RPS15A

Chr 16

ribosomal protein S15a

Also known as: DBA20, S15a, uS8

NCBI Gene: 6210 ENSG00000134419 UniProt: P62244

RPS15A encodes a ribosomal protein that is a component of the small 40S ribosomal subunit and is required for proper erythropoiesis. Mutations cause Diamond-Blackfan anemia 20, a disorder primarily affecting red blood cell production, with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (LOEUF 0.559), reflecting its essential role in ribosome function.

GeneReviews 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 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]

GeneReviews ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.56

Clinical Summary— RPS15A

⚡

Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.80) — some intolerance to loss-of-function variants.

📋

ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 8 VUS of 39 total submissions

Explore recent and relevant literature in Research Assistant →

📖

GeneReview available — RPS15A

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

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?

LoF OE?0.00 (0.00–0.56)

0≤0.351.4

Missense OE?0.27 (0.19–0.39)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 0 / 5.4Missense obs/exp: 20 / 74.2Syn Z: -0.74

This gene — mechanism propensity

0.3892th %ile

GOF

0.1699th %ile

LOF

0.73top 10%

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

LOFprediction above median · 1 literature citation

Literature Evidence

LOFIn a mother and 2 daughters with Diamond-Blackfan anemia-20 (DBA20; 618313), Ikeda et al. (2017) identified a heterozygous splicing mutation in the RPS15A gene (603674.0001) that was demonstrated to result in a loss of function and haploinsufficiency1

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

References

1.PMID 27909223 ↗

ClinVar Variant Classifications

39 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS8

Likely Benign23

Benign2

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	1	1
Likely Pathogenic	0	0	0	0
VUS	8	0	0	8
Likely Benign	0	6	17	23
Benign	0	2	0	2
Total	8	8	18	34

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap RPS15A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →