Mutagenetix > Incidental Mutation

Incidental Mutation 'R2091:Th'

323557

Institutional Source

Beutler Lab

Gene Symbol

Ensembl Gene

ENSMUSG00000000214

Gene Name

tyrosine hydroxylase

Synonyms

MMRRC Submission

040096-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R2091 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

142446516-142453732 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 142449280 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Valine at position 275 (D275V)

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: D275V

PolyPhen 2 Score 0.978 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000000219
Gene: ENSMUSG00000000214
AA Change: D275V

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

possibly damaging
Transcript: ENSMUST00000105929
AA Change: D180V

PolyPhen 2 Score 0.955 (Sensitivity: 0.79; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000101549
Gene: ENSMUSG00000000214
AA Change: D180V

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

0.8973

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.3%
20x: 95.5%

Validation Efficiency

96% (55/57)

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: 100 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4921504E06Rik	G	C	2: 19,522,357 (GRCm39)	N247K	probably damaging	Het
4930402F06Rik	T	C	2: 35,266,079 (GRCm39)	K197R	probably benign	Het
AA986860	T	C	1: 130,670,906 (GRCm39)	L376P	probably benign	Het
Adamts10	T	C	17: 33,770,166 (GRCm39)		probably null	Het
Adamts7	T	C	9: 90,070,493 (GRCm39)		probably null	Het
Adgrl1	T	C	8: 84,661,093 (GRCm39)	I862T	probably damaging	Het
Agbl1	G	A	7: 76,239,248 (GRCm39)	V583M	probably damaging	Het
Apba2	T	A	7: 64,345,341 (GRCm39)	V177D	probably benign	Het
Arfgap2	A	G	2: 91,100,586 (GRCm39)	K297R	probably benign	Het
Armh3	A	T	19: 45,941,119 (GRCm39)	L300Q	probably damaging	Het
Atg14	A	T	14: 47,780,352 (GRCm39)	I474N	probably damaging	Het
Atp2b4	C	A	1: 133,642,968 (GRCm39)	V1046F	probably benign	Het
Best1	A	G	19: 9,969,443 (GRCm39)	V205A	probably benign	Het
Bicdl1	A	G	5: 115,862,638 (GRCm39)	S206P	probably damaging	Het
Bltp1	T	C	3: 37,008,119 (GRCm39)	V1725A	probably damaging	Het
Bltp1	C	T	3: 37,042,405 (GRCm39)	T2797I	probably damaging	Het
Cacna1h	C	T	17: 25,651,850 (GRCm39)	C98Y	possibly damaging	Het
Calhm3	T	A	19: 47,140,430 (GRCm39)	D221V	probably damaging	Het
Ccdc93	T	A	1: 121,411,071 (GRCm39)		probably null	Het
Cd248	A	T	19: 5,120,074 (GRCm39)	I641F	possibly damaging	Het
Chrnb3	C	T	8: 27,884,262 (GRCm39)	T333M	probably damaging	Het
Cyb5rl	A	G	4: 106,928,203 (GRCm39)	H113R	probably damaging	Het
Dab1	C	T	4: 104,588,948 (GRCm39)	A524V	probably benign	Het
Ddx59	T	A	1: 136,344,447 (GRCm39)	D39E	probably benign	Het
Defa5	A	G	8: 21,787,513 (GRCm39)	D20G	probably damaging	Het
Dido1	A	T	2: 180,303,677 (GRCm39)	V1409E	probably benign	Het
Dlc1	A	T	8: 37,404,763 (GRCm39)	V342E	probably benign	Het
Dsc2	G	A	18: 20,166,351 (GRCm39)	T760I	possibly damaging	Het
Dync1h1	A	G	12: 110,616,022 (GRCm39)	I3057V	probably benign	Het
Etnk2	T	G	1: 133,304,791 (GRCm39)		probably null	Het
Fbp2	G	T	13: 63,006,021 (GRCm39)	L31I	probably damaging	Het
Gbp7	A	T	3: 142,240,383 (GRCm39)	I34F	probably damaging	Het
Gcfc2	A	G	6: 81,920,460 (GRCm39)	E415G	probably damaging	Het
Glp1r	T	C	17: 31,144,523 (GRCm39)	L232P	probably damaging	Het
Gm10822	A	G	2: 73,729,619 (GRCm39)		noncoding transcript	Het
Gm42669	G	A	5: 107,655,776 (GRCm39)	V1192M	probably benign	Het
Gpr37	A	G	6: 25,689,062 (GRCm39)	S12P	possibly damaging	Het
Gpt	A	G	15: 76,582,176 (GRCm39)	E211G	possibly damaging	Het
Grxcr1	T	C	5: 68,267,755 (GRCm39)	I168T	probably damaging	Het
Hat1	T	C	2: 71,264,378 (GRCm39)	V272A	probably benign	Het
Igkv8-30	A	C	6: 70,094,070 (GRCm39)	C114G	probably damaging	Het
Kcne4	T	C	1: 78,795,624 (GRCm39)	S91P	probably benign	Het
Kif5b	G	A	18: 6,213,248 (GRCm39)	Q715*	probably null	Het
Lamb1	T	A	12: 31,337,428 (GRCm39)	N386K	probably damaging	Het
Lcmt2	T	C	2: 120,969,097 (GRCm39)	N662S	probably damaging	Het
Lnx1	G	T	5: 74,780,727 (GRCm39)	H324N	probably benign	Het
Lrrc4	T	G	6: 28,830,586 (GRCm39)	D343A	probably benign	Het
Mars1	A	G	10: 127,135,154 (GRCm39)	S646P	probably damaging	Het
Mboat7	T	C	7: 3,687,010 (GRCm39)		probably benign	Het
Mlip	C	T	9: 77,072,145 (GRCm39)	V341I	possibly damaging	Het
Mterf1b	A	T	5: 4,247,057 (GRCm39)	T233S	possibly damaging	Het
Myo3a	A	T	2: 22,338,488 (GRCm39)	H442L	probably damaging	Het
Myrf	A	T	19: 10,201,964 (GRCm39)	V171D	possibly damaging	Het
Nbas	G	A	12: 13,411,046 (GRCm39)	D897N	probably benign	Het
Nfx1	T	C	4: 40,977,004 (GRCm39)	V226A	probably benign	Het
Nlrp4a	T	C	7: 26,149,578 (GRCm39)	L395P	probably damaging	Het
Nrros	C	T	16: 31,962,975 (GRCm39)	W311*	probably null	Het
Nsun6	A	G	2: 15,044,542 (GRCm39)		probably null	Het
Ntrk2	A	G	13: 59,007,115 (GRCm39)	H239R	possibly damaging	Het
Or10g9	T	C	9: 39,912,500 (GRCm39)	T8A	probably benign	Het
Or4k51	A	T	2: 111,584,731 (GRCm39)	M46L	probably benign	Het
Or5aq7	T	C	2: 86,938,606 (GRCm39)	N42D	probably damaging	Het
Or5p70	A	G	7: 107,995,068 (GRCm39)	H247R	probably damaging	Het
Pate4	C	A	9: 35,519,553 (GRCm39)	A46S	possibly damaging	Het
Pcdhb18	T	C	18: 37,623,653 (GRCm39)	S328P	probably damaging	Het
Pdk4	A	G	6: 5,494,857 (GRCm39)		probably benign	Het
Pigm	T	C	1: 172,205,100 (GRCm39)	Y279H	probably damaging	Het
Plaat3	A	G	19: 7,556,474 (GRCm39)	I92V	probably damaging	Het
Plxdc2	A	G	2: 16,718,494 (GRCm39)	I379M	probably damaging	Het
Ppp1r35	A	G	5: 137,778,156 (GRCm39)	N217S	possibly damaging	Het
Prex1	G	A	2: 166,411,285 (GRCm39)	T1438I	possibly damaging	Het
Ptger4	T	A	15: 5,272,326 (GRCm39)	I98F	possibly damaging	Het
Rasl11a	T	A	5: 146,783,927 (GRCm39)	I124N	probably damaging	Het
Rest	A	G	5: 77,429,126 (GRCm39)	K515R	possibly damaging	Het
Ryr1	A	G	7: 28,785,474 (GRCm39)	L1746P	probably damaging	Het
Ryr2	G	T	13: 11,960,863 (GRCm39)	T25K	probably benign	Het
Sacs	A	T	14: 61,429,368 (GRCm39)	I476L	possibly damaging	Het
Serpina3g	A	T	12: 104,205,417 (GRCm39)	D52V	probably damaging	Het
Skint6	T	C	4: 112,703,881 (GRCm39)	N998S	probably benign	Het
Skp2	C	A	15: 9,113,786 (GRCm39)	G376C	probably damaging	Het
Slc10a4	G	A	5: 73,174,482 (GRCm39)		probably benign	Het
Slc24a2	G	T	4: 86,929,883 (GRCm39)	P538T	probably damaging	Het
Sntg1	T	A	1: 8,665,763 (GRCm39)	T184S	probably benign	Het
Ssbp1	A	G	6: 40,453,433 (GRCm39)	Y73C	probably null	Het
St18	G	A	1: 6,898,195 (GRCm39)	V666M	probably benign	Het
Suclg1	A	G	6: 73,241,259 (GRCm39)	K193R	probably benign	Het
Tcp11l1	T	C	2: 104,514,484 (GRCm39)	I428V	possibly damaging	Het
Tnrc18	A	C	5: 142,759,396 (GRCm39)	S813R	unknown	Het
Tnrc6a	T	C	7: 122,771,343 (GRCm39)		probably null	Het
Trap1	A	C	16: 3,863,903 (GRCm39)	Y472*	probably null	Het
Trdv1	C	A	14: 54,119,626 (GRCm39)	Q96K	probably benign	Het
Trpm8	T	C	1: 88,271,048 (GRCm39)	I446T	probably damaging	Het
Tti2	T	C	8: 31,644,294 (GRCm39)	L297P	probably damaging	Het
Ttn	C	T	2: 76,565,355 (GRCm39)	G26545R	probably damaging	Het
Ttn	T	C	2: 76,587,488 (GRCm39)	D13208G	probably damaging	Het
Tubb3	A	G	8: 124,148,417 (GRCm39)		probably null	Het
Umodl1	A	G	17: 31,190,893 (GRCm39)	M247V	probably benign	Het
Wrn	T	A	8: 33,757,853 (GRCm39)	H812L	probably benign	Het
Zfp174	A	G	16: 3,672,506 (GRCm39)	R352G	possibly damaging	Het
Zfp955a	T	A	17: 33,461,731 (GRCm39)	K134*	probably null	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
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
R8970:Th	UTSW	7	142,446,796 (GRCm39)	missense	probably damaging	1.00
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'- ACGGATGTACTGTGTGCACTG -3'
(R):5'- AAGCAGGCAAAGCGTCCATG -3'

Sequencing Primer
(F):5'- GTACTGTGTGCACTGAAACAC -3'
(R):5'- CAAAGCGTCCATGGGGTG -3'

Posted On

2015-06-24