Mutagenetix > Incidental Mutation

Incidental Mutation 'R0709:Tpp1'

62656

Institutional Source

Beutler Lab

Gene Symbol

Tpp1

Ensembl Gene

ENSMUSG00000030894

Gene Name

tripeptidyl peptidase I

Synonyms

Cln2

MMRRC Submission

038892-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0709 (G1)

Quality Score

149

Status

Validated

Chromosome

Chromosomal Location

105744811-105752235 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 105749607 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Histidine at position 205 (R205H)

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: R205H

PolyPhen 2 Score 0.195 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000033184
Gene: ENSMUSG00000030894
AA Change: R205H

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: ENSMUST00000211204

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000211226

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000211560

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000211659

Meta Mutation Damage Score

0.7822

Coding Region Coverage

1x: 99.3%
3x: 98.8%
10x: 97.6%
20x: 95.8%

Validation Efficiency

98% (83/85)

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: 72 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A630010A05Rik	A	T	16: 14,618,494	D137V	probably damaging	Het
Aar2	C	T	2: 156,567,010	P378L	probably damaging	Het
Abcc5	A	T	16: 20,376,592	H718Q	possibly damaging	Het
Ace	G	T	11: 105,981,538	L319F	probably damaging	Het
Angpt4	C	A	2: 151,934,514	P321T	possibly damaging	Het
Atrip	T	C	9: 109,067,103	N282S	probably benign	Het
AW554918	A	C	18: 25,463,654	S525R	probably damaging	Het
Casc4	T	A	2: 121,867,425	V74E	probably damaging	Het
Ccdc136	T	A	6: 29,414,970	I644N	possibly damaging	Het
Ccdc178	A	G	18: 22,067,662	Y413H	probably damaging	Het
Ccdc7b	A	G	8: 129,136,646	H223R	probably benign	Het
Cd109	T	C	9: 78,671,978	V634A	possibly damaging	Het
Col7a1	T	A	9: 108,961,548		probably benign	Het
Copb2	A	T	9: 98,563,167		probably benign	Het
Csrnp3	C	T	2: 66,022,563	S445L	probably damaging	Het
Cxcl13	G	T	5: 95,958,671	C34F	probably damaging	Het
Dars2	T	C	1: 161,046,928	E397G	probably benign	Het
Dlg5	C	T	14: 24,146,255	V1625M	probably damaging	Het
Dnah12	T	G	14: 26,884,265		probably benign	Het
Eif4a1	C	A	11: 69,670,252	A76S	probably damaging	Het
Fam162b	T	A	10: 51,587,251	I107L	probably damaging	Het
Fbxo30	G	T	10: 11,291,313	C593F	possibly damaging	Het
Fut9	A	G	4: 25,620,359	F152L	probably damaging	Het
Galnt2	G	A	8: 124,343,346	G534D	probably benign	Het
Gm973	C	T	1: 59,558,234		probably benign	Het
Gprc5a	T	A	6: 135,078,950	S132T	probably damaging	Het
Hk3	G	A	13: 55,014,730	R47C	probably damaging	Het
Hrnr	A	T	3: 93,332,508	Q3351L	unknown	Het
Icam1	T	A	9: 21,019,127	F92L	probably damaging	Het
Ifi213	C	T	1: 173,589,800	V349I	possibly damaging	Het
Il12rb2	T	C	6: 67,298,904		probably benign	Het
Irx3	A	G	8: 91,799,420	V487A	possibly damaging	Het
Kalrn	A	G	16: 34,035,554	V204A	probably damaging	Het
Krt16	T	C	11: 100,246,454		probably benign	Het
Loxhd1	G	A	18: 77,404,969	V1369I	probably benign	Het
Med13	T	A	11: 86,319,596	K573N	possibly damaging	Het
Mnat1	A	G	12: 73,188,188	R204G	possibly damaging	Het
Myt1l	A	T	12: 29,827,733	D461V	unknown	Het
Nek6	T	A	2: 38,557,846	S41T	probably damaging	Het
Nudt22	T	C	19: 6,993,506	E232G	probably damaging	Het
Numbl	C	A	7: 27,273,990	F192L	probably damaging	Het
Olfr1202	C	T	2: 88,817,882	T237I	probably benign	Het
Olfr834	T	A	9: 18,988,126	I46K	probably damaging	Het
P2rx4	T	C	5: 122,714,404	V47A	probably damaging	Het
Phka1	T	A	X: 102,586,104	I478F	probably damaging	Het
Pkn2	G	A	3: 142,830,520	T200I	probably damaging	Het
Plcg1	T	A	2: 160,751,778		probably null	Het
Polg2	C	T	11: 106,768,413	G425R	probably damaging	Het
Ptprm	G	T	17: 66,944,332		probably null	Het
Reg1	G	A	6: 78,428,118	R108H	possibly damaging	Het
Slc19a2	T	A	1: 164,256,798	F86I	probably damaging	Het
Slc26a11	T	C	11: 119,374,777	L372P	probably damaging	Het
Slc2a4	C	T	11: 69,946,159	V28M	possibly damaging	Het
Snap29	A	G	16: 17,406,148	N9S	probably damaging	Het
Snd1	C	G	6: 28,545,470		probably benign	Het
Sorcs3	G	A	19: 48,487,406	A235T	probably benign	Het
Sp100	T	A	1: 85,694,281	N362K	probably damaging	Het
Sqor	A	T	2: 122,799,855	I32F	probably benign	Het
Stx6	C	T	1: 155,193,294	R189C	probably damaging	Het
Tchp	T	C	5: 114,717,453	I298T	probably damaging	Het
Themis	A	G	10: 28,761,574	I225V	probably benign	Het
Timm50	A	T	7: 28,306,941	V245E	probably damaging	Het
Tnxb	A	G	17: 34,689,354	E1327G	probably damaging	Het
Tradd	T	C	8: 105,260,644	E10G	possibly damaging	Het
Trim43a	G	A	9: 88,582,146	E37K	probably benign	Het
Ttn	T	C	2: 76,899,403		probably benign	Het
Ttr	A	T	18: 20,669,977		probably null	Het
Ubp1	A	G	9: 113,944,931	Y66C	probably damaging	Het
Vmn2r102	A	T	17: 19,677,619	M299L	probably benign	Het
Vmn2r104	A	T	17: 20,042,904	N98K	probably damaging	Het
Yipf5	A	G	18: 40,207,772	S176P	probably benign	Het
Zpbp2	C	T	11: 98,553,937	T97I	probably damaging	Het

Other mutations in Tpp1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01480:Tpp1	APN	7	105749053	missense	probably damaging	1.00
IGL01520:Tpp1	APN	7	105747729	missense	probably benign	0.32
IGL01796:Tpp1	APN	7	105747650	unclassified	probably benign
IGL01797:Tpp1	APN	7	105749252	missense	probably benign	0.07
IGL01923:Tpp1	APN	7	105751650	missense	probably benign	0.34
IGL02400:Tpp1	APN	7	105747031	missense	possibly damaging	0.91
IGL02411:Tpp1	APN	7	105749619	missense	probably damaging	1.00
IGL02423:Tpp1	APN	7	105749700	missense	probably damaging	1.00
IGL02672:Tpp1	APN	7	105746961	missense	probably benign
IGL03180:Tpp1	APN	7	105746649	missense	probably benign
R0711:Tpp1	UTSW	7	105749419	missense	probably damaging	1.00
R1222:Tpp1	UTSW	7	105746741	missense	probably benign	0.05
R1673:Tpp1	UTSW	7	105747673	missense	probably damaging	0.99
R1799:Tpp1	UTSW	7	105750308	missense	probably benign	0.00
R1822:Tpp1	UTSW	7	105749647	missense	probably benign
R1984:Tpp1	UTSW	7	105751698	missense	probably benign	0.04
R2109:Tpp1	UTSW	7	105749970	missense	probably damaging	1.00
R4304:Tpp1	UTSW	7	105750309	missense	possibly damaging	0.70
R4618:Tpp1	UTSW	7	105751706	missense	probably benign	0.05
R4746:Tpp1	UTSW	7	105748951	missense	probably damaging	1.00
R4764:Tpp1	UTSW	7	105749251	missense	probably damaging	1.00
R4837:Tpp1	UTSW	7	105746649	missense	probably benign
R4855:Tpp1	UTSW	7	105746723	missense	probably benign
R5015:Tpp1	UTSW	7	105752025	unclassified	probably benign
R5677:Tpp1	UTSW	7	105747536	missense	probably damaging	1.00
R5916:Tpp1	UTSW	7	105749380	missense	probably damaging	0.97
R6149:Tpp1	UTSW	7	105747727	missense	probably benign	0.00
R6291:Tpp1	UTSW	7	105747016	missense	probably benign	0.05
R6422:Tpp1	UTSW	7	105746956	missense	probably benign	0.01
R6671:Tpp1	UTSW	7	105749607	missense	probably benign	0.19
R6841:Tpp1	UTSW	7	105748964	missense	probably damaging	0.96
R6851:Tpp1	UTSW	7	105749712	missense	probably damaging	1.00
R7022:Tpp1	UTSW	7	105748922	missense	probably damaging	1.00
R7106:Tpp1	UTSW	7	105749911	missense	possibly damaging	0.67
R7260:Tpp1	UTSW	7	105747497	missense	probably benign	0.00
R7485:Tpp1	UTSW	7	105749544	missense	probably damaging	1.00
R8185:Tpp1	UTSW	7	105749223	critical splice donor site	probably null
R8204:Tpp1	UTSW	7	105750315	missense	probably damaging	0.98
R8513:Tpp1	UTSW	7	105749579	missense	possibly damaging	0.93
R8863:Tpp1	UTSW	7	105749607	missense	probably benign	0.19
R8937:Tpp1	UTSW	7	105747419	missense	probably benign	0.00
R9003:Tpp1	UTSW	7	105748949	missense	probably benign	0.07
R9178:Tpp1	UTSW	7	105751639	missense	probably benign	0.00
R9352:Tpp1	UTSW	7	105749674	missense	probably benign	0.00
R9501:Tpp1	UTSW	7	105749257	missense	probably benign	0.11
R9597:Tpp1	UTSW	7	105747507	missense	probably benign
R9683:Tpp1	UTSW	7	105748897	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- ATTGTGGATCAGAGAGTGAGGCCC -3'
(R):5'- TTGGTAAACCCAATGGAGTTGGTGG -3'

Sequencing Primer
(F):5'- TGAGGCCCAGGGTAGTG -3'
(R):5'- AGAGGCATAGAATCTTTCCAGTAG -3'

Posted On

2013-07-30