RNASEH2B

Chr 13

ribonuclease H2 subunit B

Also known as: AGS2, DLEU8

NCBI Gene: 79621ENSG00000136104UniProt: Q5TBB1

RNase H2 is composed of a single catalytic subunit (A) and two non-catalytic subunits (B and C) and specifically degrades the RNA of RNA:DNA hybrids. The protein encoded by this gene is the non-catalytic B subunit of RNase H2, which is thought to play a role in DNA replication. Multiple transcript variants encoding different isoforms have been found for this gene. Defects in this gene are a cause of Aicardi-Goutieres syndrome type 2 (AGS2). [provided by RefSeq, Nov 2008]

Primary Disease Associations & Inheritance

UniProtAicardi-Goutieres syndrome 2
607
ClinVar variants
123
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— RNASEH2B
🧬
Gene-Disease Validity (ClinGen)
RNASEH2B-related type 1 interferonopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
123 Pathogenic / Likely Pathogenic· 199 VUS of 607 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.25LOEUF
pLI 0.000
Z-score 0.76
OE 0.81 (0.54–1.25)
Tolerant

Highly tolerant — LoF variants common in population

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.
-0.24Z-score
OE missense 1.06 (0.93–1.21)
154 obs / 145.9 exp
Tolerant

Tolerant to missense variation

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.0.81 (0.54–1.25)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.06 (0.93–1.21)
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.1.04
0≤1.21.6
LoF obs/exp: 15 / 18.5Missense obs/exp: 154 / 145.9Syn Z: -0.23

ClinVar Variant Classifications

607 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic88
Likely Pathogenic35
VUS199
Likely Benign252
Benign17
Conflicting16
88
Pathogenic
35
Likely Pathogenic
199
VUS
252
Likely Benign
17
Benign
16
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
13
1
74
0
88
Likely Pathogenic
18
7
10
0
35
VUS
9
143
44
3
199
Likely Benign
0
2
149
101
252
Benign
1
1
14
1
17
Conflicting
—16
Total41154291105607

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

View in ClinVar →

Protein Context — Lollipop Plot

RNASEH2B · protein map & ClinVar variants

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

Gene2Phenotype Curations

RNASEH2B-related Aicardi-Goutieres syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — RNASEH2B
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Aicardi-Goutières syndrome: A monogenic type I interferonopathy.
Liu A et al.·Scand J Immunol
2023Review
ARID1A suppresses R-loop-mediated STING-type I interferon pathway activation of anti-tumor immunity.
Maxwell MB et al.·Cell
2024
Clinical and molecular phenotype of Aicardi-Goutieres syndrome.
Rice G et al.·Am J Hum Genet
2007
Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1.
Crow YJ et al.·Am J Med Genet A
2015
Diagnosis of Genetic White Matter Disorders by Singleton Whole-Exome and Genome Sequencing Using Interactome-Driven Prioritization.
Schlüter A et al.·Neurology
2022
Assessment of interferon-related biomarkers in Aicardi-Goutières syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study.
Rice GI et al.·Lancet Neurol
2013
RNASEH2B loss and PARP inhibition in advanced prostate cancer.
Carmichael J et al.·J Clin Invest
2024Clinical trial
New Phenotypes Associated With Pathogenic RNASEH2B and SAMHD1 Variants.
Abdel-Salam GMH et al.·Int J Dev Neurosci
2025Case report
Neurologic Phenotypes Associated with Mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, and IFIH1: Aicardi-Goutières Syndrome and Beyond.
Livingston JH et al.·Neuropediatrics
2016Review
Systemic complications of Aicardi Goutières syndrome using real-world data.
Peixoto de Barcelos I et al.·Mol Genet Metab
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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