0211:Tnk1	UTSW	11	69,746,007 (GRCm39)	missense	probably damaging	1.00
R0211:Tnk1	UTSW	11	69,746,007 (GRCm39)	missense	probably damaging	1.00
R0389:Tnk1	UTSW	11	69,746,508 (GRCm39)	missense	probably damaging	1.00
R0529:Tnk1	UTSW	11	69,745,990 (GRCm39)	missense	probably damaging	1.00
R1396:Tnk1	UTSW	11	69,743,962 (GRCm39)	missense	probably benign	0.01
R1436:Tnk1	UTSW	11	69,743,119 (GRCm39)	splice site	probably benign
R1494:Tnk1	UTSW	11	69,747,372 (GRCm39)	missense	possibly damaging	0.60
R1687:Tnk1	UTSW	11	69,747,299 (GRCm39)	missense	possibly damaging	0.75
R1752:Tnk1	UTSW	11	69,747,532 (GRCm39)	missense	possibly damaging	0.92
R1832:Tnk1	UTSW	11	69,747,754 (GRCm39)	missense	probably damaging	0.99
R2109:Tnk1	UTSW	11	69,746,009 (GRCm39)	missense	probably damaging	1.00
R2233:Tnk1	UTSW	11	69,746,017 (GRCm39)	splice site	probably null
R2234:Tnk1	UTSW	11	69,746,017 (GRCm39)	splice site	probably null
R2423:Tnk1	UTSW	11	69,746,587 (GRCm39)	missense	probably damaging	0.98
R3018:Tnk1	UTSW	11	69,745,737 (GRCm39)	intron	probably benign
R3689:Tnk1	UTSW	11	69,746,425 (GRCm39)	missense	probably damaging	1.00
R4746:Tnk1	UTSW	11	69,745,992 (GRCm39)	missense	probably damaging	1.00
R5653:Tnk1	UTSW	11	69,744,411 (GRCm39)	missense	probably damaging	1.00
R7384:Tnk1	UTSW	11	69,742,447 (GRCm39)	missense	probably damaging	1.00
R7649:Tnk1	UTSW	11	69,744,403 (GRCm39)	splice site	probably null
R7680:Tnk1	UTSW	11	69,747,571 (GRCm39)	missense	possibly damaging	0.89
R8021:Tnk1	UTSW	11	69,745,810 (GRCm39)	missense	probably benign	0.03
R8055:Tnk1	UTSW	11	69,747,327 (GRCm39)	missense	probably benign	0.09
R8390:Tnk1	UTSW	11	69,742,695 (GRCm39)	missense	possibly damaging	0.84
R9482:Tnk1	UTSW	11	69,743,666 (GRCm39)	missense	probably benign	0.00
R9526:Tnk1	UTSW	11	69,746,011 (GRCm39)	missense	probably damaging	1.00
X0061:Tnk1	UTSW	11	69,743,098 (GRCm39)	missense	probably damaging	1.00
Z1176:Tnk1	UTSW	11	69,746,349 (GRCm39)	missense	possibly damaging	0.94
Z1177:Tnk1	UTSW	11	69,746,503 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- ATTCTTGGACTTGACCCCTGAC -3'
(R):5'- TCCATTTAAAGCAGTCGGCC -3'

Sequencing Primer
(F):5'- CAGGGCTTCATTAAGTCTGCGC -3'
(R):5'- ATTTAAAGCAGTCGGCCATCCTC -3'

Posted On

2017-10-10