Incidental Mutation 'R0056:Etv6'
| ID |
17053 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Etv6
|
| Ensembl Gene |
ENSMUSG00000030199 |
| Gene Name |
ets variant 6 |
| Synonyms |
translocation-ets-leukemia, Tel |
| MMRRC Submission |
038350-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R0056 (G1)
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
6 |
| Chromosomal Location |
134012663-134247121 bp(+) (GRCm39) |
| Type of Mutation |
nonsense |
| DNA Base Change (assembly) |
G to T
at 134225497 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Glutamic Acid to Stop codon
at position 154
(E154*)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000107594
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000081028]
[ENSMUST00000111963]
[ENSMUST00000164648]
|
| AlphaFold |
P97360 |
| Predicted Effect |
probably null
Transcript: ENSMUST00000081028
AA Change: E243*
|
| SMART Domains |
Protein: ENSMUSP00000079818
Gene: ENSMUSG00000030199
AA Change: E243*
| Domain | Start | End | E-Value | Type |
|---|
|
SAM_PNT
|
39 |
125 |
3.49e-41 |
SMART |
|
ETS
|
334 |
420 |
7.02e-49 |
SMART |
|
| Predicted Effect |
probably null
Transcript: ENSMUST00000111963
AA Change: E154*
|
| SMART Domains |
Protein: ENSMUSP00000107594
Gene: ENSMUSG00000030199
AA Change: E154*
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:SAM_PNT
|
1 |
36 |
1.3e-10 |
PFAM |
|
ETS
|
245 |
331 |
7.02e-49 |
SMART |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000145869
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000164648
|
| SMART Domains |
Protein: ENSMUSP00000130761
Gene: ENSMUSG00000030199
| Domain | Start | End | E-Value | Type |
|---|
|
SAM_PNT
|
38 |
124 |
3.49e-41 |
SMART |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000169529
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000171098
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000204426
|
| Meta Mutation Damage Score |
0.9755 |
| Coding Region Coverage |
- 1x: 89.2%
- 3x: 86.3%
- 10x: 78.7%
- 20x: 65.9%
|
| Validation Efficiency |
89% (66/74) |
| MGI Phenotype |
FUNCTION: This gene encodes a transcriptional repressor belonging to the ETS family of proteins. Knockout of this gene in mice results in embryonic lethality due to defective angiogenesis. In humans, this gene is often involved in chromosome rearrangements associated with specific cancers. Alternate splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2014]
PHENOTYPE: Homozygotes for a targeted null mutation exhibit defective yolk sac angiogenesis, excess apoptosis of mesenchymal and neural cells, and midgestational lethality. [provided by MGI curators]
|
| Allele List at MGI |
All alleles(134) : Targeted(7) Gene trapped(127)
|
| Other mutations in this stock |
Total: 48 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Adam34l |
A |
T |
8: 44,078,540 (GRCm39) |
C561* |
probably null |
Het |
| Ankfn1 |
A |
G |
11: 89,282,502 (GRCm39) |
S1061P |
possibly damaging |
Het |
| Atp9b |
A |
G |
18: 80,809,018 (GRCm39) |
S634P |
probably damaging |
Het |
| Bche |
A |
T |
3: 73,608,654 (GRCm39) |
N257K |
possibly damaging |
Het |
| Bms1 |
A |
T |
6: 118,382,190 (GRCm39) |
D449E |
probably benign |
Het |
| C630050I24Rik |
G |
T |
8: 107,846,026 (GRCm39) |
V59F |
unknown |
Het |
| Camkk2 |
C |
T |
5: 122,880,261 (GRCm39) |
E452K |
probably damaging |
Het |
| Ccdc121rt1 |
T |
C |
1: 181,338,118 (GRCm39) |
Y278C |
probably damaging |
Het |
| Chd9 |
A |
G |
8: 91,660,165 (GRCm39) |
H375R |
possibly damaging |
Het |
| Entpd7 |
T |
A |
19: 43,713,733 (GRCm39) |
V364E |
probably benign |
Het |
| Epb41l3 |
A |
T |
17: 69,560,392 (GRCm39) |
D313V |
probably damaging |
Het |
| Fshr |
T |
G |
17: 89,295,885 (GRCm39) |
H274P |
probably damaging |
Het |
| G3bp1 |
A |
G |
11: 55,388,867 (GRCm39) |
N360D |
probably benign |
Het |
| Gdf11 |
C |
T |
10: 128,722,294 (GRCm39) |
R187H |
probably benign |
Het |
| Gpihbp1 |
T |
A |
15: 75,468,982 (GRCm39) |
I52N |
probably damaging |
Het |
| H1f8 |
G |
T |
6: 115,923,934 (GRCm39) |
|
probably benign |
Het |
| Htt |
T |
C |
5: 34,983,422 (GRCm39) |
|
probably benign |
Het |
| Iqcm |
A |
G |
8: 76,480,014 (GRCm39) |
Q324R |
probably benign |
Het |
| Kcng3 |
A |
G |
17: 83,895,185 (GRCm39) |
L427P |
probably damaging |
Het |
| Klk7 |
T |
C |
7: 43,461,434 (GRCm39) |
L17P |
possibly damaging |
Het |
| Klrd1 |
G |
A |
6: 129,570,738 (GRCm39) |
V50I |
probably benign |
Het |
| Lama5 |
A |
T |
2: 179,828,899 (GRCm39) |
|
probably benign |
Het |
| Lamtor3 |
T |
A |
3: 137,632,711 (GRCm39) |
|
probably benign |
Het |
| Lyplal1 |
G |
A |
1: 185,820,763 (GRCm39) |
T228I |
probably benign |
Het |
| Mapk6 |
A |
G |
9: 75,296,098 (GRCm39) |
Y467H |
possibly damaging |
Het |
| Marchf6 |
T |
C |
15: 31,467,880 (GRCm39) |
T776A |
possibly damaging |
Het |
| Mogat1 |
T |
G |
1: 78,500,407 (GRCm39) |
M157R |
probably damaging |
Het |
| Morc2b |
T |
A |
17: 33,357,733 (GRCm39) |
Q13L |
possibly damaging |
Het |
| Myo1h |
C |
T |
5: 114,468,273 (GRCm39) |
T356I |
probably damaging |
Het |
| Ncoa2 |
C |
A |
1: 117,516,497 (GRCm38) |
|
probably null |
Het |
| Nobox |
A |
G |
6: 43,281,853 (GRCm39) |
C407R |
probably benign |
Het |
| Nup58 |
A |
G |
14: 60,476,924 (GRCm39) |
|
probably null |
Het |
| Or56a4 |
A |
G |
7: 104,806,329 (GRCm39) |
S187P |
probably benign |
Het |
| Otoa |
A |
G |
7: 120,730,570 (GRCm39) |
Y590C |
probably benign |
Het |
| Pelp1 |
A |
T |
11: 70,284,658 (GRCm39) |
V1070E |
unknown |
Het |
| Pglyrp3 |
G |
T |
3: 91,933,111 (GRCm39) |
|
probably benign |
Het |
| Plpp2 |
A |
G |
10: 79,363,063 (GRCm39) |
F189S |
probably damaging |
Het |
| Polr2b |
T |
C |
5: 77,482,382 (GRCm39) |
I640T |
possibly damaging |
Het |
| Ryr2 |
T |
A |
13: 11,683,924 (GRCm39) |
T3047S |
probably damaging |
Het |
| Snx25 |
A |
T |
8: 46,491,550 (GRCm39) |
W847R |
probably damaging |
Het |
| Son |
T |
C |
16: 91,475,043 (GRCm39) |
Y454H |
possibly damaging |
Het |
| Sos1 |
A |
T |
17: 80,721,050 (GRCm39) |
N923K |
probably damaging |
Het |
| Tex15 |
A |
G |
8: 34,072,055 (GRCm39) |
H2534R |
probably benign |
Het |
| Ticam2 |
G |
T |
18: 46,693,401 (GRCm39) |
Q229K |
possibly damaging |
Het |
| Tnfaip3 |
A |
T |
10: 18,881,041 (GRCm39) |
V342E |
probably damaging |
Het |
| Traf6 |
A |
G |
2: 101,527,496 (GRCm39) |
I415M |
possibly damaging |
Het |
| Trpm1 |
A |
G |
7: 63,893,334 (GRCm39) |
D1062G |
probably damaging |
Het |
| Wdr59 |
C |
T |
8: 112,207,239 (GRCm39) |
|
probably benign |
Het |
|
| Other mutations in Etv6 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL01636:Etv6
|
APN |
6 |
134,225,350 (GRCm39) |
missense |
probably benign |
0.41 |
|
IGL02028:Etv6
|
APN |
6 |
134,225,696 (GRCm39) |
missense |
probably benign |
0.01 |
|
IGL02173:Etv6
|
APN |
6 |
134,225,690 (GRCm39) |
missense |
possibly damaging |
0.68 |
|
IGL03074:Etv6
|
APN |
6 |
134,199,888 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R0295:Etv6
|
UTSW |
6 |
134,243,238 (GRCm39) |
missense |
probably benign |
0.31 |
|
R2133:Etv6
|
UTSW |
6 |
134,225,717 (GRCm39) |
missense |
possibly damaging |
0.92 |
|
R3763:Etv6
|
UTSW |
6 |
134,239,975 (GRCm39) |
splice site |
probably benign |
|
|
R4405:Etv6
|
UTSW |
6 |
134,210,497 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6901:Etv6
|
UTSW |
6 |
134,243,421 (GRCm39) |
missense |
probably benign |
0.10 |
|
R8292:Etv6
|
UTSW |
6 |
134,225,509 (GRCm39) |
missense |
probably benign |
|
|
R8343:Etv6
|
UTSW |
6 |
134,225,717 (GRCm39) |
missense |
possibly damaging |
0.92 |
|
R8752:Etv6
|
UTSW |
6 |
134,243,391 (GRCm39) |
missense |
probably benign |
0.01 |
|
R9562:Etv6
|
UTSW |
6 |
134,225,672 (GRCm39) |
missense |
probably benign |
0.28 |
|
R9565:Etv6
|
UTSW |
6 |
134,225,672 (GRCm39) |
missense |
probably benign |
0.28 |
|
R9616:Etv6
|
UTSW |
6 |
134,243,295 (GRCm39) |
missense |
possibly damaging |
0.47 |
|
R9680:Etv6
|
UTSW |
6 |
134,013,062 (GRCm39) |
start gained |
probably benign |
|
|
| Protein Function and Prediction |
Etv6 encodes ETV6 (alternatively, Tel), a member of the ETS family of transcriptional activators (1). ETV6 is frequently rearranged or fused with other genes (e.g., PDGFRB, ABL, MNI, and AML1) in human leukemias of myeloid or lymphoid origins (2;3). ETV6 has a sequence-specific DNA binding domain (i.e., the Ets domain) that can also mediate protein-protein interactions [reviewed in (4)]. At the C-terminus, ETV6 has a sterile alpha motif (SAM) domain.
|
| Expression/Localization |
Northern blot detected three transcripts (6.5 kb, 4.5 kb, and 2.4 kb) in all human tissues examined (5).
|
| Background |
Mutations in ETV6 have been linked to somatic acute myeloid leukemia [OMIM: 601626; (6)].
Etv6tm1Sho/tm1Sho; MGI: 2177950
involves: 129S4/SvJae * C57BL/6
Homozygotes exhibit embryonic lethality by E13.5, defective yolk sac angiogenesis, abnormal visceral yolk sac morphology, enlarged pericardium, and growth retardation (3).
Etv6tm2.1Sho/tm2.1Sho; MGI: 3056143
involves: 129S1/Sv
Homozygotes for a targeted null mutation exhibit defective yolk sac angiogenesis, excess apoptosis of mesenchymal and neural cells, and midgestational (95% died by E11) lethality (7).
|
| References |
1. Stegmaier, K., Pendse, S., Barker, G. F., Bray-Ward, P., Ward, D. C., Montgomery, K. T., Krauter, K. S., Reynolds, C., Sklar, J., and Donnelly, M. (1995) Frequent Loss of Heterozygosity at the TEL Gene Locus in Acute Lymphoblastic Leukemia of Childhood. Blood. 86, 38-44.
2. Wlodarska, I., Mecucci, C., Baens, M., Marynen, P., and van den Berghe, H. (1996) ETV6 Gene Rearrangements in Hematopoietic Malignant Disorders. Leuk Lymphoma. 23, 287-295.
3. Wang, L. C., Kuo, F., Fujiwara, Y., Gilliland, D. G., Golub, T. R., and Orkin, S. H. (1997) Yolk Sac Angiogenic Defect and Intra-Embryonic Apoptosis in Mice Lacking the Ets-Related Factor TEL. EMBO J. 16, 4374-4383.
5. Golub, T. R., Barker, G. F., Lovett, M., and Gilliland, D. G. (1994) Fusion of PDGF Receptor Beta to a Novel Ets-Like Gene, Tel, in Chronic Myelomonocytic Leukemia with t(5;12) Chromosomal Translocation. Cell. 77, 307-316.
6. Barjesteh van Waalwijk van Doorn-Khosrovani,S., Spensberger, D., de Knegt, Y., Tang, M., Lowenberg, B., and Delwel, R. (2005) Somatic Heterozygous Mutations in ETV6 (TEL) and Frequent Absence of ETV6 Protein in Acute Myeloid Leukemia. Oncogene. 24, 4129-4137.
7. Hock, H., Meade, E., Medeiros, S., Schindler, J. W., Valk, P. J., Fujiwara, Y., and Orkin, S. H. (2004) Tel/Etv6 is an Essential and Selective Regulator of Adult Hematopoietic Stem Cell Survival. Genes Dev. 18, 2336-2341. |
| Posted On |
2013-01-20 |
| Science Writer |
Anne Murray |
Incidental Mutation