MRPL21

Chr 11

mitochondrial ribosomal protein L21

Also known as: L21mt, MRP-L21, bL21m

NCBI Gene: 219927ENSG00000197345UniProt: Q7Z2W9

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]

47
ClinVar variants
9
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MRPL21
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 31 VUS of 47 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.27Z-score
OE missense 0.93 (0.79–1.09)
108 obs / 116.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.37 (0.94–1.87)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.79–1.09)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.15
0≤1.21.6
LoF obs/exp: 18 / 13.1Missense obs/exp: 108 / 116.2Syn Z: -0.84

ClinVar Variant Classifications

47 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic4
VUS31
Likely Benign4
Benign3
5
Pathogenic
4
Likely Pathogenic
31
VUS
4
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
4
0
4
VUS
0
30
1
0
31
Likely Benign
0
2
2
0
4
Benign
0
1
2
0
3
Total03314047

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MRPL21 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
MRPL21-PARP1 axis promotes cisplatin resistance in head and neck squamous cell carcinoma by inhibiting autophagy through the PI3K/AKT/mTOR signaling pathway.
Guan R et al.·J Exp Clin Cancer Res
2025
The role of the mitochondrial ribosomal protein family in detecting hepatocellular carcinoma and predicting prognosis, immune features, and drug sensitivity.
Zhao JW et al.·Clin Transl Oncol
2024
Integrative Analysis of the Role of MRPL21 in Human Pan-Cancer and Its Relationship with the Progression of Lung Adenocarcinoma.
Xu Q et al.·Mol Biotechnol
2026
MRPS31 loss is a key driver of mitochondrial deregulation and hepatocellular carcinoma aggressiveness.
Min S et al.·Cell Death Dis
2021
The galanin signaling cascade is a candidate pathway regulating oncogenesis in human squamous cell carcinoma.
Sugimoto T et al.·Genes Chromosomes Cancer
2009
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools