Mutagenetix > Incidental Mutation

Incidental Mutation 'R1918:Tdo2'

212681

Institutional Source

Beutler Lab

Gene Symbol

Tdo2

Ensembl Gene

ENSMUSG00000028011

Gene Name

tryptophan 2,3-dioxygenase

Synonyms

chky, TO, TDO

MMRRC Submission

039936-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.148) question?

Stock #

R1918 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

81957090-81976202 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 81958940 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Tryptophan at position 339 (R339W)

Ref Sequence

ENSEMBL: ENSMUSP00000141237 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000029645] [ENSMUST00000029649] [ENSMUST00000193879]

AlphaFold

P48776

Predicted Effect

probably damaging
Transcript: ENSMUST00000029645
AA Change: R358W

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000029645
Gene: ENSMUSG00000028011
AA Change: R358W

Domain	Start	End	E-Value	Type
Pfam:Trp_dioxygenase	26	372	8e-177	PFAM
low complexity region	393	406	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000029649

SMART Domains

Protein: ENSMUSP00000029649
Gene: ENSMUSG00000028015

Domain	Start	End	E-Value	Type
signal peptide	1	23	N/A	INTRINSIC
Pept_C1	99	311	2.21e-69	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000137974

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000151089

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000155144

Predicted Effect

probably damaging
Transcript: ENSMUST00000193879
AA Change: R339W

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000141237
Gene: ENSMUSG00000028011
AA Change: R339W

Domain	Start	End	E-Value	Type
Pfam:Trp_dioxygenase	7	353	1.4e-174	PFAM
low complexity region	374	387	N/A	INTRINSIC

Meta Mutation Damage Score

0.8489

Coding Region Coverage

1x: 97.5%
3x: 97.0%
10x: 95.7%
20x: 93.5%

Validation Efficiency

97% (113/116)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a heme enzyme that plays a critical role in tryptophan metabolism by catalyzing the first and rate-limiting step of the kynurenine pathway. Increased activity of the encoded protein and subsequent kynurenine production may also play a role in cancer through the suppression of antitumor immune responses, and single nucleotide polymorphisms in this gene may be associated with autism. [provided by RefSeq, Feb 2012]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit increased plasma and brain levels of tryptophan, increased serotonin levels in the brain, decreased anxiety-related behavior, increased neuronal precursor proliferation and accelerated neurogenesis in the granule cell layer of the olfactory bulb. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 116 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
3110035E14Rik	T	C	1: 9,601,627	F15S	probably damaging	Het
4930432E11Rik	T	G	7: 29,574,089		noncoding transcript	Het
4930435E12Rik	A	G	16: 38,828,088	Y220H	possibly damaging	Het
4931440F15Rik	A	G	11: 29,824,039	S473P	probably benign	Het
A2m	T	C	6: 121,644,936	S314P	probably benign	Het
Abcc9	T	A	6: 142,697,682	I47F	probably damaging	Het
Abcd2	C	T	15: 91,191,481	R43H	probably benign	Het
Adgre5	A	G	8: 83,729,109	V190A	probably damaging	Het
Aen	C	T	7: 78,906,029	H242Y	possibly damaging	Het
Arfgef1	C	T	1: 10,199,878	A349T	probably benign	Het
Arhgap10	T	C	8: 77,259,079	I698V	probably benign	Het
Arpp21	C	T	9: 112,119,178		probably benign	Het
Atp10a	T	C	7: 58,827,935	I1294T	possibly damaging	Het
Atp13a2	T	C	4: 140,996,371	Y337H	possibly damaging	Het
BC147527	T	C	13: 120,308,222	L26P	probably damaging	Het
Bsn	C	T	9: 108,107,573	G3094D	unknown	Het
Cadm2	G	A	16: 66,747,384		probably benign	Het
Cadps	T	C	14: 12,546,372	M495V	probably damaging	Het
Cass4	A	G	2: 172,427,339	H447R	possibly damaging	Het
Ccdc124	C	A	8: 70,868,944	R108L	probably benign	Het
Ccdc141	C	T	2: 77,014,703	R1340Q	probably benign	Het
Ccdc148	T	G	2: 58,982,899	R299S	probably damaging	Het
Ccdc36	T	A	9: 108,412,985	H140L	probably benign	Het
Cd300lg	A	G	11: 102,054,110	E382G	probably damaging	Het
Cd36	A	T	5: 17,797,036	C322*	probably null	Het
Celsr2	C	T	3: 108,398,650	G2046D	probably benign	Het
Clasrp	C	T	7: 19,585,263	W492*	probably null	Het
Cmtr1	T	C	17: 29,679,009	V154A	possibly damaging	Het
Ctnnb1	C	T	9: 120,951,034	P128S	possibly damaging	Het
Cyp11a1	A	G	9: 58,026,757	I496V	probably damaging	Het
Disp2	G	A	2: 118,791,927	V1047I	probably benign	Het
Eps8l2	T	C	7: 141,361,724	V636A	probably damaging	Het
Fars2	T	C	13: 36,204,546	L6P	probably damaging	Het
Fnip1	C	T	11: 54,480,684	T177I	probably damaging	Het
Fut8	G	T	12: 77,332,218	R31L	probably benign	Het
G6pd2	T	C	5: 61,810,321	F480L	probably benign	Het
Glipr1l2	T	A	10: 112,092,645	C148*	probably null	Het
Gm10142	G	A	10: 77,715,987	V61M	probably benign	Het
Gm12169	A	G	11: 46,528,531	D58G	possibly damaging	Het
Gm5134	T	A	10: 75,976,346	M145K	possibly damaging	Het
Gm853	A	T	4: 130,211,393	V328D	probably benign	Het
Gnpda1	T	C	18: 38,333,190		probably null	Het
Gpc2	T	C	5: 138,278,379	T162A	probably benign	Het
Gtf2h4	G	A	17: 35,670,198	L246F	possibly damaging	Het
Hal	C	T	10: 93,496,607	P294S	probably damaging	Het
Hectd3	C	T	4: 117,000,343	A573V	possibly damaging	Het
Hephl1	T	A	9: 15,076,818	I665F	probably benign	Het
Herc1	T	C	9: 66,476,126		probably null	Het
Hif1an	A	G	19: 44,571,112		probably null	Het
Il12rb1	T	A	8: 70,813,680	M223K	probably benign	Het
Ilf3	C	T	9: 21,393,714	T201M	probably damaging	Het
Inpp5f	T	C	7: 128,663,969		probably benign	Het
Jcad	T	C	18: 4,674,292	Y685H	probably damaging	Het
Kcnj1	C	A	9: 32,396,738	Q153K	probably benign	Het
Kctd18	A	C	1: 57,959,220	H73Q	probably damaging	Het
Klhl36	T	A	8: 119,876,724	W573R	probably damaging	Het
Lepr	A	G	4: 101,772,836	T583A	probably benign	Het
Ltbp4	G	A	7: 27,337,569		probably benign	Het
Mapt	A	T	11: 104,298,499	E114D	probably benign	Het
Mib1	T	A	18: 10,740,972		probably null	Het
Mthfd1	G	T	12: 76,314,976	A119S	probably damaging	Het
Mylk4	A	T	13: 32,724,853	D90E	probably benign	Het
Nceh1	T	G	3: 27,183,175	L33R	probably damaging	Het
Nfat5	T	C	8: 107,366,236	I91T	probably damaging	Het
Nxn	A	G	11: 76,261,672		probably benign	Het
Oasl1	G	A	5: 114,923,469	A20T	possibly damaging	Het
Olfr1262	T	C	2: 90,002,574	F56S	probably benign	Het
Olfr141	C	T	2: 86,806,827	M57I	probably damaging	Het
Olfr1428	A	G	19: 12,109,507	V13A	probably benign	Het
Olfr1447	A	G	19: 12,900,851	*310Q	probably null	Het
Olfr164	A	T	16: 19,286,302	M147K	probably benign	Het
Olfr791	T	A	10: 129,527,049	V274D	probably damaging	Het
Pepd	T	C	7: 34,971,676	V215A	probably benign	Het
Pfkl	A	T	10: 78,001,426	N104K	probably damaging	Het
Phf24	T	C	4: 42,938,165		probably benign	Het
Pink1	T	C	4: 138,314,020	N530S	probably benign	Het
Pou3f2	T	C	4: 22,487,119	D338G	probably damaging	Het
Ppp1r13b	A	G	12: 111,834,810	V480A	probably damaging	Het
Ptgfrn	A	T	3: 101,056,307	I663N	probably benign	Het
Rad54b	A	C	4: 11,601,693	N416T	probably damaging	Het
Rasef	A	G	4: 73,744,114	S200P	possibly damaging	Het
Rbm33	T	A	5: 28,387,917	I605N	probably damaging	Het
Rps19bp1	T	C	15: 80,264,079	T31A	probably benign	Het
Ryr2	T	A	13: 11,556,698	T4885S	possibly damaging	Het
Serpinb6b	A	G	13: 32,978,240	I222V	probably benign	Het
Sik3	C	G	9: 46,221,089	H1276Q	probably benign	Het
Skor2	T	C	18: 76,859,356	S258P	unknown	Het
Slc22a29	C	T	19: 8,217,759		probably null	Het
Slc8a3	A	T	12: 81,314,844	F400L	probably damaging	Het
Slc9a8	T	C	2: 167,424,214	I37T	possibly damaging	Het
Smchd1	A	G	17: 71,407,237	I877T	possibly damaging	Het
Spag5	A	G	11: 78,304,176	N103S	probably benign	Het
Sptbn1	A	T	11: 30,142,414	F450L	probably damaging	Het
Strn4	T	A	7: 16,833,921	Y507N	probably damaging	Het
Stxbp5	C	A	10: 9,812,298	V420F	possibly damaging	Het
Syt17	G	T	7: 118,433,985	L267I	possibly damaging	Het
Ttn	A	G	2: 76,741,401	S26383P	probably damaging	Het
Ttn	G	T	2: 76,808,524	T13938K	probably damaging	Het
Tulp2	A	G	7: 45,517,941	N188D	possibly damaging	Het
Ube3c	C	T	5: 29,587,317	R37C	probably damaging	Het
Uggt2	G	T	14: 119,008,055		probably benign	Het
Umodl1	G	A	17: 30,984,043	V457M	probably damaging	Het
Usp17la	C	T	7: 104,860,746	T186I	probably benign	Het
Vmn1r226	T	C	17: 20,687,580	S25P	probably damaging	Het
Vmn1r235	T	A	17: 21,262,397	I328K	possibly damaging	Het
Vmn2r50	A	T	7: 10,047,683	S378R	probably benign	Het
Vwa2	C	T	19: 56,908,934	T557I	probably benign	Het
Wdr60	A	C	12: 116,232,601	S509A	probably damaging	Het
Yes1	G	T	5: 32,684,735	Q534H	probably benign	Het
Zbtb25	A	T	12: 76,349,301	Y382*	probably null	Het
Zc3h3	G	A	15: 75,777,118	P722S	probably damaging	Het
Zfp36l2	T	C	17: 84,186,736	T158A	probably damaging	Het
Zfp536	T	C	7: 37,480,199	T994A	probably damaging	Het
Zfp592	C	T	7: 81,037,420	Q824*	probably null	Het
Zfp629	C	A	7: 127,612,000	K212N	probably damaging	Het
Zfp930	C	A	8: 69,228,705	Q350K	probably benign	Het

Other mutations in Tdo2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02127:Tdo2	APN	3	81958925	missense	probably damaging	0.99
IGL02129:Tdo2	APN	3	81958925	missense	probably damaging	0.99
IGL02271:Tdo2	APN	3	81963917	splice site	probably benign
IGL02686:Tdo2	APN	3	81968155	missense	probably benign	0.00
IGL02802:Tdo2	APN	3	81975697	intron	probably benign
IGL03171:Tdo2	APN	3	81967029	missense	probably benign
IGL03285:Tdo2	APN	3	81958789	splice site	probably null
R0052:Tdo2	UTSW	3	81967025	missense	probably benign	0.37
R0052:Tdo2	UTSW	3	81967025	missense	probably benign	0.37
R0335:Tdo2	UTSW	3	81964000	missense	probably benign
R0720:Tdo2	UTSW	3	81962758	missense	probably damaging	1.00
R1174:Tdo2	UTSW	3	81974376	missense	probably damaging	1.00
R1175:Tdo2	UTSW	3	81974376	missense	probably damaging	1.00
R1222:Tdo2	UTSW	3	81961468	splice site	probably null
R1418:Tdo2	UTSW	3	81961468	splice site	probably null
R1868:Tdo2	UTSW	3	81960546	missense	probably benign	0.04
R2031:Tdo2	UTSW	3	81969505	missense	probably damaging	1.00
R2513:Tdo2	UTSW	3	81969505	missense	possibly damaging	0.91
R3615:Tdo2	UTSW	3	81975428	missense	possibly damaging	0.68
R3616:Tdo2	UTSW	3	81975428	missense	possibly damaging	0.68
R3872:Tdo2	UTSW	3	81968086	missense	probably benign	0.08
R5260:Tdo2	UTSW	3	81975323	critical splice donor site	probably null
R5547:Tdo2	UTSW	3	81958940	missense	probably damaging	1.00
R6029:Tdo2	UTSW	3	81961440	missense	probably damaging	1.00
R6089:Tdo2	UTSW	3	81962728	missense	probably damaging	1.00
R6163:Tdo2	UTSW	3	81975403	missense	possibly damaging	0.49
R6379:Tdo2	UTSW	3	81958795	unclassified	probably benign
R7060:Tdo2	UTSW	3	81969559	missense	probably damaging	1.00
R7544:Tdo2	UTSW	3	81971635	critical splice donor site	probably null
R7585:Tdo2	UTSW	3	81962758	missense	probably damaging	1.00
R7724:Tdo2	UTSW	3	81968083	critical splice donor site	probably null
R8942:Tdo2	UTSW	3	81969544	missense	probably benign	0.22
R9276:Tdo2	UTSW	3	81969578	missense	probably benign
R9612:Tdo2	UTSW	3	81971694	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- GAGAATCCTGTAGTTTTCACTGATG -3'
(R):5'- AATCTGTATCACTCTGGTTTGAATC -3'

Sequencing Primer
(F):5'- TACTCGGCTGTGTAAAGG -3'
(R):5'- CTGGGAAGTGATTAACATTTACA -3'

Posted On

2014-07-14