RPL5

Chr 1AD

ribosomal protein L5

Also known as: L5, MSTP030, PPP1R135, uL18

NCBI Gene: 6125ENSG00000122406UniProt: P46777OMIM: 603634

This gene encodes a ribosomal protein that is an essential component of the large 60S ribosomal subunit and binds 5S rRNA to form the 5S ribonucleoprotein particle required for ribosome assembly. Mutations cause Diamond-Blackfan anemia 6, a bone marrow failure syndrome, and follow autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.998, LOEUF 0.167), reflecting its essential role in protein synthesis.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.171 OMIM phenotype
Clinical Summary— RPL5
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Gene-Disease Validity (ClinGen)
Diamond-Blackfan anemia 6 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
54 unique Pathogenic / Likely Pathogenic· 64 VUS of 201 total submissions
Explore recent and relevant literature in Research Assistant →
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GeneReview available — RPL5
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
0.17LOEUF
pLI 0.998
Z-score 3.92
OE 0.00 (0.00–0.17)
Highly constrained

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

Missense Constraint
1.90Z-score
OE missense 0.59 (0.50–0.70)
101 obs / 171.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–0.17)
0≤0.351.4
Missense OE0.59 (0.50–0.70)
0≤0.61.4
Synonymous OE1.05
0≤1.21.6
LoF obs/exp: 0 / 17.9Missense obs/exp: 101 / 171.0Syn Z: -0.29
DN
0.2798th %ile
GOF
0.15100th %ile
LOF
0.81top 5%

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

LOFprediction above median · 1 literature citation · 87% of P/LP variants are LoF · LOEUF 0.17

Literature Evidence

LOFInvestigation of the molecular causes underlying physical abnormalities in Diamond-Blackfan anemia patients with RPL5 haploinsufficiency.PMID:34587661

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

201 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic24
VUS64
Likely Benign56
Benign5
Conflicting1
30
Pathogenic
24
Likely Pathogenic
64
VUS
56
Likely Benign
5
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
24
3
3
0
30
Likely Pathogenic
23
0
1
0
24
VUS
3
51
8
2
64
Likely Benign
1
0
29
26
56
Benign
0
0
5
0
5
Conflicting
—1
Total51544628180

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

View in ClinVar →

Protein Context — Lollipop Plot

RPL5 · 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
Ribosomal protein L5 (RPL5)/ E2F transcription factor 1 (E2F1) signaling suppresses breast cancer progression via regulating endoplasmic reticulum stress and autophagy
Ma X et al.·Bioengineered
2022
The Prognostic Value of Whole-Blood PSMB5, CXCR4, POMP, and RPL5 mRNA Expression in Patients with Multiple Myeloma Treated with Bortezomib
Robak P et al.·Cancers (Basel)
2021Cohort
Ribosomal protein L5 induces cellular senescence via p53-p21-pRb pathway to mediate relapse of acute myeloid leukemia
Zhang W et al.·Sci Rep
2025
Identification of RPL5 gene variants and the risk of hepatic vein thrombosis in Saudi patients
Hassan FM et al.·Saudi Med J
2021Cohort
Cytoplasmic Male Sterility-Associated Mitochondrial Gene orf312 Derived from Rice (Oryza sativa L.) Cultivar Tadukan
Takatsuka A et al.·Rice (N Y)
2021
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