RPL5

Chr 1AD

ribosomal protein L5

Also known as: L5, MSTP030, PPP1R135, uL18

NCBI Gene: 6125 ENSG00000122406 UniProt: P46777 OMIM: 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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, 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 four RNA species and approximately 80 structurally distinct proteins. This gene encodes a member of the L18P family of ribosomal proteins and component of the 60S subunit. The encoded protein binds 5S rRNA to form a stable complex called the 5S ribonucleoprotein particle (RNP), which is necessary for the transport of nonribosome-associated cytoplasmic 5S rRNA to the nucleolus for assembly into ribosomes. The encoded protein may also function to inhibit tumorigenesis through the activation of downstream tumor suppressors and the downregulation of oncoprotein expression. Mutations in this gene have been identified in patients with Diamond-Blackfan Anemia (DBA). This gene is co-transcribed with the small nucleolar RNA gene U21, which is located in its fifth intron. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed throughout the genome. [provided by RefSeq, Mar 2017]

GeneReviews OMIM ResearchGenerating clinical summary…

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

93 unique Pathogenic / Likely Pathogenic· 136 VUS of 384 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 OE?0.00 (0.00–0.17)

0≤0.351.4

Missense OE?0.59 (0.50–0.70)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 0 / 17.9Missense obs/exp: 101 / 171.0Syn Z: -0.29

This gene — mechanism propensity

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 · 88% of P/LP variants are LoF · LOEUF 0.17 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Literature Evidence

LOFInvestigation of the molecular causes underlying physical abnormalities in Diamond-Blackfan anemia patients with RPL5 haploinsufficiency.1

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

References

1.PMID 34587661 ↗

ClinVar Variant Classifications

384 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic61

Likely Pathogenic32

VUS136

Likely Benign105

Benign16

Conflicting12

Pathogenic

Likely Pathogenic

136

VUS

105

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	52	5	4	0	61
Likely Pathogenic	30	1	1	0	32
VUS	3	114	17	2	136
Likely Benign	1	2	59	43	105
Benign	0	0	14	2	16
Conflicting	—				12
Total	86	122	95	47	362

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

View in ClinVar →

7 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap RPL5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →