LRPPRC

Chr 2

leucine rich pentatricopeptide repeat containing

Also known as: CLONE-23970, GP130, LRP130, LSFC, MC4DN5

NCBI Gene: 10128ENSG00000138095UniProt: P42704

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]

Primary Disease Associations & Inheritance

UniProtMitochondrial complex IV deficiency, nuclear type 5
562
ClinVar variants
85
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— LRPPRC
🧬
Gene-Disease Validity (ClinGen)
Leigh syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
85 Pathogenic / Likely Pathogenic· 256 VUS of 562 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.53LOEUF
pLI 0.000
Z-score 5.00
OE 0.39 (0.29–0.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-1.93Z-score
OE missense 1.20 (1.14–1.27)
858 obs / 713.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.39 (0.29–0.53)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.20 (1.14–1.27)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.17
0≤1.21.6
LoF obs/exp: 31 / 78.9Missense obs/exp: 858 / 713.1Syn Z: -2.13

ClinVar Variant Classifications

562 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic60
VUS256
Likely Benign214
Benign5
Conflicting2
25
Pathogenic
60
Likely Pathogenic
256
VUS
214
Likely Benign
5
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
0
14
0
25
Likely Pathogenic
45
0
15
0
60
VUS
0
216
22
18
256
Likely Benign
1
12
121
80
214
Benign
0
0
5
0
5
Conflicting
—2
Total5722817798562

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

LRPPRC · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

LRPPRC-related Leigh syndrome, French-Canadian type

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — LRPPRC
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
LRPPRC and SLIRP synergize to maintain sufficient and orderly mammalian mitochondrial translation.
Rubalcava-Gracia D et al.·Nucleic Acids Res
2024
Therapeutic targeting LRPPRC-mediated OXPHOS synthesis for cancer intervention.
Liang Y et al.·Expert Opin Ther Targets
2025Review
Target oxidative stress-induced disulfidptosis: novel therapeutic avenues in Parkinson's disease.
Zhang J et al.·Mol Brain
2025
Identification and validation of the m6A-binding protein LRPPRC to promote tumorigenesis in multiple myeloma.
Tang J et al.·Hematology
2025
Targeting the miR-34a/LRPPRC/MDR1 axis collapse the chemoresistance in P53 inactive colorectal cancer.
Yang Y et al.·Cell Death Differ
2022
An LRPPRC-HAPSTR1-PSMD14 interaction regulates tumor progression in ovarian cancer.
Li D et al.·Aging (Albany NY)
2024
Super-Enhancer-Driven LncRNA UNC5B-AS1 Inhibits Inflammatory Phenotypic Transition in Pulmonary Artery Smooth Muscle Cells via Lactylation.
Zhu X et al.·Arterioscler Thromb Vasc Biol
2025
Genes and Weightlifting Performance.
Kikuchi N et al.·Genes (Basel)
2021
LRPPRC facilitates tumor progression and immune evasion through upregulation of m(6)A modification of PD-L1 mRNA in hepatocellular carcinoma.
Wang H et al.·Front Immunol
2023
Expanding the Autosomal Recessive Gene Spectrum of Parkinson's Disease: A Study within the CPD10KGP.
Zhao Y et al.·Mov Disord
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
PRKAB2 as a tumor suppressor in renal cell carcinoma: inhibiting mitophagy via the LRPPRC-PRKN/parkin interaction and cardiolipin biosynthesis.
Chen K et al.·Autophagy
2026
High expression of a novel m6A reader LRPPRC predicts immunotherapy response and prognosis in head and neck cancer.
Gopalakrishnan K et al.·Arch Oral Biol
2026
Design, synthesis, and antitumor activity of novel Flavokawain A derivatives by suppressing LRPPRC-YBX1-RPN1 cascade.
Wu R et al.·Bioorg Chem
2026
LRPPRC-Driven Oxidative Phosphorylation Is Associated with Elesclomol-Induced Cuproptosis in Ovarian Cancer.
Wu Y et al.·Int J Mol Sci
2025🔓 Open Access
Mitochondria-located circRCP regulates redox homeostasis via stabilizing LRPPRC/SLIRP complex to promote bladder urothelial carcinoma tumorigenesis.
Zhou ZH et al.·Cancer Lett
2026
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools