Incidental Mutation 'R1373:Tpmt'
ID 157413
Institutional Source Beutler Lab
Gene Symbol Tpmt
Ensembl Gene ENSMUSG00000021376
Gene Name thiopurine methyltransferase
Synonyms
MMRRC Submission 039437-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R1373 (G1)
Quality Score 225
Status Validated
Chromosome 13
Chromosomal Location 47175463-47196833 bp(-) (GRCm39)
Type of Mutation splice site (1643 bp from exon)
DNA Base Change (assembly) A to C at 47180734 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change
Ref Sequence ENSEMBL: ENSMUSP00000121827 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000021806] [ENSMUST00000110118] [ENSMUST00000136864] [ENSMUST00000154802] [ENSMUST00000224970]
AlphaFold no structure available at present
Predicted Effect probably damaging
Transcript: ENSMUST00000021806
AA Change: L202V

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000021806
Gene: ENSMUSG00000021376
AA Change: L202V

DomainStartEndE-ValueType
Pfam:TPMT 19 240 4.1e-84 PFAM
Predicted Effect possibly damaging
Transcript: ENSMUST00000110118
AA Change: L202V

PolyPhen 2 Score 0.552 (Sensitivity: 0.88; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000105745
Gene: ENSMUSG00000021376
AA Change: L202V

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 probably benign
Transcript: ENSMUST00000151509
SMART Domains Protein: ENSMUSP00000120564
Gene: ENSMUSG00000021376

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

DomainStartEndE-ValueType
Pfam:TPMT 19 182 2.9e-62 PFAM
Predicted Effect silent
Transcript: ENSMUST00000224970
Predicted Effect noncoding transcript
Transcript: ENSMUST00000226060
Meta Mutation Damage Score 0.3673 question?
Coding Region Coverage
  • 1x: 99.3%
  • 3x: 98.5%
  • 10x: 97.0%
  • 20x: 95.2%
Validation Efficiency 94% (34/36)
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: 31 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adamdec1 G A 14: 68,808,400 (GRCm39) R317C probably damaging Het
Adgrl1 T C 8: 84,664,392 (GRCm39) V1261A probably benign Het
Btla G A 16: 45,044,783 (GRCm39) G23D probably benign Het
Card19 T C 13: 49,357,440 (GRCm39) D110G probably damaging Het
Cbx7 C T 15: 79,803,074 (GRCm39) G160R probably damaging Het
Ccng2 C T 5: 93,418,914 (GRCm39) probably benign Het
Col4a3 G A 1: 82,667,808 (GRCm39) probably benign Het
Colgalt2 A G 1: 152,348,912 (GRCm39) T186A probably damaging Het
Cps1 A G 1: 67,268,583 (GRCm39) N1437S possibly damaging Het
Dcaf1 A G 9: 106,735,079 (GRCm39) I676V probably benign Het
Dnah5 T A 15: 28,314,064 (GRCm39) probably benign Het
Dock1 T C 7: 134,768,904 (GRCm39) S1758P probably benign Het
Furin C T 7: 80,041,932 (GRCm39) probably benign Het
Ice2 G A 9: 69,314,401 (GRCm39) R50H probably benign Het
Ifi207 T A 1: 173,557,913 (GRCm39) D275V unknown Het
Nrxn2 C T 19: 6,522,331 (GRCm39) T190M probably damaging Het
Odad4 T C 11: 100,436,658 (GRCm39) F11S probably damaging Het
Or14j8 T C 17: 38,263,251 (GRCm39) I221M probably damaging Het
Or2ag17 C T 7: 106,389,963 (GRCm39) V82I probably benign Het
Pcnx3 A G 19: 5,715,544 (GRCm39) L1494P probably damaging Het
Pitrm1 G T 13: 6,620,736 (GRCm39) M739I probably benign Het
Rbm15 G T 3: 107,239,946 (GRCm39) R151S possibly damaging Het
Sfr1 C G 19: 47,723,355 (GRCm39) D286E possibly damaging Het
Slx4 A G 16: 3,803,374 (GRCm39) S1147P probably benign Het
Sry C G Y: 2,662,864 (GRCm39) Q265H unknown Het
Tgfbr3 T C 5: 107,362,809 (GRCm39) I68V probably benign Het
Trpm5 A G 7: 142,640,579 (GRCm39) probably benign Het
Txlnb A G 10: 17,714,695 (GRCm39) T376A probably damaging Het
Usp25 T C 16: 76,859,273 (GRCm39) probably benign Het
Vmn1r11 G A 6: 57,114,963 (GRCm39) C209Y probably benign Het
Vps13c A T 9: 67,834,793 (GRCm39) K1707N probably damaging 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
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'- catacacacatatacataCCTGCACACACTT -3'
(R):5'- cagccccTCCTTCTTGATTTCTTGTTT -3'

Sequencing Primer
(F):5'- gcacacatacacatatacatacacac -3'
(R):5'- ccctgaactcttgaccctg -3'
Posted On 2014-02-18