RPL4

Chr 15

ribosomal protein L4

Also known as: L4, uL4

NCBI Gene: 6124 ENSG00000174444 UniProt: P36578 OMIM: 180479

Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L4E family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

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

0.12

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.12LOEUF

pLI 1.000

Z-score 4.62

OE 0.00 (0.00–0.12)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

1.27Z-score

OE missense 0.78 (0.70–0.88)

207 obs / 265.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.12)

0≤0.351.4

Missense OE?0.78 (0.70–0.88)

0≤0.61.4

Synonymous OE?1.26

0≤1.21.6

LoF obs/exp: 0 / 24.9Missense obs/exp: 207 / 265.3Syn Z: -1.83

Background carrier burden — how many people carry a rare variant somewhere in RPL4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

453 rare PASS variants

Rare truncating (LoF)

1 in 10,000

14 rare PASS variants

Rare synonymous (reference)

1 in 110

213 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RPL4. 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 250	1 in 13,000
South Asian	~43k	1 in 150	1 in 1,800
Remaining (unassigned)	~30k	1 in 150	≈ 1 in 10,000
European (Finnish)	~27k	1 in 450	none seen
Admixed American	~22k	1 in 190	≈ 1 in 5,600
African / African American	~21k	1 in 170	≈ 1 in 10,000
East Asian	~20k	1 in 130	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 620	none seen
Middle Eastern	~2,884	1 in 210	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.

Exome coverage (gnomAD): All 10 coding exons well covered in gnomAD exomes and genomes.? see exons ↓