RNASEL

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

Basic information

Region (hg38): 1:182573633-182589256

Previous symbols: [ "RNS4", "PRCA1" ]

Links

ENSG00000135828 ∙ NCBI:6041 ∙ OMIM:180435 ∙ HGNC:10050 ∙ Uniprot:Q05823 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• prostate cancer, hereditary, 1 (Limited), mode of inheritance: AD
• prostate cancer, hereditary, 1 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Prostate cancer, hereditary, 1	AD	Oncologic	Surveillance and early diagnosis could potentially be beneficial	Oncologic	11799394; 12022038; 12915880; 16054567; 17224235; 18575592
Variants may be involved in susceptibility to multiple cancer types

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RNASEL gene.

• Inborn genetic diseases (14 variants)
• not provided (7 variants)
• Prostate cancer, hereditary, 1 (6 variants)
• Ovarian cancer (5 variants)
• Malignant tumor of prostate (1 variants)
• not specified (1 variants)
• Hereditary cancer (1 variants)
• Prostate cancer, susceptibility to (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RNASEL gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					4	4
missense		2	16	3	4	25
nonsense				1		1
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region						0
non coding						0
Total	0	2	18	4	8

Highest pathogenic variant AF is 0.0000525

Variants in RNASEL

This is a list of pathogenic ClinVar variants found in the RNASEL region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-182575424-C-T		not specified	Uncertain significance (Mar 02, 2023)
1-182575430-C-T		not specified	Uncertain significance (Mar 20, 2023)
1-182575446-C-T		RNASEL-related disorder	Benign (Jan 27, 2020)
1-182575466-G-T		Ovarian cancer	Benign (Jan 01, 2022)
1-182576254-AC-A		Prostate cancer, hereditary, 1	Uncertain significance (-)
1-182576295-C-T		not specified	Uncertain significance (Feb 23, 2023)
1-182576344-T-C		not specified	Uncertain significance (Dec 12, 2023)
1-182581247-C-T		not specified	Uncertain significance (Dec 22, 2023)
1-182581307-C-T		not specified	Uncertain significance (Mar 23, 2022)
1-182581320-C-T		not specified	Uncertain significance (May 30, 2023)
1-182581321-G-A		not specified	Likely benign (Nov 17, 2023)
1-182582129-G-A		not specified	Uncertain significance (Aug 21, 2023)
1-182582234-C-T		Prostate cancer, hereditary, 1	Uncertain significance (Jul 07, 2023)
1-182584167-C-A		Prostate cancer, hereditary, 1	Uncertain significance (Mar 10, 2022)
1-182585330-T-C		not specified	Uncertain significance (Dec 13, 2022)
1-182585338-T-C		Ovarian cancer	Likely pathogenic (Jan 01, 2022)
1-182585376-CA-C		Prostate cancer, hereditary, 1	Uncertain significance (Aug 17, 2022)
1-182585378-A-T		Prostate cancer, hereditary, 1	Uncertain significance (Aug 17, 2022)
1-182585385-T-A		Prostate cancer, hereditary, 1	Uncertain significance (Aug 17, 2022)
1-182585389-T-G		Prostate cancer, hereditary, 1	Uncertain significance (Aug 17, 2022)
1-182585391-A-G		Prostate cancer, hereditary, 1	Uncertain significance (Aug 17, 2022)
1-182585391-AAC-A		Prostate cancer, hereditary, 1	Uncertain significance (Aug 17, 2022)
1-182585393-CA-C		Prostate cancer, hereditary, 1	Uncertain significance (Aug 17, 2022)
1-182585395-G-A		Prostate cancer, hereditary, 1	Uncertain significance (Aug 17, 2022)
1-182585395-GC-G		Prostate cancer, hereditary, 1	Uncertain significance (Aug 17, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RNASEL	protein_coding	protein_coding	ENST00000367559	6	15623

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.95e-10	0.405	124628	3	1114	125745	0.00445

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.159	386	395	0.977	0.0000216	4915
Missense in Polyphen		128	127.92	1.0006		1606
Synonymous	0.550	148	157	0.944	0.00000890	1433
Loss of Function	1.06	18	23.6	0.764	0.00000137	296

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00268	0.00267
Ashkenazi Jewish	0.0154	0.0151
East Asian	0.000708	0.000707
Finnish	0.00827	0.00830
European (Non-Finnish)	0.00547	0.00539
Middle Eastern	0.000708	0.000707
South Asian	0.00193	0.00193
Other	0.00394	0.00392

dbNSFP

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}.
• Pathway: 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;Cytokine Signaling in Immune system;Immune System;Interferon alpha/beta signaling;Interferon Signaling (Consensus)

Recessive Scores

• pRec: 0.121

Intolerance Scores

• loftool: 0.685
• rvis_EVS: -0.17
• rvis_percentile_EVS: 40.63

Haploinsufficiency Scores

• pHI: 0.0611
• hipred: N
• hipred_score: 0.211
• ghis: 0.491

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.255

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rnasel
• Phenotype: cellular phenotype; endocrine/exocrine gland phenotype; immune system phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: rRNA processing;mRNA processing;protein phosphorylation;regulation of mRNA stability;negative regulation of viral genome replication;fat cell differentiation;positive regulation of transcription by RNA polymerase II;positive regulation of glucose import;defense response to virus;type I interferon signaling pathway;regulation of type I interferon-mediated signaling pathway;RNA phosphodiester bond hydrolysis, endonucleolytic
• Cellular component: cellular_component;mitochondrial matrix;cytosol;nuclear matrix
• Molecular function: RNA binding;endoribonuclease activity;protein kinase activity;protein binding;ATP binding;rRNA binding;ribonucleoprotein complex binding;metal ion binding