RIOK1

Chr 6

RIO kinase 1

Also known as: AD034, RIO1, RRP10, bA288G3.1

NCBI Gene: 83732ENSG00000124784UniProt: Q9BRS2

The protein encoded by this gene competes with pICln for inclusion in the protein arginine methyltransferase 5 complex. This complex targets substrates for dimethylation. The encoded protein is essential for the last steps in the maturation of 40S subunits. [provided by RefSeq, Jan 2017]

122
ClinVar variants
31
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— RIOK1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
31 Pathogenic / Likely Pathogenic· 83 VUS of 122 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.09LOEUF
pLI 0.000
Z-score 1.13
OE 0.78 (0.57–1.09)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.51Z-score
OE missense 0.92 (0.83–1.01)
284 obs / 309.2 exp
Tolerant

Mild missense constraint

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.0.78 (0.57–1.09)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.83–1.01)
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.0.87
0≤1.21.6
LoF obs/exp: 25 / 31.9Missense obs/exp: 284 / 309.2Syn Z: 1.04

ClinVar Variant Classifications

122 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic3
VUS83
Likely Benign8
28
Pathogenic
3
Likely Pathogenic
83
VUS
8
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
28
0
28
Likely Pathogenic
0
0
3
0
3
VUS
0
78
5
0
83
Likely Benign
0
5
1
2
8
Benign
0
0
0
0
0
Total083372122

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

View in ClinVar →

Protein Context — Lollipop Plot

RIOK1 · 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
RIO KINASE 1; RIOK1
MIM #617753 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
RIOK1 phase separation restricts PTEN translation via stress granules activating tumor growth in hepatocellular carcinoma.
Meng F et al.·Nat Cancer
2025
The PRMT5 arginine methyltransferase: many roles in development, cancer and beyond.
Stopa N et al.·Cell Mol Life Sci
2015Review
Targeting the SPC25/RIOK1/MYH9 Axis to Overcome Tumor Stemness and Platinum Resistance in Epithelial Ovarian Cancer.
Jiang X et al.·Adv Sci (Weinh)
2024
RIOK1 mediates p53 degradation and radioresistance in colorectal cancer through phosphorylation of G3BP2.
Chen Y et al.·Oncogene
2022
Multiomics Identifies Potential Biomarkers in Ankylosing Spondylitis Bone Formation.
Yang L et al.·Hum Mutat
2025
The Oncogenic Protein Kinase/ATPase RIOK1 Is Up-Regulated via the c-myc/E2F Transcription Factor Axis in Prostate Cancer.
Handle F et al.·Am J Pathol
2023
Explainable machine learning reveals ribosome biogenesis biomarkers in preeclampsia risk prediction.
Chen J et al.·Front Immunol
2025
Riok1, A Novel Potential Target in MSI-High p53 Mutant Colorectal Cancer Cells.
Shechter S et al.·Molecules
2023
A role for RIO kinases in the crosshair of cancer research and therapy.
Ghandadi M et al.·Biochim Biophys Acta Rev Cancer
2024Review
DKK3's protective role in prostate cancer is partly due to the modulation of immune-related pathways.
Shareef ZA et al.·Front Immunol
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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