Mutagenetix > Incidental Mutations

Incidental Mutation 'R4870:Th'

376508

Institutional Source

Beutler Lab

Gene Symbol

Ensembl Gene

ENSMUSG00000000214

Gene Name

tyrosine hydroxylase

Synonyms

MMRRC Submission

042480-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R4870 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

142892752-142931128 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 142894097 bp

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glutamic Acid at position 321 (D321E)

Ref Sequence

ENSEMBL: ENSMUSP00000101549 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000000219] [ENSMUST00000105929] [ENSMUST00000123057] [ENSMUST00000124951] [ENSMUST00000140344]

Predicted Effect

probably benign
Transcript: ENSMUST00000000219
AA Change: D416E

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

SMART Domains

Protein: ENSMUSP00000000219
Gene: ENSMUSG00000000214
AA Change: D416E

Domain	Start	End	E-Value	Type
Pfam:TOH_N	2	26	2.3e-15	PFAM
Pfam:TOH_N	29	49	2.6e-11	PFAM
low complexity region	51	63	N/A	INTRINSIC
PDB:2MDA\|B	65	146	1e-49	PDB
low complexity region	147	158	N/A	INTRINSIC
Pfam:Biopterin_H	165	495	1.2e-180	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000105929
AA Change: D321E

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

SMART Domains

Protein: ENSMUSP00000101549
Gene: ENSMUSG00000000214
AA Change: D321E

Domain	Start	End	E-Value	Type
PDB:2MDA\|B	8	51	1e-21	PDB
low complexity region	52	63	N/A	INTRINSIC
Pfam:Biopterin_H	70	401	2.2e-196	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000123057

Predicted Effect

probably benign
Transcript: ENSMUST00000124951

SMART Domains

Protein: ENSMUSP00000122876
Gene: ENSMUSG00000000214

Domain	Start	End	E-Value	Type
Pfam:TOH_N	2	26	5e-16	PFAM
Pfam:TOH_N	28	49	4.1e-10	PFAM
low complexity region	51	63	N/A	INTRINSIC
PDB:2MDA\|B	65	146	2e-52	PDB
low complexity region	147	158	N/A	INTRINSIC
Pfam:Biopterin_H	165	232	7.2e-37	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000138482

Predicted Effect

probably benign
Transcript: ENSMUST00000140344

SMART Domains

Protein: ENSMUSP00000115434
Gene: ENSMUSG00000000214

Domain	Start	End	E-Value	Type
Pfam:TOH_N	11	29	5.2e-9	PFAM
low complexity region	31	43	N/A	INTRINSIC
PDB:2MDA\|B	45	126	7e-53	PDB
low complexity region	127	138	N/A	INTRINSIC
Pfam:Biopterin_H	145	171	3.9e-11	PFAM

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 99.1%
3x: 98.5%
10x: 96.9%
20x: 94.1%

Validation Efficiency

100% (77/77)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is involved in the conversion of tyrosine to dopamine. It is the rate-limiting enzyme in the synthesis of catecholamines, hence plays a key role in the physiology of adrenergic neurons. Mutations in this gene have been associated with autosomal recessive Segawa syndrome. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygotes for targeted null mutations are deficient in catecholamines, and usually die around embryonic day 11.5-15.5 due to cardiac failure. Treatment of the pregnant female with dihydroxyphenylalanine prevents prenatal mortality. Mice homozygous for hypomorphic targeted alleles are hypokinetic. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 68 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4931406P16Rik	C	A	7: 34,284,887	V104L	possibly damaging	Het
Abcb11	A	T	2: 69,239,196	I1285N	probably damaging	Het
Abcc8	G	A	7: 46,107,259	R721*	probably null	Het
Alox8	T	C	11: 69,186,568	Y423C	probably damaging	Het
Ankle2	T	A	5: 110,251,478		probably null	Het
Cdc14a	A	G	3: 116,423,460	I9T	probably benign	Het
Ceacam18	T	C	7: 43,641,904	C257R	probably damaging	Het
Cilp	T	C	9: 65,279,698	V1025A	probably damaging	Het
Clcn7	G	T	17: 25,153,565		probably benign	Het
Csnk1d	A	T	11: 120,983,188		probably benign	Het
Cyp11b2	A	G	15: 74,853,146	S285P	probably benign	Het
Dip2b	T	A	15: 100,195,784		probably null	Het
Dmrt1	T	A	19: 25,505,855	M1K	probably null	Het
Dnajc14	T	C	10: 128,817,350	V684A	probably benign	Het
Dnmt3b	A	G	2: 153,670,364	Q335R	probably benign	Het
Exoc3l2	T	A	7: 19,495,192	C772S	unknown	Het
F2rl1	A	T	13: 95,513,984	F130Y	probably damaging	Het
Galk2	C	G	2: 125,929,637	S194*	probably null	Het
Gm7102	C	T	19: 61,175,926	G24R	unknown	Het
Gpbp1l1	A	G	4: 116,573,517	T62A	probably benign	Het
H2-Q10	A	T	17: 35,470,460	D53V	probably damaging	Het
H2-T22	T	C	17: 36,039,032	K356R	probably benign	Het
Insrr	G	A	3: 87,811,604	V956M	probably damaging	Het
Ints7	A	G	1: 191,596,331	T239A	probably damaging	Het
Isl1	A	G	13: 116,308,270		probably benign	Het
Kcng2	A	G	18: 80,322,868	C90R	probably benign	Het
Kif3c	C	T	12: 3,401,735	P171S	probably damaging	Het
Knl1	A	G	2: 119,081,513	T1704A	probably benign	Het
Lats1	A	G	10: 7,705,785	Y778C	probably damaging	Het
Limd2	T	C	11: 106,159,389	M1V	probably null	Het
Mcm10	A	T	2: 5,004,159	I333N	probably damaging	Het
Mipep	T	A	14: 60,802,880	L283*	probably null	Het
Mixl1	A	G	1: 180,694,672	S215P	probably benign	Het
Mmp21	A	G	7: 133,678,677	L188P	probably damaging	Het
Mob1a	T	C	6: 83,340,239	S213P	probably benign	Het
Ndufaf6	T	C	4: 11,060,917	T220A	probably benign	Het
Nr4a3	A	T	4: 48,051,651	Y135F	possibly damaging	Het
Ntn1	CCTTCTTCT	CCTTCT	11: 68,213,026		probably benign	Het
Obscn	A	T	11: 59,136,206	L57Q	probably damaging	Het
Olfr1161	T	C	2: 88,025,460	L246P	probably damaging	Het
Olfr603	T	A	7: 103,383,633	D123V	probably damaging	Het
Pirb	T	A	7: 3,712,662	M839L	probably benign	Het
Plcl2	A	G	17: 50,607,226	E421G	possibly damaging	Het
Ppp1r12b	T	C	1: 134,949,033	N99S	probably benign	Het
Ptpro	A	G	6: 137,377,132	K169E	probably damaging	Het
Rita1	T	A	5: 120,611,383	K88N	probably damaging	Het
Rptn	A	T	3: 93,396,469	K370*	probably null	Het
Simc1	A	G	13: 54,539,763	D115G	probably null	Het
Stab1	T	A	14: 31,142,043	N136I	probably benign	Het
Syt4	T	A	18: 31,447,356		probably benign	Het
Sytl2	A	T	7: 90,388,898	N522I	probably damaging	Het
Tax1bp1	A	G	6: 52,729,493		probably benign	Het
Tenm2	A	T	11: 36,078,569	D847E	probably damaging	Het
Tmem44	A	T	16: 30,540,773	L46Q	probably damaging	Het
Trp53bp1	A	G	2: 121,256,641	L178P	probably damaging	Het
Trp63	A	G	16: 25,866,218	*285W	probably null	Het
Tsen34	T	C	7: 3,694,381		probably benign	Het
Tssk4	C	T	14: 55,651,815	T256I	probably benign	Het
Ttc17	A	T	2: 94,366,609	N464K	probably damaging	Het
Ttll2	C	T	17: 7,351,599	V310I	probably benign	Het
Ubn1	A	G	16: 5,077,313	E741G	probably damaging	Het
Urad	T	A	5: 147,315,454	I63F	probably damaging	Het
Vcan	T	C	13: 89,704,739	T701A	probably benign	Het
Vmn2r58	A	G	7: 41,837,215	V752A	possibly damaging	Het
Vmn2r69	C	A	7: 85,411,585	V264L	possibly damaging	Het
Zfp292	A	G	4: 34,808,917	S1376P	probably damaging	Het
Zfp955a	G	A	17: 33,241,725	R478*	probably null	Het
Znfx1	A	C	2: 167,055,269	F578L	probably benign	Het

Other mutations in Th

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00949:Th	APN	7	142897026	missense	probably benign	0.01
IGL02308:Th	APN	7	142898057	missense	possibly damaging	0.69
IGL02417:Th	APN	7	142899906	missense	probably damaging	1.00
IGL02565:Th	APN	7	142899910	missense	probably damaging	1.00
IGL02896:Th	APN	7	142895431	missense	probably damaging	1.00
R0311:Th	UTSW	7	142896041	missense	probably damaging	1.00
R1072:Th	UTSW	7	142894488	missense	probably benign
R1595:Th	UTSW	7	142897008	missense	probably benign	0.06
R1756:Th	UTSW	7	142898166	nonsense	probably null
R2091:Th	UTSW	7	142895543	missense	probably damaging	0.98
R2850:Th	UTSW	7	142894075	nonsense	probably null
R3151:Th	UTSW	7	142894075	nonsense	probably null
R4458:Th	UTSW	7	142896953	missense	probably benign	0.41
R5382:Th	UTSW	7	142895440	missense	probably damaging	1.00
R7874:Th	UTSW	7	142895571	nonsense	probably null
R8049:Th	UTSW	7	142894123	missense	probably damaging	1.00
R8425:Th	UTSW	7	142894086	missense	possibly damaging	0.86
R8431:Th	UTSW	7	142893064	missense	probably benign	0.00

Predicted Primers

PCR Primer
(F):5'- CTGAGTGTACTAAATGGGCTCTC -3'
(R):5'- ATCAGAAGGGTCCTTGGCTC -3'

Sequencing Primer
(F):5'- AGTGTACTAAATGGGCTCTCAAGTG -3'
(R):5'- AAGGGTCCTTGGCTCAGGTC -3'

Posted On

2016-03-17