MRPL47

Chr 3

mitochondrial ribosomal protein L47

Also known as: CGI-204, L47mt, MRP-L47, NCM1, uL29m

NCBI Gene: 57129 ENSG00000136522 UniProt: Q9HD33 OMIM: 611852

The protein is a component of the mitochondrial ribosome's large 39S subunit and functions in mitochondrial protein synthesis. Mutations cause autosomal recessive mitochondrial disease affecting multiple organ systems. The gene shows minimal constraint against loss-of-function variants, consistent with recessive inheritance patterns.

OMIM 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. This gene is immediately adjacent to the gene for BAF complex 53 kDa subunit protein a (BAF53a), in a tail-to-tail orientation. Two transcript variants encoding different protein isoforms have been identified. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.89

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.89LOEUF

pLI 0.000

Z-score 1.88

OE 0.49 (0.29–0.89)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.22Z-score

OE missense 1.06 (0.92–1.22)

137 obs / 129.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.49 (0.29–0.89)

0≤0.351.4

Missense OE?1.06 (0.92–1.22)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 8 / 16.2Missense obs/exp: 137 / 129.8Syn Z: -0.12

Background carrier burden — how many people carry a rare variant somewhere in MRPL47?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 270

338 rare PASS variants

Rare truncating (LoF)

1 in 1,000

89 rare PASS variants

Rare synonymous (reference)

1 in 560

109 rare PASS variants

Rare missense and truncating variants are carried at similar rates in MRPL47; this gene does not show strong loss-of-function constraint by this measure. 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 430	1 in 1,100
South Asian	~43k	1 in 200	1 in 560
Remaining (unassigned)	~30k	1 in 200	1 in 1,300
European (Finnish)	~27k	1 in 950	≈ 1 in 27,000
Admixed American	~22k	1 in 150	1 in 490
African / African American	~21k	1 in 200	1 in 1,200
East Asian	~20k	1 in 100	1 in 400
Ashkenazi Jewish	~13k	1 in 1,900	1 in 490
Middle Eastern	~2,884	1 in 200	≈ 1 in 960

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): 6 of 7 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 7.? see exons ↓