Mutagenetix > Incidental Mutation

Incidental Mutation 'R1832:Tnk1'

204881

Institutional Source

Beutler Lab

Gene Symbol

Tnk1

Ensembl Gene

ENSMUSG00000001583

Gene Name

tyrosine kinase, non-receptor, 1

Synonyms

Tnk1b, Tnk1a, Kos1

MMRRC Submission

039859-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R1832 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

69741831-69749556 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 69747754 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Methionine at position 49 (I49M)

Ref Sequence

ENSEMBL: ENSMUSP00000118490 (fasta)

Gene Model

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

AlphaFold

Q99ML2

Predicted Effect

probably benign
Transcript: ENSMUST00000001626
AA Change: I49M

PolyPhen 2 Score 0.284 (Sensitivity: 0.91; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000001626
Gene: ENSMUSG00000001583
AA Change: I49M

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 benign
Transcript: ENSMUST00000108626
AA Change: I49M

PolyPhen 2 Score 0.284 (Sensitivity: 0.91; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000104266
Gene: ENSMUSG00000001583
AA Change: I49M

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

possibly damaging
Transcript: ENSMUST00000108628
AA Change: I49M

PolyPhen 2 Score 0.589 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000104268
Gene: ENSMUSG00000001583
AA Change: I49M

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: I49M

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

SMART Domains

Protein: ENSMUSP00000118490
Gene: ENSMUSG00000001583
AA Change: I49M

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

0.6467

Coding Region Coverage

1x: 97.4%
3x: 96.7%
10x: 94.6%
20x: 90.7%

Validation Efficiency

100% (82/82)

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: 73 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700003H04Rik	T	A	3: 124,350,509 (GRCm39)	D143V	unknown	Het
Abca8a	A	T	11: 109,962,277 (GRCm39)	N525K	probably damaging	Het
Abhd12	T	A	2: 150,690,338 (GRCm39)	D119V	probably damaging	Het
Adamts20	A	T	15: 94,184,225 (GRCm39)	M1526K	probably benign	Het
Ankdd1a	A	T	9: 65,411,771 (GRCm39)		probably null	Het
Ankrd1	C	T	19: 36,092,378 (GRCm39)	C283Y	possibly damaging	Het
Arfgef1	G	C	1: 10,275,115 (GRCm39)	I312M	probably benign	Het
Bhlhe22	G	A	3: 18,109,139 (GRCm39)	C63Y	probably damaging	Het
Bmp8a	A	T	4: 123,218,885 (GRCm39)		probably benign	Het
Ccdc148	A	T	2: 58,891,911 (GRCm39)	S235T	probably damaging	Het
Ccdc88b	G	A	19: 6,830,900 (GRCm39)	Q681*	probably null	Het
Cep104	T	A	4: 154,087,003 (GRCm39)	V842E	probably benign	Het
Chac2	T	C	11: 30,927,568 (GRCm39)	N117S	probably benign	Het
Cimap3	C	T	3: 105,921,912 (GRCm39)	E4K	possibly damaging	Het
Cldn8	T	A	16: 88,359,746 (GRCm39)	I60F	probably benign	Het
Col16a1	G	A	4: 129,970,850 (GRCm39)		probably null	Het
Col4a1	A	G	8: 11,264,644 (GRCm39)		probably benign	Het
Cyp2a4	G	T	7: 26,011,635 (GRCm39)	E285D	probably damaging	Het
Cyp4a31	G	A	4: 115,426,928 (GRCm39)	G176D	probably benign	Het
Dmxl2	A	C	9: 54,368,233 (GRCm39)	Y246D	probably damaging	Het
Dync1h1	A	G	12: 110,580,493 (GRCm39)	K118R	probably damaging	Het
Dync2i1	T	A	12: 116,171,363 (GRCm39)	S958C	probably damaging	Het
Eif3h	T	C	15: 51,728,832 (GRCm39)	T8A	possibly damaging	Het
Fbh1	G	T	2: 11,772,211 (GRCm39)	L157I	probably benign	Het
Fbxo40	C	A	16: 36,789,218 (GRCm39)	G631*	probably null	Het
Gabrb1	T	A	5: 72,279,281 (GRCm39)		probably null	Het
Galc	A	G	12: 98,200,499 (GRCm39)		probably null	Het
Garin2	G	A	12: 78,762,280 (GRCm39)		probably benign	Het
H2-Q7	C	A	17: 35,658,675 (GRCm39)	S104R	probably benign	Het
Igkv13-54-1	A	T	6: 69,594,277 (GRCm39)	M31L	probably benign	Het
Lamc2	C	T	1: 153,041,933 (GRCm39)	R67Q	possibly damaging	Het
Lcn10	A	G	2: 25,575,151 (GRCm39)	D173G	probably damaging	Het
Llgl2	G	T	11: 115,741,926 (GRCm39)	R656L	probably damaging	Het
Lonrf2	G	A	1: 38,852,357 (GRCm39)	P165S	probably benign	Het
Lrrc66	G	A	5: 73,764,769 (GRCm39)	S758L	possibly damaging	Het
Ly6d	T	C	15: 74,634,615 (GRCm39)	K46E	probably damaging	Het
Map3k5	A	G	10: 19,975,306 (GRCm39)	N88D	probably damaging	Het
Mertk	A	T	2: 128,604,132 (GRCm39)	E422V	probably benign	Het
Mixl1	A	G	1: 180,522,296 (GRCm39)	V195A	probably benign	Het
Nmnat3	T	C	9: 98,281,521 (GRCm39)	V41A	probably damaging	Het
Or1r1	A	T	11: 73,875,319 (GRCm39)	N38K	probably damaging	Het
Or2a7	A	G	6: 43,151,834 (GRCm39)	R305G	probably benign	Het
Or7g34	A	G	9: 19,478,492 (GRCm39)	Y63H	possibly damaging	Het
Pappa2	T	A	1: 158,684,886 (GRCm39)	E751V	probably damaging	Het
Pcsk2	A	G	2: 143,635,189 (GRCm39)	S355G	probably damaging	Het
Pdzd2	A	G	15: 12,390,134 (GRCm39)	V821A	probably damaging	Het
Plxna4	A	C	6: 32,174,761 (GRCm39)	D1109E	probably benign	Het
Ppard	A	G	17: 28,516,084 (GRCm39)	M103V	probably benign	Het
Pramel51	T	C	12: 88,145,218 (GRCm39)	E44G	possibly damaging	Het
Ralgapa1	T	C	12: 55,804,752 (GRCm39)	T515A	probably benign	Het
Rin2	A	G	2: 145,703,091 (GRCm39)	I596V	possibly damaging	Het
Rnls	A	G	19: 33,145,895 (GRCm39)	S75P	possibly damaging	Het
Rsph10b	A	T	5: 143,903,997 (GRCm39)	Y236F	possibly damaging	Het
Runx1t1	C	T	4: 13,835,628 (GRCm39)		probably benign	Het
Sardh	A	G	2: 27,125,581 (GRCm39)	V311A	possibly damaging	Het
Sbno2	G	T	10: 79,896,439 (GRCm39)	Y889*	probably null	Het
Sclt1	A	G	3: 41,681,546 (GRCm39)	V91A	probably damaging	Het
Sema4g	T	A	19: 44,987,456 (GRCm39)	V534E	probably benign	Het
Shoc1	T	G	4: 59,066,441 (GRCm39)	I768L	probably benign	Het
Slc10a1	G	A	12: 81,000,446 (GRCm39)	S351F	probably benign	Het
Slc19a3	A	T	1: 83,000,468 (GRCm39)	V183E	probably damaging	Het
Slc25a12	A	G	2: 71,164,054 (GRCm39)	Y74H	possibly damaging	Het
Slc6a19	T	A	13: 73,841,069 (GRCm39)	I114L	probably benign	Het
Smpd2	A	T	10: 41,364,232 (GRCm39)	C189S	probably benign	Het
Spon1	T	A	7: 113,616,018 (GRCm39)	V295D	probably benign	Het
Tet3	A	G	6: 83,380,627 (GRCm39)	S514P	probably benign	Het
Trim80	A	G	11: 115,337,619 (GRCm39)	T431A	probably benign	Het
Vgf	A	T	5: 137,060,153 (GRCm39)	Q105L	possibly damaging	Het
Vmn1r37	G	T	6: 66,708,780 (GRCm39)	L135F	probably benign	Het
Vps37d	C	T	5: 135,102,594 (GRCm39)	A128T	possibly damaging	Het
Wwp1	T	C	4: 19,650,197 (GRCm39)	D323G	probably benign	Het
Zfp456	T	A	13: 67,515,482 (GRCm39)	I75L	probably benign	Het
Zfp990	A	G	4: 145,264,780 (GRCm39)	I593V	possibly 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
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
R6154:Tnk1	UTSW	11	69,747,780 (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'- TCTTGGACTTGACCCCTGAC -3'
(R):5'- TAAAGCAGTCGGCCATCCTC -3'

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

Posted On

2014-06-23