LRPPRC

leucine rich pentatricopeptide repeat containing, the group of Mitochondrial respiratory chain complex assembly factors|Pentatricopeptide repeat containing

Basic information

Region (hg38): 2:43886223-43996226

Previous symbols: [ "LSFC" ]

Links

ENSG00000138095 ∙ NCBI:10128 ∙ OMIM:607544 ∙ HGNC:15714 ∙ Uniprot:P42704 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cytochrome-c oxidase deficiency disease (Definitive), mode of inheritance: AR
• congenital lactic acidosis, Saguenay-Lac-Saint-Jean type (Definitive), mode of inheritance: AR
• congenital lactic acidosis, Saguenay-Lac-Saint-Jean type (Strong), mode of inheritance: AR
• congenital lactic acidosis, Saguenay-Lac-Saint-Jean type (Supportive), mode of inheritance: AR
• Leigh syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian)	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Craniofacial; Musculoskeletal; Neurologic	8392290; 8392291; 12529507; 21266382

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LRPPRC gene.

• not provided (1251 variants)
• Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type (431 variants)
• not specified (87 variants)
• Inborn genetic diseases (59 variants)
• Leigh syndrome (12 variants)
• LRPPRC-related condition (5 variants)
• Intellectual disability;Seizure (1 variants)
• Mitochondrial complex IV deficiency, nuclear type 5, French-Canadian (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LRPPRC gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	501	5	513
missense	1	3	228	13	6	251
nonsense	29	51				80
start loss		2				2
frameshift	39	73	3			115
inframe indel	1		8			9
splice donor/acceptor (+/-2bp)	4	56	2			62
splice region			19	113	3	135
non coding			64	191	92	347
Total	74	185	312	705	103

Highest pathogenic variant AF is 0.0000131

Variants in LRPPRC

This is a list of pathogenic ClinVar variants found in the LRPPRC region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-43886224-G-C		Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	Uncertain significance (Jan 13, 2018)
2-43886311-T-A		Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	Uncertain significance (Jan 13, 2018)
2-43886323-T-C		Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	Uncertain significance (Jan 13, 2018)
2-43886355-T-C		Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	Uncertain significance (Jan 12, 2018)
2-43886370-T-G		Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	Uncertain significance (Jan 13, 2018)
2-43886376-T-G		Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	Uncertain significance (Jan 13, 2018)
2-43886408-T-C		Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	Uncertain significance (Jan 12, 2018)
2-43886424-T-A		Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	Benign (Jan 13, 2018)
2-43886443-A-T		Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	Uncertain significance (Jan 12, 2018)
2-43886501-G-T		Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	Uncertain significance (Jan 13, 2018)
2-43886551-A-AC		Leigh syndrome	Uncertain significance (Jun 14, 2016)
2-43886558-C-A		Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	Uncertain significance (Jan 13, 2018)
2-43886559-G-A		Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	Benign (Jan 12, 2018)
2-43886559-G-T		Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	Uncertain significance (Jan 12, 2018)
2-43886619-T-A		Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	Uncertain significance (Jan 13, 2018)
2-43886639-A-G		Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	Likely benign (Jan 13, 2018)
2-43886689-C-T		Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	Uncertain significance (Jan 12, 2018)
2-43886705-C-A		Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	Uncertain significance (Jan 13, 2018)
2-43886705-C-T		Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	Uncertain significance (Jan 12, 2018)
2-43886706-G-A		Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	Uncertain significance (Jan 13, 2018)
2-43886728-G-A		Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	Uncertain significance (Jan 13, 2018)
2-43886784-A-G		Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	Uncertain significance (Jan 13, 2018)
2-43886794-T-G		Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	Uncertain significance (Jan 13, 2018)
2-43886848-G-C		Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	Uncertain significance (Jan 13, 2018)
2-43886881-C-T		Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LRPPRC	protein_coding	protein_coding	ENST00000260665	38	109498

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.30e-10	1.00	125657	0	91	125748	0.000362

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.93	858	713	1.20	0.0000367	9130
Missense in Polyphen		237	214.15	1.1067		2776
Synonymous	-2.13	311	267	1.17	0.0000143	2581
Loss of Function	5.00	31	78.9	0.393	0.00000387	1038

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000755	0.000753
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000163
Finnish	0.00106	0.00106
European (Non-Finnish)	0.000230	0.000229
Middle Eastern	0.000218	0.000163
South Asian	0.000500	0.000490
Other	0.00114	0.00114

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play a role in RNA metabolism in both nuclei and mitochondria. In the nucleus binds to HNRPA1-associated poly(A) mRNAs and is part of nmRNP complexes at late stages of mRNA maturation which are possibly associated with nuclear mRNA export. May bind mature mRNA in the nucleus outer membrane. In mitochondria binds to poly(A) mRNA. Plays a role in translation or stability of mitochondrially encoded cytochrome c oxidase (COX) subunits. May be involved in transcription regulation. Cooperates with PPARGC1A to regulate certain mitochondrially encoded genes and gluconeogenic genes and may regulate docking of PPARGC1A to transcription factors. Seems to be involved in the transcription regulation of the multidrug-related genes MDR1 and MVP. Part of a nuclear factor that binds to the invMED1 element of MDR1 and MVP gene promoters. Binds single-stranded DNA (By similarity). {ECO:0000250, ECO:0000269|PubMed:11585913, ECO:0000269|PubMed:12832482, ECO:0000269|PubMed:15081402, ECO:0000269|PubMed:15139850, ECO:0000269|PubMed:15272088, ECO:0000269|PubMed:17050673}.
• Pathway: Gene expression (Transcription);il 6 signaling pathway;role of erbb2 in signal transduction and oncology;Generic Transcription Pathway;RNA Polymerase II Transcription;Respiratory electron transport;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;TP53 Regulates Metabolic Genes;Transcriptional Regulation by TP53;TNFalpha;Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. (Consensus)

Recessive Scores

• pRec: 0.321

Intolerance Scores

• loftool: 0.792
• rvis_EVS: -1.65
• rvis_percentile_EVS: 2.77

Haploinsufficiency Scores

• pHI: 0.179
• hipred: Y
• hipred_score: 0.682
• ghis: 0.592

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.897

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Lrpprc
• Phenotype: embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); growth/size/body region phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); cellular phenotype

Gene ontology

• Biological process: negative regulation of mitochondrial RNA catabolic process;mitochondrion transport along microtubule;mRNA transport;regulation of mitochondrial translation
• Cellular component: condensed nuclear chromosome;nucleus;nuclear inner membrane;nuclear outer membrane;nucleoplasm;mitochondrion;cytoskeleton;microtubule;membrane;mitochondrial nucleoid;perinuclear region of cytoplasm;ribonucleoprotein complex
• Molecular function: single-stranded DNA binding;RNA binding;protein binding;microtubule binding;ubiquitin protein ligase binding;beta-tubulin binding;actin filament binding