DIS3

Chr 13

DIS3 exosome endoribonuclease and 3'-5' exoribonuclease

Also known as: 2810028N01Rik, EXOSC11, KIAA1008, RRP44, dis3p

NCBI Gene: 22894 ENSG00000083520 UniProt: Q9Y2L1

The DIS3 protein functions as the catalytic component of the RNA exosome complex, performing 3'-5' exoribonuclease activity essential for RNA processing, degradation, and cellular RNA surveillance in both the nucleus and cytoplasm. Mutations in DIS3 cause multiple mitochondrial dysfunctions syndrome 7, an autosomal recessive disorder characterized by early-onset developmental delay, intellectual disability, seizures, and mitochondrial dysfunction. This gene shows extreme intolerance to loss-of-function variants, indicating that even single functional copies may be insufficient for normal cellular function.

ResearchSummary from RefSeq, UniProt

Enables 3'-5'-RNA exonuclease activity; endonuclease activity; and guanyl-nucleotide exchange factor activity. Involved in CUT catabolic process; RNA processing; and rRNA catabolic process. Located in cytosol and nucleoplasm. Part of nuclear exosome (RNase complex). Implicated in primary ovarian insufficiency. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.01

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.01LOEUF

pLI 0.000

Z-score 1.51

OE 0.77 (0.60–1.01)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.69Z-score

OE missense 0.91 (0.84–0.99)

459 obs / 502.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.77 (0.60–1.01)

0≤0.351.4

Missense OE?0.91 (0.84–0.99)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 39 / 50.6Missense obs/exp: 459 / 502.7Syn Z: -0.47

Background carrier burden — how many people carry a rare variant somewhere in DIS3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 47

1,244 rare PASS variants

Rare truncating (LoF)

1 in 370

263 rare PASS variants

Rare synonymous (reference)

1 in 100

440 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DIS3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 73	1 in 390
South Asian	~43k	1 in 40	1 in 270
Remaining (unassigned)	~30k	1 in 45	1 in 490
European (Finnish)	~27k	1 in 110	1 in 1,100
Admixed American	~22k	1 in 55	1 in 300
African / African American	~21k	1 in 49	1 in 330
East Asian	~20k	1 in 49	1 in 280
Ashkenazi Jewish	~13k	1 in 200	1 in 2,600
Middle Eastern	~2,884	1 in 47	≈ 1 in 720

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 20 of 21 coding exons well covered in gnomAD exomes; exon 14 marginal. Genomes: all 21.? see exons ↓