Intellectual disability
Gene: EXOSC8

EXOSC8 (exosome component 8)
EnsemblGeneIds (GRCh38): ENSG00000120699
EnsemblGeneIds (GRCh37): ENSG00000120699
OMIM: 606019, Gene2Phenotype
EXOSC8 is in 8 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Created: 12 Mar 2026, 1:33 p.m. | Last Modified: 12 Mar 2026, 1:33 p.m.

Panel Version: 9.299

Comment on list classification: There is now sufficient evidence to promote this gene to Green at the next GMS panel update - 5 unrelated families with pontocerebellar hypoplasia due to biallelic variants in this gene. Almost all described patients exhibited psychomotor retardation (PMIDs: 24989451; 38017281; 34210538)
Created: 8 Sep 2025, 11:50 a.m. | Last Modified: 8 Sep 2025, 11:50 a.m.

Panel Version: 9.73

PMID: 34210538 (2021) - 16-year-old Spanish boy with cerebellar and spinal muscular atrophy, spasticity, psychomotor retardation, nystagmus, ophthalmoparesis, epilepsy, and mitochondrial respiratory chain (MRC) deficiency. The phenotype was described as milder compared to previous cases. WES revealed three variants in the EXOSC8 gene (c.[390+1delG];[628C>T;815G>C]) which lead to reduced mRNA expression and protein levels.

PMID: 38017281 (2024) - Homozygous missense variant c.238G>A;p.Val80Ile causing exon skipping in a patient with psychomotor retardation, spasticity, spinal muscle atrophy, respiratory problems, diaphragmatic hernia, dilated lateral ventricles, hypoplastic temporal lobes, thinning of the brain stem, dysmorphic facies, nystagmus, congenital esotropia and contractures.
Created: 8 Sep 2025, 11:45 a.m. | Last Modified: 8 Sep 2025, 11:45 a.m.

Panel Version: 9.72

Comment on list classification: Three unrelated cases, but two share the same founder mutation - Rating Amber until further cases are reported (added to watchlist).
Created: 28 Jul 2020, 10:44 a.m. | Last Modified: 28 Jul 2020, 10:44 a.m.

Panel Version: 3.205

Not associated with any phenotype in G2P.

PMID: 24989451 (2014) - 22 infants, belonging to two Roma and one Palestinian families, with a severe complex neuological disorder characterised by severe muscle weakness, spasticity, psychomotor retardation and vision and hearing impairment. A homozygous missense variant (p.Ser272Thr) segregated with disease in the two Roma families from the same region. The change was found at a frequency of 3% in the general Roma population, consistent with a founder effect. In the Palestinian family, a second homozyous missense variant (p.Ala2Val) was determined as the disease-causing change. Supporting functional data, as well as zebrafish model. Both variants affect a highly conserved residue and result in significantly decreased EXOSC8 protein in patient cells.
Created: 28 Jul 2020, 10:39 a.m. | Last Modified: 28 Jul 2020, 10:39 a.m.

Panel Version: 3.204

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pontocerebellar hypoplasia type 1C, 616081

Publications

Created: 28 Jul 2020, 10:39 a.m.
Last Modified: 28 Jul 2020, 10:39 a.m.
Panel version: 9.299

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Complex neurological phenotype includes ID.
Sources: Expert list
Created: 2 Feb 2020, 5:01 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pontocerebellar hypoplasia, type 1C, MIM#616081

Publications

Variants in this GENE are reported as part of current diagnostic practice

Created: 2 Feb 2020, 5:01 a.m.

Panel version: 3.0

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green
NHS GMS

Phenotypes

Pontocerebellar hypoplasia, type 1C, OMIM:616081

Tags

founder-effect

OMIM

606019

Clinvar variants

Variants in EXOSC8

Penetrance

None

Publications

Panels with this gene