Incidental Mutation 'R5353:Cbl'
| ID |
423913 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Cbl
|
| Ensembl Gene |
ENSMUSG00000034342 |
| Gene Name |
Casitas B-lineage lymphoma |
| Synonyms |
Cbl-2, 4732447J05Rik, c-Cbl |
| MMRRC Submission |
042932-MU
|
| Accession Numbers |
|
| Essential gene? |
Possibly essential
(E-score: 0.503)
|
| Stock # |
R5353 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
9 |
| Chromosomal Location |
44054273-44145346 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to G
at 44084620 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Phenylalanine to Leucine
at position 172
(F172L)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000146244
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000037644]
[ENSMUST00000205755]
[ENSMUST00000205968]
[ENSMUST00000206147]
[ENSMUST00000206720]
|
| AlphaFold |
P22682 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000037644
AA Change: F172L
PolyPhen 2
Score 0.961 (Sensitivity: 0.78; Specificity: 0.95)
|
| SMART Domains |
Protein: ENSMUSP00000041902
Gene: ENSMUSG00000034342
AA Change: F172L
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
8 |
23 |
N/A |
INTRINSIC |
|
low complexity region
|
34 |
46 |
N/A |
INTRINSIC |
|
Pfam:Cbl_N
|
49 |
173 |
9.4e-59 |
PFAM |
|
Pfam:Cbl_N2
|
177 |
260 |
4.7e-44 |
PFAM |
|
Pfam:Cbl_N3
|
262 |
347 |
7.2e-48 |
PFAM |
|
RING
|
379 |
417 |
1.04e-7 |
SMART |
|
low complexity region
|
454 |
463 |
N/A |
INTRINSIC |
|
low complexity region
|
530 |
549 |
N/A |
INTRINSIC |
|
UBA
|
864 |
901 |
3.17e-8 |
SMART |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000205755
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000205968
AA Change: F172L
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000206147
AA Change: F172L
PolyPhen 2
Score 0.987 (Sensitivity: 0.73; Specificity: 0.96)
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000206629
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000206720
AA Change: F172L
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| Meta Mutation Damage Score |
0.6113 |
| Coding Region Coverage |
- 1x: 99.3%
- 3x: 98.8%
- 10x: 97.6%
- 20x: 96.2%
|
| Validation Efficiency |
100% (59/59) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a proto-oncogene that encodes a RING finger E3 ubiquitin ligase. The encoded protein is one of the enzymes required for targeting substrates for degradation by the proteasome. This protein mediates the transfer of ubiquitin from ubiquitin conjugating enzymes (E2) to specific substrates. This protein also contains an N-terminal phosphotyrosine binding domain that allows it to interact with numerous tyrosine-phosphorylated substrates and target them for proteasome degradation. As such it functions as a negative regulator of many signal transduction pathways. This gene has been found to be mutated or translocated in many cancers including acute myeloid leukaemia, and expansion of CGG repeats in the 5' UTR has been associated with Jacobsen syndrome. Mutations in this gene are also the cause of Noonan syndrome-like disorder. [provided by RefSeq, Jul 2016]
PHENOTYPE: Homozygotes for targeted null mutations exhibit increased thymic CD3 and CD4 expression and tyrosine-phosphorylation, lymphoid hyperplasia, and altered splenic hemopoiesis. Females show increased ductal density and branching in mammary fat pads. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 51 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Ablim3 |
A |
G |
18: 61,934,470 (GRCm39) |
S649P |
probably damaging |
Het |
| Adam22 |
C |
A |
5: 8,140,182 (GRCm39) |
G202W |
probably damaging |
Het |
| Adamts1 |
T |
A |
16: 85,599,496 (GRCm39) |
M35L |
probably benign |
Het |
| Adgrg3 |
A |
T |
8: 95,762,556 (GRCm39) |
H202L |
probably damaging |
Het |
| Anln |
G |
T |
9: 22,271,813 (GRCm39) |
R681S |
probably damaging |
Het |
| Aprt |
A |
T |
8: 123,302,147 (GRCm39) |
M1K |
probably null |
Het |
| Arid3b |
G |
T |
9: 57,702,320 (GRCm39) |
|
probably null |
Het |
| Cd109 |
G |
T |
9: 78,617,521 (GRCm39) |
V1340L |
probably damaging |
Het |
| Cdc45 |
C |
T |
16: 18,614,647 (GRCm39) |
R205H |
probably damaging |
Het |
| Chrm3 |
A |
G |
13: 9,928,593 (GRCm39) |
Y148H |
probably damaging |
Het |
| Cog7 |
A |
C |
7: 121,540,470 (GRCm39) |
|
probably null |
Het |
| Cpsf1 |
A |
T |
15: 76,486,771 (GRCm39) |
I255N |
probably damaging |
Het |
| Crebzf |
G |
A |
7: 90,092,622 (GRCm39) |
G134R |
probably damaging |
Het |
| Crybg1 |
T |
C |
10: 43,849,661 (GRCm39) |
S1705G |
probably damaging |
Het |
| Dock6 |
A |
T |
9: 21,726,082 (GRCm39) |
H1409Q |
probably benign |
Het |
| Fank1 |
A |
G |
7: 133,478,632 (GRCm39) |
D232G |
probably damaging |
Het |
| Fat1 |
G |
T |
8: 45,489,168 (GRCm39) |
V3480L |
probably benign |
Het |
| Fchsd1 |
C |
T |
18: 38,092,926 (GRCm39) |
|
probably benign |
Het |
| Fmn2 |
G |
T |
1: 174,330,572 (GRCm39) |
G321W |
unknown |
Het |
| Greb1 |
A |
T |
12: 16,738,567 (GRCm39) |
Y1465* |
probably null |
Het |
| Hdac9 |
G |
A |
12: 34,443,392 (GRCm39) |
Q330* |
probably null |
Het |
| Kcnt2 |
C |
T |
1: 140,354,639 (GRCm39) |
T298I |
probably damaging |
Het |
| Knl1 |
A |
G |
2: 118,901,464 (GRCm39) |
D1055G |
probably benign |
Het |
| Mroh2b |
T |
C |
15: 4,946,660 (GRCm39) |
S487P |
probably damaging |
Het |
| Naa38 |
G |
A |
11: 69,287,408 (GRCm39) |
V110I |
probably benign |
Het |
| Nkd2 |
T |
C |
13: 73,969,557 (GRCm39) |
H303R |
probably damaging |
Het |
| Nr1d2 |
A |
G |
14: 18,222,125 (GRCm38) |
C49R |
probably benign |
Het |
| Or4c111 |
A |
G |
2: 88,844,099 (GRCm39) |
V103A |
probably benign |
Het |
| Or52b2 |
A |
G |
7: 104,986,324 (GRCm39) |
Y200H |
probably damaging |
Het |
| Ovch2 |
T |
A |
7: 107,393,631 (GRCm39) |
E165V |
probably damaging |
Het |
| Phyh |
A |
T |
2: 4,947,012 (GRCm39) |
|
probably benign |
Het |
| Pik3r4 |
G |
A |
9: 105,545,137 (GRCm39) |
|
probably null |
Het |
| Ppip5k1 |
A |
C |
2: 121,142,201 (GRCm39) |
V1416G |
probably benign |
Het |
| Ppm1b |
T |
C |
17: 85,301,537 (GRCm39) |
V139A |
probably benign |
Het |
| Ppp1r12a |
T |
G |
10: 108,097,077 (GRCm39) |
|
probably null |
Het |
| Pramel20 |
A |
G |
4: 143,297,807 (GRCm39) |
T76A |
probably benign |
Het |
| Psmc5 |
G |
T |
11: 106,152,327 (GRCm39) |
A115S |
probably damaging |
Het |
| Ptpn5 |
T |
A |
7: 46,731,642 (GRCm39) |
E409V |
probably benign |
Het |
| Ptprg |
T |
A |
14: 11,554,235 (GRCm38) |
|
probably benign |
Het |
| Qrich1 |
G |
T |
9: 108,422,164 (GRCm39) |
V593F |
probably damaging |
Het |
| Rbbp9 |
T |
C |
2: 144,385,741 (GRCm39) |
I175V |
probably benign |
Het |
| Selenot |
T |
C |
3: 58,493,387 (GRCm39) |
F88S |
possibly damaging |
Het |
| Sp110 |
C |
T |
1: 85,516,841 (GRCm39) |
E219K |
possibly damaging |
Het |
| Spred2 |
A |
G |
11: 19,968,155 (GRCm39) |
D208G |
possibly damaging |
Het |
| Surf1 |
T |
C |
2: 26,804,204 (GRCm39) |
T197A |
probably benign |
Het |
| Taco1 |
G |
A |
11: 105,963,539 (GRCm39) |
|
probably null |
Het |
| Tas2r109 |
A |
G |
6: 132,957,594 (GRCm39) |
V112A |
possibly damaging |
Het |
| Tpr |
C |
T |
1: 150,321,675 (GRCm39) |
R3C |
probably damaging |
Het |
| Uggt2 |
A |
G |
14: 119,319,182 (GRCm39) |
I280T |
probably benign |
Het |
| Yipf2 |
A |
G |
9: 21,503,228 (GRCm39) |
Y80H |
possibly damaging |
Het |
| Zscan12 |
T |
C |
13: 21,548,178 (GRCm39) |
V120A |
possibly damaging |
Het |
|
| Other mutations in Cbl |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00590:Cbl
|
APN |
9 |
44,112,495 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01369:Cbl
|
APN |
9 |
44,112,358 (GRCm39) |
nonsense |
probably null |
|
|
IGL01434:Cbl
|
APN |
9 |
44,075,503 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL01866:Cbl
|
APN |
9 |
44,065,122 (GRCm39) |
nonsense |
probably null |
|
|
IGL02326:Cbl
|
APN |
9 |
44,062,770 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
IGL02956:Cbl
|
APN |
9 |
44,080,331 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Bungalow
|
UTSW |
9 |
44,112,416 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Casita
|
UTSW |
9 |
44,075,462 (GRCm39) |
missense |
probably damaging |
1.00 |
|
tiny_house
|
UTSW |
9 |
44,075,449 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0068:Cbl
|
UTSW |
9 |
44,065,491 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R0390:Cbl
|
UTSW |
9 |
44,112,302 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0655:Cbl
|
UTSW |
9 |
44,070,049 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0764:Cbl
|
UTSW |
9 |
44,075,449 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1466:Cbl
|
UTSW |
9 |
44,065,541 (GRCm39) |
missense |
probably benign |
0.10 |
|
R1466:Cbl
|
UTSW |
9 |
44,065,541 (GRCm39) |
missense |
probably benign |
0.10 |
|
R1616:Cbl
|
UTSW |
9 |
44,064,197 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R1736:Cbl
|
UTSW |
9 |
44,064,192 (GRCm39) |
missense |
possibly damaging |
0.80 |
|
R1808:Cbl
|
UTSW |
9 |
44,075,526 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1865:Cbl
|
UTSW |
9 |
44,075,462 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3156:Cbl
|
UTSW |
9 |
44,070,147 (GRCm39) |
missense |
possibly damaging |
0.74 |
|
R3431:Cbl
|
UTSW |
9 |
44,062,743 (GRCm39) |
makesense |
probably null |
|
|
R4668:Cbl
|
UTSW |
9 |
44,065,145 (GRCm39) |
missense |
probably benign |
0.00 |
|
R4700:Cbl
|
UTSW |
9 |
44,084,677 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4866:Cbl
|
UTSW |
9 |
44,064,166 (GRCm39) |
missense |
probably benign |
0.00 |
|
R4900:Cbl
|
UTSW |
9 |
44,064,166 (GRCm39) |
missense |
probably benign |
0.00 |
|
R4995:Cbl
|
UTSW |
9 |
44,065,108 (GRCm39) |
missense |
possibly damaging |
0.62 |
|
R5014:Cbl
|
UTSW |
9 |
44,065,696 (GRCm39) |
splice site |
probably null |
|
|
R5324:Cbl
|
UTSW |
9 |
44,065,551 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R5382:Cbl
|
UTSW |
9 |
44,070,318 (GRCm39) |
missense |
probably benign |
|
|
R5747:Cbl
|
UTSW |
9 |
44,112,416 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5834:Cbl
|
UTSW |
9 |
44,145,076 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6307:Cbl
|
UTSW |
9 |
44,069,809 (GRCm39) |
critical splice donor site |
probably null |
|
|
R6755:Cbl
|
UTSW |
9 |
44,084,671 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R7393:Cbl
|
UTSW |
9 |
44,065,485 (GRCm39) |
critical splice donor site |
probably null |
|
|
R7779:Cbl
|
UTSW |
9 |
44,070,393 (GRCm39) |
missense |
probably benign |
|
|
R7789:Cbl
|
UTSW |
9 |
44,074,764 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8094:Cbl
|
UTSW |
9 |
44,074,696 (GRCm39) |
missense |
probably benign |
0.03 |
|
R8104:Cbl
|
UTSW |
9 |
44,069,836 (GRCm39) |
missense |
possibly damaging |
0.93 |
|
R8146:Cbl
|
UTSW |
9 |
44,076,171 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8340:Cbl
|
UTSW |
9 |
44,070,297 (GRCm39) |
missense |
possibly damaging |
0.77 |
|
R8424:Cbl
|
UTSW |
9 |
44,064,151 (GRCm39) |
missense |
possibly damaging |
0.51 |
|
R8920:Cbl
|
UTSW |
9 |
44,078,570 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R9185:Cbl
|
UTSW |
9 |
44,064,137 (GRCm39) |
missense |
probably damaging |
1.00 |
|
X0057:Cbl
|
UTSW |
9 |
44,145,064 (GRCm39) |
small deletion |
probably benign |
|
|
| Predicted Primers |
PCR Primer
(F):5'- GGTCAACTCCACTCGCTCAG -3'
(R):5'- CCCCGCTTTACATAAAGAGCAG -3'
Sequencing Primer
(F):5'- GTAGCTGACTTCAGATTCACCAG -3'
(R):5'- GCAGTAGCTATCTAGTGTCAAAAAC -3'
|
| Posted On |
2016-08-04 |
Incidental Mutation