Incidental Mutation 'R9745:Th'
ID 732051
Institutional Source Beutler Lab
Gene Symbol Th
Ensembl Gene ENSMUSG00000000214
Gene Name tyrosine hydroxylase
Synonyms
MMRRC Submission
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R9745 (G1)
Quality Score 225.009
Status Not validated
Chromosome 7
Chromosomal Location 142892752-142931128 bp(-) (GRCm38)
Type of Mutation missense
DNA Base Change (assembly) T to G at 142895114 bp (GRCm38)
Zygosity Heterozygous
Amino Acid Change Aspartic acid to Alanine at position 342 (D342A)
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: D342A

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000000219
Gene: ENSMUSG00000000214
AA Change: D342A

DomainStartEndE-ValueType
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: D247A

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000101549
Gene: ENSMUSG00000000214
AA Change: D247A

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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: 99.8%
  • 3x: 99.6%
  • 10x: 99.1%
  • 20x: 97.9%
Validation Efficiency
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: 75 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4930430A15Rik T C 2: 111,169,663 M201V unknown Het
Agap2 T A 10: 127,083,511 H488Q unknown Het
Ces1b T C 8: 93,063,997 D388G probably benign Het
Ces1f T C 8: 93,263,112 D392G probably benign Het
Ces5a A G 8: 93,502,186 V472A probably damaging Het
Chst1 A G 2: 92,613,702 D173G possibly damaging Het
Cngb1 T G 8: 95,241,291 E1294A unknown Het
Cnmd T C 14: 79,650,410 I124V possibly damaging Het
Cntnap2 A T 6: 46,234,166 M505L probably benign Het
Cntnap4 T A 8: 112,665,176 M91K possibly damaging Het
Cstad A G 2: 30,608,185 T11A unknown Het
Cyp2j6 A T 4: 96,553,384 V23E possibly damaging Het
Dapk3 C A 10: 81,192,760 T388K unknown Het
Dennd6a G A 14: 26,599,663 G120R possibly damaging Het
Disp1 A C 1: 183,087,746 S1037A probably damaging Het
Egfem1 A T 3: 29,662,383 D334V probably damaging Het
Egflam C T 15: 7,303,938 V178M probably benign Het
Ehbp1 T C 11: 22,146,692 T291A probably benign Het
Eif5b G T 1: 38,045,648 V859F probably damaging Het
Fam161a A T 11: 23,023,495 Q459L possibly damaging Het
Fcgrt A C 7: 45,093,330 D342E probably damaging Het
Fchsd1 A C 18: 37,969,372 D34E probably benign Het
Foxo4 G A X: 101,258,349 S209N probably benign Het
Galt A T 4: 41,758,185 M317L possibly damaging Het
Gfm1 A G 3: 67,451,324 D416G possibly damaging Het
Glcci1 A T 6: 8,573,278 I256L probably benign Het
Gm17018 A T 19: 45,572,442 Q103L probably benign Het
Ibtk C T 9: 85,731,227 G228S probably benign Het
Il2rb T A 15: 78,488,199 D106V probably benign Het
Map3k6 A T 4: 133,252,472 I1261F probably damaging Het
Mast2 A G 4: 116,310,618 L1014P probably benign Het
Mcm2 G A 6: 88,891,747 Q343* probably null Het
Megf8 A G 7: 25,358,708 T2136A possibly damaging Het
Mmp28 G A 11: 83,451,457 T103I probably benign Het
Mtif2 G A 11: 29,526,587 probably benign Het
Mtus2 A T 5: 148,076,501 T35S possibly damaging Het
Ncoa2 A T 1: 13,174,968 I502N probably benign Het
Nek5 A C 8: 22,083,463 D492E probably benign Het
Nin T C 12: 70,043,125 E1172G Het
Nsmaf T A 4: 6,416,662 I544F possibly damaging Het
Oas3 T C 5: 120,761,219 D763G unknown Het
Olfr1040 C T 2: 86,145,907 V276M probably damaging Het
Olfr1102 T C 2: 87,002,143 V58A probably benign Het
Olfr1110 T A 2: 87,135,439 N294I probably damaging Het
Olfr1191-ps1 T A 2: 88,642,966 F66L probably benign Het
Olfr178 A T 16: 58,889,902 L106Q probably damaging Het
Olfr434 G A 6: 43,217,324 W137* probably null Het
Olfr550 A T 7: 102,578,654 D53V probably damaging Het
Pcdh7 T C 5: 57,722,280 probably null Het
Pitx3 A G 19: 46,136,221 S236P possibly damaging Het
Plscr5 T A 9: 92,205,449 I157N probably damaging Het
Preb T C 5: 30,959,388 N54D probably benign Het
Pskh1 C T 8: 105,929,772 A360V possibly damaging Het
Ptprk T C 10: 28,263,612 L111S possibly damaging Het
Reln T A 5: 21,947,527 I2314F probably damaging Het
Siglecg A G 7: 43,418,052 D681G probably damaging Het
Snx5 A G 2: 144,254,796 V283A probably benign Het
Srpk2 C A 5: 23,675,876 probably benign Het
Tacr1 T C 6: 82,492,638 Y168H possibly damaging Het
Tal1 G T 4: 115,063,360 R77L probably benign Het
Tdrd12 T C 7: 35,486,539 probably null Het
Tdrd7 A T 4: 45,994,310 N236I possibly damaging Het
Tdrd9 T C 12: 112,042,696 F1012S probably damaging Het
Tekt2 C T 4: 126,323,651 R207H probably damaging Het
Tert T A 13: 73,636,490 L685Q probably damaging Het
Tpsg1 G T 17: 25,372,518 V31L probably damaging Het
Traf3ip1 C G 1: 91,511,373 S337* probably null Het
Trpv6 A G 6: 41,623,069 F551S probably damaging Het
Ttc30b T C 2: 75,937,917 Y164C probably benign Het
Urah A G 7: 140,835,618 N23D probably benign Het
Vangl1 A C 3: 102,165,353 probably null Het
Zc3h6 A G 2: 129,017,235 E1062G probably benign Het
Zfp37 A T 4: 62,192,407 V181E possibly damaging Het
Zfp638 T A 6: 83,944,813 S641T probably benign Het
Zkscan16 A T 4: 58,957,473 H585L possibly damaging Het
Other mutations in Th
AlleleSourceChrCoordTypePredicted EffectPPH 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
R4870:Th UTSW 7 142894097 missense probably benign
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
R8970:Th UTSW 7 142893059 missense probably damaging 1.00
R9484:Th UTSW 7 142899883 nonsense probably null
Predicted Primers PCR Primer
(F):5'- CCCCTGGGACTTGTGTTACTAG -3'
(R):5'- GAGGACCCTGAACTTGTTGC -3'

Sequencing Primer
(F):5'- AGAAACAGTCTCTGCTTCGG -3'
(R):5'- GCCCAGTAATATCCGTGTGCAATG -3'
Posted On 2022-11-14