Incidental Mutation 'R9491:Tpmt'
ID 716944
Institutional Source Beutler Lab
Gene Symbol Tpmt
Ensembl Gene ENSMUSG00000021376
Gene Name thiopurine methyltransferase
Synonyms
MMRRC Submission
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R9491 (G1)
Quality Score 225.009
Status Not validated
Chromosome 13
Chromosomal Location 47175463-47196833 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 47180752 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Threonine at position 196 (S196T)
Ref Sequence ENSEMBL: ENSMUSP00000021806 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000021806] [ENSMUST00000110118] [ENSMUST00000136864] [ENSMUST00000154802] [ENSMUST00000224970]
AlphaFold no structure available at present
Predicted Effect probably benign
Transcript: ENSMUST00000021806
AA Change: S196T

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
SMART Domains Protein: ENSMUSP00000021806
Gene: ENSMUSG00000021376
AA Change: S196T

DomainStartEndE-ValueType
Pfam:TPMT 19 240 4.1e-84 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000110118
AA Change: S196T

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000105745
Gene: ENSMUSG00000021376
AA Change: S196T

DomainStartEndE-ValueType
Pfam:TPMT 19 205 8.8e-73 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000136864
SMART Domains Protein: ENSMUSP00000120081
Gene: ENSMUSG00000021376

DomainStartEndE-ValueType
Pfam:TPMT 19 188 3.6e-65 PFAM
Predicted Effect
SMART Domains Protein: ENSMUSP00000120564
Gene: ENSMUSG00000021376
AA Change: I186N

DomainStartEndE-ValueType
Pfam:TPMT 19 73 3.3e-20 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000154802
SMART Domains Protein: ENSMUSP00000121827
Gene: ENSMUSG00000021376

DomainStartEndE-ValueType
Pfam:TPMT 19 182 2.9e-62 PFAM
Predicted Effect unknown
Transcript: ENSMUST00000224970
AA Change: H24Q
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.7%
  • 20x: 99.0%
Validation Efficiency
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: 52 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Acy1 G A 9: 106,312,994 (GRCm39) T142I probably damaging Het
Adcy9 T C 16: 4,236,052 (GRCm39) E453G probably damaging Het
Ank3 A C 10: 69,838,339 (GRCm39) probably null Het
Asmt G A X: 169,108,405 (GRCm39) G103D possibly damaging Het
Cap2 C T 13: 46,791,366 (GRCm39) P290S possibly damaging Het
Cfap43 A T 19: 47,800,505 (GRCm39) probably null Het
Clip2 C T 5: 134,533,616 (GRCm39) R487Q probably benign Het
Clstn1 T C 4: 149,731,929 (GRCm39) S950P probably damaging Het
Cluap1 G A 16: 3,758,732 (GRCm39) R398Q probably benign Het
Cmbl G T 15: 31,582,119 (GRCm39) V39L probably benign Het
Dapk1 A G 13: 60,877,369 (GRCm39) D536G probably benign Het
Ddx3y T A Y: 1,279,465 (GRCm39) D133V probably benign Het
Duox1 T A 2: 122,156,907 (GRCm39) S525T probably benign Het
Eif2s2 T C 2: 154,734,630 (GRCm39) probably benign Het
Foxo3 C T 10: 42,073,021 (GRCm39) V499M probably damaging Het
Gadd45a A T 6: 67,012,730 (GRCm39) D137E probably benign Het
Gmppa A G 1: 75,415,602 (GRCm39) D120G probably damaging Het
Gpr156 A T 16: 37,825,704 (GRCm39) R640S probably benign Het
Grik1 A T 16: 87,746,995 (GRCm39) M414K Het
Gtse1 C T 15: 85,755,734 (GRCm39) P466L probably damaging Het
H6pd T A 4: 150,080,366 (GRCm39) N160Y probably benign Het
Hectd4 T G 5: 121,452,981 (GRCm39) L496R probably damaging Het
Hnrnpk G T 13: 58,541,050 (GRCm39) Q441K probably benign Het
Incenp T C 19: 9,854,141 (GRCm39) K637E unknown Het
Irgc C T 7: 24,132,349 (GRCm39) R156H probably benign Het
Kazn C T 4: 141,845,436 (GRCm39) A383T Het
Lmln A G 16: 32,890,358 (GRCm39) E169G possibly damaging Het
Mcm5 C T 8: 75,844,168 (GRCm39) S313F probably benign Het
Mdfic T A 6: 15,799,852 (GRCm39) C326* probably null Het
Ncoa1 T A 12: 4,340,912 (GRCm39) D840V probably benign Het
Nkd1 A G 8: 89,300,875 (GRCm39) D81G probably benign Het
Or5an1c T C 19: 12,218,606 (GRCm39) T140A probably benign Het
Or8c10 T C 9: 38,278,971 (GRCm39) V33A possibly damaging Het
Parp4 G A 14: 56,832,828 (GRCm39) E384K probably damaging Het
Pcdhgb4 T A 18: 37,854,895 (GRCm39) L430H probably damaging Het
Pdgfrb A G 18: 61,212,056 (GRCm39) Y861C probably damaging Het
Pheta1 G A 5: 121,991,051 (GRCm39) A138T probably benign Het
Pipox T A 11: 77,772,359 (GRCm39) Y337F probably benign Het
Prcc A G 3: 87,774,671 (GRCm39) V377A probably benign Het
Prrg2 T A 7: 44,706,218 (GRCm39) Y133F probably damaging Het
Ptchd3 T C 11: 121,733,813 (GRCm39) V901A probably damaging Het
Rgl1 A G 1: 152,424,869 (GRCm39) L335P probably damaging Het
Setx T A 2: 29,037,835 (GRCm39) M1440K probably benign Het
Smchd1 A G 17: 71,667,020 (GRCm39) probably null Het
Tbpl2 T C 2: 23,986,532 (GRCm39) I6V probably benign Het
Tdrd12 T A 7: 35,188,689 (GRCm39) H516L Het
Tmem8b C T 4: 43,673,938 (GRCm39) R190C probably damaging Het
Trp63 A G 16: 25,695,472 (GRCm39) N478S unknown Het
Vstm5 T G 9: 15,168,586 (GRCm39) I50S probably damaging Het
Wdhd1 A T 14: 47,505,616 (GRCm39) C285* probably null Het
Zdhhc23 A C 16: 43,794,062 (GRCm39) V204G probably benign Het
Zfp653 T A 9: 21,969,622 (GRCm39) K215* probably null Het
Other mutations in Tpmt
AlleleSourceChrCoordTypePredicted EffectPPH 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
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
Predicted Primers PCR Primer
(F):5'- AAACATAAGGAGTATAATGTCTACCCT -3'
(R):5'- ATGCTTCATCCTCACCTATCTGGATT -3'

Sequencing Primer
(F):5'- AGAGAACTGGCTTCCTGCAG -3'
(R):5'- CACCTATCTGGATTCCTGAGTGG -3'
Posted On 2022-07-18