RPL8

Chr 8

ribosomal protein L8

Also known as: L8, uL2

NCBI Gene: 6132 ENSG00000161016 UniProt: P62917 OMIM: 604177

The protein is a component of the large 60S ribosomal subunit that participates in protein synthesis and likely contributes to aminoacyl-tRNA binding. Mutations cause Diamond-Blackfan anemia, an autosomal dominant ribosomopathy characterized by early-onset anemia, growth retardation, and congenital malformations. The gene is highly constrained against loss-of-function variants (pLI 0.96, LOEUF 0.31), consistent with the dominant inheritance pattern observed in affected families.

OMIM ResearchSummary from RefSeq, UniProt

Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L2P family of ribosomal proteins. It is located in the cytoplasm. In rat, the protein associates with the 5.8S rRNA, very likely participates in the binding of aminoacyl-tRNA, and is a constituent of the elongation factor 2-binding site at the ribosomal subunit interface. Alternatively spliced transcript variants encoding the same protein exist. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.31

Clinical Summary— RPL8

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

27 VUS of 41 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.31LOEUF

pLI 0.955

Z-score 2.89

OE 0.00 (0.00–0.31)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.75Z-score

OE missense 0.62 (0.53–0.73)

106 obs / 170.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.31)

0≤0.351.4

Missense OE?0.62 (0.53–0.73)

0≤0.61.4

Synonymous OE?1.39

0≤1.21.6

LoF obs/exp: 0 / 9.7Missense obs/exp: 106 / 170.2Syn Z: -2.46

This gene — mechanism propensity

0.2698th %ile

GOF

0.2198th %ile

LOF

0.85top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.31

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

41 submitted variants in ClinVar

ClinVar

Classification Summary

VUS27

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	26	1	27
Likely Benign	0	0	0
Benign	0	0	0
Total	26	1	27

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

View in ClinVar →

55 pathogenic / likely-pathogenic (of 67) ClinVar copy-number / structural variants overlap RPL8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →