GOSR2

Chr 17AR

golgi SNAP receptor complex member 2

Also known as: Bos1, EPM6, GS27, MYOS

NCBI Gene: 9570ENSG00000108433UniProt: O14653

This gene encodes a trafficking membrane protein which transports proteins among the medial- and trans-Golgi compartments. Due to its chromosomal location and trafficking function, this gene may be involved in familial essential hypertension. [provided by RefSeq, Mar 2016]

Primary Disease Associations & Inheritance

Epilepsy, progressive myoclonic 6MIM #614018
AR
Muscular dystrophy, congenital, with or without seizuresMIM #620166
AR
349
ClinVar variants
37
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— GOSR2
🧬
Gene-Disease Validity (ClinGen)
progressive myoclonus epilepsy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
37 Pathogenic / Likely Pathogenic· 158 VUS of 349 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.35LOEUF
pLI 0.000
Z-score 0.63
OE 0.81 (0.51–1.35)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.49Z-score
OE missense 1.12 (0.98–1.29)
138 obs / 122.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.81 (0.51–1.35)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.12 (0.98–1.29)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 11 / 13.5Missense obs/exp: 138 / 122.8Syn Z: -0.15

ClinVar Variant Classifications

349 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic11
VUS158
Likely Benign103
Benign34
Conflicting17
26
Pathogenic
11
Likely Pathogenic
158
VUS
103
Likely Benign
34
Benign
17
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
2
17
0
26
Likely Pathogenic
7
2
2
0
11
VUS
6
132
17
3
158
Likely Benign
0
5
53
45
103
Benign
1
2
29
2
34
Conflicting
—17
Total2114311850349

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GOSR2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Epilepsy, progressive myoclonic 6

MIM #614018

Molecular basis of disorder known

Autosomal recessive

Muscular dystrophy, congenital, with or without seizures

MIM #620166

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — GOSR2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Congenital heart disease risk loci identified by genome-wide association study in European patients.
Lahm H et al.·J Clin Invest
2021Clinical trial
The Genotypic and Phenotypic Spectrum of GOSR2 Mutations: Clinical and Pathophysiological Insights.
Polet SS et al.·J Inherit Metab Dis
2025
GOSR2: a progressive myoclonus epilepsy gene.
Dibbens LM et al.·Epileptic Disord
2016Review
Novel Genetic and Phenotypic Expansion in GOSR2-Related Progressive Myoclonus Epilepsy.
Hentrich L et al.·Genes (Basel)
2023Case report
TRAPPC11 and GOSR2 mutations associate with hypoglycosylation of α-dystroglycan and muscular dystrophy.
Larson AA et al.·Skelet Muscle
2018Case report
The natural history of progressive myoclonus ataxia.
van der Veen S et al.·Neurobiol Dis
2024Natural history
Ramsay Hunt syndrome: clinical characterization of progressive myoclonus ataxia caused by GOSR2 mutation.
van Egmond ME et al.·Mov Disord
2014
Unraveling the genomic basis of congenital heart disease.
Darbar D·J Clin Invest
2021
Compound heterozygous variants in GOSR2 associated with congenital muscular dystrophy: A case report.
Henige H et al.·Eur J Med Genet
2021Case report
'North Sea' progressive myoclonus epilepsy: phenotype of subjects with GOSR2 mutation.
Boissé Lomax L et al.·Brain
2013
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Muscular Dystrophy

Clinical Trial Readiness for the Dystroglycanopathies

RECRUITING
NCT00313677Katherine MathewsStarted 2006-04

External Resources

Links to major genomics databases and tools