PRORP

Chr 14AR

protein only RNase P catalytic subunit

Also known as: COXPD54, KIAA0391, MRPP3

NCBI Gene: 9692 ENSG00000100890 UniProt: O15091 OMIM: 609947

This protein serves as the catalytic ribonuclease component of mitochondrial ribonuclease P, which cleaves the 5' ends of mitochondrial tRNA molecules as part of tRNA processing. Biallelic mutations cause combined oxidative phosphorylation deficiency 54, an autosomal recessive mitochondrial disorder affecting cellular energy production. The gene shows relaxed constraint against loss-of-function variants (LOEUF 1.222), and a comprehensive clinical review is available in GeneReviews.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables ribonuclease P activity. Involved in mitochondrial tRNA 5'-end processing. Located in mitochondrion and nucleoplasm. Part of mitochondrial ribonuclease P complex. Implicated in combined oxidative phosphorylation deficiency 54. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 1.221 OMIM phenotype

Clinical Summary— PRORP

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

8 unique Pathogenic / Likely Pathogenic· 74 VUS of 105 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.22LOEUF

pLI 0.000

Z-score 0.68

OE 0.86 (0.61–1.22)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.78Z-score

OE missense 0.88 (0.79–0.97)

270 obs / 308.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.86 (0.61–1.22)

0≤0.351.4

Missense OE?0.88 (0.79–0.97)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 22 / 25.7Missense obs/exp: 270 / 308.4Syn Z: 0.79

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedPRORP-related mitochondrial disorderOTHERAR

This gene — mechanism propensity

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

0.6744th %ile

GOF

0.5170th %ile

LOF

0.2581th %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

105 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic7

VUS74

Likely Benign12

Benign2

Conflicting2

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	2	5	0	0	7
VUS	4	67	3	0	74
Likely Benign	0	8	0	4	12
Benign	0	1	1	0	2
Conflicting	—				2
Total	7	81	4	4	98

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

View in ClinVar →

24 pathogenic / likely-pathogenic (of 37) ClinVar copy-number / structural variants overlap PRORP — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →