RPS15A

Chr 16AD

ribosomal protein S15a

Also known as: DBA20, S15a, uS8

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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.561 OMIM phenotype
Clinical SummaryRPS15A
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.80) — some intolerance to loss-of-function variants.
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ClinVar Variants
15 unique Pathogenic / Likely Pathogenic· 14 VUS of 59 total submissions
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GeneReview available — RPS15A
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.56LOEUF
pLI 0.802
Z-score 2.14
OE 0.00 (0.000.56)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.24Z-score
OE missense 0.27 (0.190.39)
20 obs / 74.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.000.56)
00.351.4
Missense OE0.27 (0.190.39)
00.61.4
Synonymous OE1.18
01.21.6
LoF obs/exp: 0 / 5.4Missense obs/exp: 20 / 74.2Syn Z: -0.74
DN
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 haploinsufficiencyPMID:27909223

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

ClinVar Variant Classifications

59 submitted variants in 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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