RPL8

Chr 8

ribosomal protein L8

Also known as: L8, uL2

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.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.31
Clinical SummaryRPL8
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
8 unique Pathogenic / Likely Pathogenic of 8 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.31LOEUF
pLI 0.955
Z-score 2.89
OE 0.00 (0.000.31)
Highly constrained

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

Missense Constraint
1.75Z-score
OE missense 0.62 (0.530.73)
106 obs / 170.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.31)
00.351.4
Missense OE0.62 (0.530.73)
00.61.4
Synonymous OE1.39
01.21.6
LoF obs/exp: 0 / 9.7Missense obs/exp: 106 / 170.2Syn Z: -2.46
DN
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

8 submitted variants in ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic1
7
Pathogenic
1
Likely Pathogenic

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
Likely Pathogenic
1
VUS
0
Likely Benign
0
Benign
0
Total8

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RPL8 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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