Mutagenetix > Incidental Mutation

Incidental Mutation 'R2109:Tpp1'

232369

Institutional Source

Beutler Lab

Gene Symbol

Tpp1

Ensembl Gene

ENSMUSG00000030894

Gene Name

tripeptidyl peptidase I

Synonyms

Cln2

MMRRC Submission

040113-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R2109 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

105394018-105401442 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 105399177 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Leucine to Proline at position 133 (L133P)

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: L133P

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000033184
Gene: ENSMUSG00000030894
AA Change: L133P

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

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: ENSMUST00000210840

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000211226

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000211659

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000211204

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000211560

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.4%
20x: 95.4%

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: 87 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2410002F23Rik	G	T	7: 43,900,435 (GRCm39)	R113S	probably benign	Het
Ackr2	A	T	9: 121,738,026 (GRCm39)	I134F	probably damaging	Het
Actr3b	T	A	5: 26,036,709 (GRCm39)	I174N	possibly damaging	Het
Akap9	T	A	5: 4,094,847 (GRCm39)	S2214T	possibly damaging	Het
Arhgef12	C	A	9: 42,890,768 (GRCm39)	R986L	possibly damaging	Het
Brap	G	T	5: 121,801,422 (GRCm39)	S59I	possibly damaging	Het
Btnl1	C	T	17: 34,598,578 (GRCm39)	H65Y	probably damaging	Het
C1s2	T	C	6: 124,612,004 (GRCm39)	T121A	probably damaging	Het
Capn1	T	A	19: 6,064,388 (GRCm39)	Y37F	probably benign	Het
Ccdc39	T	C	3: 33,869,650 (GRCm39)	K726E	probably damaging	Het
Cd300lb	G	A	11: 114,816,865 (GRCm39)	S195F	probably damaging	Het
Cenpf	T	C	1: 189,411,264 (GRCm39)	K307E	probably damaging	Het
Chodl	A	C	16: 78,738,251 (GRCm39)	N73T	possibly damaging	Het
Cimip2c	G	A	5: 30,637,851 (GRCm39)	G66E	probably damaging	Het
Crnn	A	T	3: 93,055,747 (GRCm39)	M178L	probably benign	Het
Cyp4a12b	A	G	4: 115,290,110 (GRCm39)	D221G	probably damaging	Het
Dipk2a	A	T	9: 94,406,498 (GRCm39)	I303N	probably damaging	Het
Dmxl2	A	G	9: 54,301,097 (GRCm39)	V2338A	probably benign	Het
Dnah9	G	T	11: 65,928,411 (GRCm39)	P2086Q	probably damaging	Het
Dsg2	A	G	18: 20,725,346 (GRCm39)	I486V	probably benign	Het
E2f8	A	G	7: 48,524,855 (GRCm39)	S265P	probably damaging	Het
Eif1b	A	G	9: 120,323,296 (GRCm39)	D52G	probably benign	Het
Etl4	A	T	2: 20,790,153 (GRCm39)	T602S	probably benign	Het
Exoc3l2	A	T	7: 19,223,059 (GRCm39)		probably benign	Het
Fbxl6	C	A	15: 76,421,173 (GRCm39)	V297F	probably damaging	Het
Fgr	T	A	4: 132,725,786 (GRCm39)	N398K	probably benign	Het
G3bp1	A	G	11: 55,379,986 (GRCm39)	R107G	probably damaging	Het
Gp2	A	T	7: 119,052,155 (GRCm39)	N186K	probably benign	Het
Hbs1l	T	A	10: 21,217,831 (GRCm39)	L249*	probably null	Het
Hmgcs2	T	A	3: 98,204,337 (GRCm39)	L246*	probably null	Het
Hsp90ab1	G	T	17: 45,880,254 (GRCm39)	H96Q	probably benign	Het
Ibtk	C	T	9: 85,588,603 (GRCm39)	V1078I	probably benign	Het
Ltn1	T	C	16: 87,212,530 (GRCm39)	D677G	probably benign	Het
Lyst	C	T	13: 13,887,405 (GRCm39)	T3078I	possibly damaging	Het
Mamdc4	A	G	2: 25,459,402 (GRCm39)	F199S	probably damaging	Het
Megf6	G	T	4: 154,261,578 (GRCm39)	V68L	probably benign	Het
Mki67	G	A	7: 135,299,592 (GRCm39)	T1814I	probably damaging	Het
Msantd5l	T	A	11: 51,145,264 (GRCm39)	I108F	possibly damaging	Het
Mttp	A	T	3: 137,800,763 (GRCm39)	F766I	probably benign	Het
Nbl1	T	A	4: 138,810,915 (GRCm39)		probably null	Het
Nmrk1	T	A	19: 18,618,802 (GRCm39)	L118Q	probably damaging	Het
Nopchap1	C	T	10: 83,201,656 (GRCm39)	S143L	probably damaging	Het
Oog3	A	T	4: 143,886,082 (GRCm39)	L172H	probably damaging	Het
Or2y11	T	G	11: 49,443,260 (GRCm39)	S229A	probably damaging	Het
Osbpl1a	T	G	18: 12,892,457 (GRCm39)	Q332P	probably damaging	Het
Pik3cg	A	G	12: 32,243,709 (GRCm39)	F921L	possibly damaging	Het
Plch2	T	C	4: 155,069,054 (GRCm39)	S1086G	possibly damaging	Het
Plekha5	A	G	6: 140,369,942 (GRCm39)	T18A	possibly damaging	Het
Pogz	T	A	3: 94,786,276 (GRCm39)	S955T	probably benign	Het
Pot1b	A	T	17: 55,960,413 (GRCm39)	I639N	probably benign	Het
Prkdc	T	C	16: 15,505,254 (GRCm39)	I852T	probably benign	Het
Prps1l1	A	G	12: 35,035,521 (GRCm39)	K212R	probably benign	Het
Ptpn5	A	G	7: 46,735,807 (GRCm39)	Y304H	probably damaging	Het
Ralgapa1	A	G	12: 55,822,973 (GRCm39)	I281T	possibly damaging	Het
Rgs22	A	T	15: 36,099,880 (GRCm39)	Y278*	probably null	Het
Rif1	GCCACCA	GCCA	2: 52,000,336 (GRCm39)		probably benign	Het
Rnf213	T	A	11: 119,333,489 (GRCm39)	Y2899*	probably null	Het
Rttn	C	T	18: 89,004,197 (GRCm39)	T397I	possibly damaging	Het
Sacs	G	T	14: 61,410,902 (GRCm39)		probably null	Het
Sbf2	G	T	7: 110,060,419 (GRCm39)	Q182K	probably damaging	Het
Sec14l5	C	T	16: 4,984,968 (GRCm39)	R105*	probably null	Het
Sh2b1	A	T	7: 126,071,536 (GRCm39)	D216E	possibly damaging	Het
Sh3gl3	A	G	7: 81,920,008 (GRCm39)	N72S	possibly damaging	Het
Slc12a1	A	T	2: 125,015,619 (GRCm39)	I391F	probably damaging	Het
Slc36a2	G	A	11: 55,072,381 (GRCm39)	A77V	probably damaging	Het
Smc2	A	T	4: 52,474,987 (GRCm39)	I888L	probably benign	Het
Smoc1	C	T	12: 81,197,450 (GRCm39)	T194M	probably damaging	Het
Sorcs1	C	T	19: 50,666,630 (GRCm39)	G93R	probably benign	Het
Sox30	T	G	11: 45,882,595 (GRCm39)	F542V	probably damaging	Het
Svep1	A	G	4: 58,206,030 (GRCm39)	V116A	possibly damaging	Het
Synj2	A	G	17: 6,063,966 (GRCm39)	D330G	probably benign	Het
Tenm3	A	C	8: 48,796,384 (GRCm39)	S202A	possibly damaging	Het
Tg	C	T	15: 66,601,443 (GRCm39)	T151I	probably benign	Het
Tnfaip2	A	G	12: 111,414,527 (GRCm39)	E361G	probably damaging	Het
Tnk1	A	T	11: 69,746,009 (GRCm39)	D305E	probably damaging	Het
Trappc1	T	A	11: 69,215,243 (GRCm39)	M41K	probably damaging	Het
Tsen54	A	G	11: 115,706,549 (GRCm39)	D9G	probably damaging	Het
Ttn	T	A	2: 76,804,598 (GRCm39)	I225F	probably damaging	Het
Ube4b	T	C	4: 149,457,298 (GRCm39)	K313R	probably benign	Het
Vps50	T	C	6: 3,555,379 (GRCm39)	V425A	probably damaging	Het
Wbp2	A	T	11: 115,971,445 (GRCm39)	Y153*	probably null	Het
Xrn1	A	G	9: 95,861,273 (GRCm39)	S478G	probably benign	Het
Zfp354c	T	C	11: 50,707,969 (GRCm39)	E77G	probably benign	Het
Zfp462	T	C	4: 55,008,496 (GRCm39)	M154T	probably benign	Het
Zfp704	A	G	3: 9,539,585 (GRCm39)	V255A	probably damaging	Het
Zfp763	G	T	17: 33,238,752 (GRCm39)	A131E	probably benign	Het
Zfp931	A	T	2: 177,711,651 (GRCm39)	V32E	probably null	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
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'- TGGCATCTAAAATTCTTCAGCCTG -3'
(R):5'- AGGACTTTCTGACTTGCTGGC -3'

Sequencing Primer
(F):5'- AAAATTCTTCAGCCTGTAGACCTC -3'
(R):5'- CCGGTGAGAAGTAATGATTTCCCC -3'

Posted On

2014-09-18