Incidental Mutation 'R7544:Lef1'
ID 584067
Institutional Source Beutler Lab
Gene Symbol Lef1
Ensembl Gene ENSMUSG00000027985
Gene Name lymphoid enhancer binding factor 1
Synonyms lymphoid enhancer factor 1, Lef-1
MMRRC Submission 045616-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R7544 (G1)
Quality Score 225.009
Status Not validated
Chromosome 3
Chromosomal Location 130904120-131018005 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 130988414 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Asparagine at position 327 (I327N)
Ref Sequence ENSEMBL: ENSMUSP00000029611 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000029611] [ENSMUST00000066849] [ENSMUST00000098611] [ENSMUST00000106341]
AlphaFold P27782
PDB Structure LEF1 HMG DOMAIN (FROM MOUSE), COMPLEXED WITH DNA (15BP), NMR, 12 STRUCTURES [SOLUTION NMR]
Structure of beta-catenin with Lef-1 [X-RAY DIFFRACTION]
Structure of beta-catenin with phosphorylated Lef-1 [X-RAY DIFFRACTION]
Predicted Effect probably damaging
Transcript: ENSMUST00000029611
AA Change: I327N

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000029611
Gene: ENSMUSG00000027985
AA Change: I327N

DomainStartEndE-ValueType
Pfam:CTNNB1_binding 1 211 5e-88 PFAM
low complexity region 245 259 N/A INTRINSIC
HMG 296 366 7.68e-23 SMART
low complexity region 372 380 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000066849
AA Change: I299N

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000067808
Gene: ENSMUSG00000027985
AA Change: I299N

DomainStartEndE-ValueType
Pfam:CTNNB1_binding 1 211 1e-75 PFAM
low complexity region 217 231 N/A INTRINSIC
HMG 268 338 7.68e-23 SMART
low complexity region 344 352 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000098611
AA Change: I261N

PolyPhen 2 Score 0.987 (Sensitivity: 0.73; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000096211
Gene: ENSMUSG00000027985
AA Change: I261N

DomainStartEndE-ValueType
Pfam:CTNNB1_binding 1 145 2.8e-54 PFAM
low complexity region 179 193 N/A INTRINSIC
HMG 230 300 7.68e-23 SMART
low complexity region 306 314 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000106341
AA Change: I299N

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000101948
Gene: ENSMUSG00000027985
AA Change: I299N

DomainStartEndE-ValueType
Pfam:CTNNB1_binding 1 211 1.3e-75 PFAM
low complexity region 217 231 N/A INTRINSIC
HMG 268 338 7.68e-23 SMART
low complexity region 344 352 N/A INTRINSIC
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.7%
  • 20x: 99.0%
Validation Efficiency
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a transcription factor belonging to a family of proteins that share homology with the high mobility group protein-1. The protein encoded by this gene can bind to a functionally important site in the T-cell receptor-alpha enhancer, thereby conferring maximal enhancer activity. This transcription factor is involved in the Wnt signaling pathway, and it may function in hair cell differentiation and follicle morphogenesis. Mutations in this gene have been found in somatic sebaceous tumors. This gene has also been linked to other cancers, including androgen-independent prostate cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
PHENOTYPE: Mice homozygous for a null allele are small and die postnatally showing lack of teeth, mammary and uterine glands, whiskers, body hair, dermal-associated fat, and a dentate gyrus, as well as defects in hippocampus morphology, hair follicle development, retinal vasculature, and vascular regression. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 75 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4933427D14Rik C T 11: 72,089,765 (GRCm39) V40I probably damaging Het
Abcb11 T C 2: 69,095,830 (GRCm39) K837E probably benign Het
Arhgef10 T C 8: 15,029,854 (GRCm39) S919P probably benign Het
Atxn2 T C 5: 121,919,431 (GRCm39) S530P probably damaging Het
Bicc1 T C 10: 70,792,204 (GRCm39) E268G possibly damaging Het
Bnip5 G A 17: 29,124,298 (GRCm39) R335W probably damaging Het
Capn7 T G 14: 31,062,007 (GRCm39) L40V probably damaging Het
Cd28 A T 1: 60,808,859 (GRCm39) N191I probably damaging Het
Cfap69 G A 5: 5,645,936 (GRCm39) T588M not run Het
Csmd1 T C 8: 16,142,310 (GRCm39) E1531G probably damaging Het
Cyp4a14 T A 4: 115,348,283 (GRCm39) D398V probably damaging Het
Dchs2 T C 3: 83,262,434 (GRCm39) S2901P probably damaging Het
Ddx11 G A 17: 66,433,280 (GRCm39) G37S probably damaging Het
Diaph1 A T 18: 38,026,322 (GRCm39) probably null Het
Ech1 T C 7: 28,525,392 (GRCm39) V49A probably benign Het
Elovl4 T C 9: 83,665,271 (GRCm39) Y196C probably damaging Het
Ern2 G A 7: 121,772,422 (GRCm39) L679F probably benign Het
Fbf1 A T 11: 116,056,659 (GRCm39) M17K probably benign Het
Flvcr1 C A 1: 190,758,143 (GRCm39) G50W probably damaging Het
Fryl A G 5: 73,238,382 (GRCm39) S1455P probably benign Het
Fzd9 A G 5: 135,278,716 (GRCm39) Y390H probably damaging Het
Gnai3 C T 3: 108,025,702 (GRCm39) V126M Het
Gpc5 T C 14: 115,665,585 (GRCm39) F470L probably damaging Het
Grin1 T C 2: 25,195,086 (GRCm39) N332S probably benign Het
Gtf3c5 T A 2: 28,469,554 (GRCm39) I117F possibly damaging Het
Hydin A T 8: 111,316,157 (GRCm39) S4350C probably benign Het
Kcnh4 G T 11: 100,647,906 (GRCm39) H152Q probably benign Het
Kcnk12 A T 17: 88,053,493 (GRCm39) S390T possibly damaging Het
Klra9 T G 6: 130,168,183 (GRCm39) T28P probably benign Het
Lin54 A G 5: 100,633,129 (GRCm39) V185A possibly damaging Het
Lrrc37 T C 11: 103,506,274 (GRCm39) E1898G probably benign Het
Lrrc4b A T 7: 44,111,975 (GRCm39) I616F probably damaging Het
Mad2l1bp A G 17: 46,463,770 (GRCm39) Y85H possibly damaging Het
Mars1 T C 10: 127,147,479 (GRCm39) E7G probably benign Het
Mpnd G A 17: 56,318,666 (GRCm39) R225H probably benign Het
Muc4 T A 16: 32,555,016 (GRCm39) M1K probably null Het
Nckap5 A G 1: 125,953,948 (GRCm39) L868S possibly damaging Het
Ndst1 G A 18: 60,830,256 (GRCm39) T618M probably damaging Het
Npas1 A T 7: 16,194,899 (GRCm39) probably null Het
Nr2f2 A T 7: 70,004,499 (GRCm39) V384D probably damaging Het
Or10a3b A G 7: 108,444,528 (GRCm39) S230P probably benign Het
Or1e19 A G 11: 73,316,596 (GRCm39) L71P probably damaging Het
Or4p8 T A 2: 88,727,705 (GRCm39) I79F probably damaging Het
Paip1 T A 13: 119,582,337 (GRCm39) F188I probably damaging Het
Pcdha4 A T 18: 37,086,776 (GRCm39) I320L probably benign Het
Peg10 TCAGCATCAGGATCCCCATCAGGATGCACATCAGGATCCACATCAGGATGCACATC T 6: 4,756,427 (GRCm39) probably null Het
Pgpep1 C T 8: 71,103,168 (GRCm39) G110R unknown Het
Pidd1 T A 7: 141,020,252 (GRCm39) H558L possibly damaging Het
Ppp1r1a C T 15: 103,439,776 (GRCm39) probably null Het
Pramel18 T C 4: 101,768,599 (GRCm39) S317P possibly damaging Het
Pramel51 T A 12: 88,142,850 (GRCm39) Y451F probably benign Het
Prkcg A G 7: 3,359,081 (GRCm39) D96G probably benign Het
Prpf40b A G 15: 99,203,899 (GRCm39) N154S probably benign Het
Psg17 A G 7: 18,553,897 (GRCm39) Y118H probably benign Het
Ptpn12 A G 5: 21,214,509 (GRCm39) I209T probably damaging Het
Reln T A 5: 22,181,276 (GRCm39) K1835* probably null Het
Sf3b3 T C 8: 111,564,915 (GRCm39) M298V probably benign Het
Slc5a3 T A 16: 91,874,682 (GRCm39) N246K probably benign Het
Slmap T A 14: 26,151,001 (GRCm39) E522D probably damaging Het
Slmap C T 14: 26,151,003 (GRCm39) E522K probably damaging Het
Tcp10c T A 17: 13,581,260 (GRCm39) L230Q probably damaging Het
Tdo2 A G 3: 81,878,942 (GRCm39) probably null Het
Tet3 A T 6: 83,381,623 (GRCm39) W182R probably damaging Het
Tmem151a T A 19: 5,121,895 (GRCm39) M35L unknown Het
Tom1l2 TTGATGATG TTGATG 11: 60,171,040 (GRCm39) probably benign Het
Trak2 A T 1: 58,960,227 (GRCm39) probably null Het
Trappc11 T A 8: 47,975,449 (GRCm39) E256D possibly damaging Het
Trim62 C T 4: 128,796,346 (GRCm39) T281I probably benign Het
Trip13 T C 13: 74,081,021 (GRCm39) E115G probably benign Het
Trp63 A G 16: 25,620,837 (GRCm39) T10A probably benign Het
Urah A T 7: 140,415,565 (GRCm39) H11L probably damaging Het
Usp39 G A 6: 72,319,891 (GRCm39) T109I probably damaging Het
Wfikkn2 T C 11: 94,128,738 (GRCm39) T468A probably benign Het
Zfhx4 T G 3: 5,477,875 (GRCm39) S3497A probably damaging Het
Zfp85 C T 13: 67,897,184 (GRCm39) R296H probably benign Het
Other mutations in Lef1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00096:Lef1 APN 3 130,907,499 (GRCm39) splice site probably benign
IGL00515:Lef1 APN 3 130,997,926 (GRCm39) missense probably damaging 1.00
IGL00780:Lef1 APN 3 130,986,779 (GRCm39) missense possibly damaging 0.69
IGL02057:Lef1 APN 3 130,994,051 (GRCm39) nonsense probably null
IGL02556:Lef1 APN 3 130,988,442 (GRCm39) splice site probably null
IGL02804:Lef1 APN 3 130,988,338 (GRCm39) missense probably damaging 1.00
IGL03143:Lef1 APN 3 130,993,965 (GRCm39) nonsense probably null
IGL03169:Lef1 APN 3 130,988,312 (GRCm39) missense probably damaging 1.00
R0470:Lef1 UTSW 3 130,906,475 (GRCm39) intron probably benign
R1354:Lef1 UTSW 3 130,988,317 (GRCm39) missense probably damaging 1.00
R1677:Lef1 UTSW 3 130,993,938 (GRCm39) splice site probably benign
R1860:Lef1 UTSW 3 130,905,290 (GRCm39) missense probably damaging 0.99
R2013:Lef1 UTSW 3 130,905,236 (GRCm39) missense probably damaging 0.98
R2015:Lef1 UTSW 3 130,905,236 (GRCm39) missense probably damaging 0.98
R3440:Lef1 UTSW 3 130,978,407 (GRCm39) missense probably damaging 1.00
R3736:Lef1 UTSW 3 130,984,715 (GRCm39) missense possibly damaging 0.51
R3918:Lef1 UTSW 3 130,905,290 (GRCm39) missense probably damaging 0.99
R4052:Lef1 UTSW 3 130,988,338 (GRCm39) missense probably damaging 1.00
R4346:Lef1 UTSW 3 130,988,357 (GRCm39) missense probably damaging 1.00
R4608:Lef1 UTSW 3 130,978,382 (GRCm39) missense probably benign 0.00
R4764:Lef1 UTSW 3 130,978,382 (GRCm39) missense probably benign 0.00
R4786:Lef1 UTSW 3 130,905,173 (GRCm39) missense probably damaging 0.99
R5298:Lef1 UTSW 3 130,988,316 (GRCm39) missense possibly damaging 0.80
R5394:Lef1 UTSW 3 130,988,308 (GRCm39) missense probably damaging 1.00
R6827:Lef1 UTSW 3 130,994,053 (GRCm39) critical splice donor site probably null
R6893:Lef1 UTSW 3 130,909,149 (GRCm39) missense possibly damaging 0.77
R6974:Lef1 UTSW 3 130,905,223 (GRCm39) missense probably damaging 1.00
R7541:Lef1 UTSW 3 130,984,748 (GRCm39) missense probably benign 0.00
R7652:Lef1 UTSW 3 130,994,003 (GRCm39) missense probably damaging 1.00
R8074:Lef1 UTSW 3 130,997,954 (GRCm39) critical splice donor site probably null
R8348:Lef1 UTSW 3 130,906,461 (GRCm39) start codon destroyed probably benign 0.02
R8543:Lef1 UTSW 3 130,909,138 (GRCm39) missense possibly damaging 0.92
R8762:Lef1 UTSW 3 130,988,366 (GRCm39) missense probably damaging 1.00
Z1176:Lef1 UTSW 3 130,993,972 (GRCm39) missense probably damaging 1.00
Z1177:Lef1 UTSW 3 130,986,830 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- GGCAATGCCTACAGATCTTCTC -3'
(R):5'- GCATTCAGGTATACGTACAAGTG -3'

Sequencing Primer
(F):5'- AATGCCTACAGATCTTCTCTTCCC -3'
(R):5'- TTCAGGTATACGTACAAGTGGGCAC -3'
Posted On 2019-10-17