MRPS31

Chr 13

mitochondrial ribosomal protein S31

Also known as: IMOGN38, MRP-S31, S31mt, mS31

NCBI Gene: 10240 ENSG00000102738 UniProt: Q92665

This protein is a component of the small 28S subunit of mitochondrial ribosomes and functions in mitochondrial protein synthesis. Mutations cause autosomal recessive mitochondrial disorders affecting multiple organ systems. The gene is highly constrained against loss-of-function variants (pLI near 1.0), suggesting that complete loss of protein function is likely pathogenic.

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. The 28S subunit of the mammalian mitoribosome may play a crucial and characteristic role in translation initiation. This gene encodes a 28S subunit protein that has also been associated with type 1 diabetes; however, its relationship to the etiology of this disease remains to be clarified. Pseudogenes corresponding to this gene have been found on chromosomes 3 and 13. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.87

LOEUF

Mechanism· predicted

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 0.000

Z-score 1.98

OE 0.51 (0.32–0.87)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.10Z-score

OE missense 0.98 (0.87–1.10)

200 obs / 204.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.51 (0.32–0.87)

0≤0.351.4

Missense OE?0.98 (0.87–1.10)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 10 / 19.4Missense obs/exp: 200 / 204.1Syn Z: 0.28

Background carrier burden — how many people carry a rare variant somewhere in MRPS31?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

466 rare PASS variants

Rare truncating (LoF)

1 in 2,100

79 rare PASS variants

Rare synonymous (reference)

1 in 520

180 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MRPS31. 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 160	1 in 2,300
South Asian	~43k	1 in 100	1 in 570
Remaining (unassigned)	~30k	1 in 100	1 in 5,000
European (Finnish)	~27k	1 in 590	1 in 3,000
Admixed American	~22k	1 in 150	1 in 4,100
African / African American	~21k	1 in 140	1 in 2,200
East Asian	~20k	1 in 170	1 in 1,800
Ashkenazi Jewish	~13k	1 in 280	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 160	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): 6 of 7 coding exons well covered in gnomAD exomes; exon 5 marginal. Genomes: all 7.? see exons ↓