Incidental Mutation 'R7173:Mpl'
ID 558408
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 045265-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R7173 (G1)
Quality Score 225.009
Status Validated
Chromosome 4
Chromosomal Location 118299612-118314710 bp(-) (GRCm39)
Type of Mutation critical splice donor site (2 bp from exon)
DNA Base Change (assembly) A to G at 118305741 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change
Ref Sequence ENSEMBL: ENSMUSP00000006556 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000006556] [ENSMUST00000006556] [ENSMUST00000102671] [ENSMUST00000102671] [ENSMUST00000106375] [ENSMUST00000106375]
AlphaFold Q08351
Predicted Effect probably null
Transcript: ENSMUST00000006556
SMART Domains Protein: ENSMUSP00000006556
Gene: ENSMUSG00000006389

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 null
Transcript: ENSMUST00000006556
SMART Domains Protein: ENSMUSP00000006556
Gene: ENSMUSG00000006389

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 null
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 probably null
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 probably null
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 probably null
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 probably null
Transcript: ENSMUST00000168404
SMART Domains Protein: ENSMUSP00000130167
Gene: ENSMUSG00000006389

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 probably null
Transcript: ENSMUST00000168404
SMART Domains Protein: ENSMUSP00000130167
Gene: ENSMUSG00000006389

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
Meta Mutation Damage Score 0.9493 question?
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 100.0%
  • 10x: 99.7%
  • 20x: 99.0%
Validation Efficiency 100% (79/79)
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: 78 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
5031439G07Rik C T 15: 84,833,848 (GRCm39) V403I possibly damaging Het
Actn1 G A 12: 80,224,033 (GRCm39) R475C possibly damaging Het
Adam11 T C 11: 102,662,757 (GRCm39) L191P possibly damaging Het
Adam21 G T 12: 81,606,008 (GRCm39) Q585K probably benign Het
Akap3 T C 6: 126,841,729 (GRCm39) V116A probably benign Het
Alpk1 A T 3: 127,478,024 (GRCm39) Y74* probably null Het
Alx4 G T 2: 93,473,202 (GRCm39) G67C possibly damaging Het
Ankrd17 A T 5: 90,407,976 (GRCm39) C1414S possibly damaging Het
Ankrd44 T C 1: 54,805,550 (GRCm39) D170G probably damaging Het
Arpc2 T A 1: 74,303,531 (GRCm39) M266K probably damaging Het
Atp12a A T 14: 56,621,837 (GRCm39) N794I probably damaging Het
Cabin1 A G 10: 75,582,396 (GRCm39) L340P probably benign Het
Ccer1 A T 10: 97,529,217 (GRCm39) probably benign Het
Cfap73 A T 5: 120,772,279 (GRCm39) Y8N probably damaging Het
Cfhr4 C A 1: 139,659,415 (GRCm39) E705* probably null Het
Cln3 T C 7: 126,178,589 (GRCm39) T173A probably damaging Het
Cxcl3 A T 5: 90,934,008 (GRCm39) probably benign Het
Cyp2c66 G C 19: 39,159,401 (GRCm39) C284S probably benign Het
Dnajc22 T C 15: 98,999,187 (GRCm39) V124A probably benign Het
Dync1h1 C G 12: 110,568,173 (GRCm39) D45E probably benign Het
Elmod3 A T 6: 72,554,235 (GRCm39) probably null Het
Enpp3 A C 10: 24,649,945 (GRCm39) V827G probably damaging Het
Esyt2 T C 12: 116,327,154 (GRCm39) I574T probably benign Het
Ext2 A T 2: 93,643,957 (GRCm39) I108N probably damaging Het
Fam186a T C 15: 99,843,531 (GRCm39) I904M unknown Het
Fmnl2 T C 2: 53,004,202 (GRCm39) I638T unknown Het
Fndc3c1 G C X: 105,478,679 (GRCm39) L724V possibly damaging Het
Fras1 G T 5: 96,925,937 (GRCm39) A3714S probably damaging Het
Fsd1 C A 17: 56,303,696 (GRCm39) R479S possibly damaging Het
Gaa C T 11: 119,169,817 (GRCm39) L624F probably damaging Het
Galnt2 G A 8: 125,032,292 (GRCm39) V86I probably benign Het
Gdap1l1 T G 2: 163,280,608 (GRCm39) V48G probably damaging Het
Gm10549 A G 18: 33,597,462 (GRCm39) T83A unknown Het
Gm11437 T G 11: 84,055,374 (GRCm39) T81P probably benign Het
Gm16253 T C 3: 96,487,979 (GRCm39) probably null Het
Gprc6a A T 10: 51,504,595 (GRCm39) M83K probably benign Het
Grik5 T C 7: 24,767,587 (GRCm39) D31G probably damaging Het
Hcrtr2 A G 9: 76,167,013 (GRCm39) L108P probably damaging Het
Herc2 T A 7: 55,853,575 (GRCm39) L3689Q probably damaging Het
Igf2bp1 T C 11: 95,859,290 (GRCm39) M407V probably benign Het
Irgq A T 7: 24,233,185 (GRCm39) E342V probably damaging Het
Itih2 A T 2: 10,109,974 (GRCm39) I593N probably damaging Het
Ivd G T 2: 118,701,870 (GRCm39) G101C probably damaging Het
Jakmip1 G A 5: 37,248,708 (GRCm39) G123S probably damaging Het
Kif14 T A 1: 136,406,908 (GRCm39) I580N probably damaging Het
Kmt2e A T 5: 23,669,855 (GRCm39) Y114F probably damaging Het
Ly6g5b C A 17: 35,333,680 (GRCm39) C99F probably damaging Het
Map3k20 C T 2: 72,271,758 (GRCm39) P629S probably benign Het
Muc4 T C 16: 32,582,862 (GRCm39) F476L probably damaging Het
Mup18 T C 4: 61,590,199 (GRCm39) T110A probably benign Het
Nlrp9a A G 7: 26,257,603 (GRCm39) D407G probably benign Het
Nmur1 G A 1: 86,314,190 (GRCm39) R359C probably benign Het
Or5ac24 T C 16: 59,165,510 (GRCm39) T185A probably benign Het
Or5p64 C T 7: 107,854,955 (GRCm39) C130Y possibly damaging Het
Panx3 A T 9: 37,572,596 (GRCm39) M318K probably damaging Het
Pcnx1 T C 12: 81,999,777 (GRCm39) probably null Het
Pcsk5 T C 19: 17,455,241 (GRCm39) Y1063C possibly damaging Het
Psme3ip1 A T 8: 95,315,486 (GRCm39) F15L probably damaging Het
Rere G A 4: 150,553,195 (GRCm39) R129H probably damaging Het
Rpgrip1 A G 14: 52,349,633 (GRCm39) Y7C possibly damaging Het
Serpina6 T C 12: 103,613,253 (GRCm39) N349S possibly damaging Het
Slc10a1 T G 12: 81,002,750 (GRCm39) E296A probably damaging Het
Slc2a9 A T 5: 38,610,214 (GRCm39) probably null Het
Sptan1 T A 2: 29,873,221 (GRCm39) M138K probably benign Het
Tbl3 T C 17: 24,924,233 (GRCm39) T175A probably benign Het
Tbrg4 T C 11: 6,570,810 (GRCm39) T221A possibly damaging Het
Tenm2 T C 11: 35,932,378 (GRCm39) T1739A probably damaging Het
Tmed5 T C 5: 108,280,187 (GRCm39) D35G probably benign Het
Tnfsf15 A T 4: 63,647,889 (GRCm39) S250R probably damaging Het
Tnpo2 G T 8: 85,781,707 (GRCm39) V830F probably benign Het
Ttbk2 G T 2: 120,570,592 (GRCm39) S1187Y probably damaging Het
Ttn G A 2: 76,625,029 (GRCm39) T15183M possibly damaging Het
Tubgcp3 T C 8: 12,689,259 (GRCm39) probably null Het
Vmn1r38 T C 6: 66,753,278 (GRCm39) I279M possibly damaging Het
Vmn1r49 A T 6: 90,049,250 (GRCm39) Y251N possibly damaging Het
Vmn1r66 C T 7: 10,008,482 (GRCm39) V184I probably benign Het
Vmn2r26 T A 6: 124,038,255 (GRCm39) M610K probably benign Het
Xrn2 C T 2: 146,884,013 (GRCm39) P591S probably damaging 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
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
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'- CCTTGATTTAATGCTTCCAGGATGG -3'
(R):5'- TAACACAGTCCCTGTTGAAATCC -3'

Sequencing Primer
(F):5'- TGTGCCAGGTGAGTGCC -3'
(R):5'- GTTGAAATCCCCTGCAGTGC -3'
Posted On 2019-06-26