RPS2

Chr 16

ribosomal protein S2

Also known as: LLREP3, S2, uS5

NCBI Gene: 6187 ENSG00000140988 UniProt: P15880 OMIM: 603624

RPS2 encodes a ribosomal protein that is an essential component of the 40S ribosomal subunit and plays a critical role in protein synthesis and ribosome assembly. This gene is highly constrained against loss-of-function variants (pLI 0.85, LOEUF 0.45), reflecting its fundamental importance for cellular function. Mutations in RPS2 cause developmental delays, intellectual disability, and growth retardation, typically following an autosomal dominant inheritance pattern.

OMIM ResearchSummary from RefSeq, 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 S5P family of ribosomal proteins. It is located in the cytoplasm. This gene shares sequence similarity with mouse LLRep3. It is co-transcribed with the small nucleolar RNA gene U64, which is located in its third intron. 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]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.45

Clinical Summary— RPS2

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.85) — some intolerance to loss-of-function variants.

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ClinVar Variants

18 VUS of 38 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.45LOEUF

pLI 0.847

Z-score 2.72

OE 0.09 (0.03–0.45)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.85Z-score

OE missense 0.61 (0.53–0.72)

112 obs / 182.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.09 (0.03–0.45)

0≤0.351.4

Missense OE?0.61 (0.53–0.72)

0≤0.61.4

Synonymous OE?1.56

0≤1.21.6

LoF obs/exp: 1 / 10.5Missense obs/exp: 112 / 182.5Syn Z: -3.82

This gene — mechanism propensity

0.5181th %ile

GOF

0.1999th %ile

LOF

0.73top 10%

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

LOFprediction above median · LOEUF 0.45

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

38 submitted variants in ClinVar

ClinVar

Classification Summary

VUS18

Likely Benign2

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	18	0	18
Likely Benign	1	1	2
Benign	0	2	2
Total	19	3	22

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

View in ClinVar →

40 pathogenic / likely-pathogenic (of 58) ClinVar copy-number / structural variants overlap RPS2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →