Incidental Mutation 'R1590:Mpl'
| ID |
177792 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Mpl
|
| Ensembl Gene |
ENSMUSG00000006389 |
| Gene Name |
myeloproliferative leukemia virus oncogene |
| Synonyms |
c-mpl-I, TPO-R, thrombopoietin receptor, c-mpl, CD110, hlb219, c-mpl-II |
| MMRRC Submission |
039627-MU
|
| Accession Numbers |
|
| Essential gene? |
Non essential
(E-score: 0.000)
|
| Stock # |
R1590 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
4 |
| Chromosomal Location |
118299612-118314710 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to C
at 118301221 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Leucine to Arginine
at position 548
(L548R)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000006556
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000006556]
[ENSMUST00000102671]
[ENSMUST00000106375]
|
| AlphaFold |
Q08351 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000006556
AA Change: L548R
PolyPhen 2
Score 0.985 (Sensitivity: 0.74; Specificity: 0.96)
|
| SMART Domains |
Protein: ENSMUSP00000006556
Gene: ENSMUSG00000006389
AA Change: L548R
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:EpoR_lig-bind
|
18 |
121 |
1.9e-31 |
PFAM |
|
Pfam:IL6Ra-bind
|
27 |
118 |
1.8e-7 |
PFAM |
|
FN3
|
126 |
257 |
7.7e-3 |
SMART |
|
FN3
|
382 |
461 |
2.83e0 |
SMART |
|
transmembrane domain
|
483 |
505 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000102671
AA Change: L540R
PolyPhen 2
Score 0.980 (Sensitivity: 0.75; Specificity: 0.96)
|
| SMART Domains |
Protein: ENSMUSP00000099732
Gene: ENSMUSG00000006389
AA Change: L540R
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:EpoR_lig-bind
|
25 |
128 |
1.4e-32 |
PFAM |
|
Pfam:IL6Ra-bind
|
34 |
125 |
7.3e-9 |
PFAM |
|
FN3
|
133 |
256 |
1.09e-2 |
SMART |
|
FN3
|
381 |
460 |
2.83e0 |
SMART |
|
transmembrane domain
|
482 |
504 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000106375
AA Change: L481R
PolyPhen 2
Score 0.053 (Sensitivity: 0.94; Specificity: 0.84)
|
| SMART Domains |
Protein: ENSMUSP00000101983
Gene: ENSMUSG00000006389
AA Change: L481R
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:EpoR_lig-bind
|
18 |
121 |
9.4e-32 |
PFAM |
|
Pfam:IL6Ra-bind
|
27 |
119 |
7.4e-8 |
PFAM |
|
FN3
|
322 |
401 |
2.83e0 |
SMART |
|
transmembrane domain
|
423 |
445 |
N/A |
INTRINSIC |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000121913
|
| Predicted Effect |
silent
Transcript: ENSMUST00000168404
|
| SMART Domains |
Protein: ENSMUSP00000130167
Gene: ENSMUSG00000006389
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:EpoR_lig-bind
|
25 |
128 |
1.9e-31 |
PFAM |
|
FN3
|
133 |
264 |
7.7e-3 |
SMART |
|
FN3
|
389 |
468 |
2.83e0 |
SMART |
|
transmembrane domain
|
490 |
512 |
N/A |
INTRINSIC |
|
| Meta Mutation Damage Score |
0.0646 |
| Coding Region Coverage |
- 1x: 99.1%
- 3x: 98.3%
- 10x: 96.0%
- 20x: 91.4%
|
| Validation Efficiency |
97% (69/71) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] In 1990 an oncogene, v-mpl, was identified from the murine myeloproliferative leukemia virus that was capable of immortalizing bone marrow hematopoietic cells from different lineages. In 1992 the human homologue, named, c-mpl, was cloned. Sequence data revealed that c-mpl encoded a protein that was homologous with members of the hematopoietic receptor superfamily. Presence of anti-sense oligodeoxynucleotides of c-mpl inhibited megakaryocyte colony formation. The ligand for c-mpl, thrombopoietin, was cloned in 1994. Thrombopoietin was shown to be the major regulator of megakaryocytopoiesis and platelet formation. The protein encoded by the c-mpl gene, CD110, is a 635 amino acid transmembrane domain, with two extracellular cytokine receptor domains and two intracellular cytokine receptor box motifs . TPO-R deficient mice were severely thrombocytopenic, emphasizing the important role of CD110 and thrombopoietin in megakaryocyte and platelet formation. Upon binding of thrombopoietin CD110 is dimerized and the JAK family of non-receptor tyrosine kinases, as well as the STAT family, the MAPK family, the adaptor protein Shc and the receptors themselves become tyrosine phosphorylated. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for targeted mutations at this locus are unable to produce normal amounts of megakaryocytes and platelets. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 59 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Aamp |
A |
G |
1: 74,322,370 (GRCm39) |
S95P |
probably damaging |
Het |
| Ankmy1 |
T |
C |
1: 92,816,397 (GRCm39) |
Y239C |
probably damaging |
Het |
| Atp12a |
T |
C |
14: 56,617,512 (GRCm39) |
S601P |
probably damaging |
Het |
| Atp1b3 |
T |
C |
9: 96,225,402 (GRCm39) |
T89A |
probably benign |
Het |
| B3galt4 |
G |
A |
17: 34,169,813 (GRCm39) |
R142C |
probably damaging |
Het |
| Brme1 |
A |
T |
8: 84,893,715 (GRCm39) |
Q294L |
probably benign |
Het |
| Btnl2 |
A |
T |
17: 34,580,114 (GRCm39) |
I216F |
possibly damaging |
Het |
| Cabs1 |
A |
T |
5: 88,127,490 (GRCm39) |
H47L |
probably damaging |
Het |
| Ccdc68 |
T |
A |
18: 70,073,251 (GRCm39) |
D66E |
probably benign |
Het |
| Cdc42ep4 |
T |
C |
11: 113,619,392 (GRCm39) |
D333G |
possibly damaging |
Het |
| Ckmt1 |
G |
A |
2: 121,194,003 (GRCm39) |
D389N |
possibly damaging |
Het |
| Dact1 |
G |
T |
12: 71,364,349 (GRCm39) |
V340F |
probably benign |
Het |
| Dnah2 |
T |
C |
11: 69,412,024 (GRCm39) |
T246A |
probably benign |
Het |
| Dnah2 |
A |
G |
11: 69,313,580 (GRCm39) |
|
probably null |
Het |
| Ecm1 |
G |
A |
3: 95,643,275 (GRCm39) |
R342C |
probably damaging |
Het |
| Efcab14 |
A |
G |
4: 115,613,746 (GRCm39) |
|
probably benign |
Het |
| Eprs1 |
A |
G |
1: 185,133,707 (GRCm39) |
T795A |
probably damaging |
Het |
| Esp36 |
T |
A |
17: 38,728,202 (GRCm39) |
E26D |
possibly damaging |
Het |
| Fpr-rs7 |
T |
C |
17: 20,333,678 (GRCm39) |
T271A |
probably benign |
Het |
| Fsip2 |
A |
T |
2: 82,813,131 (GRCm39) |
H3150L |
probably benign |
Het |
| Gimap7 |
G |
A |
6: 48,700,953 (GRCm39) |
V180M |
probably damaging |
Het |
| Gtf3c1 |
T |
C |
7: 125,275,833 (GRCm39) |
H531R |
possibly damaging |
Het |
| Herc1 |
T |
A |
9: 66,399,235 (GRCm39) |
|
probably benign |
Het |
| Hip1r |
A |
G |
5: 124,140,203 (GRCm39) |
Y1061C |
probably benign |
Het |
| Ipo11 |
T |
C |
13: 107,023,225 (GRCm39) |
Y420C |
probably damaging |
Het |
| Ipo8 |
T |
C |
6: 148,712,163 (GRCm39) |
|
probably null |
Het |
| Itga10 |
C |
T |
3: 96,559,054 (GRCm39) |
|
probably benign |
Het |
| Klhl1 |
A |
T |
14: 96,606,072 (GRCm39) |
M243K |
probably damaging |
Het |
| Lrp2 |
A |
G |
2: 69,297,107 (GRCm39) |
|
probably null |
Het |
| Mag |
T |
C |
7: 30,601,277 (GRCm39) |
E439G |
probably damaging |
Het |
| Mcm3ap |
T |
A |
10: 76,332,375 (GRCm39) |
F1231I |
probably benign |
Het |
| Mcmdc2 |
C |
T |
1: 9,986,780 (GRCm39) |
Q204* |
probably null |
Het |
| Mrps2 |
C |
T |
2: 28,359,500 (GRCm39) |
A119V |
probably benign |
Het |
| Myo18b |
G |
A |
5: 113,023,132 (GRCm39) |
Q87* |
probably null |
Het |
| Nfat5 |
A |
G |
8: 108,020,522 (GRCm39) |
Y22C |
probably damaging |
Het |
| Nnt |
T |
A |
13: 119,523,197 (GRCm39) |
I232L |
possibly damaging |
Het |
| Or2a52 |
A |
G |
6: 43,144,846 (GRCm39) |
N285D |
probably damaging |
Het |
| Or8g17 |
T |
C |
9: 38,930,253 (GRCm39) |
N195D |
probably benign |
Het |
| Or9s13 |
G |
A |
1: 92,548,467 (GRCm39) |
V280M |
possibly damaging |
Het |
| Parp2 |
C |
T |
14: 51,048,001 (GRCm39) |
P76S |
probably benign |
Het |
| Pick1 |
C |
T |
15: 79,129,501 (GRCm39) |
H169Y |
probably benign |
Het |
| Prtg |
T |
A |
9: 72,750,089 (GRCm39) |
F164L |
probably benign |
Het |
| Pygb |
A |
G |
2: 150,659,583 (GRCm39) |
D422G |
possibly damaging |
Het |
| Samd9l |
C |
A |
6: 3,375,761 (GRCm39) |
C500F |
probably benign |
Het |
| Sbno1 |
A |
C |
5: 124,522,567 (GRCm39) |
N1083K |
possibly damaging |
Het |
| Septin7 |
C |
T |
9: 25,188,900 (GRCm39) |
S77F |
probably damaging |
Het |
| Slc25a44 |
A |
G |
3: 88,323,314 (GRCm39) |
V264A |
possibly damaging |
Het |
| Slco1a8 |
C |
T |
6: 141,926,598 (GRCm39) |
S576N |
probably benign |
Het |
| Slf2 |
G |
T |
19: 44,930,512 (GRCm39) |
E530* |
probably null |
Het |
| Svs5 |
A |
G |
2: 164,079,578 (GRCm39) |
S110P |
possibly damaging |
Het |
| Tmbim7 |
G |
T |
5: 3,715,338 (GRCm39) |
|
probably null |
Het |
| Tpgs2 |
T |
C |
18: 25,273,630 (GRCm39) |
D177G |
probably damaging |
Het |
| Uba1y |
T |
A |
Y: 826,893 (GRCm39) |
F516L |
probably damaging |
Het |
| Ulk1 |
A |
G |
5: 110,943,632 (GRCm39) |
V211A |
probably damaging |
Het |
| Vmn1r237 |
T |
A |
17: 21,534,301 (GRCm39) |
I8N |
probably damaging |
Het |
| Vmn2r103 |
G |
T |
17: 20,014,496 (GRCm39) |
M429I |
probably benign |
Het |
| Vmn2r112 |
T |
C |
17: 22,833,989 (GRCm39) |
|
probably null |
Het |
| Vmn2r84 |
T |
C |
10: 130,227,349 (GRCm39) |
|
probably null |
Het |
| Vwa8 |
C |
T |
14: 79,145,670 (GRCm39) |
R116C |
probably damaging |
Het |
|
| Other mutations in Mpl |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL01360:Mpl
|
APN |
4 |
118,312,858 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
IGL02096:Mpl
|
APN |
4 |
118,314,333 (GRCm39) |
missense |
possibly damaging |
0.46 |
|
IGL02681:Mpl
|
APN |
4 |
118,306,068 (GRCm39) |
splice site |
probably benign |
|
|
R0238:Mpl
|
UTSW |
4 |
118,314,060 (GRCm39) |
splice site |
probably benign |
|
|
R0309:Mpl
|
UTSW |
4 |
118,303,235 (GRCm39) |
intron |
probably benign |
|
|
R0539:Mpl
|
UTSW |
4 |
118,300,705 (GRCm39) |
missense |
possibly damaging |
0.68 |
|
R0558:Mpl
|
UTSW |
4 |
118,301,217 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R0601:Mpl
|
UTSW |
4 |
118,300,733 (GRCm39) |
missense |
probably benign |
0.08 |
|
R0784:Mpl
|
UTSW |
4 |
118,303,603 (GRCm39) |
missense |
possibly damaging |
0.59 |
|
R1016:Mpl
|
UTSW |
4 |
118,306,110 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1532:Mpl
|
UTSW |
4 |
118,305,765 (GRCm39) |
missense |
possibly damaging |
0.63 |
|
R1806:Mpl
|
UTSW |
4 |
118,300,729 (GRCm39) |
missense |
possibly damaging |
0.73 |
|
R1875:Mpl
|
UTSW |
4 |
118,314,026 (GRCm39) |
missense |
probably benign |
|
|
R1935:Mpl
|
UTSW |
4 |
118,312,936 (GRCm39) |
missense |
probably benign |
0.01 |
|
R2182:Mpl
|
UTSW |
4 |
118,314,610 (GRCm39) |
missense |
probably benign |
|
|
R2291:Mpl
|
UTSW |
4 |
118,306,197 (GRCm39) |
missense |
probably benign |
0.04 |
|
R2508:Mpl
|
UTSW |
4 |
118,312,954 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4242:Mpl
|
UTSW |
4 |
118,313,968 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R4718:Mpl
|
UTSW |
4 |
118,313,921 (GRCm39) |
missense |
probably benign |
0.02 |
|
R4775:Mpl
|
UTSW |
4 |
118,305,777 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5158:Mpl
|
UTSW |
4 |
118,313,881 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R5208:Mpl
|
UTSW |
4 |
118,313,078 (GRCm39) |
missense |
probably benign |
0.00 |
|
R5276:Mpl
|
UTSW |
4 |
118,312,918 (GRCm39) |
missense |
probably benign |
|
|
R5953:Mpl
|
UTSW |
4 |
118,311,708 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R5953:Mpl
|
UTSW |
4 |
118,311,707 (GRCm39) |
missense |
possibly damaging |
0.89 |
|
R6439:Mpl
|
UTSW |
4 |
118,305,750 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R6450:Mpl
|
UTSW |
4 |
118,305,897 (GRCm39) |
splice site |
probably null |
|
|
R6521:Mpl
|
UTSW |
4 |
118,312,314 (GRCm39) |
critical splice donor site |
probably null |
|
|
R6812:Mpl
|
UTSW |
4 |
118,312,461 (GRCm39) |
missense |
probably benign |
0.03 |
|
R6876:Mpl
|
UTSW |
4 |
118,314,317 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7095:Mpl
|
UTSW |
4 |
118,301,260 (GRCm39) |
missense |
|
|
|
R7100:Mpl
|
UTSW |
4 |
118,314,607 (GRCm39) |
missense |
|
|
|
R7173:Mpl
|
UTSW |
4 |
118,305,741 (GRCm39) |
critical splice donor site |
probably null |
|
|
R7177:Mpl
|
UTSW |
4 |
118,305,741 (GRCm39) |
critical splice donor site |
probably null |
|
|
R7512:Mpl
|
UTSW |
4 |
118,306,089 (GRCm39) |
missense |
|
|
|
R8377:Mpl
|
UTSW |
4 |
118,301,254 (GRCm39) |
missense |
|
|
|
R8411:Mpl
|
UTSW |
4 |
118,303,306 (GRCm39) |
missense |
|
|
|
R8458:Mpl
|
UTSW |
4 |
118,301,213 (GRCm39) |
critical splice donor site |
probably null |
|
|
R8498:Mpl
|
UTSW |
4 |
118,306,207 (GRCm39) |
missense |
probably benign |
|
|
R8672:Mpl
|
UTSW |
4 |
118,306,110 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8863:Mpl
|
UTSW |
4 |
118,314,602 (GRCm39) |
missense |
|
|
|
R8904:Mpl
|
UTSW |
4 |
118,301,263 (GRCm39) |
missense |
|
|
|
Z1177:Mpl
|
UTSW |
4 |
118,300,852 (GRCm39) |
missense |
|
|
|
| Predicted Primers |
PCR Primer
(F):5'- GGGTTCCACTTCTTCACAGCTATCG -3'
(R):5'- AGGCCAACCCGCTTTGACTATG -3'
Sequencing Primer
(F):5'- agggacagccagggatac -3'
(R):5'- CGCTTTGACTATGCCCCTG -3'
|
| Posted On |
2014-04-24 |
Incidental Mutation