RNASEH2B

Chr 13AR

ribonuclease H2 subunit B

Also known as: AGS2, DLEU8

NCBI Gene: 79621 ENSG00000136104 UniProt: Q5TBB1 OMIM: 610326

The protein is the non-catalytic B subunit of RNase H2, an endonuclease that degrades RNA from RNA:DNA hybrids and removes ribonucleotides during DNA replication. Mutations cause Aicardi-Goutières syndrome type 2, an early-onset autosomal recessive neuroinflammatory disorder that typically presents in infancy with features resembling congenital infection. The gene is highly intolerant to loss-of-function variants, reflecting its essential role in DNA metabolism.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.251 OMIM phenotype

Clinical Summary— RNASEH2B

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Gene-Disease Validity (ClinGen)

RNASEH2B-related type 1 interferonopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

63 unique Pathogenic / Likely Pathogenic· 193 VUS of 554 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — RNASEH2B

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

-0.24Z-score

OE missense 1.06 (0.93–1.21)

154 obs / 145.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.81 (0.54–1.25)

0≤0.351.4

Missense OE?1.06 (0.93–1.21)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 15 / 18.5Missense obs/exp: 154 / 145.9Syn Z: -0.23

ClinVar Variant Classifications

554 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30

Likely Pathogenic33

VUS193

Likely Benign252

Benign17

Conflicting16

Pathogenic

Likely Pathogenic

193

VUS

252

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	21	1	8	0	30
Likely Pathogenic	21	7	5	0	33
VUS	10	146	34	3	193
Likely Benign	0	2	149	101	252
Benign	1	1	14	1	17
Conflicting	—				16
Total	53	157	210	105	541

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

View in ClinVar →

61 pathogenic / likely-pathogenic (of 68) ClinVar copy-number / structural variants overlap RNASEH2B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →