Mutagenetix > Incidental Mutation

Incidental Mutation 'R8970:Th'

683019

Institutional Source

Beutler Lab

Gene Symbol

Ensembl Gene

ENSMUSG00000000214

Gene Name

tyrosine hydroxylase

Synonyms

MMRRC Submission

068804-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R8970 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

142446516-142453732 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 142446796 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Leucine to Proline at position 490 (L490P)

Ref Sequence

ENSEMBL: ENSMUSP00000000219 (fasta)

Gene Model

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

AlphaFold

P24529

Predicted Effect

probably damaging
Transcript: ENSMUST00000000219
AA Change: L490P

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

SMART Domains

Protein: ENSMUSP00000000219
Gene: ENSMUSG00000000214
AA Change: L490P

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 damaging
Transcript: ENSMUST00000105929
AA Change: L395P

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

SMART Domains

Protein: ENSMUSP00000101549
Gene: ENSMUSG00000000214
AA Change: L395P

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

0.9682

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 99.2%

Validation Efficiency

99% (69/70)

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: 74 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A2ml1	A	G	6: 128,545,726 (GRCm39)	V467A	probably damaging	Het
Abca2	T	C	2: 25,335,728 (GRCm39)	V2113A	probably benign	Het
Adam10	A	G	9: 70,655,458 (GRCm39)	N309D	probably benign	Het
Adcy1	T	A	11: 7,099,983 (GRCm39)	W698R	probably benign	Het
Adnp	T	C	2: 168,031,290 (GRCm39)	N7S	possibly damaging	Het
Ankar	A	G	1: 72,691,496 (GRCm39)		probably null	Het
Ankrd34b	T	A	13: 92,575,590 (GRCm39)	I274K	probably benign	Het
Apela	A	T	8: 65,489,601 (GRCm39)	L6H	unknown	Het
Ash1l	T	C	3: 88,976,307 (GRCm39)	I2629T	probably benign	Het
Auts2	C	T	5: 132,287,791 (GRCm39)	R64K	possibly damaging	Het
Bms1	A	G	6: 118,369,292 (GRCm39)	V1003A	possibly damaging	Het
C2cd3	T	C	7: 100,068,971 (GRCm39)	V555A		Het
C2cd6	T	A	1: 59,108,895 (GRCm39)	H252L	possibly damaging	Het
Capn3	G	T	2: 120,294,566 (GRCm39)	K71N	possibly damaging	Het
Chct1	A	G	11: 85,069,246 (GRCm39)	E198G	probably benign	Het
Clec2l	C	A	6: 38,657,122 (GRCm39)	T195K	possibly damaging	Het
Col27a1	T	C	4: 63,134,105 (GRCm39)	S15P	unknown	Het
Coro2b	T	C	9: 62,333,809 (GRCm39)		probably benign	Het
Crocc2	A	T	1: 93,116,687 (GRCm39)	T233S	probably benign	Het
Ddb1	A	G	19: 10,585,808 (GRCm39)	Q174R	probably benign	Het
Denr	C	T	5: 124,055,279 (GRCm39)	P48L	probably damaging	Het
Dusp26	A	G	8: 31,584,232 (GRCm39)	Y113C	probably damaging	Het
Dusp9	TAAAGCGGAGGCCAAAGCGGAGGCCAAAGCGGAGGCTAAAGCGGAGGCCAAAGCGGAGGCCAAAGCGGAGGCCAAAGCGGAGGCTAAAGCGGAGGCCAAAGCGGAGGCCAAAG	TAAAGCGGAGGCCAAAGCGGAGGCCAAAGCGGAGGCTAAAGCGGAGGCCAAAGCGGAGGCCAAAG	X: 72,684,217 (GRCm39)		probably benign	Het
Evi5l	A	G	8: 4,236,154 (GRCm39)		probably benign	Het
Fgf2	G	T	3: 37,458,767 (GRCm39)	V96F	probably benign	Het
Gpr139	A	G	7: 118,744,034 (GRCm39)	Y184H	probably damaging	Het
Gtf3c1	A	C	7: 125,272,227 (GRCm39)		probably benign	Het
Gucy1b2	A	G	14: 62,656,664 (GRCm39)	V231A	possibly damaging	Het
Gucy2g	T	C	19: 55,191,478 (GRCm39)	E991G	possibly damaging	Het
Gvin1	A	T	7: 105,762,647 (GRCm39)	H607Q	probably damaging	Het
Hal	T	C	10: 93,325,036 (GRCm39)	V15A	probably damaging	Het
Hes3	A	G	4: 152,376,036 (GRCm39)		probably null	Het
Il11	A	G	7: 4,779,181 (GRCm39)	L72P	probably damaging	Het
Iqsec3	T	A	6: 121,366,528 (GRCm39)	I785F	probably damaging	Het
Jup	C	T	11: 100,270,391 (GRCm39)	C372Y	probably damaging	Het
Lrpprc	T	A	17: 85,074,483 (GRCm39)	T475S	probably damaging	Het
Lrrc63	T	A	14: 75,362,631 (GRCm39)	T300S	unknown	Het
Lsamp	A	T	16: 41,994,528 (GRCm39)	I331F	possibly damaging	Het
Ltn1	A	T	16: 87,212,926 (GRCm39)	I545K	probably benign	Het
Mab21l4	G	C	1: 93,087,533 (GRCm39)	P107A	probably benign	Het
Med13l	G	A	5: 118,883,164 (GRCm39)	R1341H	probably damaging	Het
Msh4	T	A	3: 153,575,369 (GRCm39)	K669*	probably null	Het
Myo10	T	A	15: 25,803,467 (GRCm39)	L1558H	possibly damaging	Het
Ncbp1	G	A	4: 46,170,023 (GRCm39)	V699M	probably damaging	Het
Or12k8	T	A	2: 36,975,478 (GRCm39)	Y94F	probably benign	Het
Or56b1b	A	G	7: 108,164,997 (GRCm39)	S2P	probably benign	Het
Or5b114-ps1	T	G	19: 13,353,117 (GRCm39)	S264A	unknown	Het
Or5b99	T	A	19: 12,976,353 (GRCm39)	M1K	probably null	Het
Parpbp	G	A	10: 87,962,186 (GRCm39)	R165W	probably damaging	Het
Pcdhgb7	T	A	18: 37,885,631 (GRCm39)	M267K	probably benign	Het
Pitx3	T	A	19: 46,125,540 (GRCm39)	H68L	possibly damaging	Het
Ppfia4	A	G	1: 134,252,289 (GRCm39)	L395P	probably damaging	Het
Pramel42	T	C	5: 94,685,645 (GRCm39)	V435A	probably benign	Het
Ptprh	T	C	7: 4,583,944 (GRCm39)	D216G	possibly damaging	Het
Ptprs	A	G	17: 56,730,353 (GRCm39)	S1174P	possibly damaging	Het
Shf	A	G	2: 122,187,654 (GRCm39)	S51P	probably benign	Het
Sinhcaf	A	T	6: 148,834,624 (GRCm39)	F2I	probably damaging	Het
Slc19a3	A	T	1: 83,000,822 (GRCm39)	L65Q	probably damaging	Het
Srgap2	G	A	1: 131,226,104 (GRCm39)	L390F		Het
Srpk1	T	C	17: 28,818,493 (GRCm39)	T448A	probably benign	Het
Stat5a	A	G	11: 100,771,353 (GRCm39)	D612G	probably benign	Het
Supt4a	A	T	11: 87,633,645 (GRCm39)	E67V	probably benign	Het
Tango6	T	A	8: 107,415,871 (GRCm39)	C231S	probably damaging	Het
Tpcn1	C	T	5: 120,682,518 (GRCm39)	G497S	probably damaging	Het
Trim10	A	T	17: 37,184,168 (GRCm39)	I254F	probably benign	Het
Tyw1	G	A	5: 130,298,065 (GRCm39)	R202Q	probably damaging	Het
Vmn2r124	G	T	17: 18,294,439 (GRCm39)	R842L	probably benign	Het
Vmn2r56	T	C	7: 12,428,632 (GRCm39)	R545G	probably damaging	Het
Vmn2r84	T	C	10: 130,222,244 (GRCm39)	T659A	probably damaging	Het
Vps13c	T	C	9: 67,852,803 (GRCm39)	M2361T	probably benign	Het
Zfp217	T	C	2: 169,956,997 (GRCm39)	D667G	possibly damaging	Het
Zfp952	T	G	17: 33,221,810 (GRCm39)	C96W	probably benign	Het
Zfp959	A	G	17: 56,204,836 (GRCm39)	Q291R	possibly damaging	Het
Zscan4-ps3	T	C	7: 11,344,414 (GRCm39)	V124A	probably benign	Het

Other mutations in Th

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00949:Th	APN	7	142,450,763 (GRCm39)	missense	probably benign	0.01
IGL02308:Th	APN	7	142,451,794 (GRCm39)	missense	possibly damaging	0.69
IGL02417:Th	APN	7	142,453,643 (GRCm39)	missense	probably damaging	1.00
IGL02565:Th	APN	7	142,453,647 (GRCm39)	missense	probably damaging	1.00
IGL02896:Th	APN	7	142,449,168 (GRCm39)	missense	probably damaging	1.00
R0311:Th	UTSW	7	142,449,778 (GRCm39)	missense	probably damaging	1.00
R1072:Th	UTSW	7	142,448,225 (GRCm39)	missense	probably benign
R1595:Th	UTSW	7	142,450,745 (GRCm39)	missense	probably benign	0.06
R1756:Th	UTSW	7	142,451,903 (GRCm39)	nonsense	probably null
R2091:Th	UTSW	7	142,449,280 (GRCm39)	missense	probably damaging	0.98
R2850:Th	UTSW	7	142,447,812 (GRCm39)	nonsense	probably null
R3151:Th	UTSW	7	142,447,812 (GRCm39)	nonsense	probably null
R4458:Th	UTSW	7	142,450,690 (GRCm39)	missense	probably benign	0.41
R4870:Th	UTSW	7	142,447,834 (GRCm39)	missense	probably benign
R5382:Th	UTSW	7	142,449,177 (GRCm39)	missense	probably damaging	1.00
R7874:Th	UTSW	7	142,449,308 (GRCm39)	nonsense	probably null
R8049:Th	UTSW	7	142,447,860 (GRCm39)	missense	probably damaging	1.00
R8425:Th	UTSW	7	142,447,823 (GRCm39)	missense	possibly damaging	0.86
R8431:Th	UTSW	7	142,446,801 (GRCm39)	missense	probably benign	0.00
R9484:Th	UTSW	7	142,453,620 (GRCm39)	nonsense	probably null
R9745:Th	UTSW	7	142,448,851 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- GCGCATGCAGTAGTAAGATGTG -3'
(R):5'- AGCTACCTAACTCTAGCCTGC -3'

Sequencing Primer
(F):5'- CATGCAGTAGTAAGATGTGGTTGAG -3'
(R):5'- GGCCATTGATGTACTGGA -3'

Posted On

2021-10-11