Mutagenetix > Incidental Mutation

Incidental Mutation 'R0826:Tpmt'

78252

Institutional Source

Beutler Lab

Gene Symbol

Tpmt

Ensembl Gene

ENSMUSG00000021376

Gene Name

thiopurine methyltransferase

Synonyms

MMRRC Submission

039006-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0826 (G1)

Quality Score

213

Status

Validated

Chromosome

Chromosomal Location

47175463-47196833 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 47194965 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glutamic Acid to Glycine at position 36 (E36G)

Ref Sequence

ENSEMBL: ENSMUSP00000115361 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000021806] [ENSMUST00000037025] [ENSMUST00000110118] [ENSMUST00000124948] [ENSMUST00000136864] [ENSMUST00000143868] [ENSMUST00000154802]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000021806
AA Change: E12G

PolyPhen 2 Score 0.047 (Sensitivity: 0.94; Specificity: 0.83)

SMART Domains

Protein: ENSMUSP00000021806
Gene: ENSMUSG00000021376
AA Change: E12G

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

Predicted Effect

probably benign
Transcript: ENSMUST00000037025

SMART Domains

Protein: ENSMUSP00000038373
Gene: ENSMUSG00000038080

Domain	Start	End	E-Value	Type
Pfam:zf-CW	138	191	2.6e-13	PFAM
low complexity region	235	253	N/A	INTRINSIC
Pfam:SWIRM	286	369	6e-12	PFAM
Pfam:Pyr_redox_2	368	490	3.1e-8	PFAM
Pfam:Thi4	375	446	2.2e-10	PFAM
Pfam:FAD_binding_3	388	423	4.1e-7	PFAM
Pfam:HI0933_like	389	428	1.6e-7	PFAM
Pfam:FAD_binding_2	390	428	1.6e-6	PFAM
Pfam:Pyr_redox	390	438	8e-8	PFAM
Pfam:NAD_binding_8	393	460	1.6e-13	PFAM
Pfam:Amino_oxidase	398	824	3.7e-86	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000110118
AA Change: E12G

PolyPhen 2 Score 0.030 (Sensitivity: 0.95; Specificity: 0.82)

SMART Domains

Protein: ENSMUSP00000105745
Gene: ENSMUSG00000021376
AA Change: E12G

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

Predicted Effect

probably benign
Transcript: ENSMUST00000124948
AA Change: E36G

PolyPhen 2 Score 0.100 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000115361
Gene: ENSMUSG00000021376
AA Change: E36G

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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000133100

Predicted Effect

probably benign
Transcript: ENSMUST00000136864
AA Change: E12G

PolyPhen 2 Score 0.010 (Sensitivity: 0.96; Specificity: 0.77)

SMART Domains

Protein: ENSMUSP00000120081
Gene: ENSMUSG00000021376
AA Change: E12G

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

Predicted Effect

probably benign
Transcript: ENSMUST00000143868

SMART Domains

Protein: ENSMUSP00000117793
Gene: ENSMUSG00000038080

Domain	Start	End	E-Value	Type
Pfam:zf-CW	137	175	3.6e-13	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000154802
AA Change: E12G

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

SMART Domains

Protein: ENSMUSP00000121827
Gene: ENSMUSG00000021376
AA Change: E12G

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

Predicted Effect

unknown
Transcript: ENSMUST00000151509
AA Change: E31G

SMART Domains

Protein: ENSMUSP00000120564
Gene: ENSMUSG00000021376
AA Change: E31G

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

Meta Mutation Damage Score

0.0597

Coding Region Coverage

1x: 99.5%
3x: 98.6%
10x: 95.7%
20x: 86.3%

Validation Efficiency

100% (69/69)

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
4930433I11Rik	A	T	7: 40,642,480 (GRCm39)	T141S	probably benign	Het
4931406C07Rik	T	C	9: 15,203,292 (GRCm39)		probably null	Het
Adamts16	T	A	13: 70,916,811 (GRCm39)	D727V	possibly damaging	Het
Anxa10	A	C	8: 62,529,318 (GRCm39)	L133*	probably null	Het
Arfgef3	G	A	10: 18,465,414 (GRCm39)	T2143I	probably damaging	Het
Arhgef17	T	C	7: 100,579,950 (GRCm39)	T333A	probably benign	Het
Arhgef40	A	G	14: 52,238,450 (GRCm39)	T1310A	probably benign	Het
Atg10	C	T	13: 91,084,705 (GRCm39)		probably null	Het
Atp1a1	A	G	3: 101,492,169 (GRCm39)	F569S	probably damaging	Het
Baiap3	A	G	17: 25,464,203 (GRCm39)	W849R	possibly damaging	Het
Baz1a	A	T	12: 54,977,097 (GRCm39)	Y9*	probably null	Het
Catsperg2	C	T	7: 29,405,049 (GRCm39)	D702N	possibly damaging	Het
Clasrp	G	T	7: 19,318,226 (GRCm39)		probably benign	Het
Col11a1	G	A	3: 113,932,414 (GRCm39)	R113H	unknown	Het
Col19a1	T	C	1: 24,565,467 (GRCm39)	K288R	unknown	Het
Ctnnbl1	C	T	2: 157,641,337 (GRCm39)		probably benign	Het
Cttnbp2	A	G	6: 18,405,177 (GRCm39)		probably benign	Het
Dnah1	T	A	14: 31,025,864 (GRCm39)	I828F	probably benign	Het
Dpf2	G	T	19: 5,957,155 (GRCm39)	Q23K	probably damaging	Het
Dsc3	T	A	18: 20,114,229 (GRCm39)	I342F	probably damaging	Het
Enpp3	A	G	10: 24,671,614 (GRCm39)	L460P	probably damaging	Het
Epb41l2	A	G	10: 25,380,090 (GRCm39)	E871G	probably damaging	Het
Exoc2	T	C	13: 31,040,780 (GRCm39)		probably null	Het
Fam243	G	A	16: 92,118,075 (GRCm39)	S71L	probably benign	Het
Fpr-rs7	A	T	17: 20,333,888 (GRCm39)	S201T	probably benign	Het
Gtf2ird2	T	C	5: 134,245,797 (GRCm39)	F685S	probably damaging	Het
Helz2	C	T	2: 180,882,646 (GRCm39)	R49H	possibly damaging	Het
Ica1	A	G	6: 8,667,375 (GRCm39)		probably benign	Het
Ift56	A	G	6: 38,402,049 (GRCm39)		probably null	Het
Iqca1	C	A	1: 90,070,453 (GRCm39)	G133V	probably null	Het
Kif21a	A	G	15: 90,881,744 (GRCm39)		probably null	Het
Lamb3	T	A	1: 193,013,216 (GRCm39)	C480*	probably null	Het
Lamc2	A	G	1: 153,027,828 (GRCm39)	S199P	probably damaging	Het
Lrfn3	T	C	7: 30,059,676 (GRCm39)	N183S	probably benign	Het
Lsm14a	C	A	7: 34,070,470 (GRCm39)		probably benign	Het
Mest	C	A	6: 30,742,813 (GRCm39)	H146Q	probably damaging	Het
Mmp27	T	C	9: 7,579,010 (GRCm39)	V339A	probably damaging	Het
Myo16	T	C	8: 10,426,285 (GRCm39)		probably benign	Het
Myoz1	C	T	14: 20,703,679 (GRCm39)		probably benign	Het
Nlrp5	A	G	7: 23,117,133 (GRCm39)	M286V	probably benign	Het
Optc	T	C	1: 133,832,893 (GRCm39)	K69R	probably benign	Het
Or13c3	C	T	4: 52,855,566 (GRCm39)	V316I	probably benign	Het
Or2y1c	A	T	11: 49,361,158 (GRCm39)	Y60F	probably damaging	Het
Or4a77	A	C	2: 89,487,181 (GRCm39)	N201K	possibly damaging	Het
Or8g18	C	T	9: 39,149,725 (GRCm39)	M1I	probably null	Het
Osbpl3	A	T	6: 50,323,357 (GRCm39)	M242K	probably damaging	Het
Pdzd9	T	A	7: 120,267,624 (GRCm39)	S64C	probably damaging	Het
Pik3cg	A	G	12: 32,245,672 (GRCm39)	S859P	possibly damaging	Het
Ppp1r12a	G	T	10: 108,066,414 (GRCm39)	A202S	possibly damaging	Het
Rab32	A	T	10: 10,426,611 (GRCm39)	F112I	possibly damaging	Het
Ror2	T	C	13: 53,267,253 (GRCm39)	Y394C	probably damaging	Het
Rtn3	A	G	19: 7,445,245 (GRCm39)		probably benign	Het
Sbk1	C	T	7: 125,891,007 (GRCm39)	P147L	probably damaging	Het
Shpk	T	A	11: 73,094,857 (GRCm39)	M91K	probably damaging	Het
Slco6c1	C	T	1: 97,055,826 (GRCm39)	S25N	probably benign	Het
Snx2	A	T	18: 53,327,594 (GRCm39)	T107S	probably benign	Het
Tle2	G	A	10: 81,422,148 (GRCm39)	V397I	possibly damaging	Het
Tmem131l	T	C	3: 83,805,724 (GRCm39)	D1573G	probably damaging	Het
Tnfrsf8	A	G	4: 145,011,708 (GRCm39)		probably benign	Het
Trim30c	T	A	7: 104,032,688 (GRCm39)	T257S	probably benign	Het
Tsc2	A	G	17: 24,815,932 (GRCm39)	L150P	probably benign	Het
Upf3a	G	C	8: 13,848,338 (GRCm39)	G378A	possibly damaging	Het
Yeats2	A	T	16: 20,011,966 (GRCm39)	K514*	probably null	Het
Zfp11	A	G	5: 129,734,589 (GRCm39)	Y291H	probably benign	Het
Zfp457	T	C	13: 67,441,378 (GRCm39)	D399G	possibly 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
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
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'- TCCCTAACGATATGAGATGACAGTGTGT -3'
(R):5'- GGGCAGGTTGGAACTGTGGAATT -3'

Sequencing Primer
(F):5'- atttctaatgcttttgtttccatctc -3'
(R):5'- ttacagacagccacgagac -3'

Posted On

2013-10-16