Incidental Mutation 'R1799:Tpp1'
ID 202939
Institutional Source Beutler Lab
Gene Symbol Tpp1
Ensembl Gene ENSMUSG00000030894
Gene Name tripeptidyl peptidase I
Synonyms Cln2
MMRRC Submission 039829-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R1799 (G1)
Quality Score 225
Status Not validated
Chromosome 7
Chromosomal Location 105394018-105401442 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 105399515 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Aspartic acid to Glutamic Acid at position 84 (D84E)
Ref Sequence ENSEMBL: ENSMUSP00000033184 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000033184] [ENSMUST00000078482] [ENSMUST00000210066]
AlphaFold O89023
Predicted Effect probably benign
Transcript: ENSMUST00000033184
AA Change: D84E

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)
SMART Domains Protein: ENSMUSP00000033184
Gene: ENSMUSG00000030894
AA Change: D84E

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 unknown
Transcript: ENSMUST00000210066
AA Change: C38S
Predicted Effect noncoding transcript
Transcript: ENSMUST00000210395
Predicted Effect noncoding transcript
Transcript: ENSMUST00000210730
Predicted Effect noncoding transcript
Transcript: ENSMUST00000210840
Predicted Effect noncoding transcript
Transcript: ENSMUST00000211204
Predicted Effect noncoding transcript
Transcript: ENSMUST00000211226
Predicted Effect noncoding transcript
Transcript: ENSMUST00000211659
Predicted Effect noncoding transcript
Transcript: ENSMUST00000211560
Coding Region Coverage
  • 1x: 97.5%
  • 3x: 96.9%
  • 10x: 95.3%
  • 20x: 92.3%
Validation Efficiency
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: 102 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
A930011G23Rik A G 5: 99,382,435 (GRCm39) L271P probably benign Het
Adamts3 A C 5: 89,923,280 (GRCm39) D175E probably benign Het
Adcy4 T C 14: 56,008,929 (GRCm39) T833A probably benign Het
Adgrf5 A T 17: 43,750,958 (GRCm39) I508F probably damaging Het
Arhgap9 G T 10: 127,163,593 (GRCm39) V464L probably damaging Het
Atp10a T A 7: 58,474,182 (GRCm39) D1156E probably damaging Het
Atp2a1 A T 7: 126,049,314 (GRCm39) M576K probably benign Het
Atrx T C X: 104,891,235 (GRCm39) Q1536R probably damaging Het
Ccdc141 A C 2: 76,842,015 (GRCm39) V1472G possibly damaging Het
Cd84 A G 1: 171,700,317 (GRCm39) T145A possibly damaging Het
Celsr1 G T 15: 85,916,886 (GRCm39) N362K probably damaging Het
Cep290 G A 10: 100,352,058 (GRCm39) A755T probably benign Het
Cfap70 T A 14: 20,445,067 (GRCm39) E1071V probably damaging Het
Cps1 T C 1: 67,248,801 (GRCm39) V1176A probably damaging Het
Csf2rb2 A C 15: 78,181,268 (GRCm39) N41K probably damaging Het
Csn1s2a G A 5: 87,926,052 (GRCm39) V43M probably damaging Het
Cyp26b1 T C 6: 84,561,254 (GRCm39) D136G probably benign Het
Cyp7b1 A G 3: 18,151,616 (GRCm39) L199P probably benign Het
Dapk1 C T 13: 60,867,468 (GRCm39) T225I probably damaging Het
Dio2 T A 12: 90,696,680 (GRCm39) T103S probably benign Het
Dipk1a C A 5: 108,057,713 (GRCm39) V237F probably damaging Het
Dnhd1 T A 7: 105,304,974 (GRCm39) S339T probably benign Het
Drc1 A G 5: 30,523,841 (GRCm39) N737D probably damaging Het
Efhc1 C T 1: 21,049,762 (GRCm39) P541S probably benign Het
Elmo2 A T 2: 165,134,077 (GRCm39) I637N probably damaging Het
Eps15 T A 4: 109,240,034 (GRCm39) D492E probably damaging Het
Ermn G T 2: 57,938,249 (GRCm39) N121K probably benign Het
F5 A G 1: 164,021,100 (GRCm39) T1192A possibly damaging Het
Fbxo22 T C 9: 55,130,771 (GRCm39) F347L probably benign Het
Fbxw15 G A 9: 109,387,314 (GRCm39) S227F probably damaging Het
Foxj3 A G 4: 119,476,548 (GRCm39) N242S probably benign Het
Gjb3 G A 4: 127,220,224 (GRCm39) R103W probably damaging Het
Grm4 A G 17: 27,691,914 (GRCm39) V235A probably damaging Het
Gstm4 T C 3: 107,950,874 (GRCm39) N74S probably damaging Het
Gtf3c3 A G 1: 54,459,583 (GRCm39) V393A possibly damaging Het
Hltf T A 3: 20,159,855 (GRCm39) L702H probably damaging Het
Inpp4a T A 1: 37,432,059 (GRCm39) V153E possibly damaging Het
Kmt5c T C 7: 4,745,729 (GRCm39) probably null Het
Kynu A G 2: 43,494,169 (GRCm39) R201G possibly damaging Het
Lrp2 T A 2: 69,333,874 (GRCm39) T1456S probably benign Het
Lrrc40 G A 3: 157,742,441 (GRCm39) V19I probably benign Het
M1ap T A 6: 82,982,491 (GRCm39) C258* probably null Het
Man2a1 T C 17: 65,059,452 (GRCm39) L1113P probably benign Het
Man2a1 C T 17: 64,976,492 (GRCm39) R427W probably damaging Het
Meikin C A 11: 54,308,613 (GRCm39) Q404K probably benign Het
Mfsd4a T C 1: 131,981,334 (GRCm39) I222V possibly damaging Het
N4bp2 A G 5: 65,964,168 (GRCm39) N739S possibly damaging Het
Ncoa2 A T 1: 13,232,517 (GRCm39) probably null Het
Nisch G T 14: 30,899,228 (GRCm39) probably benign Het
Nmur2 A G 11: 55,920,447 (GRCm39) V266A probably damaging Het
Npcd G A 15: 79,712,987 (GRCm39) R147C probably damaging Het
Or4q3 T A 14: 50,583,537 (GRCm39) M121L probably benign Het
Or5ac25 T A 16: 59,182,243 (GRCm39) I113F probably benign Het
Pals2 T A 6: 50,173,525 (GRCm39) M463K probably damaging Het
Parp4 A T 14: 56,885,589 (GRCm39) H1556L unknown Het
Pcdh9 G T 14: 94,126,107 (GRCm39) A21E probably benign Het
Phtf1 A G 3: 103,903,958 (GRCm39) E436G probably benign Het
Piezo2 C A 18: 63,165,911 (GRCm39) probably null Het
Piezo2 T C 18: 63,241,158 (GRCm39) Y690C probably damaging Het
Pla2g4f T C 2: 120,141,549 (GRCm39) R183G possibly damaging Het
Plxnd1 T C 6: 115,971,018 (GRCm39) D250G probably damaging Het
Ppig A G 2: 69,579,744 (GRCm39) D426G unknown Het
Ppp3cb T C 14: 20,574,540 (GRCm39) E185G possibly damaging Het
Qsox1 A T 1: 155,670,364 (GRCm39) M151K probably null Het
Ralgapa2 T C 2: 146,184,648 (GRCm39) E1453G probably benign Het
Rnf167 G A 11: 70,540,838 (GRCm39) V191I probably benign Het
Rp1 T C 1: 4,419,055 (GRCm39) K686E possibly damaging Het
Ryr1 T G 7: 28,767,046 (GRCm39) Q2979P probably damaging Het
Scaf1 T A 7: 44,657,443 (GRCm39) I479F probably damaging Het
Septin8 A G 11: 53,425,310 (GRCm39) T68A probably benign Het
Sh3rf1 A T 8: 61,825,661 (GRCm39) N552I probably damaging Het
Shoc1 A T 4: 59,099,383 (GRCm39) V103D possibly damaging Het
Slc1a3 A G 15: 8,717,888 (GRCm39) L68P probably damaging Het
Slc39a6 G A 18: 24,718,524 (GRCm39) P511L probably benign Het
Slc9c1 A G 16: 45,374,652 (GRCm39) Y339C probably damaging Het
Smarcal1 G T 1: 72,625,120 (GRCm39) C89F probably damaging Het
Smu1 A T 4: 40,745,537 (GRCm39) M261K probably damaging Het
Spag8 T G 4: 43,653,087 (GRCm39) probably benign Het
Spag8 T C 4: 43,653,345 (GRCm39) probably benign Het
Spata31d1a T C 13: 59,851,216 (GRCm39) D304G probably benign Het
Spdl1 A T 11: 34,711,856 (GRCm39) L298* probably null Het
Stac2 C T 11: 97,930,444 (GRCm39) probably null Het
Stag1 A G 9: 100,835,515 (GRCm39) probably null Het
Stpg2 C T 3: 139,125,542 (GRCm39) P445L probably damaging Het
Sult2a8 A T 7: 14,157,451 (GRCm39) V128E probably damaging Het
Synm A G 7: 67,385,707 (GRCm39) F210L probably damaging Het
Tbck C G 3: 132,480,263 (GRCm39) A714G probably benign Het
Tcerg1 A T 18: 42,694,012 (GRCm39) Y711F possibly damaging Het
Tnfrsf25 A G 4: 152,201,465 (GRCm39) T98A probably benign Het
Togaram2 T C 17: 71,998,450 (GRCm39) S218P probably damaging Het
Trim30d G T 7: 104,132,682 (GRCm39) Q202K probably damaging Het
Trim37 T A 11: 87,068,845 (GRCm39) V397E probably damaging Het
Triml1 A T 8: 43,583,512 (GRCm39) I363N probably damaging Het
Trpm6 T A 19: 18,869,363 (GRCm39) probably null Het
Tsc2 T C 17: 24,823,382 (GRCm39) S1055G probably benign Het
Ubr5 T C 15: 37,989,621 (GRCm39) D2065G probably damaging Het
Uggt2 G T 14: 119,269,688 (GRCm39) P948Q probably benign Het
Vps13c A T 9: 67,851,399 (GRCm39) S2345C probably damaging Het
Wtap G T 17: 13,199,771 (GRCm39) R48S possibly damaging Het
Zbtb38 A G 9: 96,570,934 (GRCm39) V50A probably damaging Het
Zcchc2 T A 1: 105,958,017 (GRCm39) S829R probably benign Het
Zfp385b T C 2: 77,246,316 (GRCm39) D237G 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
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
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'- TCCCAGCACGCTTTAAACTC -3'
(R):5'- TGACGTTTCATGTCTCTCGAG -3'

Sequencing Primer
(F):5'- ACGCTTTAAACTCCCCCAATTGG -3'
(R):5'- GTTTCATGTCTCTCGAGCCTTTTC -3'
Posted On 2014-06-23