RIOK3

protein-coding

RIO kinase 3, the group of Ribosomal biogenesis factors

Gene summary

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]

Previous symbols:

SUDD

MANE transcript

NM_003831.5

Inheritance

—

ClinVar variants

U:64B:2

Top phenotype

Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset

gnomAD constraint

pLI —, LoF o/e 0.52

Max pathogenic AF

—

Genomic locus

chr18:23,453,287-23,486,603

External References & Databases

Ensembl (ENSG00000101782)

Transcript & Mutation Effects

hg38 • Region Span ~33.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RIOK3 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 56

not providedTotal: 1

Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onsetTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003831.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			60 clinvar	1 clinvar		61
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	64	2	0	66

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 47 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003831.5	RefSeq	NP_003822.2	13	MANE Select
ENST00000339486.8	Ensembl	ENSP00000341874.3	13	MANE Select
NM_001348193.2	RefSeq	NP_001335122.1	13	Standard
ENST00000577250.1	Ensembl	ENSP00000463644.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Hematopoietic Stem Cell Differentiation

Biological Process

protein phosphorylation
chromosome segregation
maturation of SSU-rRNA
negative regulation of protein homooligomerization
positive regulation of interferon-beta production

Molecular Function

protein serine/threonine kinase activity
protein binding
ATP binding
metal ion binding
caspase binding

Cellular Component

cytosol
preribosome, small subunit precursor

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000339486
Coding exons: 13
Length: 33781
Individuals with no LoFs: 125691
Homozygous LoFs: 0
Heterozygous LoFs: 56
Defined: 125747
p: 0.000223

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.06	236	287	0.823	0.0000151	3466
Missense (PolyPhen)		55	86.839	0.63336		1132
Synonymous	1.61	74	93.9	0.788	0.00000483	910
Loss of Function	2.38	15	28.8	0.521	0.00000154	357

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00018	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00028	0.00027	rare
South Asian	0.00017	0.00016	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in regulation of type I interferon (IFN)- dependent immune response which plays a critical role in the innate immune response against DNA and RNA viruses. May act as an adapter protein essential for the recruitment of TBK1 to IRF3 (PubMed:24807708). Phosphorylates IFIH1 on 'Ser-828' interfering with IFIH1 filament assembly on long dsRNA and resulting in attenuated IFIH1-signaling (PubMed:25865883). Can inhibit CASP10 isoform 7-mediated activation of the NF-kappaB signaling pathway (PubMed:19557502). May play a role in the biogenesis of the 40S ribosomal subunit. Involved in the processing of 21S pre-rRNA to the mature 18S rRNA (PubMed:22418843). {ECO:0000269|PubMed:19557502, ECO:0000269|PubMed:22418843, ECO:0000269|PubMed:24807708, ECO:0000269|PubMed:25865883}.;

Recessive Scores

pRec: 0.128

Intolerance Scores

LoFtool: 0.896
RVIS EVS: -0.23
RVIS percentile EVS: 37.32

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.952

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium