Mutagenetix > Incidental Mutation

Incidental Mutation 'R1875:Mpl'

211123

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

039897-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R1875 (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 118314026 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Histidine at position 73 (Y73H)

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: Y80H

SMART Domains

Protein: ENSMUSP00000006556
Gene: ENSMUSG00000006389
AA Change: Y80H

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: Y80H

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

SMART Domains

Protein: ENSMUSP00000099732
Gene: ENSMUSG00000006389
AA Change: Y80H

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

probably benign
Transcript: ENSMUST00000106375
AA Change: Y73H

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

SMART Domains

Protein: ENSMUSP00000101983
Gene: ENSMUSG00000006389
AA Change: Y73H

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

unknown
Transcript: ENSMUST00000168404
AA Change: Y79H

SMART Domains

Protein: ENSMUSP00000130167
Gene: ENSMUSG00000006389
AA Change: Y79H

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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000216417

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 97.4%
3x: 96.8%
10x: 95.1%
20x: 92.1%

Validation Efficiency

98% (85/87)

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: 80 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca14	A	T	7: 119,847,190 (GRCm39)	M685L	possibly damaging	Het
Abi3bp	A	G	16: 56,394,862 (GRCm39)	Y190C	probably damaging	Het
Adam26a	C	A	8: 44,022,888 (GRCm39)	V201L	probably benign	Het
Adamts20	G	T	15: 94,229,277 (GRCm39)	D947E	probably benign	Het
Ankrd26	A	G	6: 118,517,410 (GRCm39)		probably null	Het
Apol11a	C	A	15: 77,397,766 (GRCm39)	T39N	possibly damaging	Het
Arhgef38	T	A	3: 132,839,501 (GRCm39)		probably null	Het
Armh4	T	C	14: 49,919,815 (GRCm39)	D772G	probably damaging	Het
Atp11b	T	C	3: 35,893,296 (GRCm39)	L883P	probably damaging	Het
Btnl10	T	A	11: 58,814,586 (GRCm39)	I422N	probably damaging	Het
C2cd3	A	G	7: 100,056,232 (GRCm39)	K547E	possibly damaging	Het
Cdh2	T	A	18: 16,757,934 (GRCm39)	L549F	probably benign	Het
Celsr3	T	C	9: 108,713,037 (GRCm39)	V1825A	probably benign	Het
Cfap221	T	C	1: 119,881,389 (GRCm39)	I358V	probably benign	Het
Cimap2	G	A	4: 106,470,453 (GRCm39)		probably benign	Het
Csmd1	T	C	8: 15,979,101 (GRCm39)	K2828E	probably damaging	Het
Ddah2	T	C	17: 35,279,821 (GRCm39)	F137S	probably damaging	Het
Ddx21	A	G	10: 62,429,847 (GRCm39)	I299T	probably damaging	Het
Dnah7a	A	T	1: 53,495,691 (GRCm39)		probably benign	Het
Elmod1	A	G	9: 53,843,151 (GRCm39)	I9T	probably benign	Het
Epha2	A	G	4: 141,036,290 (GRCm39)	E242G	probably benign	Het
Erbb3	T	C	10: 128,410,335 (GRCm39)	H641R	possibly damaging	Het
Fbxl18	G	A	5: 142,871,978 (GRCm39)	A419V	probably damaging	Het
Fli1	T	C	9: 32,335,209 (GRCm39)	M408V	probably benign	Het
Fmo4	T	C	1: 162,631,187 (GRCm39)	N260S	possibly damaging	Het
Fry	A	G	5: 150,249,597 (GRCm39)	E136G	probably damaging	Het
Gm10477	T	A	X: 55,570,127 (GRCm39)	F9Y	probably damaging	Het
Gm8258	A	G	5: 104,924,320 (GRCm39)		noncoding transcript	Het
Gpr68	T	A	12: 100,845,049 (GRCm39)	D165V	probably damaging	Het
Htt	T	A	5: 34,951,456 (GRCm39)	M139K	probably benign	Het
Jup	A	G	11: 100,263,120 (GRCm39)		probably null	Het
Kifc5b	G	A	17: 27,136,264 (GRCm39)		probably null	Het
Krba1	T	A	6: 48,390,983 (GRCm39)		probably null	Het
Lamp1	G	A	8: 13,217,257 (GRCm39)	G89R	probably damaging	Het
Lrrc17	C	T	5: 21,765,650 (GRCm39)	S44F	possibly damaging	Het
Mdga1	T	C	17: 30,071,581 (GRCm39)	T347A	probably damaging	Het
Mical3	A	T	6: 121,019,025 (GRCm39)	W66R	probably damaging	Het
Mterf1b	T	A	5: 4,247,364 (GRCm39)	I335N	possibly damaging	Het
Mylk3	A	G	8: 86,079,494 (GRCm39)	I388T	probably damaging	Het
Myo15a	C	T	11: 60,398,354 (GRCm39)	R2775W	probably damaging	Het
Myoz2	A	T	3: 122,819,765 (GRCm39)	S65T	probably damaging	Het
Ndrg1	T	C	15: 66,802,940 (GRCm39)	T137A	possibly damaging	Het
Neil3	G	T	8: 54,052,454 (GRCm39)	N381K	probably damaging	Het
Obsl1	T	C	1: 75,474,877 (GRCm39)	Y841C	probably damaging	Het
Or2b4	A	G	17: 38,115,996 (GRCm39)		probably benign	Het
Or6b6	G	A	7: 106,571,389 (GRCm39)	S54F	possibly damaging	Het
Otogl	T	C	10: 107,735,451 (GRCm39)	D111G	probably damaging	Het
Parp10	T	C	15: 76,127,051 (GRCm39)	E103G	probably damaging	Het
Pars2	T	C	4: 106,510,913 (GRCm39)	F232L	possibly damaging	Het
Pcdh18	A	T	3: 49,709,154 (GRCm39)	F720L	probably damaging	Het
Phf3	T	C	1: 30,869,704 (GRCm39)	E448G	possibly damaging	Het
Pigc	A	G	1: 161,798,516 (GRCm39)	Y166C	probably damaging	Het
Pik3c2a	A	T	7: 116,017,206 (GRCm39)	S184T	probably benign	Het
Pkd1l1	A	G	11: 8,794,670 (GRCm39)		probably benign	Het
Plch2	G	A	4: 155,082,965 (GRCm39)	S485F	probably damaging	Het
Plxnd1	G	T	6: 115,955,045 (GRCm39)		probably null	Het
Pnliprp2	G	T	19: 58,751,821 (GRCm39)	V189L	probably benign	Het
Prl8a2	T	C	13: 27,535,037 (GRCm39)	V103A	probably benign	Het
Psg23	G	A	7: 18,344,375 (GRCm39)	T360I	probably benign	Het
Rad51c	A	T	11: 87,279,469 (GRCm39)	I323N	probably damaging	Het
Rsbn1l	C	T	5: 21,156,696 (GRCm39)	E30K	probably benign	Het
Serpina3c	C	A	12: 104,118,145 (GRCm39)	L64F	probably damaging	Het
Shroom1	A	G	11: 53,356,502 (GRCm39)	D392G	probably damaging	Het
Slc26a5	T	A	5: 22,020,725 (GRCm39)	I540L	probably benign	Het
Slc37a4	A	G	9: 44,312,808 (GRCm39)	T321A	probably damaging	Het
Slc41a2	A	G	10: 83,091,949 (GRCm39)	L438S	probably damaging	Het
Spef2	C	T	15: 9,584,194 (GRCm39)	E1624K	probably damaging	Het
Spef2	C	T	15: 9,597,487 (GRCm39)	G1390R	possibly damaging	Het
Spmap2l	A	T	5: 77,202,431 (GRCm39)	K284M	probably benign	Het
Synj2	G	T	17: 6,078,825 (GRCm39)	A740S	possibly damaging	Het
Tigd4	A	C	3: 84,502,394 (GRCm39)	D437A	probably benign	Het
Timm21	G	C	18: 84,967,387 (GRCm39)	L130V	probably damaging	Het
Tmem106a	CAGCTCAACACGACGGTA	CAGCTCAACACGACGGTAAGCTCAACACGACGGTA	11: 101,477,204 (GRCm39)		probably benign	Het
Tmem131l	A	T	3: 83,812,383 (GRCm39)	C1313*	probably null	Het
Tmem86b	A	T	7: 4,632,698 (GRCm39)	I47N	possibly damaging	Het
Tspan13	T	C	12: 36,070,550 (GRCm39)		probably null	Het
Vps54	A	G	11: 21,250,251 (GRCm39)	T396A	probably benign	Het
Zfp106	A	T	2: 120,344,096 (GRCm39)		probably null	Het
Zfp668	T	C	7: 127,465,654 (GRCm39)		probably null	Het
Zfp809	A	T	9: 22,150,027 (GRCm39)	R175*	probably null	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
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
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'- AAGCCTGATTCTGGGAGCTTG -3'
(R):5'- GAGGATTCCTGTAAATGCATGC -3'

Sequencing Primer
(F):5'- ATTCTGGGAGCTTGAGCAG -3'
(R):5'- GTAAATGCATGCTCAATACATAGCC -3'

Posted On

2014-06-30