RNASET2

Chr 6AR

ribonuclease T2

ENSG00000026297 UniProt: O00584 OMIM: 612944

This ribonuclease cleaves single-stranded RNA molecules and plays essential roles in innate immune response by degrading microbial RNAs for TLR recognition and in mitochondrial RNA processing. Mutations cause leukoencephalopathy, cystic, without megalencephaly, which is inherited in an autosomal recessive pattern. The gene shows low constraint to loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Ribonuclease that plays an essential role in innate immune response by recognizing and degrading RNAs from microbial pathogens that are subsequently sensed by TLR8 (PubMed:31778653). Cleaves preferentially single-stranded RNA molecules between purine and uridine residues, which critically contributes to the supply of catabolic uridine and the generation of purine-2',3'-cyclophosphate-terminated oligoribonucleotides (PubMed:31778653, PubMed:38697119). In turn, RNase T2 degradation products promote the RNA-dependent activation of TLR8 (PubMed:31778653). In plasmacytoid dendritic cells, it cooperates with PLD3 or PLD4 5'->3' exonucleases to process RNA fragments and release 2',3'-cyclic guanosine monophosphate (2',3'-cGMP), a potent stimulatory ligand for TLR7 (PubMed:38697119). Also plays a key role in degradation of mitochondrial RNA and processing of non-coding RNA imported from the cytosol into mitochondria (PubMed:28730546, PubMed:30184494). Participates as well in degradation of mitochondrion-associated cytosolic rRNAs (PubMed:30385512)

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.961 OMIM phenotype

Clinical Summary— RNASET2

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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

4 unique Pathogenic / Likely Pathogenic· 31 VUS of 82 total submissions

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Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.96LOEUF

pLI 0.000

Z-score 1.68

OE 0.53 (0.31–0.96)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.24Z-score

OE missense 0.94 (0.82–1.09)

133 obs / 141.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.53 (0.31–0.96)

0≤0.351.4

Missense OE?0.94 (0.82–1.09)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 8 / 15.0Missense obs/exp: 133 / 141.1Syn Z: -0.44

ClinVar Variant Classifications

82 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic2

VUS31

Likely Benign22

Benign1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	1	0	2
Likely Pathogenic	2	0	0	0	2
VUS	0	27	4	0	31
Likely Benign	0	1	12	9	22
Benign	0	0	0	1	1
Total	3	28	17	10	58

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap RNASET2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →