Mutagenetix > Incidental Mutation

Incidental Mutation 'R7485:Tpp1'

580073

Institutional Source

Beutler Lab

Gene Symbol

Tpp1

Ensembl Gene

ENSMUSG00000030894

Gene Name

tripeptidyl peptidase I

Synonyms

Cln2

MMRRC Submission

045559-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7485 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

105394018-105401442 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 105398751 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Cysteine to Tyrosine at position 226 (C226Y)

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: C226Y

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000033184
Gene: ENSMUSG00000030894
AA Change: C226Y

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

probably benign
Transcript: ENSMUST00000078482

SMART Domains

Protein: ENSMUSP00000077574
Gene: ENSMUSG00000036862

Domain	Start	End	E-Value	Type
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

probably benign
Transcript: ENSMUST00000210066

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 99.1%

Validation Efficiency

99% (99/100)

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: 100 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adat3	C	T	10: 80,442,234 (GRCm39)	A24V	probably benign	Het
Agbl1	A	T	7: 76,239,241 (GRCm39)	E832D	unknown	Het
Akap8l	G	A	17: 32,554,545 (GRCm39)	S347L	probably benign	Het
Ankmy1	G	T	1: 92,804,379 (GRCm39)	A868E	probably damaging	Het
Ankrd49	A	T	9: 14,693,837 (GRCm39)	L110*	probably null	Het
Aoc3	A	G	11: 101,228,229 (GRCm39)	T679A	probably damaging	Het
Ap1s3	A	G	1: 79,592,018 (GRCm39)	Y111H	probably damaging	Het
Arnt	T	A	3: 95,402,659 (GRCm39)	N777K	probably damaging	Het
Atp4b	A	T	8: 13,436,732 (GRCm39)	M260K	probably benign	Het
Bcl2l15	A	T	3: 103,740,729 (GRCm39)	D65V	probably damaging	Het
Bicdl1	G	T	5: 115,801,845 (GRCm39)	S340*	probably null	Het
Ccdc15	T	C	9: 37,226,574 (GRCm39)	R467G	probably benign	Het
Ccdc68	T	A	18: 70,102,084 (GRCm39)	M327K	possibly damaging	Het
Ccdc83	T	C	7: 89,873,138 (GRCm39)	T406A	probably benign	Het
Ccnf	A	T	17: 24,468,232 (GRCm39)	V55D	probably damaging	Het
Cdcp3	C	A	7: 130,830,562 (GRCm39)	P332Q	probably damaging	Het
Cldn12	A	G	5: 5,558,008 (GRCm39)	F140L	probably benign	Het
Copb1	A	C	7: 113,844,720 (GRCm39)	I213S	possibly damaging	Het
Cps1	G	A	1: 67,179,016 (GRCm39)	G76D	probably damaging	Het
Ctrc	A	G	4: 141,567,627 (GRCm39)	W159R	probably damaging	Het
Cul4a	C	T	8: 13,190,279 (GRCm39)	T572M	possibly damaging	Het
Cyp2c40	A	T	19: 39,796,050 (GRCm39)	Y109*	probably null	Het
Dcc	A	G	18: 71,553,317 (GRCm39)	Y780H	probably benign	Het
Dctn1	C	T	6: 83,166,887 (GRCm39)	A283V	possibly damaging	Het
Dio1	T	C	4: 107,154,874 (GRCm39)	D134G	probably benign	Het
Dlg5	A	T	14: 24,198,390 (GRCm39)	D1514E	probably benign	Het
Dlg5	A	T	14: 24,227,907 (GRCm39)	L338Q	probably damaging	Het
Dlgap2	A	T	8: 14,879,952 (GRCm39)	K767N	probably damaging	Het
Dst	A	T	1: 34,313,270 (GRCm39)	I4346F	probably benign	Het
Dzip1l	T	C	9: 99,543,065 (GRCm39)	F507L	probably benign	Het
Erich2	A	T	2: 70,362,109 (GRCm39)	D300V	probably damaging	Het
Fam114a2	C	T	11: 57,404,515 (GRCm39)	G83D	probably damaging	Het
Fam131a	C	T	16: 20,520,444 (GRCm39)	A299V	probably benign	Het
Fbln2	A	G	6: 91,247,143 (GRCm39)		probably null	Het
Fbn2	T	C	18: 58,204,912 (GRCm39)	D1177G	possibly damaging	Het
Fbxl6	T	C	15: 76,422,113 (GRCm39)		probably null	Het
Frem3	A	T	8: 81,339,965 (GRCm39)	I753F	probably damaging	Het
Gfra1	A	G	19: 58,288,744 (GRCm39)	S234P	probably damaging	Het
Gtse1	T	A	15: 85,752,901 (GRCm39)	S339T	probably benign	Het
Hdgfl3	T	C	7: 81,550,106 (GRCm39)	N76S	probably benign	Het
Herc6	A	G	6: 57,558,089 (GRCm39)	E23G	probably benign	Het
Hid1	T	A	11: 115,245,545 (GRCm39)	H420L	probably damaging	Het
Igsf21	G	A	4: 139,755,049 (GRCm39)	T440I	probably benign	Het
Ikzf4	T	A	10: 128,468,451 (GRCm39)	H676L	unknown	Het
Il18r1	A	G	1: 40,520,140 (GRCm39)	E177G	probably benign	Het
Iqch	A	G	9: 63,415,599 (GRCm39)	Y558H	possibly damaging	Het
Kif11	A	T	19: 37,399,072 (GRCm39)	N752I	possibly damaging	Het
Kntc1	T	A	5: 123,925,019 (GRCm39)	C1111S	possibly damaging	Het
Krtap9-5	A	G	11: 99,839,800 (GRCm39)	K167R	unknown	Het
Lgalsl2	C	T	7: 5,362,440 (GRCm39)	R24C	probably benign	Het
Lipe	G	T	7: 25,080,036 (GRCm39)	T704K	probably benign	Het
Lrrc32	A	T	7: 98,147,414 (GRCm39)	I65F	possibly damaging	Het
Mogs	C	T	6: 83,093,188 (GRCm39)	H179Y	probably damaging	Het
Mtnr1b	A	T	9: 15,774,590 (GRCm39)	Y156*	probably null	Het
Mtus1	T	C	8: 41,537,590 (GRCm39)	H42R	probably benign	Het
Mx2	T	A	16: 97,346,918 (GRCm39)	D128E	probably benign	Het
Myof	A	T	19: 37,939,939 (GRCm39)	L829*	probably null	Het
Naip6	T	C	13: 100,420,359 (GRCm39)	K1304E	probably benign	Het
Neo1	A	C	9: 58,791,826 (GRCm39)	S1307R	probably benign	Het
Nipbl	A	T	15: 8,359,779 (GRCm39)	D1475E	probably benign	Het
Nlrp9b	T	A	7: 19,757,875 (GRCm39)	F371I	probably damaging	Het
Nrip1	A	T	16: 76,088,338 (GRCm39)	M1073K	probably damaging	Het
Obox6	T	C	7: 15,567,863 (GRCm39)	N195D	probably damaging	Het
Or13a18	T	A	7: 140,190,091 (GRCm39)	I4K	probably benign	Het
Or1j18	T	A	2: 36,624,650 (GRCm39)	F106I	probably benign	Het
Or5ac24	A	T	16: 59,165,687 (GRCm39)	C126S	probably damaging	Het
Or5b99	C	T	19: 12,976,922 (GRCm39)	H191Y	probably benign	Het
Or5p64	C	A	7: 107,855,045 (GRCm39)	C100F	probably damaging	Het
Pax7	T	C	4: 139,511,880 (GRCm39)	K232E	probably benign	Het
Phldb3	C	T	7: 24,310,689 (GRCm39)		probably benign	Het
Pkd1l1	C	A	11: 8,915,148 (GRCm39)	V131L		Het
Ppp2r5a	A	G	1: 191,128,532 (GRCm39)	S28P	probably benign	Het
Prl8a1	A	G	13: 27,758,068 (GRCm39)	S214P	probably damaging	Het
Prmt2	A	T	10: 76,056,838 (GRCm39)	C228*	probably null	Het
Prpf8	C	T	11: 75,399,738 (GRCm39)	R2266*	probably null	Het
Rabl6	A	G	2: 25,474,153 (GRCm39)	S648P	unknown	Het
Ralgapa1	T	C	12: 55,759,457 (GRCm39)	K1022R	probably damaging	Het
Ralgapb	T	A	2: 158,285,275 (GRCm39)	D591E	probably benign	Het
Rprd1a	A	G	18: 24,639,889 (GRCm39)		probably null	Het
Rsu1	T	C	2: 13,221,686 (GRCm39)	R165G	probably damaging	Het
Samd8	A	G	14: 21,842,491 (GRCm39)	E334G	probably benign	Het
Scn9a	T	A	2: 66,364,561 (GRCm39)	Q804L	probably damaging	Het
Sez6	A	G	11: 77,864,711 (GRCm39)	D557G	probably benign	Het
Sgsm1	A	T	5: 113,427,501 (GRCm39)		probably null	Het
Slc17a3	T	A	13: 24,039,832 (GRCm39)	M290K		Het
Snd1	T	A	6: 28,531,449 (GRCm39)	V330E	probably benign	Het
Tceanc2	T	C	4: 107,022,852 (GRCm39)	K45R	probably damaging	Het
Tg	A	T	15: 66,568,437 (GRCm39)	I1375F	probably benign	Het
Tmem116	T	A	5: 121,633,124 (GRCm39)	I357K		Het
Tmem39a	G	T	16: 38,408,658 (GRCm39)	R407L	possibly damaging	Het
Tmem74	A	T	15: 43,730,761 (GRCm39)	M94K	probably benign	Het
Trbv21	T	C	6: 41,179,861 (GRCm39)	I59T	not run	Het
Trim11	A	G	11: 58,869,463 (GRCm39)	D133G	probably benign	Het
Uaca	G	A	9: 60,753,282 (GRCm39)	V76I	probably damaging	Het
Ugt2a3	A	G	5: 87,475,539 (GRCm39)		probably null	Het
Vmn2r104	G	T	17: 20,249,737 (GRCm39)	H845N	probably benign	Het
Wdr24	T	C	17: 26,045,101 (GRCm39)	Y279H	probably damaging	Het
Zbtb46	A	G	2: 181,065,512 (GRCm39)	S213P	probably benign	Het
Zdhhc13	C	A	7: 48,461,103 (GRCm39)	Y346*	probably null	Het
Zfp280b	A	T	10: 75,875,075 (GRCm39)	H318L	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
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
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'- AAACTGCCACCGAATAGGCG -3'
(R):5'- GTGGTAGTGTCTGTAAGACCTC -3'

Sequencing Primer
(F):5'- TAGGCGCATGAACTCAGTC -3'
(R):5'- GTAGTGTCTGTAAGACCTCCTTAAGC -3'

Posted On

2019-10-07