Mutagenetix > Incidental Mutation

Incidental Mutation 'R6372:Tpmt'

513595

Institutional Source

Beutler Lab

Gene Symbol

Tpmt

Ensembl Gene

ENSMUSG00000021376

Gene Name

thiopurine methyltransferase

Synonyms

MMRRC Submission

044522-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R6372 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

47175463-47196833 bp(-) (GRCm39)

Type of Mutation

critical splice donor site (1 bp from exon)

DNA Base Change (assembly)

C to T at 47189370 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Ref Sequence

ENSEMBL: ENSMUSP00000121827 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000021806] [ENSMUST00000110118] [ENSMUST00000124948] [ENSMUST00000136864] [ENSMUST00000154802]

AlphaFold

no structure available at present

Predicted Effect

probably null
Transcript: ENSMUST00000021806

SMART Domains

Protein: ENSMUSP00000021806
Gene: ENSMUSG00000021376

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

Predicted Effect

probably null
Transcript: ENSMUST00000110118

SMART Domains

Protein: ENSMUSP00000105745
Gene: ENSMUSG00000021376

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

Predicted Effect

probably benign
Transcript: ENSMUST00000124948

SMART Domains

Protein: ENSMUSP00000115361
Gene: ENSMUSG00000021376

Domain	Start	End	E-Value	Type
Pfam:TPMT	43	93	2.4e-18	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000133100

Predicted Effect

probably null
Transcript: ENSMUST00000136864

SMART Domains

Protein: ENSMUSP00000120081
Gene: ENSMUSG00000021376

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

Predicted Effect

probably null
Transcript: ENSMUST00000151509

SMART Domains

Protein: ENSMUSP00000120564
Gene: ENSMUSG00000021376

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

Predicted Effect

probably null
Transcript: ENSMUST00000154802

SMART Domains

Protein: ENSMUSP00000121827
Gene: ENSMUSG00000021376

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

Meta Mutation Damage Score

0.9492

Coding Region Coverage

1x: 99.9%
3x: 99.6%
10x: 98.1%
20x: 94.4%

Validation Efficiency

97% (59/61)

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: 60 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700113H08Rik	T	A	10: 87,066,088 (GRCm39)	H136Q	possibly damaging	Het
Aim2	T	A	1: 173,282,802 (GRCm39)		probably null	Het
Atp13a3	T	C	16: 30,162,273 (GRCm39)	H696R	probably damaging	Het
Atrnl1	T	C	19: 57,638,764 (GRCm39)	S301P	probably benign	Het
Atxn1	T	A	13: 45,710,932 (GRCm39)	I667F	probably damaging	Het
Cacnb4	T	A	2: 52,324,679 (GRCm39)	Y415F	probably benign	Het
Ccdc183	T	C	2: 25,506,176 (GRCm39)	D140G	probably benign	Het
Clec2g	A	C	6: 128,925,726 (GRCm39)	H45P	probably benign	Het
Col5a3	A	G	9: 20,696,882 (GRCm39)	V917A	probably damaging	Het
Cryga	T	C	1: 65,142,204 (GRCm39)	Y63C	probably damaging	Het
Dnajc28	T	C	16: 91,414,176 (GRCm39)	I23V	probably benign	Het
Elovl6	T	C	3: 129,426,751 (GRCm39)	F139S	probably damaging	Het
Fcgbp	A	G	7: 27,806,433 (GRCm39)	T2134A	probably damaging	Het
Fcrl5	C	T	3: 87,351,501 (GRCm39)	Q250*	probably null	Het
Gimap1	T	A	6: 48,720,290 (GRCm39)	*301K	probably null	Het
Gm17472	T	C	6: 42,957,823 (GRCm39)	S31P	possibly damaging	Het
Gm2381	G	A	7: 42,470,010 (GRCm39)	A38V	probably benign	Het
Gnl1	T	C	17: 36,293,427 (GRCm39)	F204S	probably damaging	Het
Helz2	C	T	2: 180,875,260 (GRCm39)	E1745K	probably damaging	Het
Hk1	T	C	10: 62,127,757 (GRCm39)	H370R	probably benign	Het
Ighv7-2	G	A	12: 113,876,075 (GRCm39)	T10I	probably benign	Het
Itga9	A	G	9: 118,726,389 (GRCm39)	K448E	probably damaging	Het
Lama4	C	A	10: 38,943,948 (GRCm39)	N750K	probably benign	Het
Megf11	T	C	9: 64,613,907 (GRCm39)	Y1077H	probably damaging	Het
Mrpl45	T	C	11: 97,212,388 (GRCm39)		probably benign	Het
Nbeal2	T	C	9: 110,457,812 (GRCm39)	D2185G	possibly damaging	Het
Ncoa3	C	T	2: 165,901,267 (GRCm39)	S953F	possibly damaging	Het
Nlrc5	T	C	8: 95,206,378 (GRCm39)	L743P	probably damaging	Het
Nol4	A	G	18: 23,171,613 (GRCm39)		probably null	Het
Nol9	T	C	4: 152,130,452 (GRCm39)	S329P	probably damaging	Het
Ntrk1	T	C	3: 87,693,355 (GRCm39)	D259G	probably benign	Het
Or2y11	A	G	11: 49,442,757 (GRCm39)	Y61C	probably damaging	Het
Or4k40	T	A	2: 111,251,147 (GRCm39)	I50F	probably benign	Het
Or5al5	T	C	2: 85,961,198 (GRCm39)	T270A	possibly damaging	Het
Or5d16	T	C	2: 87,773,319 (GRCm39)	T218A	probably benign	Het
Or8h8	T	A	2: 86,753,499 (GRCm39)	I126F	probably damaging	Het
Pbx4	C	A	8: 70,324,694 (GRCm39)	A365E	possibly damaging	Het
Pcdhb19	T	A	18: 37,630,419 (GRCm39)	N71K	probably benign	Het
Pde2a	G	A	7: 101,130,599 (GRCm39)	A80T	probably benign	Het
Psmb5	C	A	14: 54,854,130 (GRCm39)	R116L	probably damaging	Het
Recql	A	G	6: 142,322,566 (GRCm39)	V112A	probably damaging	Het
Rhbdl3	C	A	11: 80,221,482 (GRCm39)	L207I	probably damaging	Het
Rtkn	A	G	6: 83,128,882 (GRCm39)	D459G	possibly damaging	Het
Rubcnl	C	A	14: 75,285,009 (GRCm39)	S509R	probably damaging	Het
Slc26a8	T	C	17: 28,863,777 (GRCm39)	T661A	probably benign	Het
Sspo	A	T	6: 48,449,475 (GRCm39)	D2472V	probably damaging	Het
Taf4b	T	G	18: 14,937,790 (GRCm39)	V258G	probably damaging	Het
Tbc1d19	T	G	5: 54,014,252 (GRCm39)	S293R	possibly damaging	Het
Tecpr1	C	T	5: 144,153,776 (GRCm39)	R159Q	probably damaging	Het
Tlr3	A	G	8: 45,850,048 (GRCm39)	S874P	probably damaging	Het
Tnk2	T	A	16: 32,498,603 (GRCm39)	W639R	probably damaging	Het
Trappc9	T	A	15: 72,461,923 (GRCm39)	D935V	possibly damaging	Het
Trav13d-4	T	C	14: 53,995,118 (GRCm39)	V4A	probably damaging	Het
Ubn1	C	T	16: 4,899,502 (GRCm39)	T1082I	possibly damaging	Het
Usf2	G	A	7: 30,654,738 (GRCm39)	Q35*	probably null	Het
Vmn1r57	T	C	7: 5,223,826 (GRCm39)	M117T	possibly damaging	Het
Vmn2r65	G	T	7: 84,589,861 (GRCm39)	A685E	probably damaging	Het
Vxn	G	A	1: 9,683,546 (GRCm39)	E45K	probably damaging	Het
Zeb2	T	C	2: 44,892,551 (GRCm39)	E166G	probably damaging	Het
Zfp808	T	C	13: 62,320,291 (GRCm39)	S507P	probably damaging	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
R6086:Tpmt	UTSW	13	47,188,506 (GRCm39)	missense	probably damaging	0.99
R6228:Tpmt	UTSW	13	47,180,735 (GRCm39)	missense	probably benign	0.00
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'- GAGGTGTAGCTAACCTGTGG -3'
(R):5'- GGGGAACATGCCTGTTTATCG -3'

Sequencing Primer
(F):5'- CTAACCTGTGGTAGAGAGTGGC -3'
(R):5'- CCTGTTTATCGTGGTTTTTATTTTGC -3'

Posted On

2018-04-27