Mutagenetix > Incidental Mutation

Incidental Mutation 'R8738:Itk'

663175

Institutional Source

Beutler Lab

Gene Symbol

Itk

Ensembl Gene

ENSMUSG00000020395

Gene Name

IL2 inducible T cell kinase

Synonyms

Tcsk, Tsk, Emt

MMRRC Submission

068585-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.116) question?

Stock #

R8738 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

46215977-46280342 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 46231539 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Leucine to Proline at position 339 (L339P)

Ref Sequence

ENSEMBL: ENSMUSP00000104860 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000020664] [ENSMUST00000101306] [ENSMUST00000109237]

AlphaFold

Q03526

PDB Structure

INTRAMOLECULAR ITK-PROLINE COMPLEX, NMR, MINIMIZED AVERAGE STRUCTURE [SOLUTION NMR]
NMR Structures of Itk SH2 domain, Pro287cis isoform, ensemble of 20 low energy structures [SOLUTION NMR]
NMR Structure of the Itk SH2 domain, Pro287cis, Energy minimized average structure [SOLUTION NMR]
NMR Structure of the Itk SH2 domain, Pro287trans, 20 low energy structures [SOLUTION NMR]
NMR Structure of the Itk SH2 domain, Pro287trans, energy minimized average structure [SOLUTION NMR]
The NMR minimized average structure of the Itk SH2 domain bound to a phosphopeptide [SOLUTION NMR]
The NMR ensemble structure of the Itk SH2 domain bound to a phosphopeptide [SOLUTION NMR]
Solution Structure of the binary complex between the SH3 and SH2 domain of interleukin-2 tyrosine kinase [SOLUTION NMR]
Ensemble Structures of the binary complex between the SH3 and SH2 domain of interleukin-2 tyrosine kinase. [SOLUTION NMR]
NMR structure note: murine Itk SH3 domain [SOLUTION NMR]
>> 2 additional structures at PDB <<

Predicted Effect

probably damaging
Transcript: ENSMUST00000020664
AA Change: L333P

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

SMART Domains

Protein: ENSMUSP00000020664
Gene: ENSMUSG00000020395
AA Change: L333P

Domain	Start	End	E-Value	Type
PH	5	113	2.3e-13	SMART
BTK	113	149	1.1e-21	SMART
SH3	174	230	5.87e-14	SMART
SH2	237	328	9.44e-29	SMART
TyrKc	362	611	3.28e-133	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000101306

SMART Domains

Protein: ENSMUSP00000098864
Gene: ENSMUSG00000020395

Domain	Start	End	E-Value	Type
PH	5	113	2.3e-13	SMART
BTK	113	149	1.1e-21	SMART
SH3	174	230	5.87e-14	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000109237
AA Change: L339P

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

SMART Domains

Protein: ENSMUSP00000104860
Gene: ENSMUSG00000020395
AA Change: L339P

Domain	Start	End	E-Value	Type
PH	5	119	3.94e-12	SMART
BTK	119	155	1.1e-21	SMART
SH3	180	236	5.87e-14	SMART
SH2	243	334	9.44e-29	SMART
TyrKc	368	617	3.28e-133	SMART

Meta Mutation Damage Score

0.9299

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.8%
20x: 99.3%

Validation Efficiency

97% (76/78)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes an intracellular tyrosine kinase expressed in T-cells. The protein contains both SH2 and SH3 domains which are often found in intracellular kinases. It is thought to play a role in T-cell proliferation and differentiation. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for disruptions in this gene display decreased percentages of CD4 and CD8 cells, increased percentage of B cells, impaired T cell receptor signaling, and increased susceptibility to Toxoplasma gondii infection. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 80 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4931406C07Rik	G	A	9: 15,196,214 (GRCm39)	T283M	probably damaging	Het
Abca9	A	G	11: 110,056,817 (GRCm39)	M1T	probably null	Het
Ackr1	T	C	1: 173,159,952 (GRCm39)	Y189C	probably damaging	Het
Acsm4	A	G	7: 119,304,264 (GRCm39)	D303G	probably benign	Het
Arfgef2	A	T	2: 166,708,867 (GRCm39)	M1060L	probably benign	Het
Arhgef40	T	A	14: 52,238,414 (GRCm39)	F1298I	probably damaging	Het
Atg2a	T	C	19: 6,306,674 (GRCm39)	I1453T	probably benign	Het
B4galnt1	A	T	10: 127,007,584 (GRCm39)	D495V	probably benign	Het
Brpf3	T	A	17: 29,040,214 (GRCm39)	D878E	probably benign	Het
C3	A	G	17: 57,511,015 (GRCm39)	*1664R	probably null	Het
Cap2	A	G	13: 46,684,548 (GRCm39)	T73A	probably benign	Het
Ccr6	A	T	17: 8,475,394 (GRCm39)	I200F	probably damaging	Het
Cdc42bpb	C	T	12: 111,274,221 (GRCm39)	G1021R	probably benign	Het
Cidea	C	A	18: 67,499,485 (GRCm39)	S124*	probably null	Het
Cnst	C	A	1: 179,420,274 (GRCm39)	T135K	probably benign	Het
Crebbp	A	T	16: 3,936,952 (GRCm39)	M805K	probably benign	Het
Crybb1	A	G	5: 112,411,439 (GRCm39)	Y119C	probably damaging	Het
Cux1	G	T	5: 136,402,220 (GRCm39)	T121K	probably damaging	Het
Dnah11	A	T	12: 118,049,384 (GRCm39)		probably null	Het
Dnmbp	T	C	19: 43,900,677 (GRCm39)	T48A	probably damaging	Het
Dysf	G	A	6: 84,171,353 (GRCm39)	G1787E	probably damaging	Het
Gcm2	T	A	13: 41,258,096 (GRCm39)	R177S	probably benign	Het
Gdf6	G	T	4: 9,859,429 (GRCm39)	R170S	probably damaging	Het
Gm16686	A	T	4: 88,673,775 (GRCm39)	M18K	unknown	Het
Gm36864	C	T	7: 43,886,304 (GRCm39)	Q179*	probably null	Het
Golgb1	A	G	16: 36,736,675 (GRCm39)	D2015G	probably damaging	Het
Gtf2i	A	G	5: 134,324,374 (GRCm39)	L30P	probably damaging	Het
Herc2	A	G	7: 55,798,402 (GRCm39)	E1955G	possibly damaging	Het
Hes3	A	T	4: 152,372,132 (GRCm39)	D37E	probably damaging	Het
Igha	A	G	12: 113,223,144 (GRCm39)	V161A	probably damaging	Het
Isl2	T	G	9: 55,452,722 (GRCm39)	S327A	probably benign	Het
Kcnb2	T	C	1: 15,780,648 (GRCm39)	S507P	probably benign	Het
Lgals4	C	T	7: 28,540,921 (GRCm39)	R282C	probably damaging	Het
Lhfpl4	C	A	6: 113,171,034 (GRCm39)	V51L	possibly damaging	Het
Lhpp	A	G	7: 132,243,261 (GRCm39)	Y159C	probably damaging	Het
Lrwd1	C	A	5: 136,162,257 (GRCm39)	E159*	probably null	Het
Map3k13	A	G	16: 21,745,008 (GRCm39)	T856A	probably damaging	Het
Mcm8	A	G	2: 132,665,141 (GRCm39)	T206A	probably benign	Het
Megf6	A	G	4: 154,352,436 (GRCm39)	K1265R	probably benign	Het
Mrgprb2	A	G	7: 48,202,648 (GRCm39)	Y26H	probably benign	Het
Mug1	T	C	6: 121,817,208 (GRCm39)		probably benign	Het
Mysm1	C	T	4: 94,856,196 (GRCm39)	G134S	probably damaging	Het
Nlrp3	A	C	11: 59,440,216 (GRCm39)	I598L	probably benign	Het
Npas2	A	T	1: 39,331,797 (GRCm39)	I71F	possibly damaging	Het
Nr1h5	A	G	3: 102,862,015 (GRCm39)	S85P	probably benign	Het
Nrcam	T	A	12: 44,619,075 (GRCm39)	V868D	possibly damaging	Het
Oas1a	A	G	5: 121,040,019 (GRCm39)	F191L	probably damaging	Het
Or14j8	A	T	17: 38,263,673 (GRCm39)	Y81N	possibly damaging	Het
Orc3	A	T	4: 34,599,778 (GRCm39)	L125H	possibly damaging	Het
Osbpl7	A	G	11: 96,946,903 (GRCm39)	E402G	possibly damaging	Het
Otof	G	A	5: 30,545,968 (GRCm39)	Q462*	probably null	Het
Phlda2	A	C	7: 143,055,959 (GRCm39)	I90S	probably damaging	Het
Plin3	C	T	17: 56,593,490 (GRCm39)	V75I	probably benign	Het
Pms1	A	T	1: 53,321,195 (GRCm39)	S13T	possibly damaging	Het
Ppm1d	A	G	11: 85,236,732 (GRCm39)	K504E	probably damaging	Het
Rflna	A	T	5: 125,087,541 (GRCm39)	I93F	probably damaging	Het
Rnpc3	T	A	3: 113,414,805 (GRCm39)	M193L	probably benign	Het
Sema3e	A	T	5: 14,214,169 (GRCm39)	I145F	possibly damaging	Het
Serpinb1b	C	A	13: 33,271,500 (GRCm39)	N90K	probably damaging	Het
Sfswap	A	G	5: 129,620,345 (GRCm39)	D538G	possibly damaging	Het
Snx14	A	T	9: 88,289,453 (GRCm39)	D266E	possibly damaging	Het
Stat4	C	T	1: 52,115,711 (GRCm39)	T217M	possibly damaging	Het
Taf13	T	C	3: 108,485,444 (GRCm39)	M40T	probably damaging	Het
Tenm4	A	G	7: 96,523,047 (GRCm39)	T1530A	probably damaging	Het
Tenm4	C	T	7: 96,555,148 (GRCm39)	P2618S	probably benign	Het
Tnfrsf14	T	C	4: 155,007,710 (GRCm39)	I220M	possibly damaging	Het
Tnk2	T	C	16: 32,484,718 (GRCm39)	W60R	probably damaging	Het
Tph2	A	T	10: 115,015,614 (GRCm39)		probably benign	Het
Unc13b	A	T	4: 43,177,564 (GRCm39)	K2797N	unknown	Het
Upf1	C	G	8: 70,785,973 (GRCm39)	M995I	probably benign	Het
Upf1	G	A	8: 70,785,972 (GRCm39)	P996S	probably benign	Het
Vcan	C	T	13: 89,840,439 (GRCm39)	V1702M	probably benign	Het
Vmn2r57	T	C	7: 41,077,020 (GRCm39)	D382G	probably benign	Het
Xxylt1	C	T	16: 30,899,964 (GRCm39)	A64T	probably benign	Het
Zcchc8	A	G	5: 123,841,070 (GRCm39)	S407P	probably damaging	Het
Zdhhc19	T	A	16: 32,317,187 (GRCm39)	F109Y	probably damaging	Het
Zfp638	T	C	6: 83,931,745 (GRCm39)		probably null	Het
Zfp691	A	G	4: 119,027,861 (GRCm39)	S124P	probably damaging	Het
Zfp804a	T	A	2: 82,089,450 (GRCm39)	V1093D	probably damaging	Het
Zfp986	A	C	4: 145,625,550 (GRCm39)	Q70P	probably benign	Het

Other mutations in Itk

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00950:Itk	APN	11	46,258,723 (GRCm39)	missense	probably damaging	1.00
IGL01349:Itk	APN	11	46,232,027 (GRCm39)	missense	possibly damaging	0.84
IGL03290:Itk	APN	11	46,225,764 (GRCm39)	missense	probably damaging	1.00
IGL03385:Itk	APN	11	46,222,688 (GRCm39)	nonsense	probably null
Calame	UTSW	11	46,233,222 (GRCm39)	splice site	probably null
carbone	UTSW	11	46,222,776 (GRCm39)	nonsense	probably null
demon	UTSW	11	46,231,539 (GRCm39)	missense	probably damaging	1.00
goodnow	UTSW	11	46,228,926 (GRCm39)	splice site	probably null
itxaro	UTSW	11	46,229,044 (GRCm39)	missense	probably damaging	1.00
Segun	UTSW	11	46,235,710 (GRCm39)	intron	probably benign
BB009:Itk	UTSW	11	46,231,519 (GRCm39)	missense	probably benign
BB019:Itk	UTSW	11	46,231,519 (GRCm39)	missense	probably benign
R0095:Itk	UTSW	11	46,233,279 (GRCm39)	missense	probably damaging	0.99
R0265:Itk	UTSW	11	46,280,285 (GRCm39)	start gained	probably benign
R0281:Itk	UTSW	11	46,244,743 (GRCm39)	missense	probably damaging	1.00
R0463:Itk	UTSW	11	46,222,816 (GRCm39)	missense	probably damaging	1.00
R0518:Itk	UTSW	11	46,251,115 (GRCm39)	missense	probably damaging	0.98
R0521:Itk	UTSW	11	46,251,115 (GRCm39)	missense	probably damaging	0.98
R1121:Itk	UTSW	11	46,222,721 (GRCm39)	missense	possibly damaging	0.93
R1550:Itk	UTSW	11	46,280,153 (GRCm39)	missense	probably damaging	1.00
R1762:Itk	UTSW	11	46,227,309 (GRCm39)	missense	probably damaging	0.98
R2418:Itk	UTSW	11	46,229,044 (GRCm39)	missense	probably damaging	1.00
R2419:Itk	UTSW	11	46,229,044 (GRCm39)	missense	probably damaging	1.00
R2859:Itk	UTSW	11	46,235,662 (GRCm39)	intron	probably benign
R3107:Itk	UTSW	11	46,218,291 (GRCm39)	missense	probably benign	0.15
R3546:Itk	UTSW	11	46,246,675 (GRCm39)	missense	probably benign	0.00
R4601:Itk	UTSW	11	46,227,342 (GRCm39)	missense	probably benign	0.17
R4610:Itk	UTSW	11	46,227,342 (GRCm39)	missense	probably benign	0.17
R4792:Itk	UTSW	11	46,235,658 (GRCm39)	intron	probably benign
R4885:Itk	UTSW	11	46,227,171 (GRCm39)	splice site	probably null
R4934:Itk	UTSW	11	46,280,152 (GRCm39)	missense	probably damaging	1.00
R5286:Itk	UTSW	11	46,228,926 (GRCm39)	splice site	probably null
R5328:Itk	UTSW	11	46,222,703 (GRCm39)	missense	probably benign	0.04
R5399:Itk	UTSW	11	46,228,938 (GRCm39)	missense	probably benign	0.44
R5958:Itk	UTSW	11	46,235,682 (GRCm39)	intron	probably benign
R6235:Itk	UTSW	11	46,227,255 (GRCm39)	missense	probably benign	0.16
R6828:Itk	UTSW	11	46,232,045 (GRCm39)	missense	probably damaging	1.00
R6849:Itk	UTSW	11	46,222,762 (GRCm39)	missense	probably damaging	1.00
R7356:Itk	UTSW	11	46,258,659 (GRCm39)	missense	possibly damaging	0.72
R7753:Itk	UTSW	11	46,222,722 (GRCm39)	missense	probably damaging	1.00
R7932:Itk	UTSW	11	46,231,519 (GRCm39)	missense	probably benign
R7988:Itk	UTSW	11	46,246,661 (GRCm39)	missense	probably damaging	0.99
R8188:Itk	UTSW	11	46,222,776 (GRCm39)	nonsense	probably null
R8337:Itk	UTSW	11	46,233,222 (GRCm39)	splice site	probably null
R8993:Itk	UTSW	11	46,225,735 (GRCm39)	missense	probably damaging	1.00
R9028:Itk	UTSW	11	46,235,710 (GRCm39)	intron	probably benign
R9650:Itk	UTSW	11	46,222,778 (GRCm39)	missense	probably damaging	1.00
U24488:Itk	UTSW	11	46,228,971 (GRCm39)	missense	probably damaging	1.00
X0062:Itk	UTSW	11	46,256,871 (GRCm39)	missense	probably benign	0.15
Z1088:Itk	UTSW	11	46,244,689 (GRCm39)	splice site	probably null

Predicted Primers

PCR Primer
(F):5'- ACATAGGAGTACATAGGATCACTCTCC -3'
(R):5'- AGGTCACCATGTCACTGTCC -3'

Sequencing Primer
(F):5'- ACCTTCTCTCCAGTTAATCTGAC -3'
(R):5'- ATGTCACTGTCCTACTATGCTTAAGG -3'

Posted On

2021-03-08