Mutagenetix > Incidental Mutation

Incidental Mutation 'R1640:Tpmt'

173486

Institutional Source

Beutler Lab

Gene Symbol

Tpmt

Ensembl Gene

ENSMUSG00000021376

Gene Name

thiopurine methyltransferase

Synonyms

MMRRC Submission

039676-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1640 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

47175463-47196833 bp(-) (GRCm39)

Type of Mutation

nonsense

DNA Base Change (assembly)

A to T at 47180759 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Stop codon at position 193 (Y193*)

Ref Sequence

ENSEMBL: ENSMUSP00000105745 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000021806] [ENSMUST00000110118] [ENSMUST00000136864] [ENSMUST00000154802] [ENSMUST00000224970]

AlphaFold

no structure available at present

Predicted Effect

probably null
Transcript: ENSMUST00000021806
AA Change: Y193*

SMART Domains

Protein: ENSMUSP00000021806
Gene: ENSMUSG00000021376
AA Change: Y193*

Domain	Start	End	E-Value	Type
Pfam:TPMT	19	240	4.1e-84	PFAM

Predicted Effect

probably null
Transcript: ENSMUST00000110118
AA Change: Y193*

SMART Domains

Protein: ENSMUSP00000105745
Gene: ENSMUSG00000021376
AA Change: Y193*

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

Predicted Effect

probably benign
Transcript: ENSMUST00000136864

SMART Domains

Protein: ENSMUSP00000120081
Gene: ENSMUSG00000021376

Domain	Start	End	E-Value	Type
Pfam:TPMT	19	188	3.6e-65	PFAM

Predicted Effect

unknown
Transcript: ENSMUST00000151509
AA Change: C184S

SMART Domains

Protein: ENSMUSP00000120564
Gene: ENSMUSG00000021376
AA Change: C184S

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

Predicted Effect

probably benign
Transcript: ENSMUST00000154802

SMART Domains

Protein: ENSMUSP00000121827
Gene: ENSMUSG00000021376

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

Predicted Effect

unknown
Transcript: ENSMUST00000224970
AA Change: M22K

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000226060

Coding Region Coverage

1x: 99.1%
3x: 98.3%
10x: 96.1%
20x: 92.2%

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: 81 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2810004N23Rik	C	A	8: 125,566,584 (GRCm39)	V279L	probably damaging	Het
Acot6	A	T	12: 84,147,900 (GRCm39)	Y52F	probably damaging	Het
Adam22	C	T	5: 8,195,689 (GRCm39)	V284I	probably damaging	Het
Agl	A	T	3: 116,545,739 (GRCm39)	H1352Q	probably benign	Het
Aldh18a1	G	A	19: 40,573,943 (GRCm39)	P27S	probably benign	Het
C1ra	A	G	6: 124,499,233 (GRCm39)	N473S	probably benign	Het
C87436	T	C	6: 86,423,233 (GRCm39)	L269P	probably damaging	Het
Calcrl	A	G	2: 84,164,021 (GRCm39)	V390A	probably damaging	Het
Ccp110	T	G	7: 118,314,751 (GRCm39)		probably null	Het
Cerk	A	G	15: 86,033,601 (GRCm39)	V274A	probably damaging	Het
Chd1l	A	T	3: 97,488,307 (GRCm39)	S570T	probably benign	Het
Chst14	T	A	2: 118,757,379 (GRCm39)	W83R	probably damaging	Het
Chsy1	A	T	7: 65,821,262 (GRCm39)	D499V	probably benign	Het
Ckmt1	C	A	2: 121,190,198 (GRCm39)		probably null	Het
Cnot1	A	T	8: 96,496,460 (GRCm39)	V282D	probably damaging	Het
Cntn3	A	T	6: 102,218,974 (GRCm39)	S549T	possibly damaging	Het
Cntnap5c	A	T	17: 58,702,289 (GRCm39)	D1203V	probably benign	Het
Col4a4	A	G	1: 82,513,491 (GRCm39)	Y169H	unknown	Het
Cwc22	A	G	2: 77,745,874 (GRCm39)	F454S	possibly damaging	Het
Dab1	C	T	4: 104,588,948 (GRCm39)	A524V	probably benign	Het
Dhrs7	A	T	12: 72,699,089 (GRCm39)	W298R	possibly damaging	Het
Dock7	G	T	4: 98,833,483 (GRCm39)	T1906N	probably damaging	Het
Dpy19l3	T	C	7: 35,449,203 (GRCm39)	T67A	probably benign	Het
Drc1	A	G	5: 30,521,301 (GRCm39)	D654G	possibly damaging	Het
Ech1	A	T	7: 28,531,264 (GRCm39)	H284L	probably damaging	Het
Epc1	G	A	18: 6,441,175 (GRCm39)	Q8*	probably null	Het
Etv5	A	T	16: 22,254,664 (GRCm39)	D65E	probably damaging	Het
F2rl3	A	G	8: 73,489,534 (GRCm39)	R254G	probably benign	Het
Fabp5	T	G	3: 10,080,170 (GRCm39)	F73L	probably benign	Het
Fbrs	T	C	7: 127,086,483 (GRCm39)	I611T	probably damaging	Het
Flnc	T	C	6: 29,433,806 (GRCm39)	S117P	possibly damaging	Het
Frmd4b	A	C	6: 97,285,634 (GRCm39)	S291A	possibly damaging	Het
Galnt13	A	G	2: 54,950,558 (GRCm39)	Y413C	probably damaging	Het
Gfer	A	G	17: 24,914,337 (GRCm39)	Y109H	possibly damaging	Het
Gli2	T	C	1: 118,764,254 (GRCm39)	H1299R	possibly damaging	Het
Gm10110	T	C	14: 90,135,679 (GRCm39)		noncoding transcript	Het
Gprc5a	T	G	6: 135,055,652 (GRCm39)	L33W	probably damaging	Het
Grin3a	T	C	4: 49,844,721 (GRCm39)	T121A	probably benign	Het
Grk3	A	G	5: 113,163,248 (GRCm39)	V33A	probably benign	Het
Hc	A	T	2: 34,947,336 (GRCm39)	Y59*	probably null	Het
Hrnr	A	G	3: 93,239,823 (GRCm39)	I3354V	unknown	Het
Hyou1	C	G	9: 44,300,703 (GRCm39)	T924S	probably benign	Het
Ifi209	T	G	1: 173,464,931 (GRCm39)	H20Q	probably damaging	Het
Ifi44	A	G	3: 151,438,171 (GRCm39)	V372A	probably benign	Het
Igdcc4	T	A	9: 65,030,077 (GRCm39)	L328H	probably damaging	Het
Jkampl	A	G	6: 73,445,869 (GRCm39)	Y227H	probably benign	Het
Kif18a	A	G	2: 109,120,161 (GRCm39)	T155A	probably benign	Het
Kmt2d	A	G	15: 98,742,938 (GRCm39)		probably benign	Het
Kri1	T	C	9: 21,191,753 (GRCm39)	D281G	possibly damaging	Het
Larp1b	T	A	3: 40,988,507 (GRCm39)	M1K	probably null	Het
Loxhd1	A	G	18: 77,490,259 (GRCm39)	D1225G	probably damaging	Het
Mzf1	A	G	7: 12,777,197 (GRCm39)	*736Q	probably null	Het
Naip2	C	T	13: 100,298,489 (GRCm39)	A516T	possibly damaging	Het
Ncf2	T	A	1: 152,683,784 (GRCm39)	M1K	probably null	Het
Or5t15	T	A	2: 86,681,571 (GRCm39)	H157L	probably benign	Het
Or8h10	A	C	2: 86,808,963 (GRCm39)	M59R	probably damaging	Het
Parp12	T	C	6: 39,073,574 (GRCm39)	D417G	probably benign	Het
Parp12	T	C	6: 39,088,612 (GRCm39)	H208R	probably damaging	Het
Pcif1	T	C	2: 164,727,603 (GRCm39)	I132T	probably benign	Het
Pck2	A	G	14: 55,786,041 (GRCm39)	D610G	possibly damaging	Het
Plbd1	T	C	6: 136,617,123 (GRCm39)	K185E	probably benign	Het
Ppp2r5a	T	C	1: 191,086,126 (GRCm39)	M425V	probably damaging	Het
Rapgef6	T	A	11: 54,548,231 (GRCm39)	V805D	probably damaging	Het
Rprd2	C	T	3: 95,671,059 (GRCm39)		probably benign	Het
Ryr3	A	G	2: 112,731,178 (GRCm39)	S711P	probably damaging	Het
Slc17a3	T	A	13: 24,036,340 (GRCm39)	L212*	probably null	Het
Slc4a8	A	G	15: 100,681,668 (GRCm39)	D41G	probably benign	Het
Slc9a3	T	A	13: 74,306,937 (GRCm39)	V354E	probably damaging	Het
Spen	A	G	4: 141,196,254 (GRCm39)	I3632T	probably damaging	Het
Tesc	A	G	5: 118,192,914 (GRCm39)	S77G	probably benign	Het
Tet3	A	T	6: 83,346,297 (GRCm39)	V1245D	probably benign	Het
Tox4	T	A	14: 52,530,000 (GRCm39)	D553E	possibly damaging	Het
Trio	T	C	15: 27,833,130 (GRCm39)	Y1169C	probably damaging	Het
Urb1	G	A	16: 90,569,514 (GRCm39)	T1404I	probably benign	Het
Usp47	T	C	7: 111,682,334 (GRCm39)	S540P	probably damaging	Het
Vmn1r178	A	T	7: 23,593,548 (GRCm39)	M126L	possibly damaging	Het
Vmn1r223	T	C	13: 23,434,348 (GRCm39)	F314S	probably damaging	Het
Vmn2r112	A	T	17: 22,824,097 (GRCm39)	I451L	probably benign	Het
Zfc3h1	A	G	10: 115,242,806 (GRCm39)		probably null	Het
Zfp503	A	T	14: 22,034,969 (GRCm39)	L649Q	probably damaging	Het
Zfp977	A	C	7: 42,229,530 (GRCm39)	C332G	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
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'- accagccccTCCTTCTTGATTTCTT -3'

Sequencing Primer
(F):5'- gcacacatacacatatacatacacac -3'
(R):5'- ccctgaactcttgaccctg -3'

Posted On

2014-04-24