GeneBe

GOSR2

protein-coding

golgi SNAP receptor complex member 2, the group of SNAREs|MicroRNA protein coding host genes

Gene summary

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]

MANE transcript

NM_004287.5

Inheritance

AR

ClinVar variants

P:28U:142B:58

Top phenotype

Epilepsy, progessive myoclonic 6; Muscular dystrophy, congenital, with or without seizures

gnomAD constraint

pLI —, LoF o/e 0.81

Max pathogenic AF

—

Genomic locus

chr17:46,923,075-46,975,524

External References & Databases

Ensembl (ENSG00000108433)NCBI Gene (9570)OMIM (604027)HGNC:4431GenCCUniProt (O14653)AlphaFoldClinVar (GOSR2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~52.4 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

progressive myoclonic epilepsy type 6STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013526

Submitter: Labcorp Genetics (formerly Invitae)

muscular dystrophy, congenital, with or without seizuresLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0859336

Submitter: Labcorp Genetics (formerly Invitae)

progressive myoclonic epilepsy type 6STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013526

Submitter: PanelApp Australia

progressive myoclonus epilepsyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0020074

Submitter: ClinGen

*GOSR2* was first reported in relation to autosomal recessive progressive myoclonus epilepsy in 2011 (Corbett et al., PMID: 21549339). A founder variant (c.430G>T, p.Gly144Trp) has been reported in the homozygous state in at least 28 individuals with progressive myoclonus epilepsy (PMIDs: 21549339, 23449775, 24458321, 30838261, 32105965). In addition, seven other variants (splicing, nonsense, in-frame deletion, start loss, missense) have been reported in five additional probands across five publications, and are included in this curation (PMIDs: 30363482, 29855340, 33639315, 34167170, and 37895210). Most individuals reported in the literature, especially with the founder variant, have ataxia, myoclonus, seizures, scoliosis, and elevated creatine kinase. In addition to these features, some individuals who are not homozygous for the founder variant in *GOSR2* (either two non-founder variants or compound heterozygotes with a single founder variant) also present with muscular dystrophy and/or changes on muscle biopsy (PMIDs: 34167170, 29855340). There is no reported difference in disease mechanism for these cases. Because of this, and the large phenotypic overlap between these individuals and who are homozygous for the founder variant, we have lumped these cases into one curation for autosomal recessive progressive myoclonus epilepsy. The mechanism of pathogenicity appears to be loss of function (PMIDs: 21549339, 28982678). In summary, there is definitive evidence to support the relationship between *GOSR2* and autosomal recessive progressive myoclonus epilepsy. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. This classification was approved by the ClinGen Epilepsy Gene Curation Expert Panel on April 16, 2024 (SOP version 10).

progressive myoclonic epilepsy type 6SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013526

Submitter: Orphanet

muscular dystrophy, congenital, with or without seizuresSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859336

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Epilepsy, progessive myoclonic 6; Muscular dystrophy, congenital, with or without seizuresAR

Manifestation: Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 21549339; 23449775; 24458321; 29855340; 33639315Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GOSR2 variants in ClinVar

11 Conditions Cataloged
Progressive myoclonic epilepsyTotal: 247
not providedTotal: 86
Inborn genetic diseasesTotal: 62
not specifiedTotal: 26
Progressive myoclonic epilepsy type 6Total: 13
GOSR2-related disorderTotal: 9
Muscular dystrophy, congenital, with or without seizuresTotal: 8
Muscular dystrophyTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004287.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
2
clinvar
48
clinvar
 50
missense
1
clinvar
131
clinvar
9
clinvar
1
clinvar
 142
nonsense
6
clinvar
1
clinvar
2
clinvar
 9
start loss
1
clinvar
3
clinvar
3
clinvar
 7
frameshift
8
clinvar
1
clinvar
3
clinvar
 12
splice donor/acceptor (+/-2bp)
7
clinvar
1
clinvar
 8
Total1612142571228

Highest pathogenic variant AF is 0.0002255476

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 112 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_004287.5RefSeqNP_004278.26MANE Select
ENST00000640051.2EnsemblENSP00000492751.16MANE Select
NM_001012511.3RefSeqNP_001012529.15Standard
NM_001321133.2RefSeqNP_001308062.17Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • SNARE interactions in vesicular transport - Homo sapiens (human)
  • XBP1(S) activates chaperone genes
  • Vesicle-mediated transport
  • Membrane Trafficking
  • Post-translational protein modification

Biological Process

  • protein targeting to vacuole
  • endoplasmic reticulum to Golgi vesicle-mediated transport
  • intra-Golgi vesicle-mediated transport
  • Golgi to vacuole transport
  • IRE1-mediated unfolded protein response

Molecular Function

  • SNARE binding
  • SNAP receptor activity
  • protein binding

Cellular Component

  • Golgi membrane
  • endoplasmic reticulum membrane
  • Golgi apparatus
  • cytosol
  • ER to Golgi transport vesicle membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000225567
Coding exons
7
Length
104521
Individuals with no LoFs
125697
Homozygous LoFs
0
Heterozygous LoFs
50
Defined
125747
p
0.000199
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.4891381231.120.000007351415
Missense (PolyPhen)1924.7160.76873305
Synonymous-0.1514644.71.030.00000256392
Loss of Function0.6321113.50.8148.31e-7131

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000250.00025rare
Latino/Admixed American0.000290.00029rare
Ashkenazi Jewish00.0absent
East Asian0.0000540.000054rare
Finnish00.0absent
European (Non-Finnish)0.000260.00025rare
South Asian0.000130.00013rare
Other0.000330.00033rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Involved in transport of proteins from the cis/medial- Golgi to the trans-Golgi network. {ECO:0000269|PubMed:9349823}.;
Disease
DISEASE: Epilepsy, progressive myoclonic 6 (EPM6) [MIM:614018]: A neurologic disorder characterized by onset of ataxia in the first years of life, followed by action myoclonus and seizures later in childhood, and loss of independent ambulation in the second decade. Cognition is not usually affected, although mild memory difficulties may occur in the third decade. {ECO:0000269|PubMed:21549339}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.119

Intolerance Scores

LoFtool
0.845
RVIS EVS
0.35
RVIS percentile EVS
74.18

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
E
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
0.804

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium
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