Mutagenetix > Incidental Mutation

Incidental Mutation 'R7886:Tpmt'

609077

Institutional Source

Beutler Lab

Gene Symbol

Tpmt

Ensembl Gene

ENSMUSG00000021376

Gene Name

thiopurine methyltransferase

Synonyms

MMRRC Submission

045938-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7886 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

47175463-47196833 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to A at 47193638 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glycine to Cysteine at position 54 (G54C)

Ref Sequence

ENSEMBL: ENSMUSP00000021806 (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 damaging
Transcript: ENSMUST00000021806
AA Change: G54C

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000021806
Gene: ENSMUSG00000021376
AA Change: G54C

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

possibly damaging
Transcript: ENSMUST00000110118
AA Change: G54C

PolyPhen 2 Score 0.847 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000105745
Gene: ENSMUSG00000021376
AA Change: G54C

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

Predicted Effect

probably damaging
Transcript: ENSMUST00000124948
AA Change: G78C

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000115361
Gene: ENSMUSG00000021376
AA Change: G78C

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

Predicted Effect

possibly damaging
Transcript: ENSMUST00000136864
AA Change: G54C

PolyPhen 2 Score 0.847 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000120081
Gene: ENSMUSG00000021376
AA Change: G54C

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

SMART Domains

Protein: ENSMUSP00000120564
Gene: ENSMUSG00000021376
AA Change: G73C

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

Predicted Effect

possibly damaging
Transcript: ENSMUST00000154802
AA Change: G54C

PolyPhen 2 Score 0.847 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000121827
Gene: ENSMUSG00000021376
AA Change: G54C

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

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 98.9%

Validation Efficiency

100% (53/53)

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: 54 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A730049H05Rik	T	G	6: 92,811,437 (GRCm39)	I130S	unknown	Het
Ano5	A	G	7: 51,220,141 (GRCm39)	H427R	probably benign	Het
Atad2	A	T	15: 57,989,532 (GRCm39)	V182E	probably damaging	Het
B4galnt1	T	C	10: 127,002,923 (GRCm39)	Y147H	probably damaging	Het
C1s2	T	C	6: 124,605,289 (GRCm39)	S349G	possibly damaging	Het
Ccdc51	G	T	9: 108,920,655 (GRCm39)	A181S	probably damaging	Het
Dcc	G	A	18: 72,087,939 (GRCm39)	Q100*	probably null	Het
Dchs2	A	T	3: 83,212,392 (GRCm39)	I2064F	probably damaging	Het
Depdc1a	G	A	3: 159,221,706 (GRCm39)	V217I	probably benign	Het
Dnajc7	A	T	11: 100,492,629 (GRCm39)	F31I	probably benign	Het
Eftud2	C	T	11: 102,730,934 (GRCm39)	R825H	probably damaging	Het
Fam184a	T	C	10: 53,551,256 (GRCm39)	E237G	probably damaging	Het
Fdx2	A	T	9: 20,984,623 (GRCm39)		probably null	Het
Frem1	T	C	4: 82,934,643 (GRCm39)	D106G	possibly damaging	Het
Gabrg3	G	A	7: 56,374,229 (GRCm39)	R446W	probably damaging	Het
Get1	T	A	16: 95,946,768 (GRCm39)	L31Q	possibly damaging	Het
Gm42669	A	G	5: 107,656,572 (GRCm39)	E362G		Het
Hmcn1	A	T	1: 150,533,221 (GRCm39)	I3022N	possibly damaging	Het
Ifna2	C	A	4: 88,601,506 (GRCm39)	V171F	probably damaging	Het
Igsf10	T	C	3: 59,235,748 (GRCm39)	N1478D	probably benign	Het
Kcnc1	C	A	7: 46,077,045 (GRCm39)	D282E	probably damaging	Het
Klhdc2	G	A	12: 69,351,406 (GRCm39)		probably null	Het
Macrod2	G	A	2: 141,566,565 (GRCm39)	G188S	probably damaging	Het
Mapkbp1	T	C	2: 119,843,128 (GRCm39)	F186L	possibly damaging	Het
Mettl21a	T	C	1: 64,654,343 (GRCm39)	E58G	probably damaging	Het
Muc16	A	T	9: 18,497,278 (GRCm39)	C6625S	probably benign	Het
Naip5	A	T	13: 100,382,689 (GRCm39)	S7T	probably benign	Het
Nfs1	T	A	2: 155,983,981 (GRCm39)	D132V	unknown	Het
Nlgn1	T	C	3: 25,490,071 (GRCm39)	D552G	probably damaging	Het
Numa1	C	T	7: 101,663,072 (GRCm39)	T2066I	probably benign	Het
Or10k2	T	C	8: 84,268,576 (GRCm39)	S268P	possibly damaging	Het
Or2t48	C	A	11: 58,419,880 (GRCm39)	V311L	probably benign	Het
Or4k2	A	T	14: 50,424,021 (GRCm39)	Y219N	probably damaging	Het
Or7a39	A	G	10: 78,715,657 (GRCm39)	Y217C	possibly damaging	Het
Or7g29	A	T	9: 19,287,202 (GRCm39)		probably null	Het
Pde11a	C	T	2: 76,121,547 (GRCm39)	V345I	probably benign	Het
Pglyrp2	A	G	17: 32,637,735 (GRCm39)	S98P	possibly damaging	Het
Pik3c3	C	T	18: 30,452,641 (GRCm39)	Q643*	probably null	Het
Pold2	T	C	11: 5,822,714 (GRCm39)	Y402C	probably damaging	Het
Pom121	T	C	5: 135,410,848 (GRCm39)	T770A	unknown	Het
Pou4f1	A	T	14: 104,704,228 (GRCm39)	V68E	probably damaging	Het
Ppfia1	G	T	7: 144,073,020 (GRCm39)	Q265K	probably benign	Het
Pygl	A	G	12: 70,253,130 (GRCm39)		probably null	Het
Rdh19	A	G	10: 127,686,169 (GRCm39)	T94A	probably benign	Het
Scgb1b12	A	G	7: 32,033,922 (GRCm39)	T61A	probably damaging	Het
Sirpb1c	C	T	3: 15,886,366 (GRCm39)	A337T	probably benign	Het
Sltm	C	G	9: 70,493,955 (GRCm39)	P802R	possibly damaging	Het
Tbc1d23	T	C	16: 57,009,746 (GRCm39)	E381G	possibly damaging	Het
Tnik	A	G	3: 28,720,288 (GRCm39)	I1304V	probably damaging	Het
Usp25	A	T	16: 76,910,659 (GRCm39)	Q905L	probably damaging	Het
Vmn1r91	T	A	7: 19,835,490 (GRCm39)	N136K	probably benign	Het
Wdr70	C	T	15: 8,108,733 (GRCm39)	E138K	probably benign	Het
Zbed3	A	G	13: 95,472,633 (GRCm39)	D19G	possibly damaging	Het
Zfp369	A	G	13: 65,439,868 (GRCm39)	K184R	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
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
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
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'- TGTATGTTAGGTTACCCGGC -3'
(R):5'- TTTCTCAAGGCAACATAAGCAG -3'

Sequencing Primer
(F):5'- CCTCTTGAACTTACATGTAGCCAAGG -3'
(R):5'- GTCATGAAAACTCCAGGTTGC -3'

Posted On

2019-12-20