Mutagenetix > Incidental Mutation

Incidental Mutation 'R1935:Mpl'

215892

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

039953-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R1935 (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 118312936 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Threonine at position 132 (M132T)

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: M199T

SMART Domains

Protein: ENSMUSP00000006556
Gene: ENSMUSG00000006389
AA Change: M199T

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: M199T

PolyPhen 2 Score 0.011 (Sensitivity: 0.96; Specificity: 0.78)

SMART Domains

Protein: ENSMUSP00000099732
Gene: ENSMUSG00000006389
AA Change: M199T

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: M132T

PolyPhen 2 Score 0.015 (Sensitivity: 0.96; Specificity: 0.79)

SMART Domains

Protein: ENSMUSP00000101983
Gene: ENSMUSG00000006389
AA Change: M132T

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: M198T

SMART Domains

Protein: ENSMUSP00000130167
Gene: ENSMUSG00000006389
AA Change: M198T

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: 97.3%
3x: 96.7%
10x: 94.9%
20x: 91.6%

Validation Efficiency

95% (95/100)

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: 89 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca4	G	A	3: 121,846,572 (GRCm39)	V30M	probably benign	Het
Abcg8	C	T	17: 85,002,417 (GRCm39)		probably benign	Het
Ablim1	T	A	19: 57,204,397 (GRCm39)		probably null	Het
Acvr1c	A	T	2: 58,173,517 (GRCm39)	N248K	probably damaging	Het
Adgrf3	A	T	5: 30,407,304 (GRCm39)	N207K	probably benign	Het
Anapc4	T	A	5: 52,997,010 (GRCm39)	D94E	probably damaging	Het
Arfgef2	A	G	2: 166,705,523 (GRCm39)	N918S	probably benign	Het
Arhgap45	A	G	10: 79,866,788 (GRCm39)	N1097S	probably damaging	Het
Atf2	G	A	2: 73,676,563 (GRCm39)	P184S	probably damaging	Het
Atg2a	A	G	19: 6,302,566 (GRCm39)	Y963C	probably damaging	Het
Atp8a2	T	C	14: 60,097,719 (GRCm39)	K770E	probably benign	Het
Atrn	T	C	2: 130,799,955 (GRCm39)	V444A	probably damaging	Het
Avpr1a	G	A	10: 122,285,695 (GRCm39)		probably null	Het
Best3	A	C	10: 116,860,291 (GRCm39)	Q517P	probably benign	Het
C3	A	G	17: 57,525,829 (GRCm39)	L851P	probably damaging	Het
Cacna2d2	T	C	9: 107,386,455 (GRCm39)	F194S	probably damaging	Het
Carns1	T	C	19: 4,215,473 (GRCm39)	E903G	probably damaging	Het
Chn1	A	G	2: 73,455,245 (GRCm39)	C39R	probably damaging	Het
Ciao1	A	G	2: 127,088,380 (GRCm39)	S148P	possibly damaging	Het
Clrn3	A	C	7: 135,115,753 (GRCm39)	I199S	possibly damaging	Het
Cngb1	C	A	8: 96,026,320 (GRCm39)	G154W	probably damaging	Het
Cnot2	G	C	10: 116,334,320 (GRCm39)	P274R	possibly damaging	Het
Cops7a	G	A	6: 124,939,359 (GRCm39)	R97*	probably null	Het
Coro7	T	C	16: 4,446,596 (GRCm39)	E843G	probably benign	Het
Crocc	T	C	4: 140,761,369 (GRCm39)	R755G	possibly damaging	Het
Crtam	G	C	9: 40,915,846 (GRCm39)	P13A	probably benign	Het
Ddrgk1	G	T	2: 130,505,480 (GRCm39)		probably benign	Het
Defb26	T	A	2: 152,350,195 (GRCm39)	K28N	possibly damaging	Het
Dnah8	G	A	17: 30,945,870 (GRCm39)		probably benign	Het
Dnah8	A	G	17: 30,854,479 (GRCm39)	E47G	unknown	Het
Dnhd1	A	T	7: 105,323,183 (GRCm39)	M564L	probably benign	Het
Dusp15	A	G	2: 152,787,341 (GRCm39)		probably benign	Het
Dync2h1	A	G	9: 7,139,159 (GRCm39)		probably null	Het
Eapp	A	T	12: 54,720,513 (GRCm39)	M234K	probably benign	Het
Fabp3	C	T	4: 130,206,180 (GRCm39)	T57I	probably benign	Het
Gfi1b	T	C	2: 28,500,125 (GRCm39)	K302R	possibly damaging	Het
Gpatch1	A	G	7: 34,994,947 (GRCm39)	S440P	probably damaging	Het
Gpr6	T	C	10: 40,947,477 (GRCm39)	E35G	probably benign	Het
H2-Q1	A	T	17: 35,542,469 (GRCm39)	M305L	probably benign	Het
Hoxa10	C	A	6: 52,211,350 (GRCm39)	G189C	possibly damaging	Het
Kbtbd4	T	C	2: 90,737,895 (GRCm39)	V215A	probably damaging	Het
Klf16	G	A	10: 80,412,739 (GRCm39)	A99V	probably benign	Het
Lvrn	A	T	18: 47,011,387 (GRCm39)	Y448F	probably benign	Het
Med19	A	G	2: 84,516,002 (GRCm39)	H177R	possibly damaging	Het
Mif	G	T	10: 75,695,681 (GRCm39)	H41N	possibly damaging	Het
Mtcl1	G	T	17: 66,686,409 (GRCm39)	H480Q	probably benign	Het
Myo18b	T	C	5: 112,908,222 (GRCm39)	N2017S	probably benign	Het
Neurl4	C	T	11: 69,797,959 (GRCm39)	R740C	probably damaging	Het
Nlgn1	G	T	3: 26,385,939 (GRCm39)		probably benign	Het
Or14j7	T	A	17: 38,234,993 (GRCm39)	C179S	probably damaging	Het
Or2ak6	T	A	11: 58,593,172 (GRCm39)	L215Q	probably damaging	Het
Or4c11	A	C	2: 88,695,524 (GRCm39)	M192L	probably benign	Het
Or6c214	A	G	10: 129,590,584 (GRCm39)	V245A	probably damaging	Het
Paip1	T	A	13: 119,593,550 (GRCm39)	M463K	probably damaging	Het
Parp3	T	A	9: 106,351,931 (GRCm39)	Y147F	probably damaging	Het
Pgrmc2	C	A	3: 41,037,473 (GRCm39)		probably benign	Het
Phldb3	G	A	7: 24,316,832 (GRCm39)	A278T	probably benign	Het
Plxnb1	T	C	9: 108,924,715 (GRCm39)		probably null	Het
Pom121	G	A	5: 135,412,740 (GRCm39)	R481C	unknown	Het
Psg22	A	T	7: 18,453,635 (GRCm39)	N149I	probably damaging	Het
Recql5	T	C	11: 115,788,017 (GRCm39)	Y434C	probably benign	Het
Rexo1	A	G	10: 80,386,303 (GRCm39)	S252P	probably benign	Het
Rtl1	A	G	12: 109,558,354 (GRCm39)	S1162P	probably benign	Het
Samd9l	G	T	6: 3,376,269 (GRCm39)	Q331K	probably benign	Het
Sipa1l1	T	C	12: 82,419,208 (GRCm39)	Y629H	probably damaging	Het
Slc12a2	A	T	18: 58,037,425 (GRCm39)	I512L	possibly damaging	Het
Slc17a8	T	C	10: 89,413,777 (GRCm39)	M484V	probably benign	Het
Slc25a24	A	T	3: 109,043,581 (GRCm39)	E79D	probably damaging	Het
Snw1	T	A	12: 87,506,247 (GRCm39)	I218F	probably damaging	Het
Sorcs1	T	C	19: 50,221,082 (GRCm39)	D545G	probably damaging	Het
Sorcs2	A	G	5: 36,228,731 (GRCm39)	S104P	possibly damaging	Het
Spry4	A	G	18: 38,723,142 (GRCm39)	I207T	possibly damaging	Het
Tex101	A	G	7: 24,367,650 (GRCm39)	V234A	probably benign	Het
Thra	T	A	11: 98,653,899 (GRCm39)		probably benign	Het
Tmem161b	T	A	13: 84,441,585 (GRCm39)	L210Q	probably damaging	Het
Tmem50a	A	G	4: 134,630,953 (GRCm39)		probably benign	Het
Tmem63b	A	G	17: 45,989,887 (GRCm39)		probably null	Het
Tnrc6c	A	G	11: 117,646,849 (GRCm39)	D1450G	possibly damaging	Het
Trdmt1	A	G	2: 13,516,420 (GRCm39)	L386P	probably damaging	Het
Trip12	T	C	1: 84,771,822 (GRCm39)	S109G	possibly damaging	Het
Trit1	T	C	4: 122,948,033 (GRCm39)	I451T	probably benign	Het
Ttc34	G	A	4: 154,950,139 (GRCm39)	A1031T	possibly damaging	Het
Ttn	T	A	2: 76,577,522 (GRCm39)	D24457V	probably damaging	Het
Ttn	A	C	2: 76,715,834 (GRCm39)		probably benign	Het
Tubgcp4	A	T	2: 121,009,147 (GRCm39)		probably benign	Het
Ubiad1	A	G	4: 148,528,468 (GRCm39)	L147P	probably damaging	Het
Vps72	T	A	3: 95,029,851 (GRCm39)	V290D	probably benign	Het
Zfp408	A	T	2: 91,480,093 (GRCm39)	M1K	probably null	Het
Zfy2	C	A	Y: 2,121,496 (GRCm39)	M132I	probably benign	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
R1875:Mpl	UTSW	4	118,314,026 (GRCm39)	missense	probably benign
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'- TCTTCAAATCAACCCAGTCTGG -3'
(R):5'- TGTTTTGACCTCAGGCCTGC -3'

Sequencing Primer
(F):5'- CAGTCTGGGATCCCCTAAGTATG -3'
(R):5'- TCATCAAGGCCAGGGGTG -3'

Posted On

2014-07-14