Incidental Mutation 'IGL01360:Mpl'
ID75709
Institutional Source Australian Phenomics Network (link to record)
Gene Symbol Mpl
Ensembl Gene ENSMUSG00000006389
Gene Namemyeloproliferative leukemia virus oncogene
SynonymsTPO-R, thrombopoietin receptor, c-mpl, hlb219, CD110, c-mpl-I, c-mpl-II
Accession Numbers
Is this an essential gene? Non essential (E-score: 0.000) question?
Stock #IGL01360
Quality Score
Status
Chromosome4
Chromosomal Location118442415-118457513 bp(-) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) G to A at 118455661 bp
ZygosityHeterozygous
Amino Acid Change Threonine to Isoleucine at position 158 (T158I)
Ref Sequence ENSEMBL: ENSMUSP00000101983 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000006556] [ENSMUST00000102671] [ENSMUST00000106375]
Predicted Effect unknown
Transcript: ENSMUST00000006556
AA Change: T225I
SMART Domains Protein: ENSMUSP00000006556
Gene: ENSMUSG00000006389
AA Change: T225I

DomainStartEndE-ValueType
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 benign
Transcript: ENSMUST00000102671
SMART Domains Protein: ENSMUSP00000099732
Gene: ENSMUSG00000006389

DomainStartEndE-ValueType
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 possibly damaging
Transcript: ENSMUST00000106375
AA Change: T158I

PolyPhen 2 Score 0.939 (Sensitivity: 0.80; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000101983
Gene: ENSMUSG00000006389
AA Change: T158I

DomainStartEndE-ValueType
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 unknown
Transcript: ENSMUST00000168404
AA Change: T224I
SMART Domains Protein: ENSMUSP00000130167
Gene: ENSMUSG00000006389
AA Change: T224I

DomainStartEndE-ValueType
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
Predicted Effect noncoding transcript
Transcript: ENSMUST00000216417
Coding Region Coverage
Validation Efficiency
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: 47 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
6430573F11Rik A G 8: 36,512,559 I439V probably benign Het
Abca12 T A 1: 71,286,489 I1517L possibly damaging Het
Akap12 A T 10: 4,357,537 D1449V probably benign Het
Alg6 T A 4: 99,742,406 Y161N probably benign Het
Arhgap45 A T 10: 80,028,648 probably benign Het
Arhgap5 A T 12: 52,518,240 I665F probably damaging Het
Bbs4 A G 9: 59,339,848 V123A possibly damaging Het
Carm1 C T 9: 21,587,302 T480I probably benign Het
Catsperb G A 12: 101,625,254 V1032M probably damaging Het
Cdc42bpb A C 12: 111,342,075 I101S probably damaging Het
Copa C A 1: 172,087,588 probably null Het
Cramp1l T C 17: 24,997,573 I189V probably damaging Het
Dhx33 G A 11: 70,993,861 Q40* probably null Het
Egf A T 3: 129,740,020 F57Y probably damaging Het
Flt4 T C 11: 49,643,506 I1168T probably benign Het
Gm12794 A T 4: 101,940,468 D21V possibly damaging Het
Gm14178 A G 11: 99,747,443 S37P unknown Het
Gpbp1 A T 13: 111,426,541 probably benign Het
Herc1 T C 9: 66,483,699 S3980P probably benign Het
Itga6 T C 2: 71,787,326 probably null Het
Itgb4 T C 11: 115,990,940 S772P probably damaging Het
Kcng4 C A 8: 119,625,677 G498V probably benign Het
Lrp1 T G 10: 127,545,820 D3795A possibly damaging Het
Lrrk2 T A 15: 91,700,569 probably null Het
Mettl25 A T 10: 105,823,197 H408Q probably damaging Het
Mki67 T C 7: 135,705,776 E457G probably damaging Het
Mtg2 C T 2: 180,084,077 T160I probably damaging Het
Mtif2 A G 11: 29,530,110 I59V probably benign Het
Ncapg C A 5: 45,674,385 S191* probably null Het
Nup214 T C 2: 32,038,178 probably benign Het
Olfr1154 T C 2: 87,903,527 T50A probably benign Het
Phf3 T A 1: 30,808,728 T1245S probably damaging Het
Piezo2 T C 18: 63,117,699 D443G probably damaging Het
Ptchd4 C A 17: 42,317,045 H132Q probably benign Het
Pum1 T C 4: 130,728,170 probably benign Het
Slc30a7 A T 3: 115,990,116 V136E probably damaging Het
Slc5a10 A G 11: 61,715,136 V116A probably damaging Het
Sos2 A T 12: 69,590,800 S1046T probably benign Het
Svep1 A G 4: 58,116,554 S899P possibly damaging Het
Tfr2 G A 5: 137,571,691 V120I probably benign Het
Tnfrsf18 A T 4: 156,028,036 R117* probably null Het
Vmn1r77 T G 7: 12,041,388 F30L probably benign Het
Vmn2r112 T C 17: 22,618,622 M688T probably benign Het
Vmn2r93 T A 17: 18,305,248 D389E possibly damaging Het
Zpld1 T G 16: 55,226,385 N407T probably benign Het
Zranb3 C T 1: 127,959,885 W935* probably null Het
Zyx G A 6: 42,350,444 R59Q probably damaging Het
Other mutations in Mpl
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL02096:Mpl APN 4 118457136 missense possibly damaging 0.46
IGL02681:Mpl APN 4 118448871 splice site probably benign
R0238:Mpl UTSW 4 118456863 splice site probably benign
R0309:Mpl UTSW 4 118446038 intron probably benign
R0539:Mpl UTSW 4 118443508 missense possibly damaging 0.68
R0558:Mpl UTSW 4 118444020 missense probably damaging 0.99
R0601:Mpl UTSW 4 118443536 missense probably benign 0.08
R0784:Mpl UTSW 4 118446406 missense possibly damaging 0.59
R1016:Mpl UTSW 4 118448913 missense probably damaging 1.00
R1532:Mpl UTSW 4 118448568 missense possibly damaging 0.63
R1590:Mpl UTSW 4 118444024 missense probably damaging 0.99
R1806:Mpl UTSW 4 118443532 missense possibly damaging 0.73
R1875:Mpl UTSW 4 118456829 missense probably benign
R1935:Mpl UTSW 4 118455739 missense probably benign 0.01
R2182:Mpl UTSW 4 118457413 missense probably benign
R2291:Mpl UTSW 4 118449000 missense probably benign 0.04
R2508:Mpl UTSW 4 118455757 missense probably damaging 1.00
R4242:Mpl UTSW 4 118456771 missense probably damaging 0.98
R4718:Mpl UTSW 4 118456724 missense probably benign 0.02
R4775:Mpl UTSW 4 118448580 missense probably damaging 1.00
R5158:Mpl UTSW 4 118456684 missense probably damaging 0.98
R5208:Mpl UTSW 4 118455881 missense probably benign 0.00
R5276:Mpl UTSW 4 118455721 missense probably benign
R5953:Mpl UTSW 4 118454510 missense possibly damaging 0.89
R5953:Mpl UTSW 4 118454511 missense probably damaging 0.99
R6439:Mpl UTSW 4 118448553 missense probably damaging 0.98
R6450:Mpl UTSW 4 118448700 splice site probably null
R6521:Mpl UTSW 4 118455117 critical splice donor site probably null
R6812:Mpl UTSW 4 118455264 missense probably benign 0.03
R6876:Mpl UTSW 4 118457120 missense probably damaging 1.00
R7095:Mpl UTSW 4 118444063 missense
R7100:Mpl UTSW 4 118457410 missense
R7173:Mpl UTSW 4 118448544 critical splice donor site probably null
R7177:Mpl UTSW 4 118448544 critical splice donor site probably null
R7512:Mpl UTSW 4 118448892 missense
Posted On2013-10-07