Mutagenetix > Incidental Mutation

Incidental Mutation 'R4737:Lck'

359326

Institutional Source

Beutler Lab

Gene Symbol

Lck

Ensembl Gene

ENSMUSG00000000409

Gene Name

lymphocyte protein tyrosine kinase

Synonyms

Hck-3, p56

MMRRC Submission

042024-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R4737 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

129548344-129573641 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 129555984 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Isoleucine at position 229 (T229I)

Ref Sequence

ENSEMBL: ENSMUSP00000125777 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000067240] [ENSMUST00000102596] [ENSMUST00000134336] [ENSMUST00000167288]

AlphaFold

P06240

Predicted Effect

possibly damaging
Transcript: ENSMUST00000067240
AA Change: T218I

PolyPhen 2 Score 0.926 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000066209
Gene: ENSMUSG00000000409
AA Change: T218I

Domain	Start	End	E-Value	Type
SH3	64	120	3.53e-17	SMART
SH2	125	215	2.07e-34	SMART
TyrKc	245	494	2.66e-133	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000102596
AA Change: T218I

PolyPhen 2 Score 0.926 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000099656
Gene: ENSMUSG00000000409
AA Change: T218I

Domain	Start	End	E-Value	Type
SH3	64	120	3.53e-17	SMART
SH2	125	215	2.07e-34	SMART
TyrKc	245	494	2.66e-133	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000123640

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000127943

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000132030

Predicted Effect

probably benign
Transcript: ENSMUST00000134336

SMART Domains

Protein: ENSMUSP00000119263
Gene: ENSMUSG00000000409

Domain	Start	End	E-Value	Type
PDB:1Q69\|B	7	33	9e-12	PDB
SCOP:d1awj__	45	92	2e-8	SMART
PDB:1LCK\|A	53	92	3e-20	PDB
Blast:SH3	64	92	4e-13	BLAST

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000139957

Predicted Effect

possibly damaging
Transcript: ENSMUST00000167288
AA Change: T229I

PolyPhen 2 Score 0.926 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000125777
Gene: ENSMUSG00000000409
AA Change: T229I

Domain	Start	End	E-Value	Type
SH3	75	131	3.53e-17	SMART
SH2	136	226	2.07e-34	SMART
TyrKc	256	505	2.66e-133	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000183371

Meta Mutation Damage Score

0.2588

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.2%
20x: 95.3%

Validation Efficiency

100% (94/94)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a member of the Src family of protein tyrosine kinases (PTKs). The encoded protein is a key signaling molecule in the selection and maturation of developing T-cells. It contains N-terminal sites for myristylation and palmitylation, a PTK domain, and SH2 and SH3 domains which are involved in mediating protein-protein interactions with phosphotyrosine-containing and proline-rich motifs, respectively. The protein localizes to the plasma membrane and pericentrosomal vesicles, and binds to cell surface receptors, including CD4 and CD8, and other signaling molecules. Multiple alternatively spliced variants encoding different isoforms have been described. [provided by RefSeq, Aug 2016]
PHENOTYPE: Mice homozygous for mutations of this gene exhibit thymic atrophy with reduced numbers of peripheral T cells. Null mutants have few double positive and no mature single positive (SP) thymocytes. A hypomorph has decreased expression of CD3epsilon chain onSP thymocytes, whose numbers are reduced. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 88 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A430110L20Rik	A	G	1: 181,227,819 (GRCm38)		noncoding transcript	Het
Acp2	A	T	2: 91,210,723 (GRCm38)	R419W	probably benign	Het
Actr5	A	G	2: 158,628,071 (GRCm38)	N207S	probably damaging	Het
Afap1	G	A	5: 35,961,782 (GRCm38)	V254M	probably benign	Het
Arfgef1	A	T	1: 10,189,611 (GRCm38)	M544K	possibly damaging	Het
Arhgap5	A	T	12: 52,519,077 (GRCm38)	M944L	probably benign	Het
Bnip3l-ps	G	A	12: 18,216,772 (GRCm38)		noncoding transcript	Het
Carf	A	G	1: 60,109,318 (GRCm38)	T58A	probably benign	Het
Carns1	A	G	19: 4,170,928 (GRCm38)		probably benign	Het
Ccp110	T	A	7: 118,724,548 (GRCm38)	I670K	possibly damaging	Het
Cftr	T	A	6: 18,299,883 (GRCm38)	D1218E	probably benign	Het
Chrna9	A	T	5: 65,967,871 (GRCm38)	T52S	probably damaging	Het
Chst9	T	C	18: 15,452,777 (GRCm38)	Y243C	probably damaging	Het
Ciao3	A	T	17: 25,781,309 (GRCm38)	H322L	probably damaging	Het
Cilk1	A	G	9: 78,150,654 (GRCm38)	T162A	probably damaging	Het
Clk2	A	T	3: 89,168,709 (GRCm38)	H62L	probably benign	Het
Cntnap2	A	T	6: 45,060,317 (GRCm38)	R10W	possibly damaging	Het
Cpt1b	C	T	15: 89,421,406 (GRCm38)	D369N	probably benign	Het
Crhr2	G	T	6: 55,091,305 (GRCm38)	H423Q	probably damaging	Het
D8Ertd738e	T	A	8: 84,249,521 (GRCm38)	I33F	probably damaging	Het
Dbt	T	C	3: 116,539,132 (GRCm38)	I200T	probably damaging	Het
Ddhd1	A	T	14: 45,628,821 (GRCm38)		probably benign	Het
Ddx27	A	G	2: 167,029,299 (GRCm38)	I480V	probably benign	Het
Dpp9	A	C	17: 56,198,970 (GRCm38)		probably null	Het
Dpy19l3	A	T	7: 35,703,501 (GRCm38)	M562K	probably damaging	Het
Dus3l	T	C	17: 56,767,868 (GRCm38)	L330P	probably damaging	Het
Efcab7	C	T	4: 99,831,568 (GRCm38)	Q96*	probably null	Het
Egfr	T	C	11: 16,869,231 (GRCm38)	F254L	probably damaging	Het
Eml5	C	T	12: 98,798,852 (GRCm38)	V1566M	probably damaging	Het
Entpd7	T	A	19: 43,691,195 (GRCm38)	Y62*	probably null	Het
Erbb4	T	C	1: 68,343,900 (GRCm38)	M313V	probably damaging	Het
Gm5528	A	G	1: 72,004,552 (GRCm38)		noncoding transcript	Het
H2-M9	G	T	17: 36,640,739 (GRCm38)	Y281*	probably null	Het
Hmcn1	T	G	1: 150,689,595 (GRCm38)	K2260N	possibly damaging	Het
Hnf4a	A	G	2: 163,564,219 (GRCm38)	I259V	probably benign	Het
Insm1	A	T	2: 146,222,902 (GRCm38)	T213S	probably benign	Het
Iqca1	T	C	1: 90,077,822 (GRCm38)	D488G	probably damaging	Het
Kdm5a	T	A	6: 120,406,015 (GRCm38)		probably benign	Het
Kdm7a	G	C	6: 39,152,839 (GRCm38)	L468V	possibly damaging	Het
Lig3	T	C	11: 82,787,727 (GRCm38)	L265P	probably damaging	Het
Lipa	T	A	19: 34,501,634 (GRCm38)	K229*	probably null	Het
Lrrk1	C	T	7: 66,306,873 (GRCm38)	S418N	probably benign	Het
Mark2	A	G	19: 7,281,232 (GRCm38)	V126A	probably damaging	Het
Met	T	C	6: 17,491,541 (GRCm38)	C101R	probably damaging	Het
Mkln1	A	T	6: 31,426,799 (GRCm38)	K85M	probably damaging	Het
Mst1	A	G	9: 108,080,521 (GRCm38)	R15G	probably benign	Het
Muc6	T	G	7: 141,640,159 (GRCm38)		probably benign	Het
Muc6	G	T	7: 141,638,772 (GRCm38)	T1996N	possibly damaging	Het
Myo7b	T	C	18: 31,998,602 (GRCm38)	S514G	probably damaging	Het
Nars1	T	C	18: 64,516,427 (GRCm38)	E11G	probably benign	Het
Ogdh	T	A	11: 6,297,044 (GRCm38)	F23I	probably benign	Het
Or10g9	A	T	9: 40,000,422 (GRCm38)	D268E	probably damaging	Het
Or12e9	T	C	2: 87,372,321 (GRCm38)	I263T	probably damaging	Het
Or4a39	C	T	2: 89,406,486 (GRCm38)	V198I	probably benign	Het
Or4b1b	A	G	2: 90,282,381 (GRCm38)	S65P	probably damaging	Het
Or4c100	C	T	2: 88,526,225 (GRCm38)	S214F	probably damaging	Het
Or52r1c	C	T	7: 103,085,914 (GRCm38)	A127V	probably damaging	Het
Or9k2	T	A	10: 130,162,838 (GRCm38)	T163S	probably benign	Het
Otub2	T	A	12: 103,392,844 (GRCm38)	L64Q	probably benign	Het
Pappa2	T	C	1: 158,957,012 (GRCm38)	R143G	probably benign	Het
Patl2	T	A	2: 122,125,306 (GRCm38)	T250S	probably damaging	Het
Pcdhac2	C	T	18: 37,145,899 (GRCm38)	T644I	possibly damaging	Het
Pi4kb	C	T	3: 95,004,338 (GRCm38)	T690I	probably damaging	Het
Pla2g4d	T	C	2: 120,266,790 (GRCm38)	Y776C	probably benign	Het
Plekhh2	C	T	17: 84,563,959 (GRCm38)	S215L	probably benign	Het
Psmd2	T	G	16: 20,659,815 (GRCm38)		probably benign	Het
Ptpn21	T	C	12: 98,708,844 (GRCm38)	E183G	probably benign	Het
Ptprg	T	A	14: 12,226,314 (GRCm38)	D527E	probably damaging	Het
Rhobtb1	T	A	10: 69,279,497 (GRCm38)		probably null	Het
Scel	T	A	14: 103,572,037 (GRCm38)	M271K	possibly damaging	Het
Senp3	A	T	11: 69,678,829 (GRCm38)	C310*	probably null	Het
Slc25a3	T	C	10: 91,122,188 (GRCm38)	T97A	possibly damaging	Het
Srsf11	A	T	3: 158,026,732 (GRCm38)	Y82*	probably null	Het
Tbc1d8	G	A	1: 39,402,878 (GRCm38)	T211I	possibly damaging	Het
Tbkbp1	T	C	11: 97,148,648 (GRCm38)	E145G	probably damaging	Het
Tln1	T	C	4: 43,540,588 (GRCm38)	N1471S	probably benign	Het
Tnn	T	G	1: 160,146,089 (GRCm38)	D236A	probably damaging	Het
Trmt2a	C	T	16: 18,251,286 (GRCm38)		probably benign	Het
Ttn	A	T	2: 76,811,243 (GRCm38)	L5176Q	possibly damaging	Het
Ubxn10	G	A	4: 138,735,948 (GRCm38)		probably benign	Het
Ulk4	G	A	9: 121,073,872 (GRCm38)	Q1180*	probably null	Het
Usp43	T	A	11: 67,855,505 (GRCm38)	K1120N	probably damaging	Het
Uspl1	T	A	5: 149,194,339 (GRCm38)	L244Q	possibly damaging	Het
Vmn1r32	T	C	6: 66,553,645 (GRCm38)	H49R	probably damaging	Het
Vmn2r4	T	C	3: 64,409,963 (GRCm38)	D118G	probably damaging	Het
Vwce	A	G	19: 10,650,579 (GRCm38)	I468V	probably benign	Het
Zbtb7c	G	T	18: 76,146,154 (GRCm38)	R561L	probably benign	Het
Zfp956	T	C	6: 47,962,542 (GRCm38)	S175P	probably damaging	Het

Other mutations in Lck

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01824:Lck	APN	4	129,558,146 (GRCm38)	missense	probably benign	0.00
IGL02666:Lck	APN	4	129,556,419 (GRCm38)	missense	probably damaging	0.98
iconoclast	UTSW	4	129,555,604 (GRCm38)	missense	probably damaging	1.00
lockdown	UTSW	4	129,558,127 (GRCm38)	missense	probably damaging	1.00
stromberg	UTSW	4	129,555,640 (GRCm38)	missense	probably damaging	1.00
studentenkarzer	UTSW	4	129,556,305 (GRCm38)	missense	probably damaging	1.00
swan	UTSW	4	129,555,640 (GRCm38)	missense	probably damaging	1.00
R0091:Lck	UTSW	4	129,555,681 (GRCm38)	missense	possibly damaging	0.88
R0480:Lck	UTSW	4	129,555,640 (GRCm38)	missense	probably damaging	1.00
R1013:Lck	UTSW	4	129,558,127 (GRCm38)	missense	probably damaging	1.00
R1510:Lck	UTSW	4	129,555,668 (GRCm38)	missense	possibly damaging	0.92
R1569:Lck	UTSW	4	129,555,656 (GRCm38)	missense	probably damaging	0.98
R1845:Lck	UTSW	4	129,558,086 (GRCm38)	missense	probably benign	0.00
R2001:Lck	UTSW	4	129,548,937 (GRCm38)	missense	probably benign	0.00
R2141:Lck	UTSW	4	129,548,920 (GRCm38)	missense	probably damaging	1.00
R4694:Lck	UTSW	4	129,548,972 (GRCm38)	missense	possibly damaging	0.66
R5706:Lck	UTSW	4	129,551,638 (GRCm38)	critical splice acceptor site	probably null
R5712:Lck	UTSW	4	129,556,310 (GRCm38)	missense	probably benign
R7023:Lck	UTSW	4	129,548,865 (GRCm38)	missense	possibly damaging	0.89
R7411:Lck	UTSW	4	129,551,970 (GRCm38)	missense	probably benign	0.02
R9044:Lck	UTSW	4	129,556,305 (GRCm38)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- CCTGAATAGGCCAGTGTGAG -3'
(R):5'- TTCCCCTTCAGTGGATGAGG -3'

Sequencing Primer
(F):5'- TGAGAGGAAGCTCACATTCTCTC -3'
(R):5'- GTATAGAACCTGACCCTAGACCCTG -3'

Posted On

2015-11-11