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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables ribonuclease P activity. Involved in mitochondrial tRNA 5'-end processing. Located in mitochondrion. Part of mitochondrial ribonuclease P complex. Is active in mitochondrial matrix. Implicated in combined oxidative phosphorylation deficiency 54. [provided by Alliance of Genome Resources, Jun 2026]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Combined oxidative phosphorylation deficiency 54MIM #619737

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · mitochondrial disease · AR · ClinGen 2024

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.22

LOEUF

Mechanism· predicted

📖

GeneReview available — PRORP

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

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

Background carrier burden — how many people carry a rare variant somewhere in PRORP?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

689 rare PASS variants

Rare truncating (LoF)

1 in 1,100

135 rare PASS variants

Rare synonymous (reference)

1 in 330

246 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PRORP. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 150	1 in 1,300
South Asian	~43k	1 in 120	1 in 580
Remaining (unassigned)	~30k	1 in 92	1 in 750
European (Finnish)	~27k	1 in 230	1 in 370
Admixed American	~22k	1 in 100	1 in 660
African / African American	~21k	1 in 91	1 in 1,600
East Asian	~20k	1 in 110	1 in 2,200
Ashkenazi Jewish	~13k	1 in 350	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 140	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 6 of 7 coding exons well covered in gnomAD exomes; exon 5 marginal. Genomes: all 7.? see exons ↓