Incidental Mutation 'R4737:Lck'
ID 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 4
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

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

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

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

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 question?
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
GeneRefVarChr/LocMutationPredicted EffectZygosity
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
AlleleSourceChrCoordTypePredicted EffectPPH 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

Sequencing Primer
Posted On 2015-11-11