RIOK3

Chr 18

RIO kinase 3

Also known as: SUDD

NCBI Gene: 8780 ENSG00000101782 UniProt: O14730 OMIM: 603579

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene was first identified by the similarity of its product to the Aspergillus nidulans SUDD protein. This gene is now recognized as a member of the right open reading frame (RIO) kinase gene family. This gene encodes a serine/threonine kinase that localizes to the cytoplasm and plays a role in the processing of the pre-40 S ribosomal subunit. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2017]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.80

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.80LOEUF

pLI 0.000

Z-score 2.38

OE 0.52 (0.35–0.80)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.06Z-score

OE missense 0.82 (0.74–0.92)

236 obs / 286.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.52 (0.35–0.80)

0≤0.351.4

Missense OE?0.82 (0.74–0.92)

0≤0.61.4

Synonymous OE?0.79

0≤1.21.6

LoF obs/exp: 15 / 28.8Missense obs/exp: 236 / 286.7Syn Z: 1.61

Background carrier burden — how many people carry a rare variant somewhere in RIOK3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 85

608 rare PASS variants

Rare truncating (LoF)

1 in 1,500

100 rare PASS variants

Rare synonymous (reference)

1 in 420

215 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RIOK3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 140	1 in 1,600
South Asian	~43k	1 in 100	1 in 1,300
Remaining (unassigned)	~30k	1 in 110	1 in 1,600
European (Finnish)	~27k	1 in 190	1 in 2,100
Admixed American	~22k	1 in 120	1 in 1,200
African / African American	~21k	1 in 69	1 in 1,100
East Asian	~20k	1 in 120	1 in 1,200
Ashkenazi Jewish	~13k	1 in 450	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 110	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 10 of 13 coding exons well covered in gnomAD exomes; exons 2, 5, 13 marginal. Genomes: all 13.? see exons ↓