RNASEL

Chr 1AD

ribonuclease L

Also known as: PRCA1, RNS4

NCBI Gene: 6041 ENSG00000135828 UniProt: Q05823 OMIM: 180435

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismADLOEUF 1.131 OMIM phenotype

Clinical Summary— RNASEL

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

4 unique Pathogenic / Likely Pathogenic· 137 VUS of 171 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.13LOEUF

pLI 0.000

Z-score 1.06

OE 0.76 (0.53–1.13)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.16Z-score

OE missense 0.98 (0.90–1.06)

386 obs / 394.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.76 (0.53–1.13)

0≤0.351.4

Missense OE?0.98 (0.90–1.06)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 18 / 23.6Missense obs/exp: 386 / 394.9Syn Z: 0.55

This gene — mechanism propensity

0.6550th %ile

GOF

0.7028th %ile

LOF

0.2190th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

171 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic3

VUS137

Likely Benign14

Benign8

Conflicting1

Pathogenic

Likely Pathogenic

137

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	0	1
Likely Pathogenic	1	2	0	0	3
VUS	46	84	0	7	137
Likely Benign	0	11	0	3	14
Benign	0	3	0	5	8
Conflicting	—				1
Total	47	101	0	15	164

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

30 pathogenic / likely-pathogenic (of 37) ClinVar copy-number / structural variants overlap RNASEL — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →