GeneBe

RNASEL

protein-coding

ribonuclease L, the group of Endoribonucleases|Ankyrin repeat domain containing

Gene summary

This gene encodes a component of the interferon-regulated 2-5A system that functions in the antiviral and antiproliferative roles of interferons. The protein is involved in innate immunity and is active against multiple RNA viruses, including the influenza and SARS-CoV-2 viruses. Mutations in this gene have been associated with predisposition to prostate cancer and this gene is a candidate for the hereditary prostate cancer 1 (HPC1) allele. [provided by RefSeq, Nov 2021]

Previous symbols:
  • RNS4
  • PRCA1

MANE transcript

NM_021133.4

Inheritance

AR, AD

ClinVar variants

P:4U:139B:26

Top phenotype

Prostate cancer, hereditary, 1

gnomAD constraint

pLI —, LoF o/e 0.76

Max pathogenic AF

—

Genomic locus

chr1:182,573,634-182,589,256

External References & Databases

Ensembl (ENSG00000135828)NCBI Gene (6041)OMIM (180435)HGNC:10050GenCCUniProt (Q05823)AlphaFoldClinVar (RNASEL)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~15.6 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

multisystem inflammatory syndrome in children and adultsMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0035375

Submitter: PanelApp Australia

prostate cancer, hereditary, 1LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0011098

Submitter: Labcorp Genetics (formerly Invitae)

prostate cancer, hereditary, 1LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0011098

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Prostate cancer, hereditary, 1AD

Manifestation: Oncologic

Intervention: Oncologic

Rationale: Surveillance and early diagnosis could potentially be beneficial

Comments: Variants may be involved in susceptibility to multiple cancer types

Refs: 11799394; 12022038; 12915880; 16054567; 17224235; 18575592Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RNASEL variants in ClinVar

6 Conditions Cataloged
Prostate cancer, hereditary, 1Total: 77
not specifiedTotal: 73
not providedTotal: 9
RNASEL-related disorderTotal: 7
Ovarian cancerTotal: 5
Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021133.4. 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.

EffectPLPVUSLBBSum
synonymous
8
clinvar
9
clinvar
3
clinvar
 20
missense
2
clinvar
85
clinvar
10
clinvar
3
clinvar
 100
nonsense
1
clinvar
2
clinvar
1
clinvar
 4
start loss
1
clinvar
 1
frameshift
41
clinvar
 41
splice donor/acceptor (+/-2bp)
3
clinvar
 3
Total13139206169

Highest pathogenic variant AF is 0.000023543611

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_021133.4RefSeqNP_066956.16MANE Select
ENST00000367559.7EnsemblENSP00000356530.36MANE Select
ENST00000539397.1EnsemblENSP00000440844.15Standard
ENST00000539397.2EnsemblENSP00000440844.15Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Influenza A - Homo sapiens (human)
  • NOD-like receptor signaling pathway - Homo sapiens (human)
  • Hepatitis C - Homo sapiens (human)
  • Herpes simplex infection - Homo sapiens (human)
  • Senescence and Autophagy in Cancer

Biological Process

  • rRNA processing
  • mRNA processing
  • protein phosphorylation
  • regulation of mRNA stability
  • negative regulation of viral genome replication

Molecular Function

  • RNA binding
  • endoribonuclease activity
  • protein kinase activity
  • protein binding
  • ATP binding

Cellular Component

  • cellular_component
  • mitochondrial matrix
  • cytosol
  • nuclear matrix

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000367559
Coding exons
6
Length
15623
Individuals with no LoFs
124628
Homozygous LoFs
3
Heterozygous LoFs
1114
Defined
125745
p
0.00445
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.1593863950.9770.00002164915
Missense (PolyPhen)128127.921.00061606
Synonymous0.5501481570.9440.000008901433
Loss of Function1.061823.60.7640.00000137296

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000620.00062rare
Latino/Admixed American0.00210.0020notable
Ashkenazi Jewish0.0150.015notable
East Asian0.000710.00071rare
Finnish0.00830.0083notable
European (Non-Finnish)0.00550.0054notable
South Asian0.00190.0019notable
Other0.00390.0039notable

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Endoribonuclease that functions in the interferon (IFN) antiviral response. In INF treated and virus infected cells, RNASEL probably mediates its antiviral effects through a combination of direct cleavage of single-stranded viral RNAs, inhibition of protein synthesis through the degradation of rRNA, induction of apoptosis, and induction of other antiviral genes. RNASEL mediated apoptosis is the result of a JNK-dependent stress- response pathway leading to cytochrome c release from mitochondria and caspase-dependent apoptosis. Therefore, activation of RNASEL could lead to elimination of virus infected cells under some circumstances. In the crosstalk between autophagy and apoptosis proposed to induce autophagy as an early stress response to small double-stranded RNA and at later stages of prolonged stress to activate caspase-dependent proteolytic cleavage of BECN1 to terminate autophagy and promote apoptosis (PubMed:26263979). Might play a central role in the regulation of mRNA turnover (PubMed:11585831). Cleaves 3' of UpNp dimers, with preference for UU and UA sequences, to sets of discrete products ranging from between 4 and 22 nucleotides in length. {ECO:0000269|PubMed:11585831, ECO:0000269|PubMed:26263979}.;
Disease
DISEASE: Prostate cancer, hereditary, 1 (HPC1) [MIM:601518]: A condition associated with familial predisposition to cancer of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. {ECO:0000305|PubMed:11799394, ECO:0000305|PubMed:11941539, ECO:0000305|PubMed:12415269, ECO:0000305|PubMed:17344846}.;

Recessive Scores

pRec
0.121

Intolerance Scores

LoFtool
0.685
RVIS EVS
-0.17
RVIS percentile EVS
40.63

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.255

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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