MRPL48

Chr 11

mitochondrial ribosomal protein L48

Also known as: CGI-118, HSPC290, L48MT, MRP-L48, mL48

NCBI Gene: 51642 ENSG00000175581 UniProt: Q96GC5

The MRPL48 protein is a component of the large 39S subunit of mitochondrial ribosomes, which synthesize proteins within mitochondria. Mutations cause autosomal recessive mitochondrial disease with multisystem involvement including neurological manifestations. This gene is not highly constrained against loss-of-function variants, consistent with recessive inheritance patterns observed in mitochondrial ribosomal protein disorders.

ResearchSummary from RefSeq

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. A pseudogene corresponding to this gene is found on chromosome 6p. Several transcript variants, some protein-coding and some non-protein coding, have been found for this gene. [provided by RefSeq, Jan 2016]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.87

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.87LOEUF

pLI 0.004

Z-score 1.90

OE 0.44 (0.24–0.87)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.94Z-score

OE missense 0.74 (0.62–0.90)

78 obs / 105.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.44 (0.24–0.87)

0≤0.351.4

Missense OE?0.74 (0.62–0.90)

0≤0.61.4

Synonymous OE?0.79

0≤1.21.6

LoF obs/exp: 6 / 13.6Missense obs/exp: 78 / 105.2Syn Z: 1.03

Background carrier burden — how many people carry a rare variant somewhere in MRPL48?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 250

218 rare PASS variants

Rare truncating (LoF)

1 in 3,800

35 rare PASS variants

Rare synonymous (reference)

1 in 550

100 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MRPL48. 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 300	1 in 3,700
South Asian	~43k	1 in 290	1 in 3,900
Remaining (unassigned)	~30k	1 in 310	1 in 3,300
European (Finnish)	~27k	1 in 1,200	none seen
Admixed American	~22k	1 in 380	≈ 1 in 4,500
African / African American	~21k	1 in 370	≈ 1 in 4,400
East Asian	~20k	1 in 280	≈ 1 in 9,600
Ashkenazi Jewish	~13k	≈ 1 in 4,300	none seen
Middle Eastern	~2,884	1 in 570	≈ 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): All 8 coding exons well covered in gnomAD exomes and genomes.? see exons ↓