Mutagenetix > Incidental Mutation

Incidental Mutation 'R7975:Tph1'

650845

Institutional Source

Beutler Lab

Gene Symbol

Tph1

Ensembl Gene

ENSMUSG00000040046

Gene Name

tryptophan hydroxylase 1

Synonyms

MMRRC Submission

046018-MU

Accession Numbers

Essential gene?

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

Stock #

R7975 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

46294065-46321961 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 46306678 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Cysteine at position 145 (R145C)

Ref Sequence

ENSEMBL: ENSMUSP00000037752 (fasta)

Gene Model

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

AlphaFold

P17532

Predicted Effect

probably damaging
Transcript: ENSMUST00000049298
AA Change: R145C

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

SMART Domains

Protein: ENSMUSP00000037752
Gene: ENSMUSG00000040046
AA Change: R145C

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 damaging
Transcript: ENSMUST00000107669
AA Change: R145C

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

SMART Domains

Protein: ENSMUSP00000103296
Gene: ENSMUSG00000040046
AA Change: R145C

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

Predicted Effect

probably benign
Transcript: ENSMUST00000168335

SMART Domains

Protein: ENSMUSP00000128107
Gene: ENSMUSG00000040046

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: R145C

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

SMART Domains

Protein: ENSMUSP00000132489
Gene: ENSMUSG00000040046
AA Change: R145C

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: R140C

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: 100.0%
10x: 99.7%
20x: 99.3%

Validation Efficiency

100% (53/53)

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: 60 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Ano4	T	C	10: 88,952,847 (GRCm39)	I60V	possibly damaging	Het
Ano5	T	A	7: 51,216,286 (GRCm39)	M381K	probably null	Het
Aox1	T	A	1: 58,348,187 (GRCm39)	I635K	probably benign	Het
Bdp1	C	T	13: 100,156,884 (GRCm39)	C2436Y	probably benign	Het
Bod1l	T	C	5: 41,973,620 (GRCm39)	R2565G	possibly damaging	Het
Brd2	A	T	17: 34,334,424 (GRCm39)	I245N	probably damaging	Het
Capn9	G	A	8: 125,325,515 (GRCm39)	V258M	probably damaging	Het
Ccar2	C	G	14: 70,380,918 (GRCm39)	C324S	possibly damaging	Het
Cd209b	A	T	8: 3,975,948 (GRCm39)	I71N	probably benign	Het
Cdk12	A	T	11: 98,111,928 (GRCm39)	I729F	unknown	Het
Celf1	T	G	2: 90,831,423 (GRCm39)	V84G	probably damaging	Het
Cgn	G	T	3: 94,671,836 (GRCm39)	A965E	probably benign	Het
Cgnl1	T	C	9: 71,632,604 (GRCm39)	E249G	probably benign	Het
Cspg4b	A	G	13: 113,455,841 (GRCm39)	H629R		Het
Cyp2j8	T	C	4: 96,358,776 (GRCm39)	N381S	possibly damaging	Het
Dmtf1	T	C	5: 9,179,169 (GRCm39)	D343G	probably damaging	Het
Fhl5	T	A	4: 25,214,730 (GRCm39)	I16F	probably benign	Het
Gatd1	A	G	7: 140,989,781 (GRCm39)	F143S	probably damaging	Het
Gbp10	C	T	5: 105,368,967 (GRCm39)	G291R	probably benign	Het
Gm28168	T	C	1: 117,875,820 (GRCm39)	Y150H	probably benign	Het
Gm3543	T	C	14: 41,802,122 (GRCm39)	M121V	probably benign	Het
Gramd2b	A	G	18: 56,618,451 (GRCm39)	T220A	probably benign	Het
Gstcd	A	G	3: 132,777,863 (GRCm39)	L316P	probably damaging	Het
Hspg2	G	A	4: 137,282,532 (GRCm39)	G3424D	probably benign	Het
Ifi209	C	T	1: 173,468,722 (GRCm39)	S184F	probably benign	Het
Ino80	A	T	2: 119,286,948 (GRCm39)		probably null	Het
Kcnd3	G	A	3: 105,366,310 (GRCm39)	R60H	probably damaging	Het
Kif21b	T	C	1: 136,098,911 (GRCm39)	C1400R	probably damaging	Het
Lama3	C	T	18: 12,670,796 (GRCm39)	P794L	probably damaging	Het
Lgals4	A	G	7: 28,540,346 (GRCm39)	I214V	probably benign	Het
Lipo4	A	T	19: 33,490,028 (GRCm39)	L158Q	probably damaging	Het
Ltv1	A	G	10: 13,066,453 (GRCm39)	Y58H	probably damaging	Het
Mitf	T	C	6: 97,994,990 (GRCm39)	S479P	probably benign	Het
Mthfr	A	T	4: 148,127,920 (GRCm39)	D132V	probably damaging	Het
Mtrr	T	C	13: 68,727,666 (GRCm39)		probably null	Het
Neb	T	A	2: 52,050,678 (GRCm39)	H6660L	probably benign	Het
Nhlrc3	A	T	3: 53,360,966 (GRCm39)	V263E	probably damaging	Het
Oas1h	G	A	5: 121,009,890 (GRCm39)	V322M	probably damaging	Het
Or10a3n	A	T	7: 108,493,019 (GRCm39)	Y203*	probably null	Het
Or2m13	T	A	16: 19,226,301 (GRCm39)	D155V	probably damaging	Het
Or4a15	C	T	2: 89,193,413 (GRCm39)	R120H	probably benign	Het
Pappa	A	T	4: 65,212,705 (GRCm39)	D1121V	probably damaging	Het
Pax5	A	G	4: 44,537,465 (GRCm39)	S352P	probably damaging	Het
Piezo1	C	A	8: 123,222,504 (GRCm39)	R915L		Het
R3hcc1	T	C	14: 69,944,593 (GRCm39)	D7G	probably damaging	Het
Rasgrp2	A	G	19: 6,458,589 (GRCm39)	K429E	probably damaging	Het
Scn10a	A	G	9: 119,501,286 (GRCm39)	F166S	probably benign	Het
Scn9a	T	G	2: 66,314,597 (GRCm39)	N1707T	probably damaging	Het
Sec23ip	T	C	7: 128,364,201 (GRCm39)	F493S	probably damaging	Het
Slc1a7	G	A	4: 107,869,473 (GRCm39)	V513M	probably benign	Het
Slfn4	A	T	11: 83,077,982 (GRCm39)	I257F	possibly damaging	Het
Smarcal1	T	A	1: 72,652,150 (GRCm39)	D637E	probably benign	Het
Smpd3	A	C	8: 106,982,254 (GRCm39)	C617G	probably benign	Het
Sos2	A	T	12: 69,639,814 (GRCm39)	F990L	probably benign	Het
Spata31h1	C	T	10: 82,119,823 (GRCm39)	A4396T	possibly damaging	Het
Syne1	T	C	10: 4,981,786 (GRCm39)	T844A	probably benign	Het
Ubap2l	G	A	3: 89,946,076 (GRCm39)		probably null	Het
Vmn2r50	T	C	7: 9,771,272 (GRCm39)	I810V	probably benign	Het
Vmn2r59	T	C	7: 41,693,199 (GRCm39)	D467G	probably damaging	Het
Zfp618	T	A	4: 63,049,352 (GRCm39)	N417K	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
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
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'- TCAATCTTGGGAATGGGGTC -3'
(R):5'- TAGAGCTGTCATGTGTCTGC -3'

Sequencing Primer
(F):5'- ACAGGGAGTTCTGCACTGTAGTC -3'
(R):5'- GTGTCTGCTGGCTTCAAAATAAAAGC -3'

Posted On

2020-09-15