Mutagenetix > Incidental Mutation

Incidental Mutation 'R7151:Tph1'

554129

Institutional Source

Beutler Lab

Gene Symbol

Tph1

Ensembl Gene

ENSMUSG00000040046

Gene Name

tryptophan hydroxylase 1

Synonyms

MMRRC Submission

045253-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.134) question?

Stock #

R7151 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

46294065-46321961 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 46311541 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Aspartic acid at position 67 (V67D)

Ref Sequence

ENSEMBL: ENSMUSP00000037752 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000049298] [ENSMUST00000107669] [ENSMUST00000168335] [ENSMUST00000170251]

AlphaFold

P17532

Predicted Effect

possibly damaging
Transcript: ENSMUST00000049298
AA Change: V67D

PolyPhen 2 Score 0.927 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000037752
Gene: ENSMUSG00000040046
AA Change: V67D

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

possibly damaging
Transcript: ENSMUST00000107669
AA Change: V67D

PolyPhen 2 Score 0.927 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000103296
Gene: ENSMUSG00000040046
AA Change: V67D

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

Predicted Effect

probably damaging
Transcript: ENSMUST00000168335
AA Change: V67D

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000128107
Gene: ENSMUSG00000040046
AA Change: V67D

Domain	Start	End	E-Value	Type
Pfam:ACT	21	87	3.7e-9	PFAM
Pfam:Biopterin_H	109	149	1.8e-11	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000170251
AA Change: V67D

PolyPhen 2 Score 0.971 (Sensitivity: 0.77; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000132489
Gene: ENSMUSG00000040046
AA Change: V67D

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

Predicted Effect

SMART Domains

Protein: ENSMUSP00000128727
Gene: ENSMUSG00000040046
AA Change: V62D

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

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.7%

Validation Efficiency

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: 74 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
6330409D20Rik	T	A	2: 32,630,618 (GRCm39)	Q52L	unknown	Het
Acsl1	A	G	8: 46,966,634 (GRCm39)	D202G	probably damaging	Het
Adam3	A	T	8: 25,185,271 (GRCm39)	C476S	probably damaging	Het
Adam34	T	A	8: 44,104,499 (GRCm39)	E382V	probably benign	Het
Akap5	G	A	12: 76,375,023 (GRCm39)	V152I	probably benign	Het
Aldh5a1	C	T	13: 25,121,382 (GRCm39)	W57*	probably null	Het
Angptl2	C	T	2: 33,133,922 (GRCm39)	Q415*	probably null	Het
Bnc1	G	T	7: 81,623,055 (GRCm39)	T724N	possibly damaging	Het
Brca2	T	C	5: 150,464,901 (GRCm39)	V1555A	probably benign	Het
Btn1a1	T	A	13: 23,643,483 (GRCm39)	D322V	probably damaging	Het
Chsy3	T	A	18: 59,542,357 (GRCm39)	D498E	possibly damaging	Het
Ddx24	T	C	12: 103,390,347 (GRCm39)	T215A	probably benign	Het
Dhx57	A	T	17: 80,580,476 (GRCm39)	V492E	probably damaging	Het
Dnhd1	G	A	7: 105,359,234 (GRCm39)	R3523Q	probably benign	Het
Dock3	T	A	9: 106,841,916 (GRCm39)	D971V	possibly damaging	Het
Ercc8	T	C	13: 108,323,816 (GRCm39)		probably null	Het
Erich5	T	A	15: 34,471,095 (GRCm39)	L108Q	probably damaging	Het
F5	A	T	1: 164,029,230 (GRCm39)	Y1743F	probably damaging	Het
Gale	T	C	4: 135,694,503 (GRCm39)	V243A	probably damaging	Het
Gspt1	T	A	16: 11,071,692 (GRCm39)	Q57L	probably benign	Het
Gtf3a	C	A	5: 146,888,085 (GRCm39)	Q129K	probably benign	Het
Heyl	T	C	4: 123,140,254 (GRCm39)	V271A	probably benign	Het
Hsd17b4	T	C	18: 50,261,437 (GRCm39)	F7L	probably damaging	Het
Hspa12a	T	C	19: 58,810,594 (GRCm39)	T150A	probably benign	Het
Ift140	T	A	17: 25,274,699 (GRCm39)	D790E	probably damaging	Het
Igkv4-69	T	A	6: 69,260,917 (GRCm39)	Y70F	probably damaging	Het
Il1rap	T	C	16: 26,530,878 (GRCm39)	Y405H	probably damaging	Het
Insyn2a	A	C	7: 134,520,374 (GRCm39)	I52S	probably damaging	Het
Irf2bpl	G	T	12: 86,930,127 (GRCm39)	P182Q	probably benign	Het
Itm2b	C	A	14: 73,605,829 (GRCm39)		probably benign	Het
Kcnc2	T	C	10: 112,294,414 (GRCm39)	V106A	possibly damaging	Het
Krt87	C	A	15: 101,387,529 (GRCm39)	D170Y	probably damaging	Het
Lca5	T	A	9: 83,280,693 (GRCm39)	Y369F	probably benign	Het
Mgat5	T	A	1: 127,373,999 (GRCm39)	D466E	probably damaging	Het
Mier3	C	T	13: 111,851,302 (GRCm39)	P428L	probably benign	Het
Myo6	T	C	9: 80,152,418 (GRCm39)	Y167H	unknown	Het
Neu2	A	G	1: 87,524,297 (GRCm39)	E94G	probably benign	Het
Nlrp9a	A	T	7: 26,256,672 (GRCm39)	K97*	probably null	Het
Npdc1	A	G	2: 25,299,120 (GRCm39)	M306V	probably damaging	Het
Odf2l	A	T	3: 144,832,827 (GRCm39)	N95I	probably benign	Het
Or10j3	A	G	1: 173,031,633 (GRCm39)	K237E	probably damaging	Het
Or13d1	G	T	4: 52,970,665 (GRCm39)	V15L	probably benign	Het
Or5t16	A	G	2: 86,819,385 (GRCm39)	V45A	probably benign	Het
Or7g21	A	G	9: 19,033,037 (GRCm39)	Y259C	possibly damaging	Het
P2ry12	A	G	3: 59,125,127 (GRCm39)	F183L	probably benign	Het
Proser3	A	G	7: 30,239,749 (GRCm39)	F452L	possibly damaging	Het
Ptgfrn	G	T	3: 100,987,511 (GRCm39)	Y117*	probably null	Het
Rab3gap2	G	T	1: 184,980,250 (GRCm39)	V360F	probably benign	Het
Rp1l1	A	T	14: 64,266,475 (GRCm39)	D687V	possibly damaging	Het
Rxfp2	T	G	5: 149,966,572 (GRCm39)	N103K	probably benign	Het
Scfd2	T	A	5: 74,558,326 (GRCm39)	Q517L	possibly damaging	Het
Scnn1b	G	A	7: 121,517,109 (GRCm39)	A582T	probably damaging	Het
Serpinb6e	T	C	13: 34,021,818 (GRCm39)	E170G	probably damaging	Het
Serpinb8	T	A	1: 107,533,527 (GRCm39)	V194E	probably damaging	Het
Sgcz	T	A	8: 38,006,833 (GRCm39)	H191L	possibly damaging	Het
Sirt1	A	T	10: 63,159,775 (GRCm39)	L435Q	probably damaging	Het
Sorcs1	G	A	19: 50,301,420 (GRCm39)	P315S	probably damaging	Het
Spdef	T	A	17: 27,939,134 (GRCm39)	S71C	possibly damaging	Het
Spta1	T	A	1: 174,025,317 (GRCm39)	H727Q	probably damaging	Het
Srsf1	C	T	11: 87,940,084 (GRCm39)	Q199*	probably null	Het
Stard9	A	T	2: 120,526,623 (GRCm39)	D960V	probably benign	Het
Tcp10c	A	T	17: 13,576,166 (GRCm39)	I49F	possibly damaging	Het
Tgm2	T	C	2: 157,971,315 (GRCm39)	N308S	possibly damaging	Het
Tiam2	A	G	17: 3,498,660 (GRCm39)	D812G	probably benign	Het
Trps1	C	T	15: 50,685,793 (GRCm39)	R794H	possibly damaging	Het
Ttn	C	T	2: 76,683,505 (GRCm39)	A906T		Het
Vmn1r124	G	A	7: 20,994,184 (GRCm39)	P120L	probably benign	Het
Vmn2r92	A	T	17: 18,387,005 (GRCm39)	T115S	probably benign	Het
Wdr11	A	G	7: 129,208,376 (GRCm39)	D377G	probably damaging	Het
Wdr55	G	T	18: 36,895,989 (GRCm39)	A251S	possibly damaging	Het
Zbtb7b	C	T	3: 89,288,209 (GRCm39)	R203H	probably benign	Het
Zfp109	A	T	7: 23,929,231 (GRCm39)	H67Q	probably benign	Het
Zfp462	G	A	4: 55,051,271 (GRCm39)	C2248Y	probably damaging	Het
Zyg11b	T	C	4: 108,102,119 (GRCm39)	H534R	possibly damaging	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
R0485:Tph1	UTSW	7	46,299,448 (GRCm39)	missense	probably benign	0.00
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
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'- CAGAATTCTGATCGGCTCCAC -3'
(R):5'- AGCTGGTTCTCACAAGTGTTG -3'

Sequencing Primer
(F):5'- TCCCCTTGTCCTCAAAATGAATAGG -3'
(R):5'- AGCTGGTTCTCACAAGTGTTGAATTG -3'

Posted On

2019-05-15