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GOSR2
golgi SNAP receptor complex member 2
GOSR2 encodes a SNARE protein critical for maintaining Golgi membrane structure and coordinating intracellular transport. The GOSR2 gene provides instructions for producing a protein that facilitates membrane fusion within the Golgi apparatus, the cellular compartment responsible for processing and packaging proteins.
GOSR2 is located on the long (q) arm of chromosome 17, at band 17q21.32. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 17 in the library →Overview
GOSR2 encodes golgi SNAP receptor complex member 2, a specialised protein belonging to the SNARE family that coordinates membrane fusion events within cells. SNARE proteins function by bringing opposing membranes into close proximity, enabling controlled fusion necessary for transporting cellular cargo between compartments. The GOSR2 protein specifically operates within the Golgi apparatus, where it helps maintain proper membrane organisation and ensures accurate delivery of proteins to their intended destinations. Disruption of GOSR2 function interferes with these fundamental trafficking processes, affecting multiple cellular systems. Research into this gene has revealed its particular importance in neurological tissue, where efficient intracellular transport is essential for maintaining neuronal health and synaptic function.
What the gene does
The GOSR2 protein functions as a v-SNARE (vesicle-associated SNARE), mediating fusion between transport vesicles and target Golgi membranes. During normal cellular trafficking, GOSR2 forms tight complexes with partner SNARE proteins on opposing membranes, creating a structural bridge that brings lipid bilayers together. This interaction releases energy that drives membrane merger, allowing vesicle contents to transfer into the Golgi lumen. The protein participates in retrograde transport pathways, returning material from the Golgi back to the endoplasmic reticulum for quality control and recycling. GOSR2 activity helps maintain the distinct chemical environments of different Golgi compartments, which is necessary for sequential protein modifications including glycosylation. In neurons, efficient SNARE-mediated fusion appears particularly crucial for managing the high volume of membrane traffic required for neurotransmitter packaging and synaptic vesicle recycling. Loss of GOSR2 function disrupts these coordinated processes, leading to accumulation of misrouted proteins and progressive cellular dysfunction.
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Chromosome location
GOSR2 is located on chromosome 17 at position q21.32, within the long arm of the chromosome. This genomic region spans approximately 17 kilobases and contains the complete coding sequence for the 212-amino acid protein. The gene structure consists of multiple exons that undergo splicing to produce the mature messenger RNA template.
Protein structure
The GOSR2 protein comprises 212 amino acids organised into functionally distinct regions. A coiled coil domain extends from amino acids 61 to 107, forming the characteristic alpha-helical structure that mediates protein-protein interactions with partner SNARE molecules during membrane fusion. This coiled coil region provides the structural framework for assembling the four-helix bundle typical of SNARE complexes. The protein contains an IxM motif spanning amino acids 118 to 120, which serves as a signal for cargo packaging into COPII-coated vesicles. This short sequence motif enables the protein to be recognised by components of the vesicle coating machinery, ensuring its proper incorporation into transport carriers. The combination of these structural elements allows GOSR2 to both participate in membrane fusion events and regulate its own trafficking within the secretory pathway.
Key variants
Pathogenic variants in GOSR2 typically involve changes that disrupt the protein's ability to form stable SNARE complexes or interfere with its proper localisation within the Golgi. Most disease-causing variants identified to date are inherited in an autosomal recessive manner, meaning affected individuals carry alterations in both gene copies. One specific variant (c.430G>T, p.Gly144Trp) is a founder variant in populations around the North Sea region and accounts for the majority of reported EPM6 cases, though precise proportions vary between studies. When both parents are carriers of a pathogenic variant, there is a 25 per cent recurrence risk with each pregnancy. Genetic counselling can help families understand inheritance patterns and explore testing options for relatives. The functional consequences of these variants generally involve impaired membrane fusion efficiency and disrupted intracellular trafficking patterns.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.184A>T | p.Lys62Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Progressive myoclonic epilepsy |
c.22dup | p.Thr8fs | Pathogenic/Likely pathogenic | ★★☆☆ | Progressive myoclonic epilepsy |
c.336+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Progressive myoclonic epilepsy type 6 |
c.341_342del | p.Asp113_Ser114insTer | Pathogenic | ★★☆☆ | Inborn genetic diseases |
c.430G>T | p.Gly144Trp | Pathogenic | ★★☆☆ | Progressive myoclonic epilepsy type 6 |
c.82C>T | p.Gln28Ter | Pathogenic | ★★☆☆ | not provided |
g.(?_46923173)_(46940633_?)del | - | Pathogenic | ★☆☆☆ | Progressive myoclonic epilepsy |
c.161del | p.Leu54fs | Pathogenic | ★☆☆☆ | Progressive myoclonic epilepsy |
c.16C>T | p.Gln6Ter | Pathogenic | ★☆☆☆ | Progressive myoclonic epilepsy |
c.179dup | p.Pro60_Asn61insTer | Pathogenic | ★☆☆☆ | Progressive myoclonic epilepsy |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
The primary condition associated with GOSR2 variants is progressive myoclonus epilepsy-6 (EPM6), also known as North Sea progressive myoclonus epilepsy, characterised by myoclonic seizures, developmental regression, and ataxia. Affected individuals typically present in early to mid-childhood (often between ages 2 and 6 years), with onset of seizures followed by worsening gait, coordination problems, and cognitive decline as the condition progresses. Seizures are commonly drug-resistant with standard anticonvulsants. The condition follows an autosomal recessive inheritance pattern - occurring when both copies of the gene carry pathogenic variants; carrier parents have a 25 per cent recurrence risk with each pregnancy, and genetic counselling can help families understand the implications for relatives. Disease progression reflects cumulative neuronal dysfunction resulting from chronic trafficking defects, with symptoms typically worsening over time as cellular stress accumulates.
In the UK, management is coordinated through specialist epilepsy services, typically at tertiary paediatric or adult neurology centres such as the Great Ormond Street tertiary epilepsy service or other regional comprehensive epilepsy centres. Care is delivered by a multidisciplinary team including paediatric or adult neurology, clinical genetics, physiotherapy and occupational therapy, speech and language therapy, and palliative-care input where appropriate. The focus is on optimising seizure control (which may involve combination therapy under neurology guidance), supporting mobility and communication as the condition progresses, and coordinating school or social-care support for the family.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic GOSR2 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
GOSR2 appears on several NHS Genomic Medicine Service gene panels relevant to neurological conditions (R-codes are NHS panel identifiers that indicate specific testing categories). The gene holds green classification status on the Ataxia and cerebellar anomalies narrow panel, the Hereditary ataxia panel, and the Hereditary ataxia with onset in adulthood panel (R54). It is also included with green status on the Congenital muscular dystrophy panel (R79) and the Early onset or syndromic epilepsy panel (R59). This multi-panel inclusion reflects the variable neurological presentations associated with GOSR2 pathogenic variants and ensures appropriate consideration during diagnostic testing for patients presenting with ataxia, epilepsy, or neuromuscular features.
In practice, NHS testing is initiated through a regional clinical genetics service, usually following referral from a GP, paediatrician, or neurologist when the clinical picture suggests a progressive myoclonus epilepsy or undiagnosed early-onset epilepsy with ataxia. Once a pathogenic variant has been confirmed in an affected individual, cascade and carrier testing may be offered to at-risk relatives (siblings, adult children, cousins considering family planning), again through NHS clinical genetics. Genetic counselling is offered before and after testing. Panel codes and eligibility criteria are periodically reviewed - families can check the current NHS Genomic Medicine Service signed-off panels for up-to-date information.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Diet & lifestyle considerations
No specific lifestyle modifications have been shown to alter the course of GOSR2-related progressive myoclonus epilepsy. Everyday care focuses on maintaining overall physical activity within the limits of gait and seizure control, consistent sleep patterns (since sleep deprivation can lower seizure threshold), and reducing fall risk as ataxia progresses. Families should liaise with the treating neurology and physiotherapy teams about safe activity levels, adaptive equipment, and school or workplace accommodations.
Supplement considerations
No dietary supplements have been shown to modify the course of GOSR2-related conditions. Management focuses on symptomatic treatment and supportive care coordinated by the specialist neurology team. Do not start new supplements without checking with your neurology or genetics team, as some over-the-counter products can interact with anticonvulsant medications.
Frequently asked questions
What inheritance pattern do GOSR2 variants follow?
GOSR2-associated conditions are inherited in an autosomal recessive pattern. This means an individual must inherit pathogenic variants in both copies of the gene (one from each parent) to develop the condition. When both parents are carriers, each pregnancy carries a 25% chance the child will be affected, a 50% chance the child will be an unaffected carrier, and a 25% chance the child will inherit neither variant. Carriers with one pathogenic variant typically remain unaffected themselves. Genetic counselling is recommended for families to discuss testing options for relatives.
Why does GOSR2 dysfunction particularly affect the nervous system?
Neurons require exceptionally efficient intracellular trafficking to manage constant membrane recycling at synapses and maintain long cellular processes. Disrupted SNARE-mediated fusion compromises these high-demand systems, making neurological tissue especially vulnerable to GOSR2 loss of function.
What does green status on NHS panels mean for GOSR2?
Green classification indicates strong evidence supporting GOSR2's role in the listed conditions, meaning the gene meets NHS criteria for inclusion in diagnostic testing panels. Laboratories can confidently report variants in this gene when analysing samples from patients with relevant neurological presentations.