RNASEH2C

Chr 11AR

ribonuclease H2 subunit C

Also known as: AGS3, AYP1

NCBI Gene: 84153 ENSG00000172922 UniProt: Q8TDP1 OMIM: 610330

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a ribonuclease H subunit that can cleave ribonucleotides from RNA:DNA duplexes. Mutations in this gene cause Aicardi-Goutieres syndrome-3, a disease that causes severe neurologic dysfunction. A pseudogene for this gene has been identified on chromosome Y, near the sex determining region Y (SRY) gene. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.471 OMIM phenotype

Clinical Summary— RNASEH2C

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Gene-Disease Validity (ClinGen)

RNASEH2C-related type 1 interferonopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

8 unique Pathogenic / Likely Pathogenic· 207 VUS of 440 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — RNASEH2C

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?

1.47LOEUF

pLI 0.005

Z-score 0.79

OE 0.65 (0.32–1.47)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.92Z-score

OE missense 1.26 (1.09–1.47)

122 obs / 96.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.65 (0.32–1.47)

0≤0.351.4

Missense OE?1.26 (1.09–1.47)

0≤0.61.4

Synonymous OE?1.28

0≤1.21.6

LoF obs/exp: 4 / 6.1Missense obs/exp: 122 / 96.6Syn Z: -1.41

ClinVar Variant Classifications

440 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic6

VUS207

Likely Benign192

Benign14

Conflicting13

Pathogenic

Likely Pathogenic

207

VUS

192

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	2	0	0	2
Likely Pathogenic	3	3	0	0	6
VUS	13	150	42	2	207
Likely Benign	0	3	83	106	192
Benign	0	0	12	2	14
Conflicting	—				13
Total	16	158	137	110	434

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap RNASEH2C — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →