Incidental Mutation 'R5276:Mpl'
ID 403928
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 042863-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R5276 (G1)
Quality Score 225
Status Not validated
Chromosome 4
Chromosomal Location 118299612-118314710 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 118312918 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Alanine at position 138 (V138A)
Ref Sequence ENSEMBL: ENSMUSP00000101983 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000006556] [ENSMUST00000102671] [ENSMUST00000106375]
AlphaFold Q08351
Predicted Effect unknown
Transcript: ENSMUST00000006556
AA Change: V205A
SMART Domains Protein: ENSMUSP00000006556
Gene: ENSMUSG00000006389
AA Change: V205A

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: V205A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000099732
Gene: ENSMUSG00000006389
AA Change: V205A

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
AA Change: V138A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000101983
Gene: ENSMUSG00000006389
AA Change: V138A

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: V204A
SMART Domains Protein: ENSMUSP00000130167
Gene: ENSMUSG00000006389
AA Change: V204A

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: 64 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adam26a A G 8: 44,023,457 (GRCm39) F11S probably benign Het
Adipor2 T A 6: 119,334,182 (GRCm39) I343F probably damaging Het
Ahdc1 C T 4: 132,790,109 (GRCm39) P450L possibly damaging Het
Akna A C 4: 63,286,440 (GRCm39) V1353G possibly damaging Het
Baz2b G A 2: 59,792,958 (GRCm39) T390I probably benign Het
Btbd7 T C 12: 102,804,651 (GRCm39) K130E probably benign Het
Cdc42bpa A G 1: 179,965,415 (GRCm39) Y1101C probably damaging Het
Crlf2 T G 5: 109,705,501 (GRCm39) probably benign Het
Ddx59 A T 1: 136,347,186 (GRCm39) R281S probably damaging Het
Dgcr8 T G 16: 18,101,635 (GRCm39) T216P probably benign Het
Dsg4 A T 18: 20,579,896 (GRCm39) I34F probably benign Het
Enpp3 A G 10: 24,685,814 (GRCm39) S194P probably damaging Het
Entpd8 C T 2: 24,975,057 (GRCm39) R463W probably benign Het
Fam169a A G 13: 97,255,004 (GRCm39) T407A probably benign Het
Fam98b G T 2: 117,089,779 (GRCm39) V99F possibly damaging Het
Foxn3 T A 12: 99,162,687 (GRCm39) K405* probably null Het
Gsdmc T C 15: 63,673,806 (GRCm39) T160A probably benign Het
Hdac1 T C 4: 129,422,716 (GRCm39) probably null Het
Igfbp1 A C 11: 7,151,892 (GRCm39) T232P probably damaging Het
Lcor T A 19: 41,573,478 (GRCm39) H744Q probably damaging Het
Mertk G C 2: 128,643,234 (GRCm39) G878R possibly damaging Het
Metap2 G T 10: 93,704,784 (GRCm39) P281H possibly damaging Het
Metap2 T A 10: 93,704,794 (GRCm39) T278S probably benign Het
Mfn1 T C 3: 32,618,354 (GRCm39) V169A probably benign Het
Mms22l A G 4: 24,578,774 (GRCm39) D751G probably damaging Het
Myef2 T A 2: 124,937,641 (GRCm39) K533N probably damaging Het
Mylk3 C T 8: 86,082,071 (GRCm39) G309E probably damaging Het
Nid1 T C 13: 13,643,157 (GRCm39) V365A probably damaging Het
Or4d2 A T 11: 87,784,018 (GRCm39) I244N probably damaging Het
Or5p57 A T 7: 107,665,423 (GRCm39) L164* probably null Het
Or7d10 C A 9: 19,831,917 (GRCm39) N137K possibly damaging Het
Or8g19 T C 9: 39,055,611 (GRCm39) C72R probably damaging Het
Pbrm1 A G 14: 30,828,141 (GRCm39) K1323E probably damaging Het
Pcdhga12 G A 18: 37,899,728 (GRCm39) D187N possibly damaging Het
Phrf1 T C 7: 140,839,196 (GRCm39) probably benign Het
Phtf2 A G 5: 20,977,195 (GRCm39) V608A probably benign Het
Plec G A 15: 76,057,638 (GRCm39) R4122W probably damaging Het
Polm A G 11: 5,779,393 (GRCm39) S441P probably benign Het
Prrc2b T A 2: 32,104,734 (GRCm39) V1404E probably benign Het
Ptger1 T G 8: 84,395,974 (GRCm39) S344A possibly damaging Het
Rasef A T 4: 73,654,004 (GRCm39) D401E probably null Het
Rbfox3 T C 11: 118,387,178 (GRCm39) Y312C probably damaging Het
Rbm48 A G 5: 3,634,759 (GRCm39) C402R probably benign Het
Rhbdl3 G A 11: 80,210,492 (GRCm39) A82T probably benign Het
Rnf123 AT ATT 9: 107,941,202 (GRCm39) probably null Het
Sfi1 A ATCTTCCCAAAGCCAGTGC 11: 3,103,384 (GRCm39) probably benign Homo
Sidt2 T A 9: 45,866,075 (GRCm39) N44Y probably damaging Het
Slf2 T A 19: 44,923,600 (GRCm39) L138Q possibly damaging Het
Spag16 T C 1: 69,935,742 (GRCm39) probably null Het
Sspo C T 6: 48,467,401 (GRCm39) P4188S probably damaging Het
Synm C T 7: 67,384,437 (GRCm39) S1075N probably benign Het
Tacc2 G T 7: 130,331,047 (GRCm39) D2151Y probably damaging Het
Tbc1d32 C A 10: 56,027,914 (GRCm39) L729F probably damaging Het
Tnfsf4 A G 1: 161,244,584 (GRCm39) N91S possibly damaging Het
Trim63 G A 4: 134,050,444 (GRCm39) E243K probably benign Het
Trim72 T G 7: 127,603,714 (GRCm39) L20R probably damaging Het
Tubb1 A G 2: 174,299,217 (GRCm39) M300V probably damaging Het
Ubfd1 C T 7: 121,668,091 (GRCm39) A207V probably damaging Het
Usp16 T A 16: 87,267,339 (GRCm39) probably null Het
Vmn2r23 A G 6: 123,689,936 (GRCm39) T271A possibly damaging Het
Vmn2r72 T A 7: 85,387,462 (GRCm39) I701F possibly damaging Het
Wdfy4 A G 14: 32,769,232 (GRCm39) Y2078H probably damaging Het
Wdr41 T C 13: 95,153,958 (GRCm39) probably null Het
Zfp955b A G 17: 33,522,031 (GRCm39) Y500C 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
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'- AGCCTTCAGTTACCTTGGTGTG -3'
(R):5'- AACCAGGGGAACTTCAGATCC -3'

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