RIOK2

Chr 5

RIO kinase 2

Also known as: RIO2

NCBI Gene: 55781ENSG00000058729UniProt: Q9BVS4

Predicted to enable protein kinase activity. Involved in several processes, including positive regulation of rRNA processing; positive regulation of ribosomal small subunit export from nucleus; and regulation of mitotic metaphase/anaphase transition. Located in cytoplasm. Part of preribosome, small subunit precursor. [provided by Alliance of Genome Resources, Jul 2025]

109
ClinVar variants
22
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— RIOK2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 79 VUS of 109 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.
0.69LOEUF
pLI 0.000
Z-score 2.75
OE 0.42 (0.26–0.69)
Tolerant

Typical tolerance to LoF variation

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.
0.85Z-score
OE missense 0.86 (0.77–0.95)
246 obs / 286.5 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.0.42 (0.26–0.69)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.77–0.95)
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.0.95
0≤1.21.6
LoF obs/exp: 11 / 26.2Missense obs/exp: 246 / 286.5Syn Z: 0.39

ClinVar Variant Classifications

109 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic2
VUS79
Likely Benign4
Benign4
20
Pathogenic
2
Likely Pathogenic
79
VUS
4
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
20
0
20
Likely Pathogenic
0
0
2
0
2
VUS
0
71
8
0
79
Likely Benign
0
2
1
1
4
Benign
0
2
1
1
4
Total075322109

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

View in ClinVar →

Protein Context — Lollipop Plot

RIOK2 · 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 2; RIOK2
MIM #617754 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
RIOK2 kinase regulates the translocation of the FADD-RIPK1-Caspase-8 complex to the ER and the cleavage of Gasdermin D to drive pyroptosis.
Ma M et al.·Nat Commun
2025
Blockade of IL-22 signaling reverses erythroid dysfunction in stress-induced anemias.
Raundhal M et al.·Nat Immunol
2021
High Expression of RIOK2 and NOB1 Predict Human Non-small Cell Lung Cancer Outcomes.
Liu K et al.·Sci Rep
2016
A role for RIO kinases in the crosshair of cancer research and therapy.
Ghandadi M et al.·Biochim Biophys Acta Rev Cancer
2024Review
miR‑145 inhibits human non‑small-cell lung cancer growth by dual-targeting RIOK2 and NOB1.
Liu K et al.·Int J Oncol
2018
A computational biology approach to identify potential protein biomarkers and drug targets for sporadic amyotrophic lateral sclerosis.
Kumar R et al.·Cell Signal
2023
Increased Expression and Prognostic Significance of BYSL in Melanoma.
Wang ZZ et al.·J Immunother
2024
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