Incidental Mutation 'R0311:Th'
| ID |
25203 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Th
|
| Ensembl Gene |
ENSMUSG00000000214 |
| Gene Name |
tyrosine hydroxylase |
| Synonyms |
|
| MMRRC Submission |
038521-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R0311 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
7 |
| Chromosomal Location |
142446516-142453732 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to C
at 142449778 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Glutamic Acid to Glycine
at position 41
(E41G)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000000219]
[ENSMUST00000105929]
[ENSMUST00000123057]
[ENSMUST00000124951]
[ENSMUST00000140344]
|
| AlphaFold |
P24529 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000000219
AA Change: E229G
PolyPhen 2
Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)
|
| SMART Domains |
Protein: ENSMUSP00000000219
Gene: ENSMUSG00000000214
AA Change: E229G
| 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: E134G
PolyPhen 2
Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)
|
| SMART Domains |
Protein: ENSMUSP00000101549
Gene: ENSMUSG00000000214
AA Change: E134G
| 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 damaging
Transcript: ENSMUST00000124951
AA Change: E229G
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000122876
Gene: ENSMUSG00000000214
AA Change: E229G
| 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 damaging
Transcript: ENSMUST00000138482
AA Change: E41G
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| 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 |
0.9686 |
| Coding Region Coverage |
- 1x: 98.9%
- 3x: 97.9%
- 10x: 95.6%
- 20x: 91.6%
|
| Validation Efficiency |
100% (43/43) |
| 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: 42 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Abca15 |
A |
C |
7: 120,002,127 (GRCm39) |
M1547L |
probably damaging |
Het |
| Abcb4 |
A |
G |
5: 8,984,243 (GRCm39) |
K658E |
probably benign |
Het |
| Abr |
A |
G |
11: 76,399,953 (GRCm39) |
S15P |
possibly damaging |
Het |
| Adgrb2 |
G |
C |
4: 129,910,922 (GRCm39) |
A1168P |
probably damaging |
Het |
| Adgre4 |
A |
T |
17: 56,109,010 (GRCm39) |
E339V |
probably benign |
Het |
| Asprv1 |
T |
C |
6: 86,605,822 (GRCm39) |
W223R |
probably damaging |
Het |
| Ccdc89 |
A |
G |
7: 90,075,901 (GRCm39) |
E37G |
probably damaging |
Het |
| Cd48 |
C |
A |
1: 171,527,148 (GRCm39) |
Y191* |
probably null |
Het |
| Chd4 |
T |
C |
6: 125,078,628 (GRCm39) |
I257T |
probably benign |
Het |
| Clca4b |
T |
C |
3: 144,638,257 (GRCm39) |
M2V |
probably benign |
Het |
| Dnah11 |
A |
T |
12: 118,090,868 (GRCm39) |
D1025E |
probably benign |
Het |
| Erich5 |
A |
G |
15: 34,473,085 (GRCm39) |
*363W |
probably null |
Het |
| Etl4 |
A |
G |
2: 20,811,940 (GRCm39) |
D1341G |
probably damaging |
Het |
| Fbxw11 |
A |
G |
11: 32,672,083 (GRCm39) |
T184A |
probably benign |
Het |
| Fktn |
A |
G |
4: 53,744,620 (GRCm39) |
Q300R |
probably benign |
Het |
| G3bp1 |
T |
C |
11: 55,389,452 (GRCm39) |
F383L |
probably damaging |
Het |
| Gdpd3 |
G |
A |
7: 126,366,361 (GRCm39) |
R66Q |
possibly damaging |
Het |
| Hexb |
A |
G |
13: 97,320,327 (GRCm39) |
|
probably benign |
Het |
| Kdm4b |
A |
G |
17: 56,693,200 (GRCm39) |
R346G |
probably benign |
Het |
| Mbtd1 |
T |
A |
11: 93,812,183 (GRCm39) |
|
probably null |
Het |
| Med23 |
T |
A |
10: 24,773,256 (GRCm39) |
C653S |
possibly damaging |
Het |
| Nwd2 |
A |
T |
5: 63,962,341 (GRCm39) |
I642L |
probably damaging |
Het |
| Or5b12 |
T |
A |
19: 12,897,460 (GRCm39) |
Y71F |
possibly damaging |
Het |
| Or5b21 |
A |
G |
19: 12,839,233 (GRCm39) |
I31M |
probably benign |
Het |
| Or8b48 |
T |
C |
9: 38,450,593 (GRCm39) |
V134A |
probably benign |
Het |
| Pbld2 |
T |
C |
10: 62,890,286 (GRCm39) |
|
probably null |
Het |
| Pkd1l3 |
C |
G |
8: 110,350,281 (GRCm39) |
D375E |
possibly damaging |
Het |
| Pkd1l3 |
G |
A |
8: 110,350,295 (GRCm39) |
S380N |
probably benign |
Het |
| Plpp2 |
C |
T |
10: 79,363,414 (GRCm39) |
R77K |
probably damaging |
Het |
| Pym1 |
G |
T |
10: 128,601,853 (GRCm39) |
R168L |
possibly damaging |
Het |
| Rbm4 |
T |
C |
19: 4,837,584 (GRCm39) |
Y300C |
probably damaging |
Het |
| Rnf207 |
A |
G |
4: 152,400,236 (GRCm39) |
C175R |
probably damaging |
Het |
| Sema6a |
G |
A |
18: 47,423,112 (GRCm39) |
|
probably null |
Het |
| Speg |
T |
C |
1: 75,407,581 (GRCm39) |
V3196A |
probably damaging |
Het |
| Syne1 |
T |
A |
10: 5,298,943 (GRCm39) |
I1048L |
possibly damaging |
Het |
| Tmx4 |
T |
A |
2: 134,440,446 (GRCm39) |
*336L |
probably null |
Het |
| Tnfrsf18 |
T |
C |
4: 156,110,872 (GRCm39) |
V10A |
possibly damaging |
Het |
| Tnxb |
A |
T |
17: 34,935,958 (GRCm39) |
I2670F |
probably damaging |
Het |
| Tpx2 |
T |
C |
2: 152,732,412 (GRCm39) |
V562A |
probably damaging |
Het |
| Vmn2r73 |
A |
G |
7: 85,520,997 (GRCm39) |
S324P |
probably benign |
Het |
| Vps18 |
T |
C |
2: 119,127,846 (GRCm39) |
Y890H |
probably benign |
Het |
| Ythdc1 |
G |
A |
5: 86,983,564 (GRCm39) |
D670N |
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 |
|
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 |
|
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'- GCCGATAGCGACATCTCTGAATGAC -3'
(R):5'- CAATACAAGCAGTAAGGAGCCTGCC -3'
Sequencing Primer
(F):5'- GAATGACCTGATTATTTTGGGCCAC -3'
(R):5'- agactggggcagagagg -3'
|
| Posted On |
2013-04-16 |
Incidental Mutation