Ataxia and cerebellar anomalies - childhood onset
Gene: GPN2EnsemblGeneIds (GRCh38): ENSG00000142751
EnsemblGeneIds (GRCh37): ENSG00000142751
GPN2 is in 3 panels
2 reviews
Ida Ertmanska (Genomics England Curator)
Comment on list classification: As reviewed by Luke Stuart, there are now 2 pedigrees reported where individuals harbouring biallelic GPN2 variants presented with ataxia (2 sibs, age of onset not specified), and cerebellar atrophy (both families). These families were found to have shared ancestry - counted as 1 family. Based on available evidence, this gene can only be rated Red.Created: 7 Aug 2026, 4:59 p.m. | Last Modified: 14 Aug 2026, 3:08 p.m.
Panel Version: 9.30
Luke Stuart (Genomics England Curator)
Smith et al. 2026 (PMID 42392036) investigated a Perrault syndrome cohort via exome sequencing.
Family F2 comprised two affected sisters with bilateral profound sensorineural hearing loss (SNHL), primary ovarian insufficiency (POI), and cerebellar ataxia. Brain MRI revealed cerebellar atrophy in both. Both were homozygous for GPN2 c.664A>G p.Asn222Asp.
Family F3 comprised a single affected proband presenting with profound SNHL, primary amenorrhea, and mild intellectual disability, also homozygous for GPN2 c.664A>G p.Asn222Asp. Cerebellar atrophy was noted on brain MRI. N.B. Haplotype analysis in the affected members of families F2 and F3 revealed a shared homozygous region of 662 kb encompassing the GPN2 locus, indicative of a shared ancestor.
Age at onset for affected probands is unknown, however age at last examination was in the 2nd or 3rd decade (supplemental data), suggesting early onset.
Before this study, no Mendelian disease had been attributed to GPN2 or its paralogs, GPN1 and GPN3; no animal model exists supporting pathogenicity or delineating the potential mechanism.
Conclusion: A single variant with potential founder effect is implicated in ataxia (n= 2 probands from 1 family)/ cerebellar atrophy (n=3 probands from 2 families); age of onset for the probands cited is unknown.
Suggest red rating (low evidence).
Sources: LiteratureCreated: 28 Jul 2026, 4:38 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Cerebellar ataxia (MONDO:0000437)
Publications
Details
- Mode of Inheritance
- BIALLELIC, autosomal or pseudoautosomal
- Sources
-
- Expert Review Red
- Phenotypes
-
- Cerebellar ataxia, MONDO:0000437
- Tags
- Clinvar variants
- Variants in GPN2
- Penetrance
- None
- Publications
- Panels with this gene
History Filter Activity
Added Tag
Ida Ertmanska (Genomics England Curator)Tag founder-effect tag was added to gene: GPN2.
Entity classified by Genomics England curator
Ida Ertmanska (Genomics England Curator)Gene: gpn2 has been classified as Red List (Low Evidence).
Set Phenotypes
Achchuthan Shanmugasundram (Genomics England Curator)Phenotypes for gene: GPN2 were changed from Cerebellar ataxia (MONDO:0000437) to Cerebellar ataxia, MONDO:0000437
Entity classified by Genomics England curator
Ida Ertmanska (Genomics England Curator)Gene: gpn2 has been classified as Amber List (Moderate Evidence).
Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes
Luke Stuart (Genomics England Curator)gene: GPN2 was added gene: GPN2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature Mode of inheritance for gene: GPN2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GPN2 were set to 42392036 Phenotypes for gene: GPN2 were set to Cerebellar ataxia (MONDO:0000437) Review for gene: GPN2 was set to RED