Mutagenetix > Incidental Mutation

Incidental Mutation 'R7665:Tnk2'

591891

Institutional Source

Beutler Lab

Gene Symbol

Tnk2

Ensembl Gene

ENSMUSG00000022791

Gene Name

tyrosine kinase, non-receptor, 2

Synonyms

ACK1, Ack, P21cdc42Hs kinase, Pyk1, activated p21cdc42Hs kinase

MMRRC Submission

045739-MU

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.332) question?

Stock #

R7665 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

32643874-32683493 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 32680526 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Cysteine at position 886 (R886C)

Ref Sequence

ENSEMBL: ENSMUSP00000110777 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000115120] [ENSMUST00000115121] [ENSMUST00000115122] [ENSMUST00000115123] [ENSMUST00000115124] [ENSMUST00000115125] [ENSMUST00000115126] [ENSMUST00000131238] [ENSMUST00000152361]

AlphaFold

no structure available at present

Predicted Effect

probably damaging
Transcript: ENSMUST00000115120
AA Change: R381C

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

SMART Domains

Protein: ENSMUSP00000110773
Gene: ENSMUSG00000022791
AA Change: R381C

Domain	Start	End	E-Value	Type
Pfam:GTPase_binding	1	24	1.1e-8	PFAM
low complexity region	247	264	N/A	INTRINSIC
Pfam:Inhibitor_Mig-6	284	351	2.9e-30	PFAM
low complexity region	391	419	N/A	INTRINSIC
Pfam:UBA	467	505	2.7e-10	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000115121

SMART Domains

Protein: ENSMUSP00000110774
Gene: ENSMUSG00000022791

Domain	Start	End	E-Value	Type
Pfam:GTPase_binding	1	24	4.5e-9	PFAM
low complexity region	27	34	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000115122

Predicted Effect

probably damaging
Transcript: ENSMUST00000115123
AA Change: R871C

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000110776
Gene: ENSMUSG00000022791
AA Change: R871C

Domain	Start	End	E-Value	Type
low complexity region	10	21	N/A	INTRINSIC
Blast:TyrKc	43	79	3e-14	BLAST
TyrKc	126	385	1.44e-129	SMART
SH3	391	447	1.52e-7	SMART
low complexity region	737	754	N/A	INTRINSIC
Pfam:Inhibitor_Mig-6	774	841	3e-30	PFAM
low complexity region	881	909	N/A	INTRINSIC
Pfam:UBA	957	995	1.6e-10	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000115124
AA Change: R886C

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000110777
Gene: ENSMUSG00000022791
AA Change: R886C

Domain	Start	End	E-Value	Type
low complexity region	10	21	N/A	INTRINSIC
Blast:TyrKc	43	79	3e-14	BLAST
TyrKc	126	385	1.44e-129	SMART
SH3	391	447	1.52e-7	SMART
low complexity region	517	524	N/A	INTRINSIC
low complexity region	752	769	N/A	INTRINSIC
Pfam:Inhibitor_Mig-6	789	855	5.3e-29	PFAM
low complexity region	896	924	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000115125
AA Change: R871C

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000110778
Gene: ENSMUSG00000022791
AA Change: R871C

Domain	Start	End	E-Value	Type
low complexity region	10	21	N/A	INTRINSIC
Blast:TyrKc	43	79	3e-14	BLAST
TyrKc	126	385	1.44e-129	SMART
SH3	391	447	1.52e-7	SMART
low complexity region	737	754	N/A	INTRINSIC
Pfam:Inhibitor_Mig-6	774	841	7.2e-31	PFAM
low complexity region	881	909	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000115126
AA Change: R886C

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000110779
Gene: ENSMUSG00000022791
AA Change: R886C

Domain	Start	End	E-Value	Type
low complexity region	10	21	N/A	INTRINSIC
Blast:TyrKc	43	79	3e-14	BLAST
TyrKc	126	385	1.44e-129	SMART
SH3	391	447	1.52e-7	SMART
low complexity region	517	524	N/A	INTRINSIC
low complexity region	752	769	N/A	INTRINSIC
Pfam:Inhibitor_Mig-6	789	856	2.9e-30	PFAM
low complexity region	896	924	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000131238

SMART Domains

Protein: ENSMUSP00000129382
Gene: ENSMUSG00000022791

Domain	Start	End	E-Value	Type
Pfam:GTPase_binding	1	24	1e-9	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000152361

SMART Domains

Protein: ENSMUSP00000125905
Gene: ENSMUSG00000022791

Domain	Start	End	E-Value	Type
SCOP:d1jo8a_	8	38	2e-3	SMART
Pfam:GTPase_binding	39	106	2.8e-38	PFAM

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 99.2%

Validation Efficiency

100% (72/72)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a tyrosine kinase that binds Cdc42Hs in its GTP-bound form and inhibits both the intrinsic and GTPase-activating protein (GAP)-stimulated GTPase activity of Cdc42Hs. This binding is mediated by a unique sequence of 47 amino acids C-terminal to an SH3 domain. The protein may be involved in a regulatory mechanism that sustains the GTP-bound active form of Cdc42Hs and which is directly linked to a tyrosine phosphorylation signal transduction pathway. Several alternatively spliced transcript variants have been identified from this gene, but the full-length nature of only two transcript variants has been determined. [provided by RefSeq, Jul 2008]

Allele List at MGI

Other mutations in this stock

Total: 71 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930519G04Rik	A	G	5: 114,874,323		probably null	Het
A830018L16Rik	T	C	1: 11,972,099	S448P	probably damaging	Het
Abca4	C	T	3: 122,044,490		probably benign	Het
Ackr2	A	G	9: 121,909,308	M250V	probably benign	Het
Actn4	A	G	7: 28,916,207	I147T	probably damaging	Het
Adgrv1	C	T	13: 81,499,142	S3093N	probably damaging	Het
Arid5b	C	T	10: 68,098,587	G495E	probably benign	Het
Armh1	C	A	4: 117,213,741	A396S	probably benign	Het
Brwd1	G	A	16: 96,041,343	T798M	probably benign	Het
Cdk13	G	A	13: 17,772,553	T540I	possibly damaging	Het
Cdkn1c	A	G	7: 143,460,634	V25A	possibly damaging	Het
Col2a1	T	C	15: 97,976,700	E1420G	unknown	Het
Dbf4	G	A	5: 8,397,867	P448S	probably damaging	Het
Dnajb7	T	C	15: 81,407,419	N239S	probably benign	Het
Dnttip1	A	G	2: 164,754,141	D102G	probably damaging	Het
Dpp8	T	A	9: 65,078,718	V830D	probably damaging	Het
Eef1g	T	C	19: 8,968,289	V29A	probably benign	Het
Enpp2	T	A	15: 54,839,394	Y906F	probably damaging	Het
Epb41l4a	A	G	18: 34,006,016	L23P	possibly damaging	Het
Epp13	G	A	7: 6,269,892		probably null	Het
Exoc1	T	A	5: 76,543,573	M248K	probably benign	Het
Fam83b	T	C	9: 76,490,875	Y982C	probably damaging	Het
Fat4	C	T	3: 38,889,178	A740V	probably benign	Het
Fsip2	T	A	2: 82,981,805	S2823T	probably benign	Het
Gckr	T	C	5: 31,297,555			Het
Gpr150	A	T	13: 76,055,974	V284E	probably damaging	Het
Grtp1	T	G	8: 13,177,103	I344L	probably benign	Het
Heatr5a	T	A	12: 51,961,530	N10I	probably damaging	Het
Herc2	C	A	7: 56,153,155	L2109I	probably damaging	Het
Hs1bp3	T	A	12: 8,317,935	D61E	probably damaging	Het
Ifit1bl1	T	A	19: 34,594,883	Y58F	probably benign	Het
Itfg1	A	G	8: 85,764,350	F317L	probably benign	Het
Itsn1	T	C	16: 91,841,603	I764T	unknown	Het
Med8	A	C	4: 118,411,656		probably null	Het
Mpeg1	C	A	19: 12,463,094	P639T	probably damaging	Het
Nedd9	A	G	13: 41,316,309	L456P	probably benign	Het
Neo1	A	G	9: 58,925,795	S556P	probably damaging	Het
Nphp3	T	A	9: 104,005,393		probably null	Het
Nup205	T	C	6: 35,177,620	V53A	possibly damaging	Het
Nvl	A	T	1: 181,134,944	S154T	probably benign	Het
Olfr239	G	T	17: 33,199,629	G194*	probably null	Het
Olfr391-ps	A	T	11: 73,798,961	N265K	probably benign	Het
Olfr615	A	T	7: 103,561,316	I280F	probably benign	Het
Olfr706	A	T	7: 106,886,673	V48D	possibly damaging	Het
Olfr827	T	A	10: 130,211,261		probably null	Het
Olfr92	A	G	17: 37,111,391	M197T	probably benign	Het
Parvg	T	C	15: 84,337,801	I243T	probably damaging	Het
Paxip1	T	A	5: 27,765,738	M538L	unknown	Het
Pgghg	G	T	7: 140,945,469	D428Y	probably damaging	Het
Pik3cd	C	T	4: 149,654,050	V777M	possibly damaging	Het
Plcl2	A	C	17: 50,607,157	K398T	probably benign	Het
Plxna1	A	T	6: 89,324,538		probably null	Het
Rbbp6	T	C	7: 122,994,686	Y514H	possibly damaging	Het
Rbbp6	T	A	7: 122,990,032		probably null	Het
Scin	T	A	12: 40,069,415	N538I	probably damaging	Het
Sdcbp	A	G	4: 6,385,144	D121G	probably benign	Het
Sgk1	T	C	10: 21,996,662	I311T	probably damaging	Het
Shq1	A	C	6: 100,573,756	L407W	probably damaging	Het
Sipa1	A	T	19: 5,651,671	S979T	probably benign	Het
Slc25a37	G	T	14: 69,249,579	T85K	probably benign	Het
Soga3	T	A	10: 29,196,397	Y562N	probably damaging	Het
Spag9	A	T	11: 94,013,654	Q112L	probably damaging	Het
Spg11	A	T	2: 122,066,267	V1686E	probably damaging	Het
Stap2	A	G	17: 55,997,909	V291A	probably benign	Het
Tnrc6c	T	A	11: 117,720,951	D138E	possibly damaging	Het
Unc13c	A	G	9: 73,680,474	S1426P	probably benign	Het
Vav1	G	A	17: 57,297,086	V163M	probably damaging	Het
Vmn2r67	T	A	7: 85,151,988	K247*	probably null	Het
Zc2hc1c	T	C	12: 85,296,562	V491A	possibly damaging	Het
Zfp51	A	G	17: 21,463,581	T153A	probably benign	Het
Zyx	A	G	6: 42,356,162	E374G	probably damaging	Het

Other mutations in Tnk2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01419:Tnk2	APN	16	32680680	missense	probably damaging	0.99
IGL02212:Tnk2	APN	16	32680142	missense	probably damaging	0.97
IGL02445:Tnk2	APN	16	32675590	missense	probably benign	0.00
junior	UTSW	16	32680085	missense	probably benign
Rookie	UTSW	16	32679785	missense	probably damaging	1.00
IGL02799:Tnk2	UTSW	16	32665881	splice site	probably benign
R0310:Tnk2	UTSW	16	32680590	missense	probably benign
R0989:Tnk2	UTSW	16	32680358	missense	probably damaging	1.00
R1556:Tnk2	UTSW	16	32670919	critical splice donor site	probably null
R1851:Tnk2	UTSW	16	32679462	missense	probably damaging	1.00
R1854:Tnk2	UTSW	16	32680142	missense	probably damaging	0.97
R1938:Tnk2	UTSW	16	32663742	start gained	probably benign
R2137:Tnk2	UTSW	16	32670802	splice site	probably null
R2189:Tnk2	UTSW	16	32671421	missense	probably damaging	1.00
R3772:Tnk2	UTSW	16	32679822	missense	probably damaging	1.00
R4037:Tnk2	UTSW	16	32670796	missense	probably damaging	1.00
R4413:Tnk2	UTSW	16	32669501	missense	probably damaging	1.00
R4751:Tnk2	UTSW	16	32679857	missense	probably damaging	1.00
R4878:Tnk2	UTSW	16	32679630	missense	probably damaging	1.00
R4983:Tnk2	UTSW	16	32680465	missense	probably damaging	1.00
R5063:Tnk2	UTSW	16	32670850	missense	probably damaging	1.00
R5541:Tnk2	UTSW	16	32669523	missense	probably benign	0.07
R5759:Tnk2	UTSW	16	32680664	missense	probably benign
R5888:Tnk2	UTSW	16	32671367	missense	probably damaging	1.00
R6142:Tnk2	UTSW	16	32670099	missense	probably damaging	1.00
R6372:Tnk2	UTSW	16	32679785	missense	probably damaging	1.00
R6717:Tnk2	UTSW	16	32670869	missense	probably damaging	1.00
R6939:Tnk2	UTSW	16	32663878	missense	probably damaging	1.00
R7157:Tnk2	UTSW	16	32681168	missense	probably damaging	1.00
R7292:Tnk2	UTSW	16	32680800	missense	probably benign
R7362:Tnk2	UTSW	16	32675520	critical splice acceptor site	probably null
R7477:Tnk2	UTSW	16	32677891	splice site	probably null
R7558:Tnk2	UTSW	16	32680085	missense	probably benign
R7731:Tnk2	UTSW	16	32670134	missense	possibly damaging	0.69
R7867:Tnk2	UTSW	16	32681235	missense	probably damaging	0.99
R8011:Tnk2	UTSW	16	32668365	missense	probably benign	0.00
R8167:Tnk2	UTSW	16	32680262	missense	probably damaging	1.00
R8738:Tnk2	UTSW	16	32665900	missense	probably damaging	1.00
R9241:Tnk2	UTSW	16	32670098	missense	probably damaging	1.00
R9267:Tnk2	UTSW	16	32675671	missense	probably damaging	1.00
R9504:Tnk2	UTSW	16	32680143	missense	possibly damaging	0.94
R9643:Tnk2	UTSW	16	32670200	missense	probably damaging	1.00
R9786:Tnk2	UTSW	16	32680057	nonsense	probably null
X0063:Tnk2	UTSW	16	32670850	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- TGCCCACCACTCAAAGCTTTG -3'
(R):5'- ATCTGGACCTTGTCTGCTGG -3'

Sequencing Primer
(F):5'- AGCTTTGCCTCAGACCCTAAGTATG -3'
(R):5'- ACCTTGTCTGCTGGCCGAG -3'

Posted On

2019-11-12