RPL26

Chr 17AD

ribosomal protein L26

Also known as: DBA11, L26, uL24

NCBI Gene: 6154ENSG00000161970UniProt: P61254

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 L24P 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. Mutations in this gene result in Diamond-Blackfan anemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

Primary Disease Associations & Inheritance

?Diamond-Blackfan anemia 11MIM #614900
AD
120
ClinVar variants
21
Pathogenic / LP
0.92
pLI score· haploinsufficient
0
Active trials
Clinical Summary— RPL26
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.92). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
21 Pathogenic / Likely Pathogenic· 49 VUS of 120 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.38LOEUF
pLI 0.916
Z-score 2.62
OE 0.00 (0.00–0.38)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.64Z-score
OE missense 0.51 (0.40–0.66)
46 obs / 89.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.38)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.51 (0.40–0.66)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.05
0≤1.21.6
LoF obs/exp: 0 / 8.0Missense obs/exp: 46 / 89.7Syn Z: -0.21

ClinVar Variant Classifications

120 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic3
VUS49
Likely Benign42
Benign8
18
Pathogenic
3
Likely Pathogenic
49
VUS
42
Likely Benign
8
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
16
0
18
Likely Pathogenic
3
0
0
0
3
VUS
1
33
14
1
49
Likely Benign
0
1
16
25
42
Benign
0
0
8
0
8
Total6345426120

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

View in ClinVar →

Protein Context — Lollipop Plot

RPL26 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

RPL26-related Diamond-Blackfan anemia

moderate
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Diamond-Blackfan anemia 11

MIM #614900

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — RPL26
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
VCP/p97 UFMylation stabilizes BECN1 and facilitates the initiation of autophagy.
Wang Z et al.·Autophagy
2024
Stable Cas9 expression regulates cell growth by facilitating mTORC2 activation.
Yu L et al.·Nucleic Acids Res
2025
Familial RPL26 Variant Causing Congenital Anomalies Without Hematological Features of Diamond Blackfan Anemia.
Karger LM et al.·Am J Med Genet A
2025Case report
Peripheral blood GATA2 expression impacts RNF213 mutation penetrance and clinical severity in moyamoya disease.
Mineharu Y et al.·Stroke Vasc Neurol
2025
DNA Methylation Episignature as a Novel Diagnostic Tool for Diamond-Blackfan Anemia Syndrome.
Quarello P et al.·Am J Hematol
2026
The Six1 oncoprotein downregulates p53 via concomitant regulation of RPL26 and microRNA-27a-3p.
Towers CG et al.·Nat Commun
2015
Differential regulation of translational stress responses by herpesvirus ubiquitin deconjugases.
Liu J et al.·FEBS J
2026
Whole-exome sequencing study identifies rare variants and genes associated with intraocular pressure and glaucoma.
Gao XR et al.·Nat Commun
2022
[Molecular mechanisms underlying the pathology of Diamond-Blackfan anemia].
Toki T et al.·Rinsho Ketsueki
2015Functional
The effects of p53 gene inactivation on mutant proteome expression in a human melanoma cell model.
Faktor J et al.·Biochim Biophys Acta Gen Subj
2020Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools