MRPL3

Chr 3AR

mitochondrial ribosomal protein L3

Also known as: COXPD9, MRL3, RPML3, uL3m

NCBI Gene: 11222 ENSG00000114686 UniProt: P09001 OMIM: 607118

The protein is a component of the large 39S subunit of mitochondrial ribosomes and functions in mitochondrial protein synthesis. Biallelic mutations cause combined oxidative phosphorylation deficiency 9, inherited in an autosomal recessive pattern. The pathogenic mechanism involves impaired mitochondrial protein synthesis leading to defective oxidative phosphorylation.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein that belongs to the L3P ribosomal protein family. A pseudogene corresponding to this gene is found on chromosome 13q. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Combined oxidative phosphorylation deficiency 9MIM #614582

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · mitochondrial disease · AR · ClinGen 2022

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.38

LOEUF

—

Mechanism

📖

GeneReview available — MRPL3

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?

1.38LOEUF

pLI 0.000

Z-score 0.25

OE 0.94 (0.66–1.38)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.16Z-score

OE missense 1.03 (0.92–1.16)

200 obs / 193.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.94 (0.66–1.38)

0≤0.351.4

Missense OE?1.03 (0.92–1.16)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 19 / 20.2Missense obs/exp: 200 / 193.7Syn Z: -0.96

Background carrier burden — how many people carry a rare variant somewhere in MRPL3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 67

583 rare PASS variants

Rare truncating (LoF)

1 in 640

108 rare PASS variants

Rare synonymous (reference)

1 in 270

229 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MRPL3. 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 83	1 in 1,300
South Asian	~43k	1 in 120	1 in 2,300
Remaining (unassigned)	~30k	1 in 58	1 in 1,400
European (Finnish)	~27k	1 in 220	1 in 4,400
Admixed American	~22k	1 in 70	1 in 1,400
African / African American	~21k	1 in 63	1 in 1,600
East Asian	~20k	1 in 120	1 in 2,100
Ashkenazi Jewish	~13k	1 in 350	1 in 1,300
Middle Eastern	~2,884	1 in 98	≈ 1 in 940

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): 9 of 10 coding exons well covered in gnomAD exomes; exon 9 marginal. Genomes: all 10.? see exons ↓