RPL26

Chr 17AD

ribosomal protein L26

Also known as: DBA11, L26, uL24

NCBI Gene: 6154 ENSG00000161970 UniProt: P61254 OMIM: 603704

This gene encodes a ribosomal protein that is a component of the large 60S ribosomal subunit responsible for protein synthesis. Mutations cause Diamond-Blackfan anemia 11, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants (pLI 0.92, LOEUF 0.38), reflecting its essential role in ribosomal function.

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 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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.381 OMIM phenotype

Clinical Summary— RPL26

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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.

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ClinVar Variants

5 unique Pathogenic / Likely Pathogenic· 35 VUS of 89 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — RPL26

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?

0.38LOEUF

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?

1.64Z-score

OE missense 0.51 (0.40–0.66)

46 obs / 89.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.38)

0≤0.351.4

Missense OE?0.51 (0.40–0.66)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 0 / 8.0Missense obs/exp: 46 / 89.7Syn Z: -0.21

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateRPL26-related Diamond-Blackfan anemiaLOFAD

This gene — mechanism propensity

0.2997th %ile

GOF

0.1699th %ile

LOF

0.80top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 100% of P/LP variants are LoF · LOEUF 0.38

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

ClinVar Variant Classifications

89 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic3

VUS35

Likely Benign35

Benign8

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	0	0	0	2
Likely Pathogenic	3	0	0	0	3
VUS	1	30	3	1	35
Likely Benign	0	1	13	21	35
Benign	0	0	8	0	8
Total	6	31	24	22	83

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

View in ClinVar →

6 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap RPL26 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →