Mutagenetix > Incidental Mutation

Incidental Mutation 'R0485:Tph1'

42208

Institutional Source

Beutler Lab

Gene Symbol

Tph1

Ensembl Gene

ENSMUSG00000040046

Gene Name

tryptophan hydroxylase 1

Synonyms

MMRRC Submission

038684-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.146) question?

Stock #

R0485 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

46294065-46321961 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 46299448 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Lysine to Asparagine at position 364 (K364N)

Ref Sequence

ENSEMBL: ENSMUSP00000103296 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000049298] [ENSMUST00000107669] [ENSMUST00000170251]

AlphaFold

P17532

Predicted Effect

probably benign
Transcript: ENSMUST00000049298
AA Change: K364N

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000037752
Gene: ENSMUSG00000040046
AA Change: K364N

Domain	Start	End	E-Value	Type
Pfam:ACT	21	87	4.3e-8	PFAM
Pfam:Biopterin_H	109	440	4.7e-188	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000107669
AA Change: K364N

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000103296
Gene: ENSMUSG00000040046
AA Change: K364N

Domain	Start	End	E-Value	Type
Pfam:Biopterin_H	109	439	7.6e-176	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000110264

Predicted Effect

probably benign
Transcript: ENSMUST00000170251

SMART Domains

Protein: ENSMUSP00000132489
Gene: ENSMUSG00000040046

Domain	Start	End	E-Value	Type
Pfam:ACT	21	87	6.7e-8	PFAM
Pfam:Biopterin_H	109	279	3e-97	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000172386

SMART Domains

Protein: ENSMUSP00000128727
Gene: ENSMUSG00000040046

Domain	Start	End	E-Value	Type
Pfam:ACT	17	82	6.9e-9	PFAM
Pfam:Biopterin_H	105	164	8.9e-24	PFAM
low complexity region	175	188	N/A	INTRINSIC

Meta Mutation Damage Score

0.0627

Coding Region Coverage

1x: 99.1%
3x: 98.3%
10x: 96.3%
20x: 92.4%

Validation Efficiency

100% (95/95)

MGI Phenotype

FUNCTION: This gene encodes a member of the biopterin-dependent aromatic amino acid hydroxylase family. The encoded protein is one of two tryptophan hydroxylase enzymes that catalyze the first and rate limiting step in the biosynthesis of the hormone and neurotransmitter, serotonin. This gene is expressed in peripheral organs, while tryptophan hydroxylase 2 is expressed in neurons. The encoded protein is involved in the development of hypoxia-induced elevations in pulmonary pressures and pulmonary vascular remodeling, and has also been implicated as a regulator of immune tolerance. Disruption of this gene is associated with cardiac dysfunction. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2013]
PHENOTYPE: Mice homozygous for one null allele display no gross behavioral abnormalities. Mice homozygous for a second null allele display fatigue, breathing difficulties, progressive pallor, and impaired cardiac function. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 89 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700037C18Rik	A	G	16: 3,725,511 (GRCm39)	V5A	probably damaging	Het
Abi3bp	A	G	16: 56,424,375 (GRCm39)		probably null	Het
Acot11	G	A	4: 106,619,224 (GRCm39)	R184C	probably damaging	Het
Adgre5	A	T	8: 84,458,627 (GRCm39)	I133N	probably damaging	Het
Afap1	A	T	5: 36,108,347 (GRCm39)	Q231L	probably damaging	Het
Alg12	T	C	15: 88,695,630 (GRCm39)	T289A	probably benign	Het
Ank3	T	A	10: 69,718,374 (GRCm39)	S542T	possibly damaging	Het
Ankmy2	G	A	12: 36,232,389 (GRCm39)	R138Q	possibly damaging	Het
Ascc2	C	T	11: 4,622,302 (GRCm39)	A456V	probably benign	Het
Atg4c	G	A	4: 99,112,719 (GRCm39)	V289I	probably benign	Het
Bbs7	A	T	3: 36,657,022 (GRCm39)	Y269N	probably damaging	Het
Bcas3	T	A	11: 85,386,676 (GRCm39)	D370E	probably damaging	Het
Bicc1	T	G	10: 70,761,145 (GRCm39)	E955A	probably damaging	Het
Bok	T	C	1: 93,616,999 (GRCm39)	F115S	probably damaging	Het
Caap1	A	T	4: 94,438,758 (GRCm39)		probably null	Het
Cacna2d3	T	A	14: 29,256,476 (GRCm39)	M95L	possibly damaging	Het
Calcrl	T	A	2: 84,200,435 (GRCm39)	D115V	probably benign	Het
Car7	A	T	8: 105,270,170 (GRCm39)	M57L	probably benign	Het
Casq1	G	T	1: 172,037,957 (GRCm39)		probably benign	Het
Cep290	A	T	10: 100,385,206 (GRCm39)	D1894V	possibly damaging	Het
Clec4a2	T	A	6: 123,100,588 (GRCm39)	N14K	probably damaging	Het
Col16a1	G	T	4: 129,984,290 (GRCm39)		probably benign	Het
Col5a1	T	C	2: 27,880,109 (GRCm39)		probably benign	Het
Col5a2	A	T	1: 45,417,642 (GRCm39)	I1311N	probably damaging	Het
Col5a3	T	C	9: 20,694,004 (GRCm39)	T1050A	probably damaging	Het
Colgalt2	A	T	1: 152,360,622 (GRCm39)	I220F	probably damaging	Het
Cpb1	A	T	3: 20,329,792 (GRCm39)	V8E	unknown	Het
Dchs1	C	T	7: 105,421,934 (GRCm39)	R162H	probably benign	Het
Dhx37	A	G	5: 125,499,295 (GRCm39)	Y638H	probably benign	Het
Dhx40	T	G	11: 86,662,088 (GRCm39)		probably benign	Het
Ehd2	T	A	7: 15,686,001 (GRCm39)	Q357L	probably benign	Het
Ewsr1	T	C	11: 5,020,737 (GRCm39)		probably benign	Het
Fcho1	C	T	8: 72,165,204 (GRCm39)	A418T	probably benign	Het
Gid8	T	A	2: 180,355,004 (GRCm39)	Y3*	probably null	Het
Gm10212	A	C	19: 11,548,174 (GRCm39)		noncoding transcript	Het
Grin3b	T	A	10: 79,809,890 (GRCm39)	N465K	possibly damaging	Het
H1f3	A	T	13: 23,739,924 (GRCm39)	K221*	probably null	Het
Htr4	A	T	18: 62,561,225 (GRCm39)	N162I	probably damaging	Het
Irag2	T	C	6: 145,110,938 (GRCm39)	C248R	probably damaging	Het
Itga3	T	C	11: 94,952,796 (GRCm39)	D325G	probably benign	Het
Itpr3	T	G	17: 27,330,903 (GRCm39)	V1737G	probably damaging	Het
Kcnab2	C	T	4: 152,479,439 (GRCm39)	V251I	probably benign	Het
Kcnn2	A	T	18: 45,693,215 (GRCm39)	I264L	probably benign	Het
Klhl41	T	C	2: 69,501,600 (GRCm39)	Y354H	probably damaging	Het
Klra6	T	C	6: 130,000,601 (GRCm39)	I68V	probably benign	Het
Letm2	G	T	8: 26,082,574 (GRCm39)	P178Q	probably damaging	Het
Lypd11	C	A	7: 24,422,170 (GRCm39)	C193F	possibly damaging	Het
Mbtps1	A	T	8: 120,249,340 (GRCm39)		probably benign	Het
Mecom	C	T	3: 30,035,121 (GRCm39)		probably benign	Het
Mrps5	T	A	2: 127,433,745 (GRCm39)	S45T	possibly damaging	Het
Msra	T	A	14: 64,678,210 (GRCm39)	I29F	possibly damaging	Het
Mup5	T	C	4: 61,751,229 (GRCm39)		probably null	Het
Myo1a	T	C	10: 127,555,111 (GRCm39)		probably benign	Het
Myrip	C	A	9: 120,270,443 (GRCm39)	N564K	probably benign	Het
Naa20	T	A	2: 145,757,592 (GRCm39)	D148E	probably damaging	Het
Naga	T	G	15: 82,220,956 (GRCm39)		probably benign	Het
Npc1	A	G	18: 12,346,503 (GRCm39)	V231A	probably benign	Het
Nphs1	T	C	7: 30,166,940 (GRCm39)	F716L	probably benign	Het
Or8s5	T	C	15: 98,238,810 (GRCm39)	H20R	probably benign	Het
Parn	G	C	16: 13,472,299 (GRCm39)		probably benign	Het
Polk	A	T	13: 96,620,272 (GRCm39)	C664S	probably benign	Het
Prkar2b	A	G	12: 32,026,034 (GRCm39)		probably benign	Het
Prkdc	A	G	16: 15,651,604 (GRCm39)	E3747G	probably damaging	Het
Prmt5	A	T	14: 54,748,712 (GRCm39)	M362K	probably damaging	Het
Prob1	T	C	18: 35,786,878 (GRCm39)	T459A	possibly damaging	Het
Rttn	C	T	18: 89,108,543 (GRCm39)		probably benign	Het
Scn1a	T	C	2: 66,104,269 (GRCm39)	M1664V	probably damaging	Het
Sez6	T	A	11: 77,844,639 (GRCm39)	L154H	probably damaging	Het
Sh3tc1	A	G	5: 35,859,356 (GRCm39)		probably benign	Het
Shkbp1	C	T	7: 27,048,006 (GRCm39)	G334D	probably damaging	Het
Slc8a1	A	T	17: 81,955,422 (GRCm39)	F539I	probably damaging	Het
Spata31e5	G	T	1: 28,817,223 (GRCm39)	Q270K	probably damaging	Het
Sptan1	T	C	2: 29,903,860 (GRCm39)		probably benign	Het
Ssc5d	C	T	7: 4,940,470 (GRCm39)	T861M	probably damaging	Het
Tbx5	A	T	5: 120,021,523 (GRCm39)	M510L	probably benign	Het
Tdp1	A	G	12: 99,876,101 (GRCm39)	T351A	probably benign	Het
Tmc8	T	A	11: 117,682,904 (GRCm39)		probably benign	Het
Tmco5	T	A	2: 116,720,588 (GRCm39)	D205E	probably benign	Het
Tmprss2	T	C	16: 97,373,194 (GRCm39)		probably benign	Het
Top6bl	A	T	19: 4,708,442 (GRCm39)	I350N	probably damaging	Het
Trim24	T	C	6: 37,934,001 (GRCm39)	L648P	probably damaging	Het
Trmt6	C	A	2: 132,650,950 (GRCm39)		probably benign	Het
Ube2i	A	T	17: 25,488,259 (GRCm39)		probably benign	Het
Vcan	A	C	13: 89,852,779 (GRCm39)	L727R	possibly damaging	Het
Vmn2r28	T	C	7: 5,491,689 (GRCm39)	Y186C	probably damaging	Het
Wars1	C	A	12: 108,841,083 (GRCm39)	D232Y	probably damaging	Het
Xrcc5	T	C	1: 72,378,104 (GRCm39)		probably benign	Het
Zbtb24	T	A	10: 41,340,532 (GRCm39)	S543T	probably damaging	Het
Zfp91	A	G	19: 12,753,353 (GRCm39)		probably benign	Het

Other mutations in Tph1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00226:Tph1	APN	7	46,306,294 (GRCm39)	missense	probably benign	0.02
IGL01318:Tph1	APN	7	46,314,662 (GRCm39)	missense	probably damaging	0.99
IGL01538:Tph1	APN	7	46,303,177 (GRCm39)	missense	probably damaging	1.00
IGL01564:Tph1	APN	7	46,300,305 (GRCm39)	splice site	probably benign
IGL02021:Tph1	APN	7	46,306,421 (GRCm39)	missense	possibly damaging	0.55
IGL02202:Tph1	APN	7	46,303,185 (GRCm39)	missense	probably benign	0.40
IGL03072:Tph1	APN	7	46,302,283 (GRCm39)	missense	probably damaging	0.99
I1329:Tph1	UTSW	7	46,299,437 (GRCm39)	missense	probably damaging	0.99
R0166:Tph1	UTSW	7	46,297,020 (GRCm39)	missense	probably damaging	1.00
R0433:Tph1	UTSW	7	46,303,245 (GRCm39)	missense	probably damaging	1.00
R0501:Tph1	UTSW	7	46,299,412 (GRCm39)	nonsense	probably null
R1456:Tph1	UTSW	7	46,296,907 (GRCm39)	nonsense	probably null
R1474:Tph1	UTSW	7	46,303,286 (GRCm39)	missense	probably benign	0.00
R1846:Tph1	UTSW	7	46,309,863 (GRCm39)	missense	probably damaging	0.98
R1967:Tph1	UTSW	7	46,311,538 (GRCm39)	missense	probably benign	0.30
R2102:Tph1	UTSW	7	46,309,834 (GRCm39)	splice site	probably null
R2176:Tph1	UTSW	7	46,311,463 (GRCm39)	missense	possibly damaging	0.91
R2225:Tph1	UTSW	7	46,314,598 (GRCm39)	critical splice donor site	probably null
R4773:Tph1	UTSW	7	46,306,376 (GRCm39)	missense	probably damaging	1.00
R4914:Tph1	UTSW	7	46,303,283 (GRCm39)	missense	probably damaging	1.00
R5590:Tph1	UTSW	7	46,303,216 (GRCm39)	missense	probably damaging	1.00
R5622:Tph1	UTSW	7	46,296,969 (GRCm39)	nonsense	probably null
R5960:Tph1	UTSW	7	46,311,429 (GRCm39)	critical splice donor site	probably null
R5985:Tph1	UTSW	7	46,303,205 (GRCm39)	missense	probably damaging	1.00
R6362:Tph1	UTSW	7	46,296,867 (GRCm39)	missense	possibly damaging	0.94
R7151:Tph1	UTSW	7	46,311,541 (GRCm39)	missense	possibly damaging	0.93
R7329:Tph1	UTSW	7	46,306,285 (GRCm39)	splice site	probably null
R7395:Tph1	UTSW	7	46,306,627 (GRCm39)	splice site	probably null
R7975:Tph1	UTSW	7	46,306,678 (GRCm39)	missense	probably damaging	1.00
R8012:Tph1	UTSW	7	46,306,303 (GRCm39)	missense	probably damaging	1.00
R8169:Tph1	UTSW	7	46,303,233 (GRCm39)	synonymous	silent
R8261:Tph1	UTSW	7	46,303,173 (GRCm39)	synonymous	silent
R9232:Tph1	UTSW	7	46,311,529 (GRCm39)	missense	probably benign

Predicted Primers

PCR Primer
(F):5'- TGGGGAGGAACCAATGTCTCAGTG -3'
(R):5'- GTGCAGTCAGGACCCTTGTGTAAC -3'

Sequencing Primer
(F):5'- GAGGAACCAATGTCTCAGTGTATCC -3'
(R):5'- GGACCCTTGTGTAACTCAGATCAG -3'

Posted On

2013-05-23