RIOK2

protein-coding

RIO kinase 2, the group of Ribosomal biogenesis factors

Gene summary

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]

MANE transcript

NM_018343.3

Inheritance

ClinVar variants

U:78B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.42

Max pathogenic AF

—

Genomic locus

chr5:97,160,867-97,183,247

External References & Databases

Ensembl (ENSG00000058729)

Transcript & Mutation Effects

hg38 • Region Span ~22.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

male infertility with azoospermia or oligozoospermia due to single gene mutationLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0018393

Submitter: King Faisal Specialist Hospital and Research Center

Alhathal et al., 2020 (PMID: 32719396) reported a missense variant in a large male infertility cohort (n=285 infertile man and case–control fertile man). Gene is scored according to ClinGen classification. Limited with total score of 4. Single variant segregation (3 points), experimental evidence: testicular expression (1 points) (PMID: 27965440).

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RIOK2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 74

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018343.3. 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 clinvar	1 clinvar	3
missense			76 clinvar	2 clinvar	2 clinvar	80
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	78	3	3	84

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018343.3	RefSeq	NP_060813.2	10	MANE Select
ENST00000283109.8	Ensembl	ENSP00000283109.3	10	MANE Select
NM_001159749.2	RefSeq	NP_001153221.1	8	Standard
ENST00000508447.1	Ensembl	ENSP00000420932.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ribosome biogenesis in eukaryotes - Homo sapiens (human)

Biological Process

cell cycle
regulation of mitotic metaphase/anaphase transition
maturation of SSU-rRNA
ribosomal small subunit biogenesis
protein autophosphorylation

Molecular Function

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

Cellular Component

nucleus
nucleoplasm
cytoplasm
cytosol
preribosome, small subunit precursor

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000283109
Coding exons: 10
Length: 22394
Individuals with no LoFs: 125691
Homozygous LoFs: 0
Heterozygous LoFs: 55
Defined: 125746
p: 0.000219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.850	246	287	0.859	0.0000147	3646
Missense (PolyPhen)		63	81.197	0.77589		946
Synonymous	0.389	92	96.9	0.950	0.00000485	979
Loss of Function	2.75	11	26.2	0.420	0.00000124	360

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.000064	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00034	0.00033	rare
South Asian	0.00026	0.00026	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Serine/threonine-protein kinase involved in the final steps of cytoplasmic maturation of the 40S ribosomal subunit. Involved in export of the 40S pre-ribosome particles (pre-40S) from the nucleus to the cytoplasm. Its kinase activity is required for the release of NOB1, PNO1 and LTV1 from the late pre-40S and the processing of 18S-E pre-rRNA to the mature 18S rRNA (PubMed:19564402). Regulates the timing of the metaphase-anaphase transition during mitotic progression, and its phosphorylation, most likely by PLK1, regulates this function (PubMed:21880710). {ECO:0000269|PubMed:16037817, ECO:0000269|PubMed:19564402, ECO:0000269|PubMed:21880710}.;

Recessive Scores

pRec: 0.0917

Intolerance Scores

LoFtool: 0.985
RVIS EVS: 1.07
RVIS percentile EVS: 91.61

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.813

Gene Damage Prediction

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