Incidental Mutation 'R6422:Tpp1'
| ID |
518211 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Tpp1
|
| Ensembl Gene |
ENSMUSG00000030894 |
| Gene Name |
tripeptidyl peptidase I |
| Synonyms |
Cln2 |
| MMRRC Submission |
044563-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R6422 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Validated
|
| Chromosome |
7 |
| Chromosomal Location |
105394018-105401442 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
G to A
at 105396163 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Threonine to Isoleucine
at position 512
(T512I)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000033184
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000033182]
[ENSMUST00000033184]
[ENSMUST00000141116]
[ENSMUST00000149695]
[ENSMUST00000163389]
[ENSMUST00000210066]
|
| AlphaFold |
O89023 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000033182
|
| SMART Domains |
Protein: ENSMUSP00000033182
Gene: ENSMUSG00000030890
| Domain | Start | End | E-Value | Type |
|---|
|
ANK
|
33 |
62 |
4.71e-6 |
SMART |
|
ANK
|
66 |
95 |
1.04e-7 |
SMART |
|
ANK
|
99 |
128 |
1.02e-1 |
SMART |
|
Pfam:Pkinase
|
193 |
445 |
1.5e-25 |
PFAM |
|
Pfam:Pkinase_Tyr
|
193 |
446 |
7.2e-40 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000033184
AA Change: T512I
PolyPhen 2
Score 0.011 (Sensitivity: 0.96; Specificity: 0.78)
|
| SMART Domains |
Protein: ENSMUSP00000033184
Gene: ENSMUSG00000030894
AA Change: T512I
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
2 |
17 |
N/A |
INTRINSIC |
|
Pro-kuma_activ
|
32 |
176 |
4.53e-50 |
SMART |
|
low complexity region
|
177 |
189 |
N/A |
INTRINSIC |
|
Pfam:Peptidase_S8
|
251 |
492 |
1.1e-9 |
PFAM |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000054556
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000127298
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000130565
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000131683
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000141116
|
| SMART Domains |
Protein: ENSMUSP00000118105
Gene: ENSMUSG00000043866
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
17 |
39 |
N/A |
INTRINSIC |
|
low complexity region
|
45 |
91 |
N/A |
INTRINSIC |
|
Pfam:TFIID_30kDa
|
128 |
177 |
6.1e-30 |
PFAM |
|
low complexity region
|
181 |
192 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000149695
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000210730
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000211560
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000211659
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000210840
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000210395
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000163389
|
| SMART Domains |
Protein: ENSMUSP00000130341
Gene: ENSMUSG00000030890
| Domain | Start | End | E-Value | Type |
|---|
|
ANK
|
33 |
62 |
4.71e-6 |
SMART |
|
ANK
|
66 |
95 |
1.04e-7 |
SMART |
|
ANK
|
99 |
128 |
1.02e-1 |
SMART |
|
Pfam:Pkinase_Tyr
|
193 |
446 |
4e-39 |
PFAM |
|
Pfam:Pkinase
|
195 |
445 |
3e-23 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000210066
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000211204
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000152508
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000146999
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000210018
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000211226
|
| Coding Region Coverage |
- 1x: 99.9%
- 3x: 99.5%
- 10x: 97.5%
- 20x: 91.8%
|
| Validation Efficiency |
97% (30/31) |
| MGI Phenotype |
FUNCTION: This gene encodes a lysosomal serine protease that cleaves N-terminal tripeptides from protein substrates. The encoded preproprotein undergoes autocatalytic processing to generate a mature enzyme. Mice lacking the encoded protein exhibit a progressive neurodegeneration and a greatly shortened lifespan. At the cellular level, mice lacking the encoded protein exhibit accumulation of autofluorescent lipopigments. Mutations in the human ortholog of this gene cause classical late-infantile neuronal ceroid lipofuscinosis. [provided by RefSeq, Nov 2015]
PHENOTYPE: Mice homozygous for targeted mutations exhibit progressive motor defects, reduced lifespan, and respiratory difficulty. One mutation also shows extensive neuronal degeneration and an accumulation of lysosomal storage material. Mice homozygous for a different allele exhibit prenatal lethality. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 31 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| A430005L14Rik |
T |
A |
4: 154,045,381 (GRCm39) |
F137I |
probably damaging |
Het |
| Adam11 |
A |
G |
11: 102,665,109 (GRCm39) |
K417R |
possibly damaging |
Het |
| Btbd9 |
G |
A |
17: 30,749,230 (GRCm39) |
A28V |
probably benign |
Het |
| Cabin1 |
A |
G |
10: 75,492,626 (GRCm39) |
Y1890H |
probably damaging |
Het |
| Castor2 |
T |
A |
5: 134,164,549 (GRCm39) |
M170K |
probably benign |
Het |
| Cep162 |
G |
T |
9: 87,114,069 (GRCm39) |
N334K |
possibly damaging |
Het |
| Cep85l |
A |
T |
10: 53,167,876 (GRCm39) |
M634K |
possibly damaging |
Het |
| Col20a1 |
C |
A |
2: 180,656,612 (GRCm39) |
T1161N |
possibly damaging |
Het |
| Dip2b |
T |
A |
15: 100,096,892 (GRCm39) |
D1155E |
probably damaging |
Het |
| Dlst |
T |
A |
12: 85,177,659 (GRCm39) |
|
probably null |
Het |
| Dsc1 |
A |
C |
18: 20,228,090 (GRCm39) |
L422R |
probably damaging |
Het |
| Gcn1 |
T |
C |
5: 115,747,603 (GRCm39) |
W1699R |
probably damaging |
Het |
| Gm14443 |
G |
A |
2: 175,012,174 (GRCm39) |
Q91* |
probably null |
Het |
| Gm8159 |
T |
C |
14: 15,850,210 (GRCm39) |
I143T |
probably damaging |
Het |
| Il4i1 |
G |
T |
7: 44,489,560 (GRCm39) |
A442S |
probably damaging |
Het |
| Kif26a |
T |
G |
12: 112,135,309 (GRCm39) |
L337R |
possibly damaging |
Het |
| Lat2 |
T |
C |
5: 134,632,015 (GRCm39) |
D144G |
probably benign |
Het |
| Ndst1 |
G |
T |
18: 60,836,025 (GRCm39) |
H419Q |
probably benign |
Het |
| Notch4 |
T |
C |
17: 34,803,533 (GRCm39) |
I1484T |
probably benign |
Het |
| Or51v14 |
T |
G |
7: 103,261,221 (GRCm39) |
E113A |
probably damaging |
Het |
| Paxbp1 |
A |
T |
16: 90,820,332 (GRCm39) |
M697K |
probably benign |
Het |
| Plxnb1 |
A |
G |
9: 108,937,992 (GRCm39) |
Y1246C |
probably damaging |
Het |
| Prr5 |
C |
T |
15: 84,578,005 (GRCm39) |
R96C |
probably damaging |
Het |
| Ptpn7 |
G |
T |
1: 135,062,240 (GRCm39) |
C62F |
probably damaging |
Het |
| Rsrc1 |
C |
T |
3: 66,901,982 (GRCm39) |
P44L |
unknown |
Het |
| Sall2 |
A |
C |
14: 52,550,181 (GRCm39) |
*1003G |
probably null |
Het |
| Slc5a4b |
C |
A |
10: 75,939,696 (GRCm39) |
V147F |
probably damaging |
Het |
| Snapc4 |
A |
G |
2: 26,258,315 (GRCm39) |
W702R |
probably benign |
Het |
| Tbc1d32 |
A |
T |
10: 55,904,157 (GRCm39) |
C1203* |
probably null |
Het |
| Tmprss11d |
T |
A |
5: 86,457,284 (GRCm39) |
Y125F |
probably damaging |
Het |
| Tyw5 |
G |
A |
1: 57,440,570 (GRCm39) |
A64V |
probably damaging |
Het |
|
| Other mutations in Tpp1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL01480:Tpp1
|
APN |
7 |
105,398,260 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01520:Tpp1
|
APN |
7 |
105,396,936 (GRCm39) |
missense |
probably benign |
0.32 |
|
IGL01796:Tpp1
|
APN |
7 |
105,396,857 (GRCm39) |
unclassified |
probably benign |
|
|
IGL01797:Tpp1
|
APN |
7 |
105,398,459 (GRCm39) |
missense |
probably benign |
0.07 |
|
IGL01923:Tpp1
|
APN |
7 |
105,400,857 (GRCm39) |
missense |
probably benign |
0.34 |
|
IGL02400:Tpp1
|
APN |
7 |
105,396,238 (GRCm39) |
missense |
possibly damaging |
0.91 |
|
IGL02411:Tpp1
|
APN |
7 |
105,398,826 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02423:Tpp1
|
APN |
7 |
105,398,907 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02672:Tpp1
|
APN |
7 |
105,396,168 (GRCm39) |
missense |
probably benign |
|
|
IGL03180:Tpp1
|
APN |
7 |
105,395,856 (GRCm39) |
missense |
probably benign |
|
|
R0709:Tpp1
|
UTSW |
7 |
105,398,814 (GRCm39) |
missense |
probably benign |
0.19 |
|
R0711:Tpp1
|
UTSW |
7 |
105,398,626 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1222:Tpp1
|
UTSW |
7 |
105,395,948 (GRCm39) |
missense |
probably benign |
0.05 |
|
R1673:Tpp1
|
UTSW |
7 |
105,396,880 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R1799:Tpp1
|
UTSW |
7 |
105,399,515 (GRCm39) |
missense |
probably benign |
0.00 |
|
R1822:Tpp1
|
UTSW |
7 |
105,398,854 (GRCm39) |
missense |
probably benign |
|
|
R1984:Tpp1
|
UTSW |
7 |
105,400,905 (GRCm39) |
missense |
probably benign |
0.04 |
|
R2109:Tpp1
|
UTSW |
7 |
105,399,177 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4304:Tpp1
|
UTSW |
7 |
105,399,516 (GRCm39) |
missense |
possibly damaging |
0.70 |
|
R4618:Tpp1
|
UTSW |
7 |
105,400,913 (GRCm39) |
missense |
probably benign |
0.05 |
|
R4746:Tpp1
|
UTSW |
7 |
105,398,158 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4764:Tpp1
|
UTSW |
7 |
105,398,458 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4837:Tpp1
|
UTSW |
7 |
105,395,856 (GRCm39) |
missense |
probably benign |
|
|
R4855:Tpp1
|
UTSW |
7 |
105,395,930 (GRCm39) |
missense |
probably benign |
|
|
R5015:Tpp1
|
UTSW |
7 |
105,401,232 (GRCm39) |
unclassified |
probably benign |
|
|
R5677:Tpp1
|
UTSW |
7 |
105,396,743 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5916:Tpp1
|
UTSW |
7 |
105,398,587 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R6149:Tpp1
|
UTSW |
7 |
105,396,934 (GRCm39) |
missense |
probably benign |
0.00 |
|
R6291:Tpp1
|
UTSW |
7 |
105,396,223 (GRCm39) |
missense |
probably benign |
0.05 |
|
R6671:Tpp1
|
UTSW |
7 |
105,398,814 (GRCm39) |
missense |
probably benign |
0.19 |
|
R6841:Tpp1
|
UTSW |
7 |
105,398,171 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R6851:Tpp1
|
UTSW |
7 |
105,398,919 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7022:Tpp1
|
UTSW |
7 |
105,398,129 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7106:Tpp1
|
UTSW |
7 |
105,399,118 (GRCm39) |
missense |
possibly damaging |
0.67 |
|
R7260:Tpp1
|
UTSW |
7 |
105,396,704 (GRCm39) |
missense |
probably benign |
0.00 |
|
R7485:Tpp1
|
UTSW |
7 |
105,398,751 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8185:Tpp1
|
UTSW |
7 |
105,398,430 (GRCm39) |
critical splice donor site |
probably null |
|
|
R8204:Tpp1
|
UTSW |
7 |
105,399,522 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R8513:Tpp1
|
UTSW |
7 |
105,398,786 (GRCm39) |
missense |
possibly damaging |
0.93 |
|
R8863:Tpp1
|
UTSW |
7 |
105,398,814 (GRCm39) |
missense |
probably benign |
0.19 |
|
R8937:Tpp1
|
UTSW |
7 |
105,396,626 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9003:Tpp1
|
UTSW |
7 |
105,398,156 (GRCm39) |
missense |
probably benign |
0.07 |
|
R9178:Tpp1
|
UTSW |
7 |
105,400,846 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9352:Tpp1
|
UTSW |
7 |
105,398,881 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9501:Tpp1
|
UTSW |
7 |
105,398,464 (GRCm39) |
missense |
probably benign |
0.11 |
|
R9597:Tpp1
|
UTSW |
7 |
105,396,714 (GRCm39) |
missense |
probably benign |
|
|
R9683:Tpp1
|
UTSW |
7 |
105,398,104 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Predicted Primers |
PCR Primer
(F):5'- TCAGACAGGACTCATGGCAG -3'
(R):5'- ATCTTTGCAAGCATCATCCCTTAG -3'
Sequencing Primer
(F):5'- TCATGGCAGCCGTGGGTTAC -3'
(R):5'- TTGCAAGCATCATCCCTTAGAAGTC -3'
|
| Posted On |
2018-05-24 |
Incidental Mutation