RNASEH2C

Chr 11AR

ribonuclease H2 subunit C

This gene encodes a non-catalytic subunit of RNase H2, an endonuclease that degrades RNA from RNA:DNA hybrids and excises single ribonucleotides from DNA:RNA duplexes during DNA replication. Mutations cause Aicardi-Goutieres syndrome-3, an autosomal recessive disorder characterized by severe neurologic dysfunction. Loss of function mutations impair the enzyme's ability to remove RNA primers and ribonucleotides during DNA replication, leading to accumulation of nucleic acid species that trigger innate immune responses.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.471 OMIM phenotype
Clinical SummaryRNASEH2C
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Gene-Disease Validity (ClinGen)
RNASEH2C-related type 1 interferonopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
3 unique Pathogenic / Likely Pathogenic· 33 VUS of 100 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.47LOEUF
pLI 0.005
Z-score 0.79
OE 0.65 (0.321.47)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.92Z-score
OE missense 1.26 (1.091.47)
122 obs / 96.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.65 (0.321.47)
00.351.4
Missense OE1.26 (1.091.47)
00.61.4
Synonymous OE1.28
01.21.6
LoF obs/exp: 4 / 6.1Missense obs/exp: 122 / 96.6Syn Z: -1.41

ClinVar Variant Classifications

100 submitted variants in ClinVar

Classification Summary

Pathogenic1
Likely Pathogenic2
VUS33
Likely Benign56
Conflicting2
1
Pathogenic
2
Likely Pathogenic
33
VUS
56
Likely Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
0
0
1
Likely Pathogenic
1
0
1
0
2
VUS
2
30
1
0
33
Likely Benign
0
1
22
33
56
Benign
0
0
0
0
0
Conflicting
2
Total332243394

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

View in ClinVar →

Protein Context — Lollipop Plot

RNASEH2C · 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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