Mutagenetix > Incidental Mutation

Incidental Mutation 'R7022:Tpp1'

545694

Institutional Source

Beutler Lab

Gene Symbol

Tpp1

Ensembl Gene

ENSMUSG00000030894

Gene Name

tripeptidyl peptidase I

Synonyms

Cln2

MMRRC Submission

045123-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7022 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

105394018-105401442 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to G at 105398129 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Lysine to Glutamine at position 345 (K345Q)

Ref Sequence

ENSEMBL: ENSMUSP00000033184 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000033184] [ENSMUST00000078482] [ENSMUST00000141116] [ENSMUST00000210066]

AlphaFold

O89023

Predicted Effect

probably damaging
Transcript: ENSMUST00000033184
AA Change: K345Q

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000033184
Gene: ENSMUSG00000030894
AA Change: K345Q

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: 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: ENSMUST00000210066

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 98.9%

Validation Efficiency

100% (75/75)

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
Abca8a	A	T	11: 109,974,326 (GRCm39)	S203T	probably damaging	Het
Adat1	A	T	8: 112,716,494 (GRCm39)	M76K	probably damaging	Het
Ankrd33	G	C	15: 101,014,780 (GRCm39)	V56L	probably benign	Het
Ascc3	T	A	10: 50,592,725 (GRCm39)	L1134I	possibly damaging	Het
C3	T	G	17: 57,524,286 (GRCm39)	D948A	probably damaging	Het
Ccdc121rt3	A	C	5: 112,503,395 (GRCm39)	M103R	probably benign	Het
Ccdc40	A	G	11: 119,122,612 (GRCm39)	E138G	possibly damaging	Het
Cd80	A	G	16: 38,306,866 (GRCm39)		probably null	Het
Cdca7	T	A	2: 72,309,873 (GRCm39)		probably null	Het
Chit1	A	G	1: 134,079,030 (GRCm39)	S447G	probably benign	Het
Cmya5	C	T	13: 93,205,786 (GRCm39)		probably null	Het
Cnnm2	A	T	19: 46,750,989 (GRCm39)	I260F	probably damaging	Het
Cnnm2	T	A	19: 46,847,379 (GRCm39)		probably null	Het
Col1a2	T	C	6: 4,534,639 (GRCm39)	L881P	unknown	Het
Crebbp	A	T	16: 3,935,187 (GRCm39)	S901T	probably damaging	Het
Dcun1d2	T	C	8: 13,321,637 (GRCm39)	Y158C	probably damaging	Het
Dnhd1	C	T	7: 105,370,005 (GRCm39)	P4477S	probably benign	Het
Donson	A	G	16: 91,478,218 (GRCm39)	Y428H	probably damaging	Het
Dsp	G	T	13: 38,375,716 (GRCm39)	W1167L	probably benign	Het
Elmo2	C	T	2: 165,136,961 (GRCm39)	V592M	probably damaging	Het
Enpp3	T	A	10: 24,702,093 (GRCm39)	E60D	probably damaging	Het
Erfl	A	T	7: 24,631,089 (GRCm39)		probably null	Het
Fam83b	TAAGA	T	9: 76,409,394 (GRCm39)		probably null	Het
Fbxo38	A	G	18: 62,669,295 (GRCm39)	C52R	probably damaging	Het
Gm10912	T	C	2: 103,897,055 (GRCm39)	W65R	probably damaging	Het
Gm43518	A	T	5: 124,074,490 (GRCm39)	M44L	probably benign	Het
Gnb1	T	A	4: 155,637,913 (GRCm39)	D212E	probably damaging	Het
Gnl1	A	G	17: 36,299,620 (GRCm39)	N597S	probably damaging	Het
Gprin1	T	G	13: 54,886,855 (GRCm39)	E473A	probably benign	Het
Ighv1-69	T	A	12: 115,586,834 (GRCm39)	M100L	probably benign	Het
Igkv14-100	T	C	6: 68,496,193 (GRCm39)	S29P	probably damaging	Het
Ints6	A	G	14: 62,951,786 (GRCm39)	V232A	probably damaging	Het
Jup	A	G	11: 100,270,379 (GRCm39)	L376P	probably damaging	Het
Kdr	A	T	5: 76,132,920 (GRCm39)	Y119*	probably null	Het
Kif1a	T	G	1: 92,993,820 (GRCm39)	T377P	probably benign	Het
Lama5	C	A	2: 179,822,524 (GRCm39)	V2850L	probably damaging	Het
Lrp2	T	C	2: 69,313,552 (GRCm39)	Y2393C	probably damaging	Het
Mfsd13a	C	T	19: 46,356,763 (GRCm39)	Q255*	probably null	Het
Msh3	A	C	13: 92,372,096 (GRCm39)	D891E	probably damaging	Het
Msl2	A	G	9: 100,957,335 (GRCm39)	N2D	possibly damaging	Het
Myo19	T	C	11: 84,791,373 (GRCm39)	L476P	probably damaging	Het
Nbeal2	G	A	9: 110,467,686 (GRCm39)	R501W	probably damaging	Het
Nfasc	C	A	1: 132,548,787 (GRCm39)	K293N	probably damaging	Het
Npbwr1	A	T	1: 5,987,319 (GRCm39)	L65Q	probably damaging	Het
Nrbp1	T	A	5: 31,401,825 (GRCm39)	D34E	probably damaging	Het
Nup205	T	A	6: 35,220,871 (GRCm39)	V1891D	probably benign	Het
Or51g2	T	A	7: 102,623,175 (GRCm39)	N8I	possibly damaging	Het
Or5g29	T	A	2: 85,420,942 (GRCm39)	D19E	probably benign	Het
Or5k1b	T	C	16: 58,581,482 (GRCm39)	N19S	probably benign	Het
Or8g22	G	T	9: 38,958,379 (GRCm39)	C156*	probably null	Het
Oscp1	G	A	4: 125,976,783 (GRCm39)		probably null	Het
Pcdhgb7	A	G	18: 37,886,086 (GRCm39)	T419A	probably damaging	Het
Pdzph1	T	C	17: 59,281,121 (GRCm39)	D387G	probably benign	Het
Phc1	A	G	6: 122,311,990 (GRCm39)	F56S	probably damaging	Het
Pik3c2g	A	G	6: 139,599,061 (GRCm39)	E59G	possibly damaging	Het
Prickle1	G	T	15: 93,398,752 (GRCm39)	T692K	possibly damaging	Het
Rbm45	T	A	2: 76,206,738 (GRCm39)	L250Q	probably damaging	Het
Ror1	T	A	4: 100,265,108 (GRCm39)	M194K	probably damaging	Het
Rrbp1	T	A	2: 143,799,722 (GRCm39)		probably null	Het
Rundc3b	T	C	5: 8,562,348 (GRCm39)	K340R	probably null	Het
Scn1a	T	A	2: 66,148,243 (GRCm39)	T1101S	probably damaging	Het
Sdk1	C	G	5: 142,080,412 (GRCm39)		probably null	Het
Skic2	A	G	17: 35,064,183 (GRCm39)	F501S	possibly damaging	Het
Slc20a1	T	A	2: 129,041,979 (GRCm39)	M114K	probably damaging	Het
Sorl1	A	C	9: 41,881,047 (GRCm39)	I2158S	probably benign	Het
Strip1	A	T	3: 107,534,111 (GRCm39)	F174L	probably benign	Het
Sucnr1	A	T	3: 59,993,699 (GRCm39)	I76L	probably benign	Het
Syt17	C	T	7: 118,007,242 (GRCm39)	V412I	probably benign	Het
Tie1	T	A	4: 118,346,850 (GRCm39)	H18L	probably benign	Het
Trcg1	G	A	9: 57,148,852 (GRCm39)	M141I	possibly damaging	Het
Trpc4ap	T	C	2: 155,499,742 (GRCm39)	N260S	probably benign	Het
Vps41	C	A	13: 19,026,438 (GRCm39)	T512K	possibly damaging	Het
Vps52	A	T	17: 34,178,293 (GRCm39)	M147L	probably benign	Het
Ywhaq	A	G	12: 21,441,752 (GRCm39)		probably benign	Het
Zfp619	A	G	7: 39,184,387 (GRCm39)	N139S	probably benign	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
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'- CACCTCAGAGTACTCAGGTCAAATC -3'
(R):5'- GGCTGAAGGGAGATTCTAGC -3'

Sequencing Primer
(F):5'- TCAGCAGACCCTGTTAAGGCTC -3'
(R):5'- CTGAAGGGAGATTCTAGCAACCATC -3'

Posted On

2019-05-13