LRPPRC

Chr 2

leucine rich pentatricopeptide repeat containing

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

This protein localizes to mitochondria and is involved in transcriptional regulation of mitochondrial genes, though its precise function remains unclear. Mutations cause French-Canadian type Leigh syndrome (mitochondrial complex IV deficiency, nuclear type 5) through an autosomal recessive inheritance pattern. The pathogenic mechanism appears to be dominant negative.

GeneReviewsResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismLOEUF 0.53
Clinical SummaryLRPPRC
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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.
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ClinVar Variants
104 unique Pathogenic / Likely Pathogenic· 282 VUS of 500 total submissions
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GeneReview available — LRPPRC
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: TypeError: fetch failed

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.53LOEUF
pLI 0.000
Z-score 5.00
OE 0.39 (0.290.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
-1.93Z-score
OE missense 1.20 (1.141.27)
858 obs / 713.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.39 (0.290.53)
00.351.4
Missense OE1.20 (1.141.27)
00.61.4
Synonymous OE1.17
01.21.6
LoF obs/exp: 31 / 78.9Missense obs/exp: 858 / 713.1Syn Z: -2.13
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveLRPPRC-related Leigh syndrome, French-Canadian typeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7034th %ile
GOF
0.5562th %ile
LOF
0.2288th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

500 submitted variants in ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic91
VUS282
Likely Benign72
Benign1
Conflicting3
13
Pathogenic
91
Likely Pathogenic
282
VUS
72
Likely Benign
1
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
0
10
0
13
Likely Pathogenic
83
3
5
0
91
VUS
0
233
30
19
282
Likely Benign
0
11
40
21
72
Benign
0
0
1
0
1
Conflicting
3
Total862478640462

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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