RIOK3

Chr 18

RIO kinase 3

Also known as: SUDD

The RIOK3 protein is a serine/threonine kinase that regulates ribosome quality control by promoting degradation of stalled 40S ribosomal subunits and modulates type I interferon immune responses. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability, seizures, and growth abnormalities. This gene is not highly constrained against loss-of-function variants, consistent with recessive inheritance patterns.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
9
Pubs (1 yr)
36
P/LP submissions
0%
P/LP missense
0.80
LOEUF
DN
Mechanism· predicted
Clinical SummaryRIOK3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
34 unique Pathogenic / Likely Pathogenic· 63 VUS of 113 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.80LOEUF
pLI 0.000
Z-score 2.38
OE 0.52 (0.350.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.06Z-score
OE missense 0.82 (0.740.92)
236 obs / 286.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.52 (0.350.80)
00.351.4
Missense OE0.82 (0.740.92)
00.61.4
Synonymous OE0.79
01.21.6
LoF obs/exp: 15 / 28.8Missense obs/exp: 236 / 286.7Syn Z: 1.61
DN
0.7228th %ile
GOF
0.5465th %ile
LOF
0.2873th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

113 submitted variants in ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic1
VUS63
Likely Benign3
Benign1
33
Pathogenic
1
Likely Pathogenic
63
VUS
3
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
33
0
33
Likely Pathogenic
0
0
1
0
1
VUS
1
54
8
0
63
Likely Benign
0
1
1
1
3
Benign
0
0
1
0
1
Total155441101

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

View in ClinVar →

Protein Context — Lollipop Plot

RIOK3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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