Incidental Mutation 'R6228:Tpmt'
ID 504496
Institutional Source Beutler Lab
Gene Symbol Tpmt
Ensembl Gene ENSMUSG00000021376
Gene Name thiopurine methyltransferase
Synonyms
MMRRC Submission 044357-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R6228 (G1)
Quality Score 225.009
Status Validated
Chromosome 13
Chromosomal Location 47175463-47196833 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to A at 47180735 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Arginine to Serine at position 201 (R201S)
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: R201S

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)
SMART Domains Protein: ENSMUSP00000021806
Gene: ENSMUSG00000021376
AA Change: R201S

DomainStartEndE-ValueType
Pfam:TPMT 19 240 4.1e-84 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000110118
AA Change: R201S

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
SMART Domains Protein: ENSMUSP00000105745
Gene: ENSMUSG00000021376
AA Change: R201S

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 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: G30V
Predicted Effect noncoding transcript
Transcript: ENSMUST00000226060
Coding Region Coverage
  • 1x: 99.9%
  • 3x: 99.7%
  • 10x: 98.6%
  • 20x: 95.9%
Validation Efficiency 100% (93/93)
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: 93 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abcc6 G T 7: 45,679,680 (GRCm39) T9K probably benign Het
Ankrd28 T C 14: 31,429,177 (GRCm39) H925R probably damaging Het
Antxrl A T 14: 33,778,556 (GRCm39) T128S probably damaging Het
Atosa A G 9: 74,913,645 (GRCm39) M100V possibly damaging Het
Atp8b5 T C 4: 43,304,674 (GRCm39) Y62H probably damaging Het
Bmpr2 G T 1: 59,906,595 (GRCm39) V563L probably benign Het
Btn1a1 A T 13: 23,648,521 (GRCm39) L104Q probably damaging Het
Caskin1 C G 17: 24,726,154 (GRCm39) D1420E probably damaging Het
Cdc14a A T 3: 116,144,862 (GRCm39) I150N probably damaging Het
Cdc26 C T 4: 62,321,031 (GRCm39) R4Q probably damaging Het
Cfap46 T C 7: 139,236,496 (GRCm39) D160G probably damaging Het
Cxcr4 A C 1: 128,519,920 (GRCm39) probably null Het
Dab1 C T 4: 104,588,948 (GRCm39) A524V probably benign Het
Dgat1 T C 15: 76,387,493 (GRCm39) N317S possibly damaging Het
Disp1 G A 1: 182,880,589 (GRCm39) T228M possibly damaging Het
Dixdc1 A C 9: 50,614,656 (GRCm39) probably null Het
Dnase1l2 C A 17: 24,661,492 (GRCm39) probably benign Het
Dsg2 T C 18: 20,727,350 (GRCm39) probably null Het
Duox2 A T 2: 122,117,674 (GRCm39) F887I probably benign Het
Duxf4 A G 10: 58,071,344 (GRCm39) M290T probably benign Het
Efcab6 T C 15: 83,851,825 (GRCm39) D351G possibly damaging Het
Ep400 A G 5: 110,818,808 (GRCm39) V2621A probably damaging Het
Epg5 G T 18: 77,991,677 (GRCm39) V125F possibly damaging Het
Ephb1 T C 9: 101,800,783 (GRCm39) R953G probably damaging Het
Etfdh G T 3: 79,519,336 (GRCm39) Y272* probably null Het
Fam117b A G 1: 60,008,207 (GRCm39) E347G probably damaging Het
Gfra3 A T 18: 34,828,846 (GRCm39) C183S probably damaging Het
Gmip A G 8: 70,268,773 (GRCm39) D466G probably damaging Het
Golga5 G A 12: 102,450,740 (GRCm39) M464I probably benign Het
Gpd1 A T 15: 99,621,146 (GRCm39) Q320L possibly damaging Het
H2-Oa G T 17: 34,312,851 (GRCm39) D43Y probably damaging Het
Hecw1 T A 13: 14,520,623 (GRCm39) I205F probably damaging Het
Ighv8-13 A G 12: 115,728,973 (GRCm39) Y95H probably damaging Het
Igkv6-20 T C 6: 70,313,081 (GRCm39) M31V possibly damaging Het
Itih1 T C 14: 30,653,217 (GRCm39) D737G probably benign Het
Kcnc4 G C 3: 107,355,693 (GRCm39) H252D probably damaging Het
Kcnj14 T A 7: 45,468,921 (GRCm39) T195S probably damaging Het
Limch1 A T 5: 67,173,845 (GRCm39) D642V probably damaging Het
Lrp2 T G 2: 69,312,710 (GRCm39) D2526A possibly damaging Het
Lrrc8a A G 2: 30,146,565 (GRCm39) T460A possibly damaging Het
Lrrn4cl A G 19: 8,829,135 (GRCm39) T38A probably benign Het
Lypd8 A T 11: 58,277,629 (GRCm39) Q137L possibly damaging Het
Mapkapk3 A G 9: 107,137,262 (GRCm39) Y206H probably damaging Het
Mrc1 G A 2: 14,276,115 (GRCm39) G483D probably benign Het
Mrpl35 C A 6: 71,800,661 (GRCm39) probably benign Het
Mycbp2 T A 14: 103,497,665 (GRCm39) H936L probably benign Het
Myh3 A T 11: 66,978,312 (GRCm39) Y433F probably benign Het
Napb C T 2: 148,540,098 (GRCm39) probably null Het
Nbeal1 C A 1: 60,335,083 (GRCm39) Q2288K probably benign Het
Ndst3 G A 3: 123,465,301 (GRCm39) Q224* probably null Het
Nkapd1 A G 9: 50,518,971 (GRCm39) S214P possibly damaging Het
Nkd2 A G 13: 73,969,579 (GRCm39) S284P probably benign Het
Or10a2 T C 7: 106,673,343 (GRCm39) Y103H probably damaging Het
Or5b12 A T 19: 12,897,301 (GRCm39) V124E probably damaging Het
Or6k2 G A 1: 173,979,712 (GRCm39) S210N probably benign Het
Or8h10 T C 2: 86,809,035 (GRCm39) Y35C probably damaging Het
Pcdhb8 A G 18: 37,490,037 (GRCm39) T572A probably benign Het
Pcdhb9 A G 18: 37,535,115 (GRCm39) I370V probably benign Het
Pcsk5 T G 19: 17,558,631 (GRCm39) E592A possibly damaging Het
Pigc T C 1: 161,798,036 (GRCm39) V6A probably benign Het
Pla2g6 T G 15: 79,189,924 (GRCm39) I389L probably benign Het
Pnliprp2 T C 19: 58,751,874 (GRCm39) probably null Het
Psmb11 T C 14: 54,863,646 (GRCm39) V288A probably benign Het
Rapgef5 A G 12: 117,685,398 (GRCm39) probably null Het
Rcn3 T C 7: 44,732,720 (GRCm39) N316S probably damaging Het
Rgs6 A G 12: 83,112,738 (GRCm39) K183E probably damaging Het
Rhoc A G 3: 104,700,297 (GRCm39) probably null Het
Serinc5 T C 13: 92,844,616 (GRCm39) C453R probably damaging Het
Slc14a1 A C 18: 78,159,614 (GRCm39) M93R probably damaging Het
Slc25a3 A T 10: 90,958,090 (GRCm39) D83E probably damaging Het
Slc36a3 T C 11: 55,015,777 (GRCm39) Y459C probably benign Het
Slc44a5 A T 3: 153,944,800 (GRCm39) Y139F probably benign Het
Spag17 A T 3: 99,929,918 (GRCm39) Q539L probably benign Het
Stap2 C T 17: 56,306,976 (GRCm39) V234M probably damaging Het
Stard9 A G 2: 120,544,231 (GRCm39) Y4450C probably damaging Het
Taf6l C T 19: 8,756,030 (GRCm39) R206Q probably benign Het
Tbc1d23 C T 16: 57,003,266 (GRCm39) V501I probably damaging Het
Thap2 T C 10: 115,208,751 (GRCm39) H123R probably damaging Het
Tlx3 C A 11: 33,152,432 (GRCm39) W221L probably benign Het
Tmem262 T A 19: 6,130,567 (GRCm39) probably null Het
Trpm6 T C 19: 18,831,655 (GRCm39) S1507P probably damaging Het
Ttc9c T C 19: 8,795,847 (GRCm39) E64G possibly damaging Het
Ttn A T 2: 76,640,790 (GRCm39) S13653T probably damaging Het
Ugt3a1 G T 15: 9,310,726 (GRCm39) W336L possibly damaging Het
Vmn1r215 C A 13: 23,260,633 (GRCm39) N224K probably benign Het
Vmn2r59 C T 7: 41,691,835 (GRCm39) probably null Het
Wdfy3 A G 5: 102,046,295 (GRCm39) S1853P possibly damaging Het
Wdr36 A T 18: 32,975,059 (GRCm39) Y137F possibly damaging Het
Zdhhc17 T C 10: 110,792,216 (GRCm39) D324G probably benign Het
Zfp217 T C 2: 169,961,497 (GRCm39) T277A probably benign Het
Zfp451 A G 1: 33,842,219 (GRCm39) probably benign Het
Zfp709 TCGACG TCG 8: 72,644,552 (GRCm39) probably benign Het
Zfp871 T C 17: 32,994,858 (GRCm39) S106G possibly 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
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
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'- AAACATAAGGAGTATAATGTCTACCCT -3'
(R):5'- TGGATTCCTGAGTGGTTTACAGAATA -3'

Sequencing Primer
(F):5'- AGAGAACTGGCTTCCTGCAG -3'
(R):5'- CCTGAGTGGTTTACAGAATAAGTGTC -3'
Posted On 2018-02-28