RNASEH2A

Chr 19AR

ribonuclease H2 subunit A

Also known as: AGS4, RNASEHI, RNHIA, RNHL

RNASEH2A encodes the catalytic subunit of RNase HII, an endonuclease that degrades RNA in RNA:DNA hybrids and excises single ribonucleotides from DNA duplexes during DNA replication. Mutations cause Aicardi-Goutières syndrome, an autosomal recessive neuroinflammatory disorder characterized by progressive microcephaly, psychomotor retardation, intracranial calcifications, and elevated interferon-alpha levels in cerebrospinal fluid. The gene shows low constraint to loss-of-function variation (pLI 0.004, LOEUF 0.88).

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.881 OMIM phenotype
Clinical SummaryRNASEH2A
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Gene-Disease Validity (ClinGen)
RNASEH2A-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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.88LOEUF
pLI 0.004
Z-score 1.88
OE 0.45 (0.240.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.19Z-score
OE missense 0.96 (0.851.09)
171 obs / 178.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.45 (0.240.88)
00.351.4
Missense OE0.96 (0.851.09)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 6 / 13.5Missense obs/exp: 171 / 178.2Syn Z: -0.59
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveRNASEH2A-related Aicardi-Goutieres syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6454th %ile
GOF
0.4578th %ile
LOF
0.3068th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

RNASEH2A · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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