Mutagenetix > Incidental Mutation

Incidental Mutation 'R6086:Tpmt'

482504

Institutional Source

Beutler Lab

Gene Symbol

Tpmt

Ensembl Gene

ENSMUSG00000021376

Gene Name

thiopurine methyltransferase

Synonyms

MMRRC Submission

044427-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R6086 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

47175463-47196833 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 47188506 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Valine at position 132 (D132V)

Ref Sequence

ENSEMBL: ENSMUSP00000120081 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000021806] [ENSMUST00000110118] [ENSMUST00000136864] [ENSMUST00000154802]

AlphaFold

no structure available at present

Predicted Effect

probably damaging
Transcript: ENSMUST00000021806
AA Change: D132V

PolyPhen 2 Score 0.992 (Sensitivity: 0.70; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000021806
Gene: ENSMUSG00000021376
AA Change: D132V

Domain	Start	End	E-Value	Type
Pfam:TPMT	19	240	4.1e-84	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000110118
AA Change: D132V

PolyPhen 2 Score 0.712 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000105745
Gene: ENSMUSG00000021376
AA Change: D132V

Domain	Start	End	E-Value	Type
Pfam:TPMT	19	205	8.8e-73	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000133100

Predicted Effect

probably damaging
Transcript: ENSMUST00000136864
AA Change: D132V

PolyPhen 2 Score 0.992 (Sensitivity: 0.70; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000120081
Gene: ENSMUSG00000021376
AA Change: D132V

Domain	Start	End	E-Value	Type
Pfam:TPMT	19	188	3.6e-65	PFAM

Predicted Effect

unknown
Transcript: ENSMUST00000151509
AA Change: D151V

SMART Domains

Protein: ENSMUSP00000120564
Gene: ENSMUSG00000021376
AA Change: D151V

Domain	Start	End	E-Value	Type
Pfam:TPMT	19	73	3.3e-20	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000154802
AA Change: D132V

PolyPhen 2 Score 0.712 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000121827
Gene: ENSMUSG00000021376
AA Change: D132V

Domain	Start	End	E-Value	Type
Pfam:TPMT	19	182	2.9e-62	PFAM

Meta Mutation Damage Score

0.5158

Coding Region Coverage

1x: 99.9%
3x: 99.6%
10x: 98.2%
20x: 94.9%

Validation Efficiency

96% (65/68)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes the enzyme that metabolizes thiopurine drugs via S-adenosyl-L-methionine as the S-methyl donor and S-adenosyl-L-homocysteine as a byproduct. Thiopurine drugs such as 6-mercaptopurine are used as chemotherapeutic agents. Genetic polymorphisms that affect this enzymatic activity are correlated with variations in sensitivity and toxicity to such drugs within individuals, causing thiopurine S-methyltransferase deficiency. Related pseudogenes have been identified on chromosomes 3, 18 and X. [provided by RefSeq, Aug 2014]
PHENOTYPE: Homozygous and heterozygous mutation of this gene results in increased sensitivity to mercaptopurine. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 65 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Apob	G	T	12: 8,065,164 (GRCm39)	K4044N	probably benign	Het
Asic4	G	A	1: 75,449,887 (GRCm39)	V468I	possibly damaging	Het
Atf4	T	A	15: 80,141,654 (GRCm39)	V348D	probably benign	Het
Bcl9	A	G	3: 97,112,840 (GRCm39)	V1205A	possibly damaging	Het
Bora	A	T	14: 99,299,730 (GRCm39)	Q234L	possibly damaging	Het
Cap2	C	A	13: 46,789,188 (GRCm39)	P131Q	probably damaging	Het
Cdyl2	A	G	8: 117,316,035 (GRCm39)	S318P	probably damaging	Het
Ces1a	T	G	8: 93,753,981 (GRCm39)	N341H	probably benign	Het
Cimap2	T	C	4: 106,470,403 (GRCm39)	E218G	probably damaging	Het
Crlf3	C	T	11: 79,939,436 (GRCm39)	V352M	possibly damaging	Het
Cybb	C	G	X: 9,316,989 (GRCm39)	D246H	probably benign	Het
Cyren	A	G	6: 34,851,555 (GRCm39)	S127P	probably damaging	Het
Dnah2	T	C	11: 69,406,834 (GRCm39)	T529A	probably benign	Het
Dnah9	C	T	11: 65,880,741 (GRCm39)	D2619N	probably damaging	Het
Dnah9	A	C	11: 65,976,000 (GRCm39)	S1350A	probably benign	Het
Dnajc6	C	T	4: 101,455,004 (GRCm39)	S65L	probably benign	Het
Dnm3	C	A	1: 162,148,602 (GRCm39)	R256S	probably damaging	Het
Enpp2	T	C	15: 54,709,230 (GRCm39)	D795G	probably damaging	Het
Fah	A	T	7: 84,238,120 (GRCm39)	W367R	probably damaging	Het
Fam220a	T	A	5: 143,548,796 (GRCm39)	H69Q	probably benign	Het
Fgd3	T	A	13: 49,440,772 (GRCm39)	T220S	probably benign	Het
Furin	G	T	7: 80,045,179 (GRCm39)	H248Q	probably damaging	Het
Gabrg1	A	T	5: 70,911,396 (GRCm39)	L410Q	probably damaging	Het
Gm10801	AAGT	AAGTAGT	2: 98,494,148 (GRCm39)		probably null	Het
Gm9742	T	C	13: 8,080,069 (GRCm39)		noncoding transcript	Het
Gpcpd1	A	G	2: 132,380,034 (GRCm39)	S252P	probably damaging	Het
Hnrnpdl	C	T	5: 100,184,340 (GRCm39)	G398S	probably null	Het
Hspa1l	T	C	17: 35,197,131 (GRCm39)	V390A	possibly damaging	Het
Htr3b	T	C	9: 48,858,598 (GRCm39)	S94G	probably benign	Het
Klf10	G	T	15: 38,297,181 (GRCm39)	S271R	probably benign	Het
Klk1b3	T	A	7: 43,851,158 (GRCm39)	L197Q	probably damaging	Het
Knl1	A	G	2: 118,924,549 (GRCm39)	R1861G	probably damaging	Het
Myo9a	C	T	9: 59,697,340 (GRCm39)	Q374*	probably null	Het
Myt1l	G	A	12: 29,882,331 (GRCm39)	G509R	unknown	Het
Ncapg	T	C	5: 45,850,578 (GRCm39)	L728P	probably damaging	Het
Nfxl1	A	C	5: 72,698,362 (GRCm39)	F228V	probably benign	Het
Ntaq1	C	A	15: 58,014,024 (GRCm39)	A71E	probably damaging	Het
Oc90	A	G	15: 65,761,560 (GRCm39)	S153P	probably damaging	Het
Or4c123	A	G	2: 89,127,198 (GRCm39)	C139R	probably damaging	Het
Or5b105	A	G	19: 13,079,745 (GRCm39)	*308Q	probably null	Het
Pbk	A	T	14: 66,052,702 (GRCm39)	K182*	probably null	Het
Piezo1	A	G	8: 123,228,396 (GRCm39)	F296S	possibly damaging	Het
Psmg1	T	A	16: 95,781,244 (GRCm39)	Y288F	probably damaging	Het
Rab11fip4	G	A	11: 79,574,306 (GRCm39)	D132N	probably damaging	Het
Recql4	T	C	15: 76,588,787 (GRCm39)	D1051G	probably damaging	Het
Reep5	A	C	18: 34,490,184 (GRCm39)	D104E	probably damaging	Het
Rnpepl1	T	C	1: 92,845,403 (GRCm39)	Y441H	probably damaging	Het
Scnm1	T	C	3: 95,037,596 (GRCm39)	I157V	probably benign	Het
Sema3b	T	C	9: 107,478,047 (GRCm39)	D446G	probably damaging	Het
Sema4d	C	T	13: 51,867,781 (GRCm39)	R190Q	probably damaging	Het
Slco3a1	G	A	7: 73,968,338 (GRCm39)	R461C	possibly damaging	Het
Spmap2l	T	A	5: 77,209,152 (GRCm39)	V458E	probably benign	Het
Tenm2	T	A	11: 35,899,473 (GRCm39)	I2562F	possibly damaging	Het
Tmem40	G	T	6: 115,710,628 (GRCm39)	N120K	possibly damaging	Het
Tmod3	T	C	9: 75,407,405 (GRCm39)	H351R	probably benign	Het
Tnn	C	T	1: 159,913,690 (GRCm39)	V1268M	probably damaging	Het
Trgc3	T	C	13: 19,447,454 (GRCm39)	S136P	probably damaging	Het
Trib1	G	A	15: 59,526,324 (GRCm39)	R298H	probably damaging	Het
Tsen2	A	G	6: 115,537,036 (GRCm39)	E264G	probably benign	Het
Urah	A	G	7: 140,416,711 (GRCm39)	I60M	probably benign	Het
Vmn2r26	T	A	6: 124,016,519 (GRCm39)	S328T	possibly damaging	Het
Vmn2r27	G	C	6: 124,168,958 (GRCm39)	T724R	probably damaging	Het
Washc2	A	G	6: 116,233,177 (GRCm39)		probably null	Het
Zfp955b	T	A	17: 33,521,478 (GRCm39)	W316R	probably benign	Het
Zranb2	T	C	3: 157,248,883 (GRCm39)		probably null	Het

Other mutations in Tpmt

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02865:Tpmt	APN	13	47,178,878 (GRCm39)	missense	probably benign	0.16
R0666:Tpmt	UTSW	13	47,185,930 (GRCm39)	missense	probably damaging	1.00
R0826:Tpmt	UTSW	13	47,194,965 (GRCm39)	missense	probably benign	0.10
R1373:Tpmt	UTSW	13	47,180,734 (GRCm39)	splice site	probably null
R1640:Tpmt	UTSW	13	47,180,759 (GRCm39)	nonsense	probably null
R5644:Tpmt	UTSW	13	47,182,435 (GRCm39)	missense	probably benign	0.41
R6228:Tpmt	UTSW	13	47,180,735 (GRCm39)	missense	probably benign	0.00
R6372:Tpmt	UTSW	13	47,189,370 (GRCm39)	critical splice donor site	probably null
R7035:Tpmt	UTSW	13	47,193,584 (GRCm39)	missense	probably damaging	1.00
R7325:Tpmt	UTSW	13	47,194,960 (GRCm39)	nonsense	probably null
R7886:Tpmt	UTSW	13	47,193,638 (GRCm39)	missense	probably damaging	1.00
R9311:Tpmt	UTSW	13	47,185,892 (GRCm39)	critical splice donor site	probably null
R9491:Tpmt	UTSW	13	47,180,752 (GRCm39)	missense	probably benign	0.00

Predicted Primers

PCR Primer
(F):5'- CATACTCACACGTCATGGGC -3'
(R):5'- AAGGTCCAGTTAAAGCCTAATGAAC -3'

Posted On

2017-07-14