Mutagenetix > Incidental Mutation

Incidental Mutation 'R2176:Tph1'

236877

Institutional Source

Beutler Lab

Gene Symbol

Tph1

Ensembl Gene

ENSMUSG00000040046

Gene Name

tryptophan hydroxylase 1

Synonyms

MMRRC Submission

040178-MU

Accession Numbers

Essential gene?

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

Stock #

R2176 (G1)

Quality Score

223

Status

Validated

Chromosome

Chromosomal Location

46294065-46321961 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 46311463 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Valine at position 88 (D88V)

Gene Model

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

AlphaFold

P17532

Predicted Effect

probably benign
Transcript: ENSMUST00000049298
AA Change: D93V

PolyPhen 2 Score 0.095 (Sensitivity: 0.93; Specificity: 0.85)

SMART Domains

Protein: ENSMUSP00000037752
Gene: ENSMUSG00000040046
AA Change: D93V

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: D93V

PolyPhen 2 Score 0.095 (Sensitivity: 0.93; Specificity: 0.85)

SMART Domains

Protein: ENSMUSP00000103296
Gene: ENSMUSG00000040046
AA Change: D93V

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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000163468

Predicted Effect

probably benign
Transcript: ENSMUST00000168335
AA Change: D93V

PolyPhen 2 Score 0.320 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000128107
Gene: ENSMUSG00000040046
AA Change: D93V

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

noncoding transcript
Transcript: ENSMUST00000170045

Predicted Effect

probably benign
Transcript: ENSMUST00000170251
AA Change: D93V

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000132489
Gene: ENSMUSG00000040046
AA Change: D93V

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

Predicted Effect

possibly damaging
Transcript: ENSMUST00000172386
AA Change: D88V

PolyPhen 2 Score 0.914 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000128727
Gene: ENSMUSG00000040046
AA Change: D88V

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

0.1795

Coding Region Coverage

1x: 99.2%
3x: 98.7%
10x: 97.5%
20x: 95.6%

Validation Efficiency

100% (64/64)

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: 65 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adam1a	T	A	5: 121,657,649 (GRCm39)	Y548F	probably benign	Het
Armc9	T	C	1: 86,127,614 (GRCm39)	L83P	probably damaging	Het
BC051665	A	T	13: 60,932,344 (GRCm39)		probably benign	Het
Casp3	A	G	8: 47,082,791 (GRCm39)	N3S	probably damaging	Het
Ccdc174	G	A	6: 91,865,070 (GRCm39)	M109I	probably benign	Het
Ccr6	T	A	17: 8,475,073 (GRCm39)	F93I	probably damaging	Het
Clvs2	T	C	10: 33,471,811 (GRCm39)	S165G	probably damaging	Het
Cntnap5c	T	C	17: 58,320,941 (GRCm39)	V171A	probably benign	Het
Dennd5a	C	A	7: 109,504,327 (GRCm39)		probably null	Het
Dock2	T	A	11: 34,586,044 (GRCm39)	Y546F	probably benign	Het
Fat2	A	G	11: 55,158,401 (GRCm39)		probably null	Het
Focad	T	A	4: 88,197,481 (GRCm39)	Y625N	unknown	Het
Fyb1	A	G	15: 6,609,435 (GRCm39)	K3E	probably damaging	Het
Gm14496	G	A	2: 181,633,130 (GRCm39)	D38N	probably benign	Het
Gm20403	T	C	12: 55,033,155 (GRCm39)	T54A	probably benign	Het
Gm9830	A	G	9: 44,375,556 (GRCm39)		noncoding transcript	Het
Hectd1	A	T	12: 51,792,277 (GRCm39)	S2487R	probably damaging	Het
Il5ra	A	G	6: 106,715,233 (GRCm39)	L175S	probably benign	Het
Inhca	A	G	9: 103,136,566 (GRCm39)		probably benign	Het
Itgav	C	T	2: 83,633,599 (GRCm39)	R983C	probably damaging	Het
Kcna10	T	C	3: 107,102,032 (GRCm39)	V221A	probably damaging	Het
Kif13b	G	A	14: 64,907,120 (GRCm39)	V35I	probably benign	Het
Kif6	G	A	17: 50,062,258 (GRCm39)	E473K	probably damaging	Het
Mfsd14a	T	C	3: 116,426,042 (GRCm39)	T452A	probably benign	Het
Mllt1	A	G	17: 57,204,398 (GRCm39)	S382P	probably benign	Het
Myo15b	T	C	11: 115,757,398 (GRCm39)	W1083R	probably damaging	Het
Nell2	T	C	15: 95,333,038 (GRCm39)	I174V	probably damaging	Het
Noct	G	A	3: 51,157,117 (GRCm39)		probably null	Het
Nvl	A	T	1: 180,962,639 (GRCm39)		probably benign	Het
Ofcc1	T	C	13: 40,250,595 (GRCm39)	S574G	probably benign	Het
Or10a3m	G	A	7: 108,313,339 (GRCm39)	V248I	probably damaging	Het
Or11h4	T	C	14: 50,973,681 (GRCm39)	M313V	probably benign	Het
Or4a75	A	T	2: 89,447,924 (GRCm39)	M204K	possibly damaging	Het
Pip5k1a	A	T	3: 94,972,807 (GRCm39)	S415T	probably damaging	Het
Pkhd1	G	A	1: 20,623,741 (GRCm39)	P785S	probably damaging	Het
Plcg2	A	G	8: 118,339,733 (GRCm39)	Y1048C	probably damaging	Het
Ppp3cb	A	T	14: 20,570,720 (GRCm39)	V337E	probably benign	Het
Prkg2	T	C	5: 99,114,368 (GRCm39)		probably benign	Het
Prl7a2	T	G	13: 27,843,089 (GRCm39)	Y238S	probably benign	Het
Psg28	T	A	7: 18,161,804 (GRCm39)	D233V	probably damaging	Het
Rad50	A	G	11: 53,589,036 (GRCm39)	C221R	probably benign	Het
Rgl3	A	G	9: 21,887,254 (GRCm39)		probably benign	Het
Rgsl1	T	A	1: 153,701,014 (GRCm39)		probably benign	Het
Ror1	C	A	4: 100,299,071 (GRCm39)	R815S	probably damaging	Het
Rrp1b	C	A	17: 32,275,534 (GRCm39)	D360E	probably benign	Het
Ryr3	T	C	2: 112,496,680 (GRCm39)	Q3682R	possibly damaging	Het
Sdr42e1	A	T	8: 118,389,616 (GRCm39)	F342I	possibly damaging	Het
Setd5	A	G	6: 113,128,114 (GRCm39)	R1337G	probably benign	Het
Siglecf	T	C	7: 43,001,140 (GRCm39)	V36A	probably damaging	Het
Slc4a5	G	A	6: 83,239,542 (GRCm39)	G152D	probably damaging	Het
Sptbn4	T	G	7: 27,063,587 (GRCm39)	M2280L	probably benign	Het
Syngr2	T	C	11: 117,703,406 (GRCm39)	I74T	probably damaging	Het
Tm9sf1	T	C	14: 55,878,866 (GRCm39)	I175M	possibly damaging	Het
Tmc3	A	G	7: 83,258,516 (GRCm39)	E502G	probably damaging	Het
Tpr	A	G	1: 150,295,691 (GRCm39)	K979E	possibly damaging	Het
Usp47	A	G	7: 111,691,934 (GRCm39)	T799A	probably benign	Het
Utf1	A	G	7: 139,523,920 (GRCm39)	E45G	possibly damaging	Het
Vmn1r208	A	T	13: 22,956,772 (GRCm39)	C242S	probably damaging	Het
Wrnip1	T	C	13: 33,004,223 (GRCm39)	I498T	probably damaging	Het
Ypel2	T	A	11: 86,862,699 (GRCm39)	H18L	probably benign	Het
Zan	T	G	5: 137,420,110 (GRCm39)	D2849A	unknown	Het
Zfp647	A	T	15: 76,795,860 (GRCm39)	F267I	probably damaging	Het
Zfp786	G	T	6: 47,797,905 (GRCm39)	H344Q	possibly damaging	Het
Zswim3	G	T	2: 164,662,614 (GRCm39)	A365S	probably benign	Het
Zswim5	T	C	4: 116,830,238 (GRCm39)	W538R	probably 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
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'- GAATTCTGATCGGCTCCACTC -3'
(R):5'- GATGATTAGCATCCGAGGCG -3'

Sequencing Primer
(F):5'- GATCGGCTCCACTCTGTCTTC -3'
(R):5'- GGGTCCGTGCAGTCTTTTCC -3'

Posted On

2014-10-02