Mutagenetix > Incidental Mutation

Incidental Mutation 'R8937:Tpp1'

680724

Institutional Source

Beutler Lab

Gene Symbol

Tpp1

Ensembl Gene

ENSMUSG00000030894

Gene Name

tripeptidyl peptidase I

Synonyms

Cln2

MMRRC Submission

068710-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R8937 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

105394018-105401442 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 105396626 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Valine at position 464 (M464V)

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: M464V

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000033184
Gene: ENSMUSG00000030894
AA Change: M464V

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: ENSMUST00000130565

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

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

Meta Mutation Damage Score

0.0846

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 99.0%

Validation Efficiency

95% (71/75)

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: 75 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930455H04Rik	C	A	3: 116,762,120 (GRCm39)		probably benign	Het
Actn3	C	T	19: 4,921,798 (GRCm39)		probably null	Het
Akap13	T	A	7: 75,184,601 (GRCm39)		probably null	Het
Akap9	A	T	5: 4,094,048 (GRCm39)	Q2190L	possibly damaging	Het
Ankrd6	A	T	4: 32,823,452 (GRCm39)	V190D	possibly damaging	Het
Atrn	T	A	2: 130,841,157 (GRCm39)	D1186E	probably benign	Het
Bank1	A	T	3: 135,989,934 (GRCm39)	V52E	probably damaging	Het
Blmh	A	G	11: 76,857,883 (GRCm39)	N342D	probably benign	Het
Card6	TTGGGAGGACTGTGGATGAGAGGGCTTAGCATGGGAGGACTGTGGATGAGAGGGCTTAGCATGGGAGGACTGTGGATGAGAGGGCTTAGCATGGGAGGACTGCGGATGAGAGGGCTTAGCATGGGAGGACTG	TTGGGAGGACTGTGGATGAGAGGGCTTAGCATGGGAGGACTGTGGATGAGAGGGCTTAGCATGGGAGGACTGCGGATGAGAGGGCTTAGCATGGGAGGACTG	15: 5,128,173 (GRCm39)		probably benign	Het
Ces2f	A	G	8: 105,677,669 (GRCm39)	T225A	probably damaging	Het
Clic6	G	T	16: 92,296,245 (GRCm39)	D302Y	probably damaging	Het
Clmn	T	A	12: 104,763,341 (GRCm39)	N95I	probably damaging	Het
Cmya5	A	T	13: 93,232,840 (GRCm39)	F749L	probably benign	Het
Cramp1	A	G	17: 25,202,956 (GRCm39)	F358L	probably damaging	Het
Dhx38	T	C	8: 110,283,098 (GRCm39)	D573G	probably damaging	Het
Dync1h1	T	C	12: 110,584,471 (GRCm39)	Y625H	probably damaging	Het
Enpep	A	G	3: 129,115,007 (GRCm39)		probably null	Het
Fat1	T	C	8: 45,483,350 (GRCm39)	L3146P	probably damaging	Het
Gal3st2b	G	A	1: 93,868,570 (GRCm39)	S265N	probably benign	Het
Glis3	G	A	19: 28,643,266 (GRCm39)	A92V	possibly damaging	Het
Gm266	T	C	12: 111,452,173 (GRCm39)	D11G	probably benign	Het
Hmcn2	A	T	2: 31,204,427 (GRCm39)	M1L	probably benign	Het
Kcnj15	G	A	16: 95,097,548 (GRCm39)		probably benign	Het
Krt27	A	G	11: 99,239,551 (GRCm39)	S310P	probably damaging	Het
Lama2	A	T	10: 26,862,816 (GRCm39)	D2982E	probably damaging	Het
Lrfn3	A	G	7: 30,059,451 (GRCm39)	V258A	probably benign	Het
Lrit3	A	T	3: 129,594,193 (GRCm39)	M128K	probably damaging	Het
Ltbp3	A	G	19: 5,797,512 (GRCm39)	T417A	probably benign	Het
Mettl25	T	C	10: 105,601,122 (GRCm39)	T554A	probably benign	Het
Micall1	A	G	15: 79,011,198 (GRCm39)	S523G	probably damaging	Het
Mmp21	G	A	7: 133,280,700 (GRCm39)	A90V	probably benign	Het
Mon2	T	C	10: 122,895,110 (GRCm39)	N53S	probably benign	Het
Muc15	T	C	2: 110,562,252 (GRCm39)		probably null	Het
Myo15b	A	T	11: 115,773,127 (GRCm39)	M431L	probably benign	Het
Nicn1	C	T	9: 108,171,708 (GRCm39)	R163C	possibly damaging	Het
Nt5c3	T	C	6: 56,861,701 (GRCm39)	D195G	probably damaging	Het
Or3a1b	T	A	11: 74,012,874 (GRCm39)	M253K	probably benign	Het
Or52h1	A	G	7: 103,828,949 (GRCm39)	L222P	possibly damaging	Het
Pals1	T	A	12: 78,866,115 (GRCm39)	D313E	probably benign	Het
Pgrmc2	A	G	3: 41,037,125 (GRCm39)	L102P	probably damaging	Het
Plekha1	T	G	7: 130,502,241 (GRCm39)		probably benign	Het
Pramel23	T	C	4: 143,423,562 (GRCm39)	Y409C	probably damaging	Het
Prss59	A	T	6: 40,902,999 (GRCm39)	Y124*	probably null	Het
Ralgapa1	T	G	12: 55,749,345 (GRCm39)	I1233L	probably damaging	Het
Rb1cc1	T	A	1: 6,333,441 (GRCm39)	D68E	probably benign	Het
Rere	C	A	4: 150,699,331 (GRCm39)		probably benign	Het
Rnf213	A	T	11: 119,321,100 (GRCm39)	H1185L	possibly damaging	Het
Robo2	G	T	16: 73,770,150 (GRCm39)	P529T	probably damaging	Het
Robo2	G	A	16: 73,770,149 (GRCm39)	P529L	probably damaging	Het
Shprh	A	G	10: 11,061,181 (GRCm39)	T1165A	possibly damaging	Het
Slc22a26	C	T	19: 7,768,390 (GRCm39)		probably benign	Het
Slc43a1	T	C	2: 84,690,450 (GRCm39)	L456P	probably damaging	Het
Slc5a8	T	C	10: 88,740,885 (GRCm39)	Y267H	probably damaging	Het
Snrnp200	T	C	2: 127,068,902 (GRCm39)	I927T	probably benign	Het
Sorbs1	T	C	19: 40,362,006 (GRCm39)	D156G	probably benign	Het
Sox5	A	T	6: 143,853,169 (GRCm39)	S370T	probably benign	Het
Spen	T	C	4: 141,201,374 (GRCm39)	T2418A	probably damaging	Het
St8sia6	A	T	2: 13,701,705 (GRCm39)	L104H	probably damaging	Het
Stox1	T	A	10: 62,500,430 (GRCm39)	N710I	probably damaging	Het
Syncrip	T	C	9: 88,344,900 (GRCm39)		probably benign	Het
Syt11	G	A	3: 88,655,051 (GRCm39)	P417S	probably damaging	Het
Taf2	A	T	15: 54,910,849 (GRCm39)	N608K	probably benign	Het
Tfcp2l1	G	A	1: 118,596,447 (GRCm39)	G394E	possibly damaging	Het
Tial1	A	G	7: 128,056,715 (GRCm39)	I13T	probably damaging	Het
Tmem108	T	C	9: 103,361,981 (GRCm39)	D535G	probably benign	Het
Trrap	C	A	5: 144,757,063 (GRCm39)	N2108K	probably damaging	Het
Tspan3	T	C	9: 56,053,883 (GRCm39)	D156G	probably benign	Het
Ttn	C	T	2: 76,592,607 (GRCm39)	V20842I	probably benign	Het
Ubr4	T	A	4: 139,190,886 (GRCm39)	W4078R	probably damaging	Het
Uts2r	G	A	11: 121,051,795 (GRCm39)	V220M	possibly damaging	Het
Vmn2r19	G	A	6: 123,293,283 (GRCm39)		probably null	Het
Vmn2r3	A	T	3: 64,166,673 (GRCm39)	F819L	probably damaging	Het
Wdtc1	T	C	4: 133,031,470 (GRCm39)	Y250C	probably damaging	Het
Zan	T	C	5: 137,393,888 (GRCm39)	H4521R	unknown	Het
Zfp219	A	T	14: 52,244,224 (GRCm39)	C652S	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
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
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'- AGGGTAGTTCCTGAGTAGAGC -3'
(R):5'- AGCAATGTTTTCCCACGGC -3'

Sequencing Primer
(F):5'- AGTTCCTGAGTAGAGCGTTTAG -3'
(R):5'- TCAGTCCTGCAGCTTGCTGAG -3'

Posted On

2021-08-31