Mutagenetix > Incidental Mutation

Incidental Mutation 'R0539:Mpl'

49675

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

038731-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R0539 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

118299612-118314710 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 118300705 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Threonine at position 541 (M541T)

Ref Sequence

ENSEMBL: ENSMUSP00000101983 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000006556] [ENSMUST00000102671] [ENSMUST00000106375]

AlphaFold

Q08351

Predicted Effect

probably benign
Transcript: ENSMUST00000006556
AA Change: M608T

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000006556
Gene: ENSMUSG00000006389
AA Change: M608T

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 benign
Transcript: ENSMUST00000102671
AA Change: M600T

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000099732
Gene: ENSMUSG00000006389
AA Change: M600T

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

possibly damaging
Transcript: ENSMUST00000106375
AA Change: M541T

PolyPhen 2 Score 0.682 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000101983
Gene: ENSMUSG00000006389
AA Change: M541T

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

probably benign
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

0.0604

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.8%
20x: 94.3%

Validation Efficiency

100% (107/107)

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: 108 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
5730480H06Rik	T	A	5: 48,536,692 (GRCm39)	H129Q	probably damaging	Het
Abca14	G	A	7: 119,807,020 (GRCm39)	R22Q	probably damaging	Het
Abcg5	T	A	17: 84,976,503 (GRCm39)	M445L	probably benign	Het
Abhd3	T	A	18: 10,645,208 (GRCm39)	N357I	possibly damaging	Het
Adamts5	C	T	16: 85,665,580 (GRCm39)	G574S	probably damaging	Het
Adgrg5	T	A	8: 95,665,260 (GRCm39)	N389K	probably damaging	Het
Ankk1	A	G	9: 49,329,330 (GRCm39)	V80A	probably benign	Het
Arhgap20	A	G	9: 51,761,455 (GRCm39)	Q1066R	probably benign	Het
Arhgap21	T	A	2: 20,919,610 (GRCm39)	K32*	probably null	Het
AW209491	T	C	13: 14,812,317 (GRCm39)	F390S	probably damaging	Het
Axl	A	T	7: 25,478,142 (GRCm39)		probably benign	Het
Bri3bp	A	G	5: 125,531,603 (GRCm39)	Y183C	probably damaging	Het
Cad	T	C	5: 31,232,801 (GRCm39)		probably benign	Het
Capns2	A	G	8: 93,628,360 (GRCm39)	Q83R	possibly damaging	Het
Ccdc180	G	T	4: 45,922,010 (GRCm39)	R1028L	probably damaging	Het
Cdh19	C	A	1: 110,852,892 (GRCm39)	V348F	possibly damaging	Het
Chrm2	T	C	6: 36,500,641 (GRCm39)	V166A	possibly damaging	Het
Clmp	A	G	9: 40,693,782 (GRCm39)	Y333C	probably benign	Het
Cntn3	A	G	6: 102,254,178 (GRCm39)		probably null	Het
Copz1	A	G	15: 103,199,792 (GRCm39)	Y69C	probably damaging	Het
Crybg1	T	C	10: 43,874,894 (GRCm39)	D738G	probably benign	Het
Ctnna2	T	A	6: 76,950,882 (GRCm39)	I165F	probably damaging	Het
Dcaf7	T	G	11: 105,942,652 (GRCm39)	S200A	probably damaging	Het
Deup1	T	A	9: 15,493,893 (GRCm39)	R416S	possibly damaging	Het
Dmxl1	T	A	18: 49,990,497 (GRCm39)		probably benign	Het
Dnaaf11	A	T	15: 66,319,455 (GRCm39)	V305D	probably damaging	Het
Dnase2b	A	T	3: 146,294,910 (GRCm39)		probably benign	Het
Dst	C	T	1: 34,228,200 (GRCm39)	P1606L	probably damaging	Het
Eef2	C	CN	10: 81,014,602 (GRCm39)		probably null	Het
Ephb2	T	C	4: 136,383,287 (GRCm39)	Y931C	probably damaging	Het
Fam83h	T	C	15: 75,875,076 (GRCm39)	S754G	possibly damaging	Het
Fibp	T	A	19: 5,513,216 (GRCm39)	V177D	probably damaging	Het
Gfpt2	T	C	11: 49,723,725 (GRCm39)	I571T	probably damaging	Het
Grm7	T	G	6: 111,336,055 (GRCm39)		probably benign	Het
Gsdma3	A	G	11: 98,526,745 (GRCm39)	Y335C	probably damaging	Het
H2-T23	A	T	17: 36,343,033 (GRCm39)		probably benign	Het
H4c3	A	G	13: 23,882,131 (GRCm39)	F101S	probably damaging	Het
Hydin	A	G	8: 111,249,704 (GRCm39)	I2216V	probably benign	Het
Ipo8	A	G	6: 148,719,606 (GRCm39)	M113T	probably benign	Het
Kdm6a	A	G	X: 18,128,664 (GRCm39)	E1045G	probably damaging	Het
Kyat1	C	T	2: 30,078,229 (GRCm39)	E117K	probably damaging	Het
Lin7b	A	G	7: 45,019,326 (GRCm39)		probably benign	Het
Lipn	G	A	19: 34,062,003 (GRCm39)		probably benign	Het
Lrfn2	C	A	17: 49,378,072 (GRCm39)	N384K	probably damaging	Het
Map1b	T	C	13: 99,570,526 (GRCm39)	K732E	unknown	Het
Mprip	T	C	11: 59,631,943 (GRCm39)		probably benign	Het
Mrc1	T	C	2: 14,274,937 (GRCm39)		probably benign	Het
Ms4a13	T	C	19: 11,149,235 (GRCm39)		probably benign	Het
Myo18b	G	T	5: 112,871,734 (GRCm39)	R2116S	probably damaging	Het
Nav2	A	G	7: 49,111,686 (GRCm39)	T731A	probably damaging	Het
Ncoa6	G	T	2: 155,257,617 (GRCm39)	A642D	probably benign	Het
Ndufs7	T	A	10: 80,090,665 (GRCm39)		probably benign	Het
Nfkbiz	G	A	16: 55,638,242 (GRCm39)	T406M	probably benign	Het
Nr4a1	A	G	15: 101,168,765 (GRCm39)	E267G	probably damaging	Het
Nrxn2	T	G	19: 6,543,434 (GRCm39)	F1103V	probably damaging	Het
Or10ab4	C	T	7: 107,655,029 (GRCm39)	T280I	probably damaging	Het
Or10d3	A	T	9: 39,461,593 (GRCm39)	D191E	probably damaging	Het
Or1e22	T	C	11: 73,376,889 (GRCm39)	T254A	probably benign	Het
Or5a3	C	T	19: 12,400,173 (GRCm39)	L167F	probably damaging	Het
Or5g27	T	A	2: 85,410,119 (GRCm39)	C179S	probably damaging	Het
Or5m11	G	T	2: 85,782,353 (GRCm39)	M315I	probably benign	Het
Or8u9	A	T	2: 86,001,387 (GRCm39)	M258K	probably damaging	Het
Phf1	A	G	17: 27,153,432 (GRCm39)		probably null	Het
Pip	C	T	6: 41,826,819 (GRCm39)	Q53*	probably null	Het
Ppp2ca	T	C	11: 52,008,989 (GRCm39)		probably null	Het
Prl2c5	A	G	13: 13,363,906 (GRCm39)		probably null	Het
Psph	T	A	5: 129,843,641 (GRCm39)		probably benign	Het
Ptch1	C	T	13: 63,691,294 (GRCm39)		probably benign	Het
Ptprs	C	T	17: 56,765,255 (GRCm39)	V10M	probably damaging	Het
Rarg	T	C	15: 102,147,312 (GRCm39)	R358G	probably damaging	Het
Rbl2	T	C	8: 91,839,133 (GRCm39)		probably benign	Het
Robo2	A	T	16: 73,782,462 (GRCm39)		probably benign	Het
Scin	A	T	12: 40,131,765 (GRCm39)	D256E	possibly damaging	Het
Scn8a	T	C	15: 100,914,449 (GRCm39)	Y1152H	probably damaging	Het
Sh2b2	T	G	5: 136,254,155 (GRCm39)		probably benign	Het
Slc13a2	G	A	11: 78,289,964 (GRCm39)	P450L	probably damaging	Het
Slc2a12	A	G	10: 22,568,129 (GRCm39)	I519V	probably benign	Het
Slc30a9	C	T	5: 67,491,953 (GRCm39)	T260M	probably damaging	Het
Slc9a7	A	T	X: 20,069,001 (GRCm39)	F184Y	probably damaging	Het
Smc2	G	T	4: 52,458,558 (GRCm39)	K466N	probably benign	Het
Snx16	T	C	3: 10,491,278 (GRCm39)	E209G	probably damaging	Het
Sp3	A	T	2: 72,800,876 (GRCm39)	I423N	possibly damaging	Het
Ssh2	G	T	11: 77,345,620 (GRCm39)	V1202F	probably benign	Het
Stam2	A	T	2: 52,593,268 (GRCm39)		probably benign	Het
Stox2	T	C	8: 47,647,070 (GRCm39)	Y194C	probably damaging	Het
Sult3a1	A	G	10: 33,742,519 (GRCm39)	T49A	probably damaging	Het
Supt3	A	T	17: 45,314,018 (GRCm39)	I136F	possibly damaging	Het
Syne2	A	T	12: 76,070,895 (GRCm39)	R103S	possibly damaging	Het
Synj2	T	A	17: 6,047,163 (GRCm39)	M1K	probably null	Het
Tas2r110	T	C	6: 132,845,334 (GRCm39)	S122P	possibly damaging	Het
Tln1	A	G	4: 43,543,434 (GRCm39)		probably null	Het
Tmem117	A	G	15: 94,612,793 (GRCm39)	T110A	possibly damaging	Het
Tmem247	A	G	17: 87,224,906 (GRCm39)	D5G	probably benign	Het
Tmem39a	T	A	16: 38,411,337 (GRCm39)	F363I	probably benign	Het
Tmem80	G	A	7: 140,915,808 (GRCm39)	A73T	possibly damaging	Het
Trpm4	C	T	7: 44,954,896 (GRCm39)	G901S	probably damaging	Het
Upk3bl	T	C	5: 136,092,840 (GRCm39)		probably benign	Het
Vmn1r120	A	T	7: 20,787,397 (GRCm39)	C105S	probably damaging	Het
Vmn1r69	A	T	7: 10,314,874 (GRCm39)		probably benign	Het
Vmn2r95	T	C	17: 18,672,362 (GRCm39)	F700L	probably damaging	Het
Wdr70	G	A	15: 7,915,118 (GRCm39)	T550M	possibly damaging	Het
Zbtb22	A	G	17: 34,137,118 (GRCm39)	D421G	possibly damaging	Het
Zbtb45	G	A	7: 12,740,260 (GRCm39)	R452C	probably damaging	Het
Zfhx3	T	C	8: 109,527,141 (GRCm39)	Y1013H	probably damaging	Het
Zfp329	C	T	7: 12,540,520 (GRCm39)		probably null	Het
Zfp532	T	A	18: 65,756,837 (GRCm39)	S257T	probably benign	Het
Zfp933	G	A	4: 147,911,005 (GRCm39)	T197I	probably benign	Het
Zgrf1	T	A	3: 127,408,841 (GRCm39)	N1649K	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
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
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'- TTTGGAGCTACAGGGCATGGCAAC -3'
(R):5'- TGTGAAGAAGTGGAACCCAGCCTC -3'

Sequencing Primer
(F):5'- catagcaagttataggtcatcagag -3'
(R):5'- CCTGGAAATCCTCCCTAAGTC -3'

Posted On

2013-06-12