Incidental Mutation 'R5298:Lef1'
| ID |
405523 |
| 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 |
042881-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R5298 (G1)
|
| Quality Score |
225 |
|
Status
|
Not validated
|
| Chromosome |
3 |
| Chromosomal Location |
130904120-131018005 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to T
at 130988316 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Arginine to Serine
at position 294
(R294S)
|
| 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 |
possibly damaging
Transcript: ENSMUST00000029611
AA Change: R294S
PolyPhen 2
Score 0.798 (Sensitivity: 0.84; Specificity: 0.93)
|
| SMART Domains |
Protein: ENSMUSP00000029611
Gene: ENSMUSG00000027985
AA Change: R294S
| Domain | Start | End | E-Value | Type |
|---|
|
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 benign
Transcript: ENSMUST00000066849
AA Change: R266S
PolyPhen 2
Score 0.062 (Sensitivity: 0.94; Specificity: 0.84)
|
| SMART Domains |
Protein: ENSMUSP00000067808
Gene: ENSMUSG00000027985
AA Change: R266S
| Domain | Start | End | E-Value | Type |
|---|
|
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 benign
Transcript: ENSMUST00000098611
AA Change: R228S
PolyPhen 2
Score 0.284 (Sensitivity: 0.91; Specificity: 0.88)
|
| SMART Domains |
Protein: ENSMUSP00000096211
Gene: ENSMUSG00000027985
AA Change: R228S
| Domain | Start | End | E-Value | Type |
|---|
|
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 benign
Transcript: ENSMUST00000106341
AA Change: R266S
PolyPhen 2
Score 0.355 (Sensitivity: 0.90; Specificity: 0.89)
|
| SMART Domains |
Protein: ENSMUSP00000101948
Gene: ENSMUSG00000027985
AA Change: R266S
| Domain | Start | End | E-Value | Type |
|---|
|
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 |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000198624
|
| Coding Region Coverage |
- 1x: 99.3%
- 3x: 98.6%
- 10x: 97.1%
- 20x: 94.6%
|
| 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: 36 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Ackr4 |
A |
G |
9: 103,976,086 (GRCm39) |
V287A |
possibly damaging |
Het |
| Adat2 |
A |
G |
10: 13,432,650 (GRCm39) |
N51D |
probably benign |
Het |
| Alms1-ps1 |
T |
C |
6: 85,729,100 (GRCm39) |
|
noncoding transcript |
Het |
| Ccdc97 |
A |
G |
7: 25,415,432 (GRCm39) |
V12A |
probably damaging |
Het |
| Cdcp2 |
T |
C |
4: 106,964,182 (GRCm39) |
V344A |
probably benign |
Het |
| Clasp1 |
A |
G |
1: 118,475,650 (GRCm39) |
D929G |
possibly damaging |
Het |
| Clip4 |
A |
G |
17: 72,141,220 (GRCm39) |
N525D |
probably damaging |
Het |
| Csde1 |
T |
A |
3: 102,954,525 (GRCm39) |
|
probably null |
Het |
| D330020A13Rik |
T |
C |
6: 120,271,777 (GRCm39) |
|
probably benign |
Het |
| Dnah2 |
C |
T |
11: 69,349,746 (GRCm39) |
R2399Q |
probably benign |
Het |
| Ehmt2 |
C |
T |
17: 35,118,067 (GRCm39) |
R40* |
probably null |
Het |
| Fuca1 |
C |
A |
4: 135,664,237 (GRCm39) |
Y374* |
probably null |
Het |
| Gle1 |
C |
G |
2: 29,838,955 (GRCm39) |
P457A |
probably benign |
Het |
| Hadhb |
T |
C |
5: 30,382,009 (GRCm39) |
|
probably null |
Het |
| Klhl18 |
G |
C |
9: 110,265,195 (GRCm39) |
N335K |
possibly damaging |
Het |
| Lrriq4 |
G |
T |
3: 30,699,481 (GRCm39) |
M1I |
probably null |
Het |
| Magi2 |
T |
C |
5: 20,774,160 (GRCm39) |
S884P |
probably damaging |
Het |
| Mon2 |
A |
G |
10: 122,846,511 (GRCm39) |
I1353T |
probably benign |
Het |
| Or4c127 |
T |
A |
2: 89,832,804 (GRCm39) |
L18Q |
possibly damaging |
Het |
| Or5p81 |
A |
G |
7: 108,267,279 (GRCm39) |
I219V |
probably benign |
Het |
| Parg |
C |
A |
14: 31,924,210 (GRCm39) |
A3E |
probably damaging |
Het |
| Per3 |
A |
T |
4: 151,113,666 (GRCm39) |
D297E |
probably damaging |
Het |
| Pkhd1l1 |
A |
T |
15: 44,367,442 (GRCm39) |
Y780F |
probably benign |
Het |
| Plcg2 |
A |
G |
8: 118,331,988 (GRCm39) |
Y858C |
probably benign |
Het |
| Prkca |
A |
T |
11: 107,903,510 (GRCm39) |
N287K |
probably damaging |
Het |
| Qsox2 |
A |
C |
2: 26,104,074 (GRCm39) |
S484A |
probably damaging |
Het |
| Reep4 |
G |
A |
14: 70,785,637 (GRCm39) |
G225D |
possibly damaging |
Het |
| Scn4a |
T |
C |
11: 106,230,212 (GRCm39) |
E532G |
probably damaging |
Het |
| Sfi1 |
A |
ATCTTCCCAAAGCCAGTGC |
11: 3,103,384 (GRCm39) |
|
probably benign |
Het |
| Slc23a1 |
A |
G |
18: 35,755,563 (GRCm39) |
|
probably null |
Het |
| Sowaha |
C |
T |
11: 53,370,355 (GRCm39) |
R127Q |
probably benign |
Het |
| Spag9 |
T |
C |
11: 93,990,961 (GRCm39) |
W626R |
probably damaging |
Het |
| Tasor2 |
T |
C |
13: 3,645,613 (GRCm39) |
|
probably null |
Het |
| Trim45 |
A |
G |
3: 100,832,787 (GRCm39) |
D340G |
probably damaging |
Het |
| Vmn1r193 |
A |
T |
13: 22,403,725 (GRCm39) |
F89Y |
probably damaging |
Het |
| Zfp507 |
T |
C |
7: 35,475,421 (GRCm39) |
N931D |
probably damaging |
Het |
|
| Other mutations in Lef1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH 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 |
|
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 |
|
R7544:Lef1
|
UTSW |
3 |
130,988,414 (GRCm39) |
missense |
probably damaging |
1.00 |
|
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'- TCCAGTGTCACTGTGGAAATG -3'
(R):5'- TGGCAGCCATCAACATCATC -3'
Sequencing Primer
(F):5'- TTTCATCGGGTGAGCCACAG -3'
(R):5'- AACATCATCCGCGCATCGTTATTAC -3'
|
| Posted On |
2016-07-22 |
Incidental Mutation