Mutagenetix > Incidental Mutation

Incidental Mutation 'R8049:Th'

618931

Institutional Source

Beutler Lab

Gene Symbol

Ensembl Gene

ENSMUSG00000000214

Gene Name

tyrosine hydroxylase

Synonyms

MMRRC Submission

067486-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R8049 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

142446516-142453732 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 142447860 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Proline to Serine at position 408 (P408S)

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: P408S

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000000219
Gene: ENSMUSG00000000214
AA Change: P408S

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: P313S

PolyPhen 2 Score 0.989 (Sensitivity: 0.72; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000101549
Gene: ENSMUSG00000000214
AA Change: P313S

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

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.8%

Validation Efficiency

100% (55/55)

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: 57 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2310034C09Rik	A	T	16: 88,555,992 (GRCm39)	T69S	probably benign	Het
5730455P16Rik	A	G	11: 80,268,798 (GRCm39)	S4P	possibly damaging	Het
Abca13	T	A	11: 9,241,867 (GRCm39)	N1243K	probably damaging	Het
Adgrg6	A	T	10: 14,303,943 (GRCm39)	S824T	probably benign	Het
Armh4	G	T	14: 50,010,993 (GRCm39)	A238E	probably damaging	Het
C3ar1	T	A	6: 122,827,059 (GRCm39)	Y386F	probably damaging	Het
Cdc14a	T	C	3: 116,087,577 (GRCm39)	N527S	probably benign	Het
Cfap69	A	T	5: 5,669,085 (GRCm39)		probably benign	Het
Col7a1	C	T	9: 108,804,631 (GRCm39)	P2279S	unknown	Het
Crb2	G	A	2: 37,683,252 (GRCm39)	G918D	probably benign	Het
Dcn	C	A	10: 97,349,479 (GRCm39)	N250K	probably damaging	Het
Dctn5	G	A	7: 121,732,466 (GRCm39)		probably benign	Het
Ddx55	T	C	5: 124,694,821 (GRCm39)	V83A	probably damaging	Het
Dnaja2	T	A	8: 86,265,876 (GRCm39)	H403L	possibly damaging	Het
Dpy19l4	T	C	4: 11,303,982 (GRCm39)	I143V	probably benign	Het
Efna5	G	T	17: 62,957,977 (GRCm39)	T93K	probably benign	Het
Eml6	A	G	11: 29,843,201 (GRCm39)	V171A	possibly damaging	Het
Esyt1	C	G	10: 128,347,955 (GRCm39)	V942L	probably benign	Het
Fam184a	C	A	10: 53,509,802 (GRCm39)	E126*	probably null	Het
Fam78a	C	A	2: 31,973,035 (GRCm39)		probably benign	Het
Fat2	A	G	11: 55,202,892 (GRCm39)	Y61H	probably benign	Het
Fbxw14	A	T	9: 109,105,211 (GRCm39)	M318K	probably damaging	Het
Gm14295	A	G	2: 176,500,871 (GRCm39)	I120M	probably benign	Het
Gm14403	T	A	2: 177,200,311 (GRCm39)	Y86N	probably benign	Het
Gmcl1	G	T	6: 86,698,408 (GRCm39)	A163E	probably damaging	Het
Gpr137b	T	C	13: 13,533,991 (GRCm39)	Y355C		Het
Gpr55	T	C	1: 85,869,419 (GRCm39)	D54G	probably benign	Het
Gtf2b	T	G	3: 142,483,975 (GRCm39)	S50A	probably damaging	Het
Ifit3	A	T	19: 34,565,480 (GRCm39)	E342V	possibly damaging	Het
Iqgap3	T	A	3: 88,011,609 (GRCm39)	I798N	probably damaging	Het
Kplce	A	T	3: 92,776,202 (GRCm39)	Y160*	probably null	Het
Lpin1	T	C	12: 16,613,685 (GRCm39)	D494G		Het
Lsm12	T	C	11: 102,056,235 (GRCm39)	E149G	possibly damaging	Het
Mtfr2	T	C	10: 20,228,603 (GRCm39)	S50P	possibly damaging	Het
Ndnf	T	C	6: 65,680,414 (GRCm39)	M231T	probably benign	Het
Noc3l	A	T	19: 38,800,873 (GRCm39)	V203E	probably benign	Het
Or1e27-ps1	G	T	11: 73,555,988 (GRCm39)	K184N	possibly damaging	Het
Or52h2	C	A	7: 103,839,017 (GRCm39)	L132F	probably damaging	Het
Or5c1	A	T	2: 37,222,346 (GRCm39)	T196S	probably damaging	Het
Or9r7	A	T	10: 129,962,469 (GRCm39)	Y152*	probably null	Het
Pcnx1	C	T	12: 81,965,593 (GRCm39)	R59*	probably null	Het
Pde6b	C	T	5: 108,573,118 (GRCm39)	P496L	probably benign	Het
Plppr1	A	T	4: 49,300,942 (GRCm39)	M92L	probably benign	Het
Pphln1-ps1	C	T	16: 13,495,623 (GRCm39)	R241C	probably damaging	Het
Ptprk	C	G	10: 28,259,565 (GRCm39)	S335C	possibly damaging	Het
Rars2	T	A	4: 34,650,217 (GRCm39)	M334K	probably benign	Het
Rasl10a	A	T	11: 5,009,823 (GRCm39)	I124F	probably damaging	Het
Rgs12	T	A	5: 35,183,374 (GRCm39)	V1007E	possibly damaging	Het
Rnf122	T	A	8: 31,618,608 (GRCm39)	C119S	probably damaging	Het
Scn11a	T	A	9: 119,584,149 (GRCm39)	I1489F	probably damaging	Het
Setd6	C	A	8: 96,443,316 (GRCm39)	S186R	probably benign	Het
Tex19.1	A	G	11: 121,038,148 (GRCm39)	T169A	probably benign	Het
Trappc13	T	C	13: 104,281,052 (GRCm39)	M337V	probably benign	Het
Treml2	A	T	17: 48,609,762 (GRCm39)	K65*	probably null	Het
Ubxn4	T	C	1: 128,183,933 (GRCm39)	S98P	probably damaging	Het
Wrnip1	A	G	13: 33,005,960 (GRCm39)	S601G	probably benign	Het
Zfp1006	A	T	8: 129,946,555 (GRCm39)	L90H	probably damaging	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
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'- GTGTACTAAATGGGCTCTCAAGTG -3'
(R):5'- TCTCATCAGAAGGGTCCTTGG -3'

Sequencing Primer
(F):5'- CTCTCAAGTGAAGACAAGGCCTG -3'
(R):5'- ATCAGAAGGGTCCTTGGCTCAG -3'

Posted On

2020-01-23