Mutagenetix > Incidental Mutation

Incidental Mutation 'R4618:Tpp1'

345097

Institutional Source

Beutler Lab

Gene Symbol

Tpp1

Ensembl Gene

ENSMUSG00000030894

Gene Name

tripeptidyl peptidase I

Synonyms

Cln2

MMRRC Submission

041884-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4618 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

105394018-105401442 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 105400913 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Leucine to Glutamine at position 38 (L38Q)

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: L38Q

PolyPhen 2 Score 0.050 (Sensitivity: 0.94; Specificity: 0.83)

SMART Domains

Protein: ENSMUSP00000033184
Gene: ENSMUSG00000030894
AA Change: L38Q

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: ENSMUST00000211560

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000211659

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000211226

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000211204

Meta Mutation Damage Score

0.1201

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.3%
20x: 95.2%

Validation Efficiency

98% (89/91)

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: 77 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930432M17Rik	A	T	3: 121,473,095 (GRCm39)	K83N	unknown	Het
Adamtsl3	T	A	7: 82,255,728 (GRCm39)	M1580K	probably benign	Het
Adprhl1	A	G	8: 13,292,250 (GRCm39)		probably null	Het
Akap3	G	T	6: 126,843,406 (GRCm39)	C675F	probably benign	Het
Asap1	A	T	15: 64,024,744 (GRCm39)	H318Q	probably damaging	Het
Atf7ip	G	T	6: 136,542,104 (GRCm39)	A18S	probably damaging	Het
Bcl2a1a	A	C	9: 88,839,357 (GRCm39)	N85T	probably damaging	Het
Btnl6	G	A	17: 34,733,120 (GRCm39)	P248S	probably damaging	Het
C9	A	G	15: 6,520,944 (GRCm39)	D51G	probably damaging	Het
Ccdc14	T	A	16: 34,526,865 (GRCm39)	C257S	probably benign	Het
Cd5l	A	G	3: 87,275,926 (GRCm39)	T299A	probably benign	Het
Cstdc3	T	A	16: 36,132,952 (GRCm39)	D76E	possibly damaging	Het
Endou	C	T	15: 97,611,763 (GRCm39)	V292M	possibly damaging	Het
Fbxo36	T	C	1: 84,877,749 (GRCm39)	I137T	probably damaging	Het
Fcer1a	T	C	1: 173,050,208 (GRCm39)	I161V	possibly damaging	Het
Fsip2	A	G	2: 82,818,103 (GRCm39)	Y4612C	probably benign	Het
Gcnt2	T	A	13: 41,111,670 (GRCm39)	L353*	probably null	Het
Ghrhr	T	C	6: 55,358,739 (GRCm39)	F172S	probably damaging	Het
Gins1	T	A	2: 150,759,781 (GRCm39)		probably null	Het
Gm16519	T	G	17: 71,236,237 (GRCm39)	L62R	probably damaging	Het
Gpr20	T	C	15: 73,567,585 (GRCm39)	N268S	probably benign	Het
Greb1l	A	G	18: 10,498,965 (GRCm39)	T283A	probably benign	Het
Grin2c	T	A	11: 115,143,573 (GRCm39)	D729V	probably damaging	Het
Heatr4	T	G	12: 84,024,841 (GRCm39)	T327P	probably damaging	Het
Hes2	A	C	4: 152,244,845 (GRCm39)	S105R	probably benign	Het
Hsph1	A	G	5: 149,542,308 (GRCm39)	V705A	probably benign	Het
Ighv1-82	T	C	12: 115,916,280 (GRCm39)	T77A	probably benign	Het
Itih1	A	T	14: 30,651,788 (GRCm39)	D851E	probably benign	Het
Klhdc7b	A	G	15: 89,271,472 (GRCm39)	T785A	probably benign	Het
Lmbr1	G	T	5: 29,551,863 (GRCm39)	A74E	probably damaging	Het
Lonp1	A	C	17: 56,929,511 (GRCm39)	H175Q	probably benign	Het
Maml2	T	C	9: 13,531,371 (GRCm39)	F195S	probably damaging	Het
Man2b2	G	T	5: 36,974,983 (GRCm39)	T436K	probably benign	Het
Man2c1	T	C	9: 57,049,439 (GRCm39)		probably null	Het
Mrps15	G	A	4: 125,940,837 (GRCm39)		probably benign	Het
Mtrf1l	C	A	10: 5,767,586 (GRCm39)	V177F	probably benign	Het
Naxd	A	T	8: 11,559,489 (GRCm39)	I213F	probably damaging	Het
Nbeal1	T	A	1: 60,267,890 (GRCm39)		probably benign	Het
Nfatc1	T	C	18: 80,741,047 (GRCm39)	I318V	probably damaging	Het
Nid2	T	A	14: 19,858,078 (GRCm39)	I1297N	probably damaging	Het
Nol10	T	C	12: 17,398,562 (GRCm39)	V3A	probably damaging	Het
Nop14	G	T	5: 34,796,562 (GRCm39)	P765Q	probably damaging	Het
Noxa1	C	T	2: 24,981,761 (GRCm39)	G114D	probably damaging	Het
Ntmt2	A	T	1: 163,552,597 (GRCm39)	F10I	probably damaging	Het
Opa1	T	C	16: 29,405,857 (GRCm39)	W141R	probably damaging	Het
Or10a2	G	A	7: 106,673,761 (GRCm39)	C242Y	probably damaging	Het
Or13p4	A	T	4: 118,546,667 (GRCm39)		probably benign	Het
Or5d18	A	G	2: 87,864,898 (GRCm39)	V195A	probably benign	Het
Or8h10	A	G	2: 86,808,618 (GRCm39)	I174T	possibly damaging	Het
Pde4d	A	T	13: 110,070,411 (GRCm39)	M7L	probably benign	Het
Phykpl	G	A	11: 51,483,056 (GRCm39)	A188T	probably damaging	Het
Pkd2l1	C	A	19: 44,142,573 (GRCm39)	A490S	probably damaging	Het
Pkhd1l1	T	A	15: 44,403,078 (GRCm39)	V2260D	probably damaging	Het
Ptprt	T	C	2: 161,395,765 (GRCm39)	E1136G	probably damaging	Het
Rad21	A	T	15: 51,833,420 (GRCm39)	L353Q	probably damaging	Het
Rfx4	G	T	10: 84,716,760 (GRCm39)	A425S	probably benign	Het
Rnf38	A	G	4: 44,142,450 (GRCm39)	S169P	probably damaging	Het
Samd9l	C	A	6: 3,376,347 (GRCm39)	V305F	probably damaging	Het
Serpini1	A	G	3: 75,523,883 (GRCm39)	K164E	probably benign	Het
Sirt6	A	G	10: 81,462,408 (GRCm39)	L37P	probably damaging	Het
Sorbs1	T	C	19: 40,361,962 (GRCm39)	T141A	probably damaging	Het
Tacc2	A	T	7: 130,227,946 (GRCm39)	T1563S	probably benign	Het
Tbc1d14	A	C	5: 36,687,725 (GRCm39)		probably benign	Het
Tbrg4	G	A	11: 6,570,185 (GRCm39)		probably benign	Het
Tox2	T	C	2: 163,162,567 (GRCm39)	L479P	probably damaging	Het
Trhr	A	G	15: 44,061,037 (GRCm39)	N186D	probably benign	Het
Trmt1l	C	T	1: 151,329,799 (GRCm39)	Q581*	probably null	Het
Tsen54	T	A	11: 115,706,247 (GRCm39)		probably benign	Het
Tsg101	A	G	7: 46,542,257 (GRCm39)	I138T	possibly damaging	Het
Usp22	A	G	11: 61,052,269 (GRCm39)	S237P	probably damaging	Het
Vmn1r209	A	G	13: 22,990,619 (GRCm39)	S24P	possibly damaging	Het
Vmn2r18	A	T	5: 151,508,424 (GRCm39)	H233Q	possibly damaging	Het
Vmn2r45	A	T	7: 8,486,436 (GRCm39)	I284N	probably benign	Het
Vmn2r66	T	C	7: 84,644,296 (GRCm39)	I705V	possibly damaging	Het
Vsig1	G	T	X: 139,827,135 (GRCm39)	A95S	probably benign	Het
Zdhhc11	T	A	13: 74,127,349 (GRCm39)	M242K	probably benign	Het
Zfp352	A	G	4: 90,113,318 (GRCm39)	K486R	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
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'- ATGATCTGCACCAGCCAGTG -3'
(R):5'- GACGCTTGGTCCTAGCTTTC -3'

Sequencing Primer
(F):5'- AGTGCCTGCCTGGTCCTG -3'
(R):5'- AACTGCTCCTAGTACCCACTCTGTAG -3'

Posted On

2015-09-25