RPS15A

Chr 16AD

ribosomal protein S15a

Also known as: DBA20, S15a, uS8

NCBI Gene: 6210ENSG00000134419UniProt: P62244

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 40S subunit. The protein belongs to the S8P 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]

Primary Disease Associations & Inheritance

?Diamond-Blackfan anemia 20MIM #618313
AD
54
ClinVar variants
15
Pathogenic / LP
0.80
pLI score
0
Active trials
Clinical Summary— RPS15A
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.80) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
15 Pathogenic / Likely Pathogenic· 14 VUS of 54 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.56LOEUF
pLI 0.802
Z-score 2.14
OE 0.00 (0.00–0.56)
Moderately 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.
2.24Z-score
OE missense 0.27 (0.19–0.39)
20 obs / 74.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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 (0.00–0.56)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.27 (0.19–0.39)
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.1.18
0≤1.21.6
LoF obs/exp: 0 / 5.4Missense obs/exp: 20 / 74.2Syn Z: -0.74

ClinVar Variant Classifications

54 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
VUS14
Likely Benign23
Benign2
15
Pathogenic
14
VUS
23
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
1
15
Likely Pathogenic
0
0
0
0
0
VUS
0
8
6
0
14
Likely Benign
0
0
6
17
23
Benign
0
0
2
0
2
Total08281854

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

View in ClinVar →

Protein Context — Lollipop Plot

RPS15A · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Diamond-Blackfan anemia 20

MIM #618313

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — RPS15A
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Ribosomal protein S15a promotes tumor angiogenesis via enhancing Wnt/β-catenin-induced FGF18 expression in hepatocellular carcinoma.
Guo P et al.·Oncogene
2018
RPS15A promotes gastric cancer progression via activation of the Akt/IKK-β/NF-κB signalling pathway.
Liu C et al.·J Cell Mol Med
2019
Ribosomal protein S15A augments human osteosarcoma cell proliferation in vitro.
Zhang C et al.·Cancer Biother Radiopharm
2014
Integrative multiomics and weighted network approach reveals the prognostic role of RPS7 in lung squamous cell carcinoma pathogenesis.
Singh P et al.·J Appl Genet
2023
Functional analysis across model systems implicates ribosomal proteins in growth and proliferation defects associated with hypoplastic left heart syndrome.
Nielsen T et al.·Elife
2025Functional
m(6)A‑modified HOXC10 promotes HNSCC progression via co‑activation of ADAM17/EGFR and Wnt/β‑catenin signaling.
Zhou Y et al.·Int J Oncol
2024
Identification of Key Genes and Pathways Involved in Circulating Tumor Cells in Colorectal Cancer.
Pan R et al.·Anal Cell Pathol (Amst)
2022
Ribosomal protein genes RPS10 and RPS26 are commonly mutated in Diamond-Blackfan anemia.
Doherty L et al.·Am J Hum Genet
2010
Factors determining sensitivity or resistance of tumor cell lines towards artesunate.
Sertel S et al.·Chem Biol Interact
2010
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