Mutagenetix > Incidental Mutation

Incidental Mutation 'R2047:Ttbk2'

222071

Institutional Source

Beutler Lab

Gene Symbol

Ttbk2

Ensembl Gene

ENSMUSG00000090100

Gene Name

tau tubulin kinase 2

Synonyms

B930008N24Rik, 2610507N02Rik, TTK

MMRRC Submission

040054-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R2047 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

120732816-120850604 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 120748916 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Arginine at position 506 (H506R)

Ref Sequence

ENSEMBL: ENSMUSP00000121996 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000028740] [ENSMUST00000057135] [ENSMUST00000085840] [ENSMUST00000131389] [ENSMUST00000143051]

AlphaFold

Q3UVR3

Predicted Effect

probably damaging
Transcript: ENSMUST00000028740
AA Change: H575R

PolyPhen 2 Score 0.975 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000028740
Gene: ENSMUSG00000090100
AA Change: H575R

Domain	Start	End	E-Value	Type
Pfam:Pkinase	90	347	7e-31	PFAM
Pfam:Pkinase_Tyr	90	348	8.2e-19	PFAM
low complexity region	369	383	N/A	INTRINSIC
low complexity region	1143	1156	N/A	INTRINSIC
low complexity region	1205	1242	N/A	INTRINSIC
low complexity region	1254	1271	N/A	INTRINSIC
low complexity region	1285	1309	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000057135
AA Change: H506R

PolyPhen 2 Score 0.505 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000055032
Gene: ENSMUSG00000090100
AA Change: H506R

Domain	Start	End	E-Value	Type
Pfam:Pkinase	21	274	1.2e-32	PFAM
Pfam:Pkinase_Tyr	21	280	3.8e-19	PFAM
low complexity region	300	314	N/A	INTRINSIC
low complexity region	1074	1087	N/A	INTRINSIC
low complexity region	1136	1173	N/A	INTRINSIC
low complexity region	1185	1202	N/A	INTRINSIC
low complexity region	1216	1240	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000085840
AA Change: H506R

PolyPhen 2 Score 0.505 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000083001
Gene: ENSMUSG00000090100
AA Change: H506R

Domain	Start	End	E-Value	Type
Pfam:Pkinase	21	274	1.2e-32	PFAM
Pfam:Pkinase_Tyr	21	280	3.8e-19	PFAM
low complexity region	300	314	N/A	INTRINSIC
low complexity region	1074	1087	N/A	INTRINSIC
low complexity region	1136	1173	N/A	INTRINSIC
low complexity region	1185	1202	N/A	INTRINSIC
low complexity region	1216	1240	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000131389

SMART Domains

Protein: ENSMUSP00000118905
Gene: ENSMUSG00000090100

Domain	Start	End	E-Value	Type
Pfam:Pkinase	21	145	1.3e-18	PFAM
Pfam:Pkinase_Tyr	21	148	9.7e-12	PFAM
Pfam:Pkinase	145	239	1.2e-5	PFAM
low complexity region	265	279	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000143051
AA Change: H506R

PolyPhen 2 Score 0.988 (Sensitivity: 0.73; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000121996
Gene: ENSMUSG00000090100
AA Change: H506R

Domain	Start	End	E-Value	Type
Pfam:Pkinase	21	274	2.4e-32	PFAM
Pfam:Pkinase_Tyr	21	280	7.7e-19	PFAM
low complexity region	300	314	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000148285

Meta Mutation Damage Score

0.1706

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 97.0%
20x: 94.4%

Validation Efficiency

100% (57/57)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a serine-threonine kinase that putatively phosphorylates tau and tubulin proteins. Mutations in this gene cause spinocerebellar ataxia type 11 (SCA11); a neurodegenerative disease characterized by progressive ataxia and atrophy of the cerebellum and brainstem. [provided by RefSeq, Aug 2009]
PHENOTYPE: Mice homozygous for a knock-in allele exhibit complete preweaning lethality, decreased embryo size, growth retardation, and incomplete turning. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 56 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4933402N03Rik	A	G	7: 131,146,107	F52S	probably damaging	Het
Acot12	T	C	13: 91,783,003	S457P	probably damaging	Het
Adcy5	G	A	16: 35,290,108	V882M	possibly damaging	Het
Ahnak	A	G	19: 9,014,300	D4316G	possibly damaging	Het
Aldh1l2	G	A	10: 83,506,743	A401V	probably damaging	Het
Apol7e	A	G	15: 77,717,610	H136R	probably benign	Het
Arl5a	A	G	2: 52,412,060		probably null	Het
Asns	G	T	6: 7,680,093	A341E	probably damaging	Het
C7	A	G	15: 5,045,661	L183P	probably damaging	Het
Cacng2	C	T	15: 78,118,837	A19T	probably damaging	Het
Ccr4	A	G	9: 114,492,565	F144S	probably damaging	Het
Ckap2	A	G	8: 22,168,747	V660A	probably benign	Het
Cramp1l	A	T	17: 25,003,215	Y176*	probably null	Het
Dgki	A	G	6: 36,913,646	S922P	possibly damaging	Het
Drd5	C	T	5: 38,320,336	S224L	probably damaging	Het
Ei24	T	C	9: 36,780,163	K341E	probably benign	Het
Eno2	A	T	6: 124,767,696		probably benign	Het
Epb41l4a	T	C	18: 33,828,206	N425S	probably benign	Het
F13b	T	G	1: 139,508,223	C256G	probably damaging	Het
Gm6588	A	G	5: 112,450,709	N374S	probably benign	Het
Gp6	A	T	7: 4,373,271		probably benign	Het
H2-Q7	A	T	17: 35,440,147	R191S	probably damaging	Het
Ivns1abp	T	A	1: 151,351,631	S63R	possibly damaging	Het
Kcnj16	A	G	11: 111,025,120		probably null	Het
Lpcat4	T	C	2: 112,244,797		probably null	Het
Lrrc14b	T	C	13: 74,363,442	K173R	probably benign	Het
Maml3	C	A	3: 51,690,445	R939S	probably damaging	Het
Mrgpra2b	C	T	7: 47,464,160	V249I	probably benign	Het
Mrpl46	T	A	7: 78,781,564	Y82F	probably damaging	Het
Mthfs	T	A	9: 89,215,303	I71N	probably damaging	Het
Nectin4	T	C	1: 171,385,152	V351A	possibly damaging	Het
Npas3	T	C	12: 54,068,829	F827L	probably damaging	Het
Nrp1	G	A	8: 128,498,096		probably benign	Het
Ocln	C	A	13: 100,535,124	A242S	probably damaging	Het
Olfr1164	A	T	2: 88,093,893	N14K	probably benign	Het
Olfr288	T	A	15: 98,187,039	T253S	probably damaging	Het
Olfr309	G	A	7: 86,306,804	T103I	probably damaging	Het
Pappa	T	C	4: 65,231,141		probably benign	Het
Ptpn6	T	C	6: 124,721,789	T480A	probably benign	Het
Pycr1	A	T	11: 120,641,686	D168E	possibly damaging	Het
Rnf6	T	C	5: 146,211,864	T126A	probably damaging	Het
Slc25a39	G	A	11: 102,405,831		probably benign	Het
Slc35f4	G	T	14: 49,303,572		probably benign	Het
Sppl2a	C	T	2: 126,926,852	A112T	probably damaging	Het
Sptbn1	A	C	11: 30,138,360		probably benign	Het
Sqle	T	C	15: 59,326,058	Y376H	probably benign	Het
Terb1	A	T	8: 104,485,462	Y296N	probably damaging	Het
Ttn	T	C	2: 76,907,535	D4220G	probably benign	Het
Tub	A	G	7: 109,026,732	D230G	probably benign	Het
Ube2d3	T	A	3: 135,465,206	I137K	probably benign	Het
Vldlr	G	T	19: 27,234,838	C84F	probably damaging	Het
Vmn1r54	A	T	6: 90,269,988	I295F	probably damaging	Het
Vmn2r56	A	G	7: 12,732,991	S39P	probably damaging	Het
Zfp358	A	G	8: 3,495,934	H172R	probably damaging	Het
Zfp619	T	C	7: 39,537,638	C1031R	probably damaging	Het
Zfp777	A	G	6: 48,044,346	I114T	probably benign	Het

Other mutations in Ttbk2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00091:Ttbk2	APN	2	120748833	nonsense	probably null
IGL00484:Ttbk2	APN	2	120773886	nonsense	probably null
IGL00767:Ttbk2	APN	2	120745745	missense	probably benign
IGL00809:Ttbk2	APN	2	120760269	missense	probably damaging	1.00
IGL01484:Ttbk2	APN	2	120739833	missense	possibly damaging	0.95
IGL01974:Ttbk2	APN	2	120786083	missense	probably damaging	1.00
IGL02488:Ttbk2	APN	2	120755871	missense	probably benign	0.00
IGL02874:Ttbk2	APN	2	120745712	missense	probably damaging	0.99
IGL02893:Ttbk2	APN	2	120783729	missense	probably damaging	1.00
IGL03210:Ttbk2	APN	2	120822492	missense	probably damaging	0.99
R0279:Ttbk2	UTSW	2	120748960	missense	probably benign	0.00
R0362:Ttbk2	UTSW	2	120745783	missense	possibly damaging	0.90
R0376:Ttbk2	UTSW	2	120777581	missense	probably damaging	1.00
R0400:Ttbk2	UTSW	2	120750242	missense	probably benign	0.02
R0601:Ttbk2	UTSW	2	120825296	missense	possibly damaging	0.73
R0606:Ttbk2	UTSW	2	120773872	missense	probably damaging	1.00
R0664:Ttbk2	UTSW	2	120748821	missense	probably damaging	0.99
R0718:Ttbk2	UTSW	2	120745160	missense	probably benign	0.00
R0718:Ttbk2	UTSW	2	120748575	missense	probably benign	0.01
R0783:Ttbk2	UTSW	2	120739977	missense	possibly damaging	0.74
R0906:Ttbk2	UTSW	2	120783781	missense	probably damaging	1.00
R1141:Ttbk2	UTSW	2	120806851	missense	probably damaging	1.00
R1363:Ttbk2	UTSW	2	120806908	critical splice acceptor site	probably null
R1420:Ttbk2	UTSW	2	120745912	missense	probably benign	0.00
R1734:Ttbk2	UTSW	2	120755838	missense	probably benign	0.01
R2033:Ttbk2	UTSW	2	120806849	missense	probably damaging	0.98
R2893:Ttbk2	UTSW	2	120745610	splice site	probably null
R3783:Ttbk2	UTSW	2	120773815	splice site	probably benign
R3785:Ttbk2	UTSW	2	120773815	splice site	probably benign
R3870:Ttbk2	UTSW	2	120740019	missense	probably damaging	1.00
R4024:Ttbk2	UTSW	2	120760255	missense	possibly damaging	0.91
R4039:Ttbk2	UTSW	2	120745795	missense	probably benign	0.01
R4060:Ttbk2	UTSW	2	120748984	missense	probably benign	0.26
R4624:Ttbk2	UTSW	2	120773323	missense	probably benign	0.19
R4634:Ttbk2	UTSW	2	120740192	missense	probably damaging	1.00
R4708:Ttbk2	UTSW	2	120739861	missense	probably damaging	1.00
R4727:Ttbk2	UTSW	2	120745370	missense	probably benign	0.01
R4811:Ttbk2	UTSW	2	120740070	missense	possibly damaging	0.62
R4962:Ttbk2	UTSW	2	120745150	missense	probably damaging	1.00
R4964:Ttbk2	UTSW	2	120773277	missense	possibly damaging	0.66
R4966:Ttbk2	UTSW	2	120773277	missense	possibly damaging	0.66
R5369:Ttbk2	UTSW	2	120825262	start gained	probably benign
R5430:Ttbk2	UTSW	2	120777565	missense	probably damaging	1.00
R5607:Ttbk2	UTSW	2	120806824	missense	possibly damaging	0.89
R5812:Ttbk2	UTSW	2	120822559	missense	probably damaging	0.99
R5898:Ttbk2	UTSW	2	120745040	missense	probably benign	0.08
R5951:Ttbk2	UTSW	2	120773283	missense	probably benign	0.02
R6135:Ttbk2	UTSW	2	120750317	missense	probably damaging	1.00
R6889:Ttbk2	UTSW	2	120773353	missense	probably damaging	1.00
R6907:Ttbk2	UTSW	2	120825270	missense	probably benign	0.00
R7013:Ttbk2	UTSW	2	120745784	missense	possibly damaging	0.89
R7128:Ttbk2	UTSW	2	120746088	missense	probably benign	0.00
R7173:Ttbk2	UTSW	2	120740111	missense	probably damaging	1.00
R7358:Ttbk2	UTSW	2	120790310	missense	probably damaging	1.00
R7475:Ttbk2	UTSW	2	120748640	missense	probably benign	0.01
R7891:Ttbk2	UTSW	2	120786029	missense	probably damaging	1.00
R8529:Ttbk2	UTSW	2	120773857	missense	possibly damaging	0.67
R9050:Ttbk2	UTSW	2	120806838	missense	probably benign	0.09
R9051:Ttbk2	UTSW	2	120745430	nonsense	probably null
R9372:Ttbk2	UTSW	2	120773285	missense	probably benign	0.31
R9485:Ttbk2	UTSW	2	120745505	missense	probably benign	0.32
RF010:Ttbk2	UTSW	2	120790339	nonsense	probably null
RF021:Ttbk2	UTSW	2	120748634	missense	probably benign

Predicted Primers

PCR Primer
(F):5'- TCTGAAGGGCTTCCAGTTGTC -3'
(R):5'- TGTTCCGCATAGAGTTTATCAGG -3'

Sequencing Primer
(F):5'- TTGTCCTAAAGTCCTGAAGGTC -3'
(R):5'- TCCGCATAGAGTTTATCAGGATATAG -3'

Posted On

2014-08-25