Incidental Mutation 'R0711:Tpp1'
ID 62739
Institutional Source Beutler Lab
Gene Symbol Tpp1
Ensembl Gene ENSMUSG00000030894
Gene Name tripeptidyl peptidase I
Synonyms Cln2
MMRRC Submission 038894-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R0711 (G1)
Quality Score 209
Status Validated
Chromosome 7
Chromosomal Location 105394018-105401442 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 105398626 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Leucine to Proline at position 230 (L230P)
Ref Sequence ENSEMBL: ENSMUSP00000033184 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000033184] [ENSMUST00000078482] [ENSMUST00000210066]
AlphaFold O89023
Predicted Effect probably damaging
Transcript: ENSMUST00000033184
AA Change: L230P

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000033184
Gene: ENSMUSG00000030894
AA Change: L230P

DomainStartEndE-ValueType
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 probably benign
Transcript: ENSMUST00000078482
SMART Domains Protein: ENSMUSP00000077574
Gene: ENSMUSG00000036862

DomainStartEndE-ValueType
signal peptide 1 36 N/A INTRINSIC
CA 58 135 5.2e-11 SMART
CA 159 247 6.1e-17 SMART
CA 271 354 2.6e-30 SMART
CA 382 464 7.8e-26 SMART
CA 489 570 1.2e-34 SMART
CA 594 677 1.9e-27 SMART
CA 701 782 5.3e-11 SMART
CA 806 886 1e-12 SMART
CA 910 990 3.3e-14 SMART
CA 1016 1097 3.6e-18 SMART
CA 1121 1203 3.1e-34 SMART
CA 1233 1307 8.8e-16 SMART
low complexity region 1323 1335 N/A INTRINSIC
CA 1344 1427 9.9e-9 SMART
CA 1451 1537 1.5e-23 SMART
CA 1560 1640 7.2e-32 SMART
CA 1664 1742 1.8e-31 SMART
CA 1765 1846 7.8e-30 SMART
CA 1870 1951 3.7e-26 SMART
low complexity region 1957 1965 N/A INTRINSIC
CA 1979 2059 1.1e-6 SMART
CA 2083 2162 2.7e-18 SMART
CA 2186 2268 2.2e-26 SMART
CA 2291 2367 1e-18 SMART
CA 2391 2473 1.8e-23 SMART
CA 2497 2593 3.5e-21 SMART
CA 2617 2697 1.2e-25 SMART
CA 2721 2804 1.9e-18 SMART
CA 2828 2919 3e-3 SMART
transmembrane domain 2932 2954 N/A INTRINSIC
low complexity region 3001 3017 N/A INTRINSIC
low complexity region 3046 3055 N/A INTRINSIC
low complexity region 3088 3097 N/A INTRINSIC
low complexity region 3185 3196 N/A INTRINSIC
low complexity region 3237 3259 N/A INTRINSIC
Predicted Effect noncoding transcript
Transcript: ENSMUST00000210018
Predicted Effect probably benign
Transcript: ENSMUST00000210066
Predicted Effect noncoding transcript
Transcript: ENSMUST00000210395
Predicted Effect noncoding transcript
Transcript: ENSMUST00000210730
Predicted Effect noncoding transcript
Transcript: ENSMUST00000211560
Predicted Effect noncoding transcript
Transcript: ENSMUST00000211204
Predicted Effect noncoding transcript
Transcript: ENSMUST00000211226
Predicted Effect noncoding transcript
Transcript: ENSMUST00000211659
Predicted Effect noncoding transcript
Transcript: ENSMUST00000210840
Meta Mutation Damage Score 0.8917 question?
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.4%
  • 10x: 96.4%
  • 20x: 91.4%
Validation Efficiency 100% (91/91)
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: 68 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1110002E22Rik T A 3: 137,773,986 (GRCm39) D1058E probably damaging Het
4933405L10Rik A T 8: 106,435,563 (GRCm39) probably null Het
Adamtsl3 T A 7: 82,114,907 (GRCm39) probably benign Het
Afdn C T 17: 14,072,698 (GRCm39) P874S probably damaging Het
Ankrd6 G A 4: 32,815,326 (GRCm39) A391V probably damaging Het
Arhgef28 T G 13: 98,067,762 (GRCm39) T1388P probably damaging Het
Asxl3 G T 18: 22,657,508 (GRCm39) M1839I probably benign Het
BC005537 T C 13: 24,989,923 (GRCm39) F129L probably damaging Het
Celf2 A G 2: 6,726,226 (GRCm39) probably null Het
Chid1 C T 7: 141,076,590 (GRCm39) V325I probably benign Het
Cnn3 T A 3: 121,243,633 (GRCm39) D31E probably benign Het
Col12a1 G A 9: 79,559,317 (GRCm39) P1857L probably damaging Het
Cpeb1 T A 7: 81,001,618 (GRCm39) R430W probably benign Het
Daw1 T C 1: 83,169,059 (GRCm39) probably benign Het
Dcaf13 A G 15: 39,001,484 (GRCm39) Y264C probably damaging Het
Dnah6 T C 6: 73,064,585 (GRCm39) I2666V probably damaging Het
Dnai2 A C 11: 114,645,158 (GRCm39) D531A probably benign Het
Dock10 A T 1: 80,501,692 (GRCm39) F1833I probably damaging Het
Efhd2 C T 4: 141,587,183 (GRCm39) A200T probably damaging Het
Epb41l5 T A 1: 119,551,641 (GRCm39) probably benign Het
Ermp1 A G 19: 29,608,788 (GRCm39) Y164H possibly damaging Het
Gkn2 T C 6: 87,350,401 (GRCm39) probably benign Het
Golgb1 A T 16: 36,739,152 (GRCm39) Q2497L probably damaging Het
Gzme A T 14: 56,355,196 (GRCm39) M245K probably damaging Het
Iars2 A T 1: 185,054,585 (GRCm39) probably benign Het
Icosl T A 10: 77,909,775 (GRCm39) V240D probably damaging Het
Igsf3 T C 3: 101,334,709 (GRCm39) M262T probably benign Het
Ing3 G T 6: 21,971,236 (GRCm39) E336* probably null Het
Kat2a A T 11: 100,597,297 (GRCm39) V625E probably damaging Het
Ksr1 A G 11: 78,929,073 (GRCm39) probably benign Het
Lypd8 A T 11: 58,277,583 (GRCm39) M122L probably benign Het
Mdfi A T 17: 48,143,855 (GRCm39) probably benign Het
Med13 A G 11: 86,192,179 (GRCm39) probably benign Het
Msh6 C T 17: 88,294,112 (GRCm39) R956C probably damaging Het
Myo15b A G 11: 115,774,664 (GRCm39) E670G probably damaging Het
Myo1d A G 11: 80,375,158 (GRCm39) L972P probably damaging Het
Or4s2b A G 2: 88,509,018 (GRCm39) D266G probably damaging Het
Or51ai2 G A 7: 103,587,024 (GRCm39) A146T probably benign Het
Or7g12 T A 9: 18,899,447 (GRCm39) N54K probably benign Het
Pde8b C G 13: 95,244,325 (GRCm39) S143T possibly damaging Het
Pias4 G T 10: 80,993,364 (GRCm39) probably benign Het
Prkca A G 11: 107,872,480 (GRCm39) Y427H probably benign Het
Psg25 G A 7: 18,263,485 (GRCm39) Q113* probably null Het
Rab3gap2 T A 1: 184,982,123 (GRCm39) S392T probably damaging Het
Scrib A G 15: 75,938,756 (GRCm39) probably benign Het
Sdk2 A G 11: 113,793,970 (GRCm39) probably benign Het
Serpinb1c T A 13: 33,070,266 (GRCm39) probably benign Het
Serpinb9f T A 13: 33,511,904 (GRCm39) W136R probably damaging Het
Skic3 C T 13: 76,331,010 (GRCm39) P1480L probably damaging Het
Skint10 C A 4: 112,573,102 (GRCm39) probably benign Het
Slc25a13 T C 6: 6,117,128 (GRCm39) T196A probably damaging Het
Slc26a5 T C 5: 22,052,230 (GRCm39) H33R probably damaging Het
Slc27a6 T C 18: 58,731,829 (GRCm39) probably benign Het
Slitrk6 A T 14: 110,987,251 (GRCm39) Y819N probably damaging Het
Spata46 C T 1: 170,139,603 (GRCm39) Q201* probably null Het
Sptbn1 A T 11: 30,064,739 (GRCm39) V1920E probably damaging Het
Taf6l A G 19: 8,755,881 (GRCm39) F256L probably benign Het
Tmco3 T A 8: 13,342,039 (GRCm39) N104K probably damaging Het
Tmem200c A G 17: 69,149,249 (GRCm39) T611A probably damaging Het
Tmem202 T G 9: 59,432,655 (GRCm39) Y24S probably damaging Het
Trim56 C T 5: 137,141,846 (GRCm39) E557K probably benign Het
Trrap C T 5: 144,790,309 (GRCm39) L3590F probably damaging Het
Tulp4 A G 17: 6,189,387 (GRCm39) T70A possibly damaging Het
Vcp G C 4: 42,986,201 (GRCm39) A297G probably benign Het
Vwf T A 6: 125,603,234 (GRCm39) H861Q probably benign Het
Wdr64 T C 1: 175,599,751 (GRCm39) I536T probably benign Het
Zfp850 T C 7: 27,689,698 (GRCm39) N170S probably benign Het
Zfp87 G A 13: 74,524,544 (GRCm39) probably benign Het
Other mutations in Tpp1
AlleleSourceChrCoordTypePredicted EffectPPH 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
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
R6422:Tpp1 UTSW 7 105,396,163 (GRCm39) missense probably benign 0.01
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'- AGCAATACCAGGGCTACTGTAGACC -3'
(R):5'- TCTGTGCTCCGTCAGCGATACAAC -3'

Sequencing Primer
(F):5'- GGCTACTGTAGACCCAAGTG -3'
(R):5'- ACCTGACAGCCAAAGATGTG -3'
Posted On 2013-07-30