EXOSC2

Chr 9

exosome component 2

Also known as: RRP4, Rrp4p, SHRF, hRrp4p, p7

NCBI Gene: 23404 ENSG00000130713 UniProt: Q13868

The EXOSC2 protein is a non-catalytic component of the RNA exosome complex that processes and degrades various RNA species in both the nucleus and cytoplasm. Biallelic mutations cause an autosomal recessive syndrome characterized by short stature, hearing loss, retinitis pigmentosa, and distinctive facial features. The gene is highly constrained against loss-of-function variants (pLI near 1), indicating that complete loss of function is poorly tolerated.

ResearchSummary from RefSeq, OMIM, UniProt

Predicted to enable RNA binding activity. Involved in RNA catabolic process; RNA processing; and positive regulation of cell growth. Located in cytosol; nucleolus; and nucleoplasm. Part of nuclear exosome (RNase complex). Implicated in short stature, hearing loss, retinitis pigmentosa, and distinctive facies. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtShort stature, hearing loss, retinitis pigmentosa, and distinctive facies

Clinical highlights

Gene–disease validity (ClinGen)

Limited · retinitis pigmentosa-hearing loss-premature aging-short stature-facial dysmorphism syndrome · AR · ClinGen 2025

not for standalone diagnostic reporting

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.10

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?

1.10LOEUF

pLI 0.000

Z-score 1.28

OE 0.66 (0.42–1.10)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.39Z-score

OE missense 0.92 (0.80–1.05)

153 obs / 167.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.66 (0.42–1.10)

0≤0.351.4

Missense OE?0.92 (0.80–1.05)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 11 / 16.6Missense obs/exp: 153 / 167.2Syn Z: 0.60

Background carrier burden — how many people carry a rare variant somewhere in EXOSC2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

410 rare PASS variants

Rare truncating (LoF)

1 in 1,200

73 rare PASS variants

Rare synonymous (reference)

1 in 220

145 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for EXOSC2. 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 190	1 in 1,200
South Asian	~43k	1 in 130	1 in 3,000
Remaining (unassigned)	~30k	1 in 140	1 in 1,200
European (Finnish)	~27k	1 in 670	1 in 3,200
Admixed American	~22k	1 in 200	1 in 470
African / African American	~21k	1 in 140	1 in 1,000
East Asian	~20k	1 in 270	1 in 2,200
Ashkenazi Jewish	~13k	1 in 2,200	≈ 1 in 4,400
Middle Eastern	~2,884	1 in 140	≈ 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): All 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓