RNASEK

Chr 17

ribonuclease K

NCBI Gene: 440400ENSG00000219200UniProt: Q6P5S7

Enables RNA endonuclease activity. Involved in endosomal lumen acidification; proton transmembrane transport; and receptor-mediated endocytosis of virus by host cell. Located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

48
ClinVar variants
19
Pathogenic / LP
0.50
pLI score
0
Active trials
Clinical Summary— RNASEK
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.50) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 28 VUS of 48 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.78LOEUF
pLI 0.504
Z-score 1.91
OE 0.16 (0.06–0.78)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.50Z-score
OE missense 0.85 (0.70–1.03)
71 obs / 83.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.16 (0.06–0.78)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.70–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 1 / 6.1Missense obs/exp: 71 / 83.8Syn Z: -0.03

ClinVar Variant Classifications

48 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic1
VUS28
Likely Benign1
18
Pathogenic
1
Likely Pathogenic
28
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
0
0
1
0
1
VUS
0
11
17
0
28
Likely Benign
0
0
0
1
1
Benign
0
0
0
0
0
Total01136148

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

View in ClinVar →

Protein Context — Lollipop Plot

RNASEK · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
RIBONUCLEASE K; RNASEK
MIM #617098 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Loss of RNASEK Terminates Egg Cylinder Development by Impairing Lysosomal Function Associated With V-ATPase in Mouse.
Wan M et al.·FASEB J
2025Functional
Pan-Cancer Analysis Reveals Ribonuclease K (RNASEK) as a Potential Prognostic Biomarker in Pancreatic Cancer and a Diagnostic Indicator Across Multiple Human Cancers.
Hassan Elsheikh NA et al.·Cureus
2025🔓 Open Access
RNASEK interacting with PEDV structural proteins facilitates virus entry via clathrin-mediated endocytosis.
Qin W et al.·J Virol
2025🔓 Open Access
The V-ATPase complex component RNAseK is required for lysosomal hydrolase delivery and autophagosome degradation.
Makar AN et al.·Nat Commun
2024🔓 Open Access
Fish Paralog Proteins RNASEK-a and -b Enhance Type I Interferon Secretion and Promote Apoptosis.
Sun ZC et al.·Front Immunol
2021🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools