MRPL44

Chr 2AR

mitochondrial ribosomal protein L44

Also known as: COXPD16, L44MT, MRP-L44, mL44

NCBI Gene: 65080 ENSG00000135900 UniProt: Q9H9J2 OMIM: 611849

MRPL44 encodes a protein component of the large 39S subunit of mitochondrial ribosomes, which synthesize proteins essential for oxidative phosphorylation within mitochondria. Mutations cause combined oxidative phosphorylation deficiency 16, inherited in an autosomal recessive pattern. The pathogenic mechanism involves impaired mitochondrial protein synthesis leading to defective respiratory chain function.

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. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Combined oxidative phosphorylation deficiency 16MIM #615395

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · mitochondrial disease · AR · ClinGen 2022

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.64

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.64LOEUF

pLI 0.000

Z-score -0.16

OE 1.05 (0.68–1.64)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.08Z-score

OE missense 0.98 (0.87–1.11)

177 obs / 180.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.05 (0.68–1.64)

0≤0.351.4

Missense OE?0.98 (0.87–1.11)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 13 / 12.4Missense obs/exp: 177 / 180.0Syn Z: 0.21

Background carrier burden — how many people carry a rare variant somewhere in MRPL44?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

451 rare PASS variants

Rare truncating (LoF)

1 in 2,700

69 rare PASS variants

Rare synonymous (reference)

1 in 390

180 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MRPL44. 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 170	1 in 3,300
South Asian	~43k	1 in 140	1 in 900
Remaining (unassigned)	~30k	1 in 99	1 in 3,800
European (Finnish)	~27k	1 in 610	1 in 1,400
Admixed American	~22k	1 in 150	1 in 3,200
African / African American	~21k	1 in 100	≈ 1 in 4,200
East Asian	~20k	1 in 160	1 in 2,100
Ashkenazi Jewish	~13k	1 in 210	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 120	≈ 1 in 1,400

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 ↓