RPS19

Chr 19AD

ribosomal protein S19

Also known as: DBA, DBA1, LOH19CR1, S19, eS19

NCBI Gene: 6223ENSG00000105372UniProt: P39019OMIM: 603474

RPS19 encodes a ribosomal protein that is a component of the small 40S ribosomal subunit and is required for pre-rRNA processing and maturation of ribosomal subunits. Mutations cause Diamond-Blackfan anemia, a constitutional anemia characterized by absent or decreased red blood cell precursors, with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.92), reflecting its essential role in protein synthesis.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.371 OMIM phenotype
Clinical Summary— RPS19
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Gene-Disease Validity (ClinGen)
Diamond-Blackfan anemia · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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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Clinical Trials
5 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.37LOEUF
pLI 0.921
Z-score 2.64
OE 0.00 (0.00–0.37)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.45Z-score
OE missense 0.57 (0.46–0.72)
53 obs / 92.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–0.37)
0≤0.351.4
Missense OE0.57 (0.46–0.72)
0≤0.61.4
Synonymous OE1.44
0≤1.21.6
LoF obs/exp: 0 / 8.1Missense obs/exp: 53 / 92.2Syn Z: -2.13
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveRPS19-related Diamond-Blackfan anemiaLOFAD
DN
0.4190th %ile
GOF
0.2099th %ile
LOF
0.74top 10%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · 1 literature citation · LOEUF 0.37
DN1 literature citation

Literature Evidence

DNA transgenic mouse model demonstrates a dominant negative effect of a point mutation in the RPS19 gene associated with Diamond-Blackfan anemia.PMID:20606162
LOFp53-Independent cell cycle and erythroid differentiation defects in murine embryonic stem cells haploinsufficient for Diamond Blackfan anemia-proteins: RPS19 versus RPL5.PMID:24558476

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

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

RPS19 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Multi-omics analysis reveals the role of ribosome biogenesis in malignant clear cell renal cell carcinoma and the development of a machine learning-based prognostic model.
Xie Z et al.·Front Immunol
2025Functional
Identification and validation of RNA-binding protein SLC3A2 regulates melanocyte ferroptosis in vitiligo by integrated analysis of single-cell and bulk RNA-sequencing.
Zhang J et al.·BMC Genomics
2024
Molecular analysis and genotype-phenotype correlation of Diamond-Blackfan anemia.
Arbiv OA et al.·Clin Genet
2018
Integrated systematic functional screen and fine-mapping decipher the role and genetic regulation of RPS19 in colorectal cancer development.
Chen C et al.·Arch Toxicol
2024Functional
Czech and Slovak Diamond-Blackfan Anemia (DBA) Registry update: Clinical data and novel causative genetic lesions.
Volejnikova J et al.·Blood Cells Mol Dis
2020
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients