Mutagenetix > Incidental Mutation

Incidental Mutation 'R7325:Tpmt'

568839

Institutional Source

Beutler Lab

Gene Symbol

Tpmt

Ensembl Gene

ENSMUSG00000021376

Gene Name

thiopurine methyltransferase

Synonyms

MMRRC Submission

045419-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7325 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

47175463-47196833 bp(-) (GRCm39)

Type of Mutation

nonsense

DNA Base Change (assembly)

G to A at 47194960 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glutamine to Stop codon at position 14 (Q14*)

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 null
Transcript: ENSMUST00000021806
AA Change: Q14*

SMART Domains

Protein: ENSMUSP00000021806
Gene: ENSMUSG00000021376
AA Change: Q14*

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 null
Transcript: ENSMUST00000110118
AA Change: Q14*

SMART Domains

Protein: ENSMUSP00000105745
Gene: ENSMUSG00000021376
AA Change: Q14*

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

Predicted Effect

probably null
Transcript: ENSMUST00000124948
AA Change: Q38*

SMART Domains

Protein: ENSMUSP00000115361
Gene: ENSMUSG00000021376
AA Change: Q38*

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

Predicted Effect

probably null
Transcript: ENSMUST00000136864
AA Change: Q14*

SMART Domains

Protein: ENSMUSP00000120081
Gene: ENSMUSG00000021376
AA Change: Q14*

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 null
Transcript: ENSMUST00000151509
AA Change: Q33*

SMART Domains

Protein: ENSMUSP00000120564
Gene: ENSMUSG00000021376
AA Change: Q33*

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

Predicted Effect

probably null
Transcript: ENSMUST00000154802
AA Change: Q14*

SMART Domains

Protein: ENSMUSP00000121827
Gene: ENSMUSG00000021376
AA Change: Q14*

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

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 99.1%

Validation Efficiency

100% (62/62)

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: 61 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adgrb3	T	A	1: 25,571,711 (GRCm39)	Q402L	probably benign	Het
Afap1l1	T	C	18: 61,869,917 (GRCm39)	T638A	probably benign	Het
Agtr1a	A	C	13: 30,565,890 (GRCm39)	K318N	possibly damaging	Het
Anks1b	A	G	10: 90,777,294 (GRCm39)	T1095A	probably damaging	Het
Ap3d1	A	T	10: 80,559,637 (GRCm39)	I207N	probably damaging	Het
Arhgef11	T	C	3: 87,620,599 (GRCm39)	L484P	possibly damaging	Het
Astn2	C	T	4: 65,460,906 (GRCm39)	S1076N	probably benign	Het
Baat	C	A	4: 49,490,213 (GRCm39)	L290F	probably benign	Het
Boll	T	C	1: 55,343,757 (GRCm39)	Y222C	probably damaging	Het
Bphl	A	T	13: 34,234,324 (GRCm39)	I147F	possibly damaging	Het
Cadps2	T	G	6: 23,409,934 (GRCm39)	D766A	unknown	Het
Cd300lb	T	A	11: 114,815,858 (GRCm39)	K210M	probably damaging	Het
Cdan1	T	C	2: 120,555,185 (GRCm39)	Q797R	probably benign	Het
Celsr1	T	A	15: 85,917,209 (GRCm39)	S255C	probably damaging	Het
Cfap91	T	A	16: 38,141,963 (GRCm39)		probably null	Het
Cip2a	T	A	16: 48,826,184 (GRCm39)	M417K	probably benign	Het
Csmd1	G	A	8: 16,108,721 (GRCm39)	S1894L	probably damaging	Het
Dennd5b	T	A	6: 148,922,068 (GRCm39)	K815N	probably benign	Het
Exd1	A	G	2: 119,350,620 (GRCm39)	V547A	probably benign	Het
Fbxo15	C	T	18: 84,977,243 (GRCm39)	R52C	probably damaging	Het
Fip1l1	A	G	5: 74,697,460 (GRCm39)		probably null	Het
Flg2	T	A	3: 93,110,679 (GRCm39)	N902K	unknown	Het
Fyttd1	T	A	16: 32,704,618 (GRCm39)	N76K	probably benign	Het
Gins1	T	A	2: 150,758,086 (GRCm39)	D57E	probably benign	Het
Gm5565	G	C	5: 146,095,171 (GRCm39)		probably null	Het
Gpsm2	T	C	3: 108,610,244 (GRCm39)	Y72C	probably damaging	Het
Hace1	C	A	10: 45,465,603 (GRCm39)	S53*	probably null	Het
Insig2	A	G	1: 121,234,666 (GRCm39)	V188A	possibly damaging	Het
Ism1	T	C	2: 139,598,963 (GRCm39)	V312A	probably damaging	Het
Jmy	A	T	13: 93,609,251 (GRCm39)	Y353N	probably damaging	Het
Maz	A	C	7: 126,624,725 (GRCm39)	V265G	probably benign	Het
Mtmr14	T	A	6: 113,246,509 (GRCm39)	I426N	probably damaging	Het
Or1e34	C	T	11: 73,779,101 (GRCm39)	M32I	probably benign	Het
Or5b113	A	G	19: 13,342,001 (GRCm39)	E3G	probably benign	Het
Or8k22	A	G	2: 86,163,344 (GRCm39)	S119P	possibly damaging	Het
Pcdhac2	T	A	18: 37,278,413 (GRCm39)	N464K	probably damaging	Het
Pcdhb7	T	A	18: 37,476,440 (GRCm39)	H525Q	probably benign	Het
Pcp4l1	G	A	1: 171,002,034 (GRCm39)	A42V	possibly damaging	Het
Podn	C	T	4: 107,874,899 (GRCm39)		probably null	Het
Prim1	A	G	10: 127,858,788 (GRCm39)	D232G	probably null	Het
Prrt1	T	A	17: 34,851,161 (GRCm39)	M283K	possibly damaging	Het
Rgs9	A	T	11: 109,167,407 (GRCm39)	I65N	probably damaging	Het
Scgb2b26	C	A	7: 33,643,782 (GRCm39)	V53L	probably benign	Het
Shank2	C	A	7: 143,965,422 (GRCm39)	P1010Q	probably benign	Het
Slc12a4	C	T	8: 106,682,347 (GRCm39)	G121S	probably damaging	Het
Slc17a6	G	T	7: 51,294,766 (GRCm39)	A158S	probably damaging	Het
Slc9a9	C	T	9: 94,594,951 (GRCm39)	H154Y	probably benign	Het
Slco1a8	T	C	6: 141,934,951 (GRCm39)	K379E	probably damaging	Het
Slco2a1	T	A	9: 102,962,948 (GRCm39)		probably null	Het
Snapc3	T	C	4: 83,353,507 (GRCm39)	I182T	probably benign	Het
Taok2	A	G	7: 126,470,260 (GRCm39)	V856A	probably benign	Het
Tep1	T	A	14: 51,103,495 (GRCm39)	N265I	probably damaging	Het
Tespa1	A	T	10: 130,197,910 (GRCm39)	N311Y	probably damaging	Het
Trim33	T	C	3: 103,228,952 (GRCm39)	F353L	possibly damaging	Het
Upp1	T	C	11: 9,084,743 (GRCm39)	V154A	probably damaging	Het
Usp34	T	C	11: 23,369,052 (GRCm39)	I1747T		Het
Vmn1r47	T	C	6: 89,999,254 (GRCm39)	S129P	probably benign	Het
Vmn2r93	A	G	17: 18,524,249 (GRCm39)	Y81C	probably benign	Het
Ybx2	A	T	11: 69,831,181 (GRCm39)	T259S	probably benign	Het
Zfp536	T	C	7: 37,179,285 (GRCm39)	T1107A	probably benign	Het
Zfp583	C	T	7: 6,319,585 (GRCm39)	A476T	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
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
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'- CCCTAACGATATGAGATGACAGTG -3'
(R):5'- AGCTATTGCCCTAGGTAGAGG -3'

Sequencing Primer
(F):5'- ATTACATGCATATGCCACTGCG -3'
(R):5'- AGGGTTTTGTAGCGTTCATTAATAG -3'

Posted On

2019-09-13