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…

Primary Disease Associations & Inheritance

Diamond-Blackfan anemia 6MIM #612561

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · Diamond-Blackfan anemia 6 · AD · ClinGen 2023

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.17

LOEUF· LoF intol.

LOF

Mechanism· predicted

📖

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

Background carrier burden — how many people carry a rare variant somewhere in RPL5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 440

267 rare PASS variants

Rare truncating (LoF)

1 in 41,000

9 rare PASS variants

Rare synonymous (reference)

1 in 710

123 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RPL5. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 490	1 in 26,000
South Asian	~43k	1 in 130	none seen
Remaining (unassigned)	~30k	1 in 400	≈ 1 in 30,000
European (Finnish)	~27k	1 in 1,700	≈ 1 in 25,000
Admixed American	~22k	1 in 560	none seen
African / African American	~21k	1 in 550	none seen
East Asian	~20k	1 in 210	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 820	none seen
Middle Eastern	~2,884	1 in 520	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.