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…

ARLOEUF 1.381 OMIM phenotype

Clinical Summary— MRPL3

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ARModerate

Moderate evidence — consider for supplementary testing

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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

5 unique Pathogenic / Likely Pathogenic· 71 VUS of 172 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — MRPL3

Authoritative clinical overview · Recommended first read

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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

ClinVar Variant Classifications

172 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic3

VUS71

Likely Benign50

Benign22

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	2	0	0	0	2
Likely Pathogenic	2	1	0	0	3
VUS	4	65	1	1	71
Likely Benign	0	4	32	14	50
Benign	0	1	18	3	22
Conflicting	—				2
Total	8	71	51	18	150

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap MRPL3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →