Mutagenetix > Incidental Mutation

Incidental Mutation 'R1595:Thpo'

175760

Institutional Source

Beutler Lab

Gene Symbol

Thpo

Ensembl Gene

ENSMUSG00000022847

Gene Name

thrombopoietin

Synonyms

Mpllg, TPO-3, TPO-4, TPO-2, TPO, TPO-1, myeloproliferative leukemia virus oncogene ligand

MMRRC Submission

039632-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R1595 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

20543204-20553261 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to A at 20547206 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Tyrosine at position 81 (D81Y)

Ref Sequence

ENSEMBL: ENSMUSP00000155952 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000007171] [ENSMUST00000076422] [ENSMUST00000115423] [ENSMUST00000115437] [ENSMUST00000153299] [ENSMUST00000231636] [ENSMUST00000231698] [ENSMUST00000231826] [ENSMUST00000232217] [ENSMUST00000232646]

AlphaFold

P40226

Predicted Effect

probably benign
Transcript: ENSMUST00000007171

SMART Domains

Protein: ENSMUSP00000007171
Gene: ENSMUSG00000006958

Domain	Start	End	E-Value	Type
signal peptide	1	26	N/A	INTRINSIC
VWC	51	125	9.33e-2	SMART
CHRD	170	274	1.27e-14	SMART
CHRD	281	395	4.63e-17	SMART
CHRD	400	517	7.81e-24	SMART
CHRD	528	643	2.03e-31	SMART
low complexity region	676	687	N/A	INTRINSIC
VWC	701	758	4.69e-10	SMART
VWC	779	845	5.3e-9	SMART
VWC	867	927	1.68e-1	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000076422
AA Change: D52Y

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000075756
Gene: ENSMUSG00000022847
AA Change: D52Y

Domain	Start	End	E-Value	Type
signal peptide	1	21	N/A	INTRINSIC
Pfam:EPO_TPO	24	188	9.4e-78	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000115423

SMART Domains

Protein: ENSMUSP00000111083
Gene: ENSMUSG00000006958

Domain	Start	End	E-Value	Type
signal peptide	1	26	N/A	INTRINSIC
VWC	51	125	9.33e-2	SMART
CHRD	170	274	1.27e-14	SMART
CHRD	281	395	4.63e-17	SMART
CHRD	400	517	7.81e-24	SMART
CHRD	528	605	3.92e-1	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000115437
AA Change: D52Y

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000111097
Gene: ENSMUSG00000022847
AA Change: D52Y

Domain	Start	End	E-Value	Type
signal peptide	1	21	N/A	INTRINSIC
Pfam:EPO_TPO	25	193	5.4e-49	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000153299

SMART Domains

Protein: ENSMUSP00000138259
Gene: ENSMUSG00000006958

Domain	Start	End	E-Value	Type
signal peptide	1	26	N/A	INTRINSIC
VWC	51	125	9.33e-2	SMART
Blast:CHRD	170	236	1e-21	BLAST

Predicted Effect

probably benign
Transcript: ENSMUST00000231636

Predicted Effect

probably benign
Transcript: ENSMUST00000231698

Predicted Effect

probably damaging
Transcript: ENSMUST00000231826
AA Change: D52Y

PolyPhen 2 Score 0.976 (Sensitivity: 0.76; Specificity: 0.96)

Predicted Effect

probably damaging
Transcript: ENSMUST00000232217
AA Change: D81Y

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

Predicted Effect

probably benign
Transcript: ENSMUST00000232646

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000232104

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000232020

Meta Mutation Damage Score

0.6467

Coding Region Coverage

1x: 99.1%
3x: 98.3%
10x: 96.1%
20x: 92.1%

Validation Efficiency

97% (77/79)

MGI Phenotype

FUNCTION: This gene encodes a humoral growth factor necessary for megakaryocyte proliferation and maturation, as well as for thrombopoiesis. The encoded protein is a ligand for the product of the myeloproliferative leukemia virus oncogene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]
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: 72 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcb6	C	T	1: 75,153,944 (GRCm39)		probably null	Het
Abcc10	G	T	17: 46,633,164 (GRCm39)	P556H	probably damaging	Het
Abcc9	A	T	6: 142,578,821 (GRCm39)	D914E	probably benign	Het
Adgrf4	A	G	17: 42,978,764 (GRCm39)	V193A	probably benign	Het
Adm	A	T	7: 110,228,298 (GRCm39)	T160S	probably damaging	Het
Ammecr1l	T	C	18: 31,905,173 (GRCm39)		probably null	Het
Angpt2	T	C	8: 18,748,129 (GRCm39)	D377G	probably damaging	Het
Ankfn1	A	G	11: 89,313,593 (GRCm39)		probably null	Het
Arhgap30	T	G	1: 171,235,909 (GRCm39)	M761R	probably benign	Het
Asb4	T	G	6: 5,390,692 (GRCm39)	N28K	probably damaging	Het
Cd177	A	T	7: 24,444,389 (GRCm39)	D696E	probably benign	Het
Cd200	G	A	16: 45,215,214 (GRCm39)	T123I	probably benign	Het
Cfap70	A	G	14: 20,497,604 (GRCm39)	V50A	probably benign	Het
Chaf1b	T	C	16: 93,701,987 (GRCm39)		probably null	Het
Chgb	A	C	2: 132,635,657 (GRCm39)	D533A	probably benign	Het
Col12a1	A	G	9: 79,509,536 (GRCm39)	Y3041H	probably damaging	Het
Crot	T	C	5: 9,024,186 (GRCm39)	N337D	probably benign	Het
Csad	G	A	15: 102,086,217 (GRCm39)	A51V	probably damaging	Het
Cstdc7	T	C	18: 42,306,454 (GRCm39)	M7T	probably benign	Het
Cyp2b9	A	G	7: 25,900,332 (GRCm39)	Y380C	possibly damaging	Het
Dpysl2	G	T	14: 67,052,952 (GRCm39)	A299E	probably damaging	Het
Efcc1	A	G	6: 87,708,440 (GRCm39)	E189G	probably damaging	Het
Egfr	T	C	11: 16,856,847 (GRCm39)	I940T	probably damaging	Het
Etnk2	T	G	1: 133,300,917 (GRCm39)	L228R	possibly damaging	Het
Fitm2	A	G	2: 163,311,610 (GRCm39)	I201T	probably benign	Het
Foxo1	A	T	3: 52,253,375 (GRCm39)	M513L	probably benign	Het
Galnt16	A	T	12: 80,637,410 (GRCm39)	K379I	probably damaging	Het
Gm57858	C	T	3: 36,073,146 (GRCm39)	A379T	probably damaging	Het
Gtf2a1	T	A	12: 91,556,323 (GRCm39)	N6Y	probably damaging	Het
Kcnc1	G	A	7: 46,077,010 (GRCm39)	V271M	probably benign	Het
Klhdc8b	T	A	9: 108,328,362 (GRCm39)	D30V	probably damaging	Het
Lrrc7	G	A	3: 157,882,914 (GRCm39)	Q448*	probably null	Het
Med29	T	C	7: 28,091,928 (GRCm39)	D54G	probably damaging	Het
Mfn2	T	C	4: 147,979,153 (GRCm39)	T60A	probably benign	Het
Mroh1	T	C	15: 76,317,730 (GRCm39)		probably benign	Het
Mxd1	A	T	6: 86,628,453 (GRCm39)	V149E	possibly damaging	Het
Naip6	A	T	13: 100,435,602 (GRCm39)	Y974N	probably damaging	Het
Ndn	C	T	7: 61,998,256 (GRCm39)	P34L	probably benign	Het
Nhsl1	G	T	10: 18,402,096 (GRCm39)	K1107N	probably damaging	Het
Nlrc3	T	C	16: 3,783,166 (GRCm39)	E81G	probably benign	Het
Or10al3	G	T	17: 38,012,004 (GRCm39)	A148S	probably benign	Het
Or9e1	G	T	11: 58,732,478 (GRCm39)	M179I	probably benign	Het
Osbpl5	C	T	7: 143,256,955 (GRCm39)	V392M	possibly damaging	Het
Pcdhb22	T	A	18: 37,653,506 (GRCm39)	V401E	probably damaging	Het
Pcm1	T	A	8: 41,762,672 (GRCm39)	H1444Q	probably damaging	Het
Pdlim2	A	G	14: 70,402,193 (GRCm39)	Y308H	probably damaging	Het
Phf14	T	G	6: 11,988,752 (GRCm39)	L664R	possibly damaging	Het
Phkb	T	C	8: 86,753,182 (GRCm39)		probably benign	Het
Ptchd3	T	A	11: 121,721,420 (GRCm39)	F98I	probably damaging	Het
Ptprt	C	T	2: 161,652,469 (GRCm39)		probably null	Het
Rbp3	A	T	14: 33,678,155 (GRCm39)	H701L	possibly damaging	Het
Rgl1	T	C	1: 152,550,774 (GRCm39)		probably benign	Het
Satb1	A	T	17: 52,089,729 (GRCm39)	S373T	possibly damaging	Het
Scn3a	T	A	2: 65,329,323 (GRCm39)	Y769F	probably damaging	Het
Senp7	A	G	16: 56,005,131 (GRCm39)	I922V	probably damaging	Het
Serpina3g	A	G	12: 104,205,531 (GRCm39)	E90G	probably benign	Het
Sh3rf2	C	T	18: 42,244,353 (GRCm39)	T273I	probably damaging	Het
Slc15a3	A	G	19: 10,831,675 (GRCm39)	T350A	probably benign	Het
Socs5	T	C	17: 87,441,623 (GRCm39)	C188R	probably damaging	Het
Tacr1	A	G	6: 82,380,723 (GRCm39)	T45A	probably benign	Het
Th	A	G	7: 142,450,745 (GRCm39)	V117A	probably benign	Het
Tmem229b-ps	A	G	10: 53,351,385 (GRCm39)		noncoding transcript	Het
Trpc4	A	G	3: 54,223,236 (GRCm39)	E724G	probably benign	Het
Ttn	T	C	2: 76,576,977 (GRCm39)	T24639A	probably damaging	Het
Ulk4	A	G	9: 120,873,904 (GRCm39)	S1176P	probably damaging	Het
Urgcp	T	C	11: 5,667,447 (GRCm39)	D297G	probably damaging	Het
Vmn1r168	G	A	7: 23,240,620 (GRCm39)	G159D	probably damaging	Het
Vmn1r67	A	T	7: 10,181,597 (GRCm39)	N226I	probably benign	Het
Vmn2r27	T	C	6: 124,208,574 (GRCm39)	E57G	probably benign	Het
Zdhhc14	G	T	17: 5,543,831 (GRCm39)	R37L	probably benign	Het
Zfp512b	G	A	2: 181,230,229 (GRCm39)	T499I	probably damaging	Het
Zmym2	A	T	14: 57,158,187 (GRCm39)	K575N	probably benign	Het

Other mutations in Thpo

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01085:Thpo	APN	16	20,547,205 (GRCm39)	missense	probably damaging	0.99
R3838:Thpo	UTSW	16	20,547,498 (GRCm39)	missense	probably damaging	1.00
R5911:Thpo	UTSW	16	20,547,546 (GRCm39)	missense	probably null	1.00
R6113:Thpo	UTSW	16	20,547,597 (GRCm39)	unclassified	probably benign
R6977:Thpo	UTSW	16	20,544,433 (GRCm39)	missense	probably damaging	0.99
R7769:Thpo	UTSW	16	20,544,401 (GRCm39)	missense	probably benign	0.00
R7862:Thpo	UTSW	16	20,547,540 (GRCm39)	missense	probably benign	0.06
R8079:Thpo	UTSW	16	20,545,144 (GRCm39)	missense	probably benign
R8281:Thpo	UTSW	16	20,544,525 (GRCm39)	missense	possibly damaging	0.91
R8804:Thpo	UTSW	16	20,544,707 (GRCm39)	missense	probably damaging	0.97
R8922:Thpo	UTSW	16	20,547,680 (GRCm39)	missense	unknown
R9101:Thpo	UTSW	16	20,544,557 (GRCm39)	missense	possibly damaging	0.90

Predicted Primers

PCR Primer
(F):5'- AAGTCTCACTCTAGTCCATCCTGGC -3'
(R):5'- ATAAACTGCTGCGTGACTCCCACC -3'

Sequencing Primer
(F):5'- ccatcctggcccggaac -3'
(R):5'- ATTGTCTTTGGCGAGACCAC -3'

Posted On

2014-04-24