RPL15

Chr 3AD

ribosomal protein L15

Also known as: DBA12, EC45, L15, RPL10, RPLY10, RPYL10, eL15

NCBI Gene: 6138ENSG00000174748UniProt: P61313OMIM: 604174

This gene encodes a ribosomal protein that is a component of the large 60S ribosomal subunit responsible for protein synthesis. Mutations cause Diamond-Blackfan anemia 12, inherited in an autosomal dominant pattern, which typically presents as severe anemia in infancy along with growth retardation and congenital malformations. The gene is highly constrained against loss-of-function variants (pLI 0.97), reflecting its essential role in ribosome function.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.271 OMIM phenotype
Clinical Summary— RPL15
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
19 unique Pathogenic / Likely Pathogenic· 81 VUS of 200 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — RPL15
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.27LOEUF
pLI 0.971
Z-score 3.07
OE 0.00 (0.00–0.27)
Highly constrained

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

Missense Constraint
1.83Z-score
OE missense 0.54 (0.45–0.66)
70 obs / 128.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–0.27)
0≤0.351.4
Missense OE0.54 (0.45–0.66)
0≤0.61.4
Synonymous OE1.39
0≤1.21.6
LoF obs/exp: 0 / 11.0Missense obs/exp: 70 / 128.5Syn Z: -2.00
DN
0.2598th %ile
GOF
0.1899th %ile
LOF
0.80top 5%

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

LOFprediction above median · 1 literature citation · 37% of P/LP variants are LoF · LOEUF 0.27

Literature Evidence

LOFLandowski et al. 2013 studied 87 unrelated patients with a clinical diagnosis of Diamond Blackfan Anemia (DBA) (thought to be a disorder of ribosome biogenesis and/or function); all patients had previously had negative sequencing studies of all currently known ribosomal protein (RP) genes. The autPMID:23812780

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

200 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic2
VUS81
Likely Benign66
Benign15
Conflicting2
17
Pathogenic
2
Likely Pathogenic
81
VUS
66
Likely Benign
15
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
2
9
0
17
Likely Pathogenic
1
1
0
0
2
VUS
2
73
3
3
81
Likely Benign
0
2
19
45
66
Benign
0
1
11
3
15
Conflicting
—2
Total9794251183

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

View in ClinVar →

Protein Context — Lollipop Plot

RPL15 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients