RPS14

Chr 5

ribosomal protein S14

Also known as: EMTB, S14, uS11

NCBI Gene: 6208ENSG00000164587UniProt: P62263

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 S11P family of ribosomal proteins. It is located in the cytoplasm. Transcript variants utilizing alternative transcription initiation sites have been described in the literature. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. In Chinese hamster ovary cells, mutations in this gene can lead to resistance to emetine, a protein synthesis inhibitor. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Macrocytic anemia, refractory, due to 5q deletion, somaticMIM #153550
19
ClinVar variants
10
Pathogenic / LP
0.90
pLI score· haploinsufficient
0
Active trials
Clinical Summary— RPS14
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.90). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 6 VUS of 19 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.40LOEUF
pLI 0.904
Z-score 2.55
OE 0.00 (0.00–0.40)
Highly 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.
2.52Z-score
OE missense 0.29 (0.21–0.39)
28 obs / 98.1 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 (0.00–0.40)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.29 (0.21–0.39)
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.1.04
0≤1.21.6
LoF obs/exp: 0 / 7.6Missense obs/exp: 28 / 98.1Syn Z: -0.19

ClinVar Variant Classifications

19 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
VUS6
Likely Benign3
10
Pathogenic
6
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
0
0
0
VUS
0
5
1
0
6
Likely Benign
0
0
1
2
3
Benign
0
0
0
0
0
Total0512219

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

View in ClinVar →

Protein Context — Lollipop Plot

RPS14 · 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

Macrocytic anemia, refractory, due to 5q deletion, somatic

MIM #153550

Molecular basis of disorder known

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Fusobacterium nucleatum promotes colorectal cancer through neogenesis of tumor stem cells.
Wang Q et al.·J Clin Invest
2025
Rps14, Csnk1a1 and miRNA145/miRNA146a deficiency cooperate in the clinical phenotype and activation of the innate immune system in the 5q- syndrome.
Ribezzo F et al.·Leukemia
2019
The molecular pathogenesis of the myelodysplastic syndromes.
Pellagatti A et al.·Eur J Haematol
2015Review
MMP9 inhibition increases erythropoiesis in RPS14-deficient del(5q) MDS models through suppression of TGF-β pathways.
Youn M et al.·Blood Adv
2019Functional
A precision medicine approach to the myelodysplastic syndrome with isolated deletion 5q, 50 years after its discovery.
Roncador M et al.·Blood
2025Review
Advances in the 5q- syndrome.
Boultwood J et al.·Blood
2010Review
Ribosomopathies: human disorders of ribosome dysfunction.
Narla A et al.·Blood
2010Review
Molecular dissection of the 5q deletion in myelodysplastic syndrome.
Ebert BL·Semin Oncol
2011Review
TLR7 ligation augments hematopoiesis in Rps14 (uS11) deficiency via paradoxical suppression of inflammatory signaling.
Peña OA et al.·Blood Adv
2021
Genetic deletions in AML and MDS.
Ebert BL·Best Pract Res Clin Haematol
2010Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
RPS14 as an aging-related biomarker for early-onset alterations of testicular senescence-associated genes in spermatogenic dysfunction at childbearing age.
Dong F et al.·J Gerontol A Biol Sci Med Sci
2026
A novel MAP7D1 mutation causes mitotic defects and RPS14 accumulation in Shwachman-Diamond syndrome patient cells.
Kucukvardar S et al.·Dis Model Mech
2025🔓 Open Access
Distinct uS11/Rps14 interactions with the translation preinitiation complex differentially alter the accuracy of start codon recognition.
Gupta N et al.·Nucleic Acids Res
2025
Genome-wide functional integration identified MAZ-controlled RPS14 dysregulation in hepatocellular carcinoma.
Han L et al.·Arch Toxicol
2024Functional
miR-146b-5p promotes duck Tembusu virus replication by targeting RPS14.
Huang J et al.·Poult Sci
2023🔓 Open Access
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