Mutagenetix > Incidental Mutation

Incidental Mutation 'R0027:Lrpprc'

15065

Institutional Source

Beutler Lab

Gene Symbol

Lrpprc

Ensembl Gene

ENSMUSG00000024120

Gene Name

leucine-rich PPR-motif containing

Synonyms

Lrp130, 3110001K13Rik

MMRRC Submission

038322-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0027 (G1) of strain 730

Quality Score

Status

Validated

Chromosome

Chromosomal Location

85012675-85098214 bp(-) (GRCm39)

Type of Mutation

nonsense

DNA Base Change (assembly)

G to A at 85074435 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Stop codon at position 491 (R491*)

Ref Sequence

ENSEMBL: ENSMUSP00000107927 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000112308]

AlphaFold

Q6PB66

Predicted Effect

probably null
Transcript: ENSMUST00000112308
AA Change: R491*

SMART Domains

Protein: ENSMUSP00000107927
Gene: ENSMUSG00000024120
AA Change: R491*

Domain	Start	End	E-Value	Type
signal peptide	1	16	N/A	INTRINSIC
low complexity region	32	50	N/A	INTRINSIC
low complexity region	123	136	N/A	INTRINSIC
Pfam:PPR_3	196	228	9.1e-4	PFAM
Pfam:PPR	197	227	2.3e-4	PFAM
Pfam:PPR_3	231	264	7.9e-6	PFAM
Pfam:PPR	232	262	4e-4	PFAM
Pfam:PPR_3	266	297	9.7e-3	PFAM
internal_repeat_2	391	477	3.13e-7	PROSPERO
Pfam:PPR	750	778	3.4e-4	PFAM
low complexity region	1017	1028	N/A	INTRINSIC
internal_repeat_1	1042	1362	1.09e-11	PROSPERO
low complexity region	1366	1375	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000159222

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000161299

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000161928

Meta Mutation Damage Score

0.9642

Coding Region Coverage

1x: 77.1%
3x: 64.8%
10x: 37.0%
20x: 19.3%

Validation Efficiency

92% (60/65)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a leucine-rich protein that has multiple pentatricopeptide repeats (PPR). The precise role of this protein is unknown but studies suggest it may play a role in cytoskeletal organization, vesicular transport, or in transcriptional regulation of both nuclear and mitochondrial genes. The protein localizes primarily to mitochondria and is predicted to have an N-terminal mitochondrial targeting sequence. Mutations in this gene are associated with the French-Canadian type of Leigh syndrome. [provided by RefSeq, Mar 2012]
PHENOTYPE: Mice homozygous for a gene trap allele exhibit embryonic lethality during organogenesis associated with growth retardation. Mice homozygous for a knock-out allele exhibit embryonic lethality between somite formation and embryo turning. [provided by MGI curators]

Allele List at MGI

All alleles(13) : Targeted(3) Gene trapped(10)

Other mutations in this stock

Total: 18 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adamts12	A	T	15: 11,285,959 (GRCm39)	I723F	probably damaging	Het
Anapc1	G	T	2: 128,483,431 (GRCm39)	D1221E	possibly damaging	Het
Arhgef28	T	A	13: 98,082,204 (GRCm39)	E1201V	possibly damaging	Het
Cdkl3	C	T	11: 51,923,176 (GRCm39)		probably benign	Het
Col1a2	G	A	6: 4,518,822 (GRCm39)		probably benign	Het
Fam131b	T	A	6: 42,295,182 (GRCm39)	M304L	probably benign	Het
Ints15	G	A	5: 143,293,817 (GRCm39)	T220I	probably damaging	Het
Kif11	C	T	19: 37,395,431 (GRCm39)		probably benign	Het
Mbtd1	T	C	11: 93,815,375 (GRCm39)	V321A	possibly damaging	Het
Mon2	G	A	10: 122,871,953 (GRCm39)	S357L	possibly damaging	Het
Nopchap1	G	A	10: 83,200,393 (GRCm39)		probably benign	Het
Papola	A	C	12: 105,799,395 (GRCm39)	S675R	probably benign	Het
Pcdh9	T	A	14: 94,126,081 (GRCm39)	I30F	probably null	Het
Prl6a1	T	A	13: 27,502,011 (GRCm39)	L126Q	probably damaging	Het
Rad9b	A	G	5: 122,489,786 (GRCm39)		probably benign	Het
Snrnp40	T	A	4: 130,262,066 (GRCm39)	H151Q	probably damaging	Het
Stard9	A	T	2: 120,533,982 (GRCm39)	Q3413L	probably benign	Het
Ubr4	C	A	4: 139,127,704 (GRCm39)	N567K	probably damaging	Het

Other mutations in Lrpprc

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00341:Lrpprc	APN	17	85,057,953 (GRCm39)	missense	possibly damaging	0.91
IGL01319:Lrpprc	APN	17	85,012,840 (GRCm39)	utr 3 prime	probably benign
IGL01380:Lrpprc	APN	17	85,030,158 (GRCm39)	missense	probably benign
IGL01560:Lrpprc	APN	17	85,015,547 (GRCm39)	missense	probably benign	0.07
IGL01582:Lrpprc	APN	17	85,061,971 (GRCm39)	missense	probably null	0.00
IGL01996:Lrpprc	APN	17	85,080,698 (GRCm39)	missense	probably benign
IGL02109:Lrpprc	APN	17	85,033,998 (GRCm39)	nonsense	probably null
IGL02163:Lrpprc	APN	17	85,060,900 (GRCm39)	missense	probably damaging	0.97
IGL02248:Lrpprc	APN	17	85,078,895 (GRCm39)	missense	probably damaging	0.99
IGL02503:Lrpprc	APN	17	85,033,767 (GRCm39)	missense	probably benign
IGL02545:Lrpprc	APN	17	85,082,853 (GRCm39)	missense	probably benign
IGL02570:Lrpprc	APN	17	85,057,981 (GRCm39)	missense	probably damaging	1.00
IGL02636:Lrpprc	APN	17	85,060,532 (GRCm39)	unclassified	probably benign
IGL02943:Lrpprc	APN	17	85,078,878 (GRCm39)	missense	probably benign	0.00
IGL03008:Lrpprc	APN	17	85,058,675 (GRCm39)	missense	probably benign	0.05
elusory	UTSW	17	85,020,215 (GRCm39)	missense	probably benign	0.01
phantom	UTSW	17	85,079,575 (GRCm39)	missense	probably damaging	1.00
R6807_Lrpprc_629	UTSW	17	85,056,531 (GRCm39)	missense	possibly damaging	0.93
Stereotype	UTSW	17	85,074,483 (GRCm39)	missense	probably damaging	1.00
thus	UTSW	17	85,078,355 (GRCm39)	missense	probably benign	0.01
P0023:Lrpprc	UTSW	17	85,033,766 (GRCm39)	missense	probably benign	0.00
R0027:Lrpprc	UTSW	17	85,074,435 (GRCm39)	nonsense	probably null
R0302:Lrpprc	UTSW	17	85,047,506 (GRCm39)	missense	possibly damaging	0.76
R0389:Lrpprc	UTSW	17	85,060,540 (GRCm39)	critical splice donor site	probably null
R0448:Lrpprc	UTSW	17	85,078,322 (GRCm39)	missense	probably benign	0.09
R1396:Lrpprc	UTSW	17	85,033,731 (GRCm39)	missense	possibly damaging	0.68
R1759:Lrpprc	UTSW	17	85,047,509 (GRCm39)	missense	probably damaging	1.00
R2019:Lrpprc	UTSW	17	85,059,759 (GRCm39)	missense	possibly damaging	0.56
R2169:Lrpprc	UTSW	17	85,077,505 (GRCm39)	missense	probably benign	0.00
R2312:Lrpprc	UTSW	17	85,080,686 (GRCm39)	missense	probably damaging	0.96
R2319:Lrpprc	UTSW	17	85,033,818 (GRCm39)	missense	probably benign
R2568:Lrpprc	UTSW	17	85,034,077 (GRCm39)	missense	probably damaging	1.00
R3013:Lrpprc	UTSW	17	85,074,497 (GRCm39)	missense	probably benign	0.04
R3620:Lrpprc	UTSW	17	85,077,452 (GRCm39)	missense	probably benign	0.01
R3789:Lrpprc	UTSW	17	85,078,956 (GRCm39)	missense	probably benign	0.25
R3848:Lrpprc	UTSW	17	85,078,355 (GRCm39)	missense	probably benign	0.01
R3973:Lrpprc	UTSW	17	85,078,269 (GRCm39)	critical splice donor site	probably null
R4111:Lrpprc	UTSW	17	85,033,766 (GRCm39)	missense	probably benign	0.00
R4164:Lrpprc	UTSW	17	85,038,617 (GRCm39)	missense	possibly damaging	0.47
R4331:Lrpprc	UTSW	17	85,047,970 (GRCm39)	critical splice donor site	probably null
R4531:Lrpprc	UTSW	17	85,020,215 (GRCm39)	missense	probably benign	0.01
R4832:Lrpprc	UTSW	17	85,014,584 (GRCm39)	missense	probably benign	0.24
R4947:Lrpprc	UTSW	17	85,078,966 (GRCm39)	missense	probably benign	0.02
R5134:Lrpprc	UTSW	17	85,058,684 (GRCm39)	missense	probably benign	0.00
R5333:Lrpprc	UTSW	17	85,097,821 (GRCm39)	missense	probably benign	0.01
R5950:Lrpprc	UTSW	17	85,047,598 (GRCm39)	missense	possibly damaging	0.86
R5972:Lrpprc	UTSW	17	85,020,250 (GRCm39)	missense	possibly damaging	0.88
R6185:Lrpprc	UTSW	17	85,074,452 (GRCm39)	missense	probably benign
R6253:Lrpprc	UTSW	17	85,048,065 (GRCm39)	missense	probably benign	0.00
R6488:Lrpprc	UTSW	17	85,058,781 (GRCm39)	missense	probably damaging	1.00
R6807:Lrpprc	UTSW	17	85,056,531 (GRCm39)	missense	possibly damaging	0.93
R6911:Lrpprc	UTSW	17	85,063,711 (GRCm39)	missense	possibly damaging	0.67
R6933:Lrpprc	UTSW	17	85,030,131 (GRCm39)	missense	probably benign	0.42
R6955:Lrpprc	UTSW	17	85,084,417 (GRCm39)	missense	probably damaging	0.98
R7448:Lrpprc	UTSW	17	85,079,567 (GRCm39)	missense	probably damaging	0.99
R7727:Lrpprc	UTSW	17	85,084,375 (GRCm39)	missense	probably benign	0.00
R8003:Lrpprc	UTSW	17	85,059,745 (GRCm39)	missense	probably benign	0.01
R8178:Lrpprc	UTSW	17	85,079,575 (GRCm39)	missense	probably damaging	1.00
R8310:Lrpprc	UTSW	17	85,080,524 (GRCm39)	missense	probably damaging	1.00
R8322:Lrpprc	UTSW	17	85,047,496 (GRCm39)	critical splice donor site	probably null
R8389:Lrpprc	UTSW	17	85,080,742 (GRCm39)	missense	possibly damaging	0.79
R8560:Lrpprc	UTSW	17	85,047,495 (GRCm39)	splice site	probably benign
R8777:Lrpprc	UTSW	17	85,058,657 (GRCm39)	missense	probably benign	0.30
R8777-TAIL:Lrpprc	UTSW	17	85,058,657 (GRCm39)	missense	probably benign	0.30
R8868:Lrpprc	UTSW	17	85,078,920 (GRCm39)	missense	probably damaging	0.99
R8970:Lrpprc	UTSW	17	85,074,483 (GRCm39)	missense	probably damaging	1.00
R9042:Lrpprc	UTSW	17	85,059,736 (GRCm39)	critical splice donor site	probably null
R9493:Lrpprc	UTSW	17	85,015,548 (GRCm39)	missense	probably damaging	0.99
R9664:Lrpprc	UTSW	17	85,020,262 (GRCm39)	missense	probably damaging	0.99
X0026:Lrpprc	UTSW	17	85,018,090 (GRCm39)	missense	probably benign	0.42
Z1088:Lrpprc	UTSW	17	85,077,928 (GRCm39)	critical splice acceptor site	probably null
Z1088:Lrpprc	UTSW	17	85,039,212 (GRCm39)	nonsense	probably null
Z1176:Lrpprc	UTSW	17	85,077,859 (GRCm39)	missense	possibly damaging	0.93

Protein Function and Prediction

LRPPRC (leucine-rich pentatricopeptide repeat-containing) is an RNA-binding protein that functions in vesicular trafficking, nucleocytosolic shuttling, transcription, chromosome remodeling, and cytokinesis (1;2). LRPPRC is also proposed to function as a chaperone in the assembly of mitochondrial complex IV (3). A complex composed of LRPPRC and SLIRP binds and stabilizes select mitochondrial mRNAs by suppressing PNPase- and SUV3-mediated 3′ exonucleolytic mRNA degradation and promoting mitochondrial poly(A) polymerase (MTPAP)-mediated mRNA polyadenylation (4-6). Knockdown of LRPPRC leads to decreases in mRNA levels; tRNA and rRNA levels are not changed (7). Tissue-specific disruption of Lrpprc in the heart leads to mitochondrial cardiomyopathy and reduction in steady-state levels of most mitochondrial mRNAs (6). LRPPRC is also involved in the maturation of cytochrome c oxidase (COX) and stabilizes mitochondrial mRNAs encoding COS transcripts (8).

Expression/Localization

LRPPRC is ubiquitously expressed, with highest expression in heart, skeletal muscle, kidney, and liver, intermediate in brain, nonmucosal colon, spleen, and placenta, and lowest in small intestine, thymus, lung, and peripheral blood leukocytes (1). Following formaldehyde crosslinking, LRPPRC copurified with mtDNA and was identified as a core nucleoid protein (2;3).

Background

Mutations in LRPPRC are linked to French-Canadian type Leigh syndrome [OMIM: #220111; (9)], an autosomal recessive severe neurologic disorder with onset in infancy. Features include delayed psychomotor development, mental retardation, mild dysmorphic facial features, hypotonia, ataxia, and the development of lesions in the brainstem and basal ganglia. Affected individuals tend to have episodic metabolic and/or neurologic crises in early childhood, which often lead to early death [summary by (10)].

Lrpprc^{Gt(AX0080)Wtsi/Gt(AX0080)Wtsi}; MGI:3857306

involves: 129P2/OlaHsd * C57BL/6

Mice homozygous for a gene trap allele exhibit embryonic lethality during organogenesis associated with growth retardation (8).

Lrpprc^{tm1.2Lrsn/tm1.2Lrsn}; MGI:5438913

involves: 129S1/Sv * 129X1/SvJ

Mice homozygous for a knock-out allele exhibit embryonic lethality between somite formation and embryo turning (6).

References

1. Liu, L., and McKeehan, W. L. (2002) Sequence Analysis of LRPPRC and its SEC1 Domain Interaction Partners Suggests Roles in Cytoskeletal Organization, Vesicular Trafficking, Nucleocytosolic Shuttling, and Chromosome Activity. Genomics. 79, 124-136.

2. Sterky, F. H., Ruzzenente, B., Gustafsson, C. M., Samuelsson, T., and Larsson, N. G. (2010) LRPPRC is a Mitochondrial Matrix Protein that is Conserved in Metazoans. Biochem Biophys Res Commun. 398, 759-764.

3. Bogenhagen, D. F., Rousseau, D., and Burke, S. (2008) The Layered Structure of Human Mitochondrial DNA Nucleoids. J Biol Chem. 283, 3665-3675.

4. Sasarman, F., Brunel-Guitton, C., Antonicka, H., Wai, T., Shoubridge, E. A., and LSFC Consortium. (2010) LRPPRC and SLIRP Interact in a Ribonucleoprotein Complex that Regulates Posttranscriptional Gene Expression in Mitochondria. Mol Biol Cell. 21, 1315-1323.

5. Chujo, T., Ohira, T., Sakaguchi, Y., Goshima, N., Nomura, N., Nagao, A., and Suzuki, T. (2012) LRPPRC/SLIRP Suppresses PNPase-Mediated mRNA Decay and Promotes Polyadenylation in Human Mitochondria. Nucleic Acids Res. 40, 8033-8047.