MRPL49

Chr 11AR

mitochondrial ribosomal protein L49

Also known as: C11orf4, COXPD60, L49mt, MRP-L49, NOF, NOF1, mL49

NCBI Gene: 740 ENSG00000149792 UniProt: Q13405 OMIM: 606866

This protein is a component of the large 39S subunit of mitochondrial ribosomes and functions in mitochondrial protein synthesis. Mutations cause combined oxidative phosphorylation deficiency 60, which follows autosomal recessive inheritance. The gene shows tolerance to loss-of-function variants (pLI 0.0003, LOEUF 1.5), suggesting that complete loss of function may be required for disease manifestation.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM

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. Pseudogenes corresponding to this gene are found on chromosomes 5q and 8p. [provided by RefSeq, May 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Combined oxidative phosphorylation deficiency 60MIM #621195

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Combined oxidative phosphorylation deficiency 60; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.50

LOEUF

Mechanism· predicted

📖

GeneReview available — MRPL49

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?

1.50LOEUF

pLI 0.000

Z-score 0.60

OE 0.77 (0.42–1.50)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.28Z-score

OE missense 0.92 (0.78–1.09)

94 obs / 102.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.77 (0.42–1.50)

0≤0.351.4

Missense OE?0.92 (0.78–1.09)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 6 / 7.8Missense obs/exp: 94 / 102.0Syn Z: -0.90

Background carrier burden — how many people carry a rare variant somewhere in MRPL49?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

281 rare PASS variants

Rare truncating (LoF)

1 in 1,700

59 rare PASS variants

Rare synonymous (reference)

1 in 260

103 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MRPL49. 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 290	1 in 1,800
South Asian	~43k	1 in 220	1 in 3,100
Remaining (unassigned)	~30k	1 in 180	1 in 1,700
European (Finnish)	~27k	1 in 1,300	≈ 1 in 6,700
Admixed American	~22k	1 in 140	1 in 1,100
African / African American	~21k	1 in 270	1 in 410
East Asian	~20k	1 in 350	1 in 3,600
Ashkenazi Jewish	~13k	1 in 620	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 100	none seen

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): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓