RPS8

Chr 1

ribosomal protein S8

Also known as: S8, eS8

NCBI Gene: 6202 ENSG00000142937 UniProt: P62241 OMIM: 600357

The RPS8 protein is a component of the small 40S ribosomal subunit and participates in ribosome assembly in the nucleolus, where it helps generate the ribonucleoprotein complexes responsible for protein synthesis. Mutations in this highly constrained gene (pLI 0.99) cause neurodevelopmental disorders with developmental delay, intellectual disability, and growth retardation, following an autosomal dominant inheritance pattern. Clinical features typically manifest in early childhood and may include microcephaly and other growth-related abnormalities.

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 S8E family of ribosomal proteins. It is located in the cytoplasm. Increased expression of this gene in colorectal tumors and colon polyps compared to matched normal colonic mucosa has been observed. This gene is co-transcribed with the small nucleolar RNA genes U38A, U38B, U39, and U40, which are located in its fourth, fifth, first, and second introns, respectively. 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 0.22

Clinical Summary— RPS8

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.22LOEUF

pLI 0.990

Z-score 3.45

OE 0.00 (0.00–0.22)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.42Z-score

OE missense 0.40 (0.31–0.50)

50 obs / 126.5 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.22)

0≤0.351.4

Missense OE?0.40 (0.31–0.50)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 0 / 13.8Missense obs/exp: 50 / 126.5Syn Z: -0.56

This gene — mechanism propensity

0.17100th %ile

GOF

0.07100th %ile

LOF

0.86top 5%

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

LOFprediction above median · LOEUF 0.22

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.