RPL22

Chr 1

ribosomal protein L22

Also known as: EAP, HBP15, HBP15/L22, L22, eL22

NCBI Gene: 6146 ENSG00000116251 UniProt: P35268 OMIM: 180474

The RPL22 protein is a component of the large 60S ribosomal subunit that synthesizes proteins in the cell. Mutations cause Diamond-Blackfan anemia, an inherited bone marrow failure syndrome with autosomal dominant inheritance. The gene shows moderate tolerance to loss-of-function variants, which is typical for ribosomal protein genes associated with Diamond-Blackfan anemia.

OMIM ResearchSummary from RefSeq, 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 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a cytoplasmic ribosomal protein that is a component of the 60S subunit. The protein belongs to the L22E family of ribosomal proteins. Its initiating methionine residue is post-translationally removed. The protein can bind specifically to Epstein-Barr virus-encoded RNAs (EBERs) 1 and 2. The mouse protein has been shown to be capable of binding to heparin. Transcript variants utilizing alternative polyA signals exist. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. It was previously thought that this gene mapped to 3q26 and that it was fused to the acute myeloid leukemia 1 (AML1) gene located at 21q22 in some therapy-related myelodysplastic syndrome patients with 3;21 translocations; however, these fusions actually involve a ribosomal protein L22 pseudogene located at 3q26, and this gene actually maps to 1p36.3-p36.2. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.04

Clinical Summary— RPL22

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.

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ClinVar Variants

4 VUS of 14 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.04LOEUF

pLI 0.156

Z-score 1.53

OE 0.33 (0.13–1.04)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.67Z-score

OE missense 0.45 (0.34–0.60)

32 obs / 71.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.33 (0.13–1.04)

0≤0.351.4

Missense OE?0.45 (0.34–0.60)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 2 / 6.1Missense obs/exp: 32 / 71.8Syn Z: 0.13

This gene — mechanism propensity

0.6358th %ile

GOF

0.2497th %ile

LOF

0.4726th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

14 submitted variants in ClinVar

ClinVar

Classification Summary

VUS4

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	4	4
Likely Benign	0	0
Benign	0	0
Total	4	4

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

View in ClinVar →

57 pathogenic / likely-pathogenic (of 64) ClinVar copy-number / structural variants overlap RPL22 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →