MRPL21

Chr 11

mitochondrial ribosomal protein L21

Also known as: L21mt, MRP-L21, bL21m

NCBI Gene: 219927 ENSG00000197345 UniProt: Q7Z2W9

This protein is a component of the large 39S subunit of mitochondrial ribosomes, which synthesize proteins within mitochondria. Mutations cause autosomal recessive mitochondrial disease with neurological and developmental features. The gene shows low constraint against loss-of-function variants, which is consistent with recessive inheritance patterns.

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. Multiple transcript variants encoding different isoforms were identified through sequence analysis although some may be subject to nonsense-mediated decay (NMD). [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.87

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?

1.87LOEUF

pLI 0.000

Z-score -1.25

OE 1.37 (0.94–1.87)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.27Z-score

OE missense 0.93 (0.79–1.09)

108 obs / 116.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.37 (0.94–1.87)

0≤0.351.4

Missense OE?0.93 (0.79–1.09)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 18 / 13.1Missense obs/exp: 108 / 116.2Syn Z: -0.84

Background carrier burden — how many people carry a rare variant somewhere in MRPL21?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 81

396 rare PASS variants

Rare truncating (LoF)

1 in 460

62 rare PASS variants

Rare synonymous (reference)

1 in 180

165 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MRPL21. 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 110	1 in 1,200
South Asian	~43k	1 in 120	1 in 1,400
Remaining (unassigned)	~30k	1 in 74	1 in 2,500
European (Finnish)	~27k	1 in 1,000	1 in 3,300
Admixed American	~22k	1 in 78	1 in 820
African / African American	~21k	1 in 75	1 in 560
East Asian	~20k	1 in 120	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 1,800	≈ 1 in 9,900
Middle Eastern	~2,884	1 in 98	≈ 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 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓