Incidental Mutation 'R5208:Mpl'
ID 402142
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 042783-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R5208 (G1)
Quality Score 225
Status Not validated
Chromosome 4
Chromosomal Location 118299612-118314710 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to G at 118313078 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Leucine at position 152 (I152L)
Ref Sequence ENSEMBL: ENSMUSP00000099732 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000006556] [ENSMUST00000102671] [ENSMUST00000106375]
AlphaFold Q08351
Predicted Effect unknown
Transcript: ENSMUST00000006556
AA Change: I152L
SMART Domains Protein: ENSMUSP00000006556
Gene: ENSMUSG00000006389
AA Change: I152L

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
AA Change: I152L

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)
SMART Domains Protein: ENSMUSP00000099732
Gene: ENSMUSG00000006389
AA Change: I152L

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 probably benign
Transcript: ENSMUST00000106375
SMART Domains Protein: ENSMUSP00000101983
Gene: ENSMUSG00000006389

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: I151L
SMART Domains Protein: ENSMUSP00000130167
Gene: ENSMUSG00000006389
AA Change: I151L

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
  • 1x: 99.3%
  • 3x: 98.6%
  • 10x: 97.3%
  • 20x: 95.3%
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: 63 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Aadacl4 A T 4: 144,344,398 (GRCm39) N58I probably benign Het
Adgra3 T C 5: 50,168,857 (GRCm39) D163G probably damaging Het
Alcam C A 16: 52,115,411 (GRCm39) E236* probably null Het
Ank3 G A 10: 69,838,395 (GRCm39) R1566K possibly damaging Het
Aplf G T 6: 87,619,008 (GRCm39) probably null Het
Arl4a A T 12: 40,086,744 (GRCm39) M1K probably null Het
Asic4 A G 1: 75,427,870 (GRCm39) D132G probably damaging Het
Bbs12 T C 3: 37,374,422 (GRCm39) I290T probably benign Het
BC024139 A G 15: 76,008,865 (GRCm39) S290P probably benign Het
Bmp6 G A 13: 38,653,673 (GRCm39) A247T probably benign Het
Cadps A G 14: 12,457,711 (GRCm38) S1057P possibly damaging Het
Caprin1 A C 2: 103,599,778 (GRCm39) probably null Het
Cdc42bpg G A 19: 6,371,750 (GRCm39) R1343K probably benign Het
Cdk18 A T 1: 132,045,218 (GRCm39) probably null Het
Cenpf A T 1: 189,403,243 (GRCm39) probably null Het
Cfhr1 A T 1: 139,484,068 (GRCm39) probably null Het
Chn2 A T 6: 54,272,786 (GRCm39) I201F probably damaging Het
Chrdl2 A G 7: 99,673,129 (GRCm39) D175G probably damaging Het
Disp2 G T 2: 118,622,286 (GRCm39) R1006L probably damaging Het
Dnah2 C T 11: 69,349,746 (GRCm39) R2399Q probably benign Het
Dnah3 C G 7: 119,631,861 (GRCm39) D1365H probably damaging Het
Efcab8 T A 2: 153,644,343 (GRCm39) Y372* probably null Het
Eftud2 G A 11: 102,732,011 (GRCm39) P768S probably damaging Het
Ehmt1 A C 2: 24,691,545 (GRCm39) S1170A probably benign Het
Gdpd4 A C 7: 97,664,118 (GRCm39) K572Q probably benign Het
Gm7356 T C 17: 14,221,456 (GRCm39) E191G probably damaging Het
Gm8674 A T 13: 50,055,957 (GRCm39) noncoding transcript Het
Gulp1 T G 1: 44,820,199 (GRCm39) H235Q probably benign Het
Hormad1 T C 3: 95,485,418 (GRCm39) V202A possibly damaging Het
Inpp5b G A 4: 124,645,110 (GRCm39) D179N possibly damaging Het
Kcnk4 T A 19: 6,905,069 (GRCm39) Y194F possibly damaging Het
Lars1 A C 18: 42,350,622 (GRCm39) S896A probably benign Het
Lonp1 A G 17: 56,924,793 (GRCm39) V538A probably damaging Het
Map3k14 A T 11: 103,129,972 (GRCm39) L315Q probably damaging Het
Met T A 6: 17,526,422 (GRCm39) Y500* probably null Het
Mga T G 2: 119,778,462 (GRCm39) I2093M possibly damaging Het
Mthfsd G A 8: 121,835,058 (GRCm39) probably benign Het
Mup4 A G 4: 59,958,119 (GRCm39) F150L probably damaging Het
Mybph T A 1: 134,121,273 (GRCm39) V11D probably benign Het
Or4f54 A T 2: 111,122,946 (GRCm39) E111V probably damaging Het
Or52n2c A G 7: 104,574,933 (GRCm39) F13L probably benign Het
Or5ak20 T A 2: 85,184,142 (GRCm39) I43F probably benign Het
Pde4a T C 9: 21,114,854 (GRCm39) probably null Het
Pex2 C T 3: 5,626,428 (GRCm39) R127H probably benign Het
Pgap3 A G 11: 98,288,874 (GRCm39) W94R probably damaging Het
Prl4a1 T C 13: 28,202,467 (GRCm39) V14A probably benign Het
Psg25 A T 7: 18,260,460 (GRCm39) I146N probably benign Het
Ptprn2 A G 12: 116,822,548 (GRCm39) Y209C probably damaging Het
Scart2 C A 7: 139,877,949 (GRCm39) A977D probably benign Het
Sema4c T A 1: 36,589,407 (GRCm39) D573V probably damaging Het
Setx A T 2: 29,056,379 (GRCm39) I2192F possibly damaging Het
Skic3 G A 13: 76,295,886 (GRCm39) E1050K possibly damaging Het
Sp4 A G 12: 118,263,281 (GRCm39) L255P probably damaging Het
Spaca7 A G 8: 12,636,456 (GRCm39) Y94C probably damaging Het
Stt3a T G 9: 36,657,891 (GRCm39) I390L possibly damaging Het
Tars2 A G 3: 95,654,905 (GRCm39) W128R probably damaging Het
Tll1 G A 8: 64,504,527 (GRCm39) T623M probably damaging Het
Tmem129 A T 5: 33,812,850 (GRCm39) V166E probably damaging Het
Tmem200a T A 10: 25,870,051 (GRCm39) I73F probably benign Het
Tnks1bp1 T C 2: 84,900,976 (GRCm39) M1561T probably damaging Het
Zfat A T 15: 68,052,570 (GRCm39) I401N probably damaging Het
Zfp142 A T 1: 74,610,027 (GRCm39) V1153E probably benign Het
Zwilch T C 9: 64,060,205 (GRCm39) I354V probably benign Het
Other mutations in Mpl
AlleleSourceChrCoordTypePredicted EffectPPH 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
R1590:Mpl UTSW 4 118,301,221 (GRCm39) missense probably damaging 0.99
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
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'- AGAAGGGGAGGGTACTTCTC -3'
(R):5'- GGGAGTTCAGAGTTGCTCTC -3'

Sequencing Primer
(F):5'- TGCTGTCGGATGAACACAC -3'
(R):5'- GAGTTGCTCTCTACAGCCTTCGG -3'
Posted On 2016-07-22