GOSR2

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

Basic information

Region (hg38): 17:46923074-46975524

Links

ENSG00000108433 ∙ NCBI:9570 ∙ OMIM:604027 ∙ HGNC:4431 ∙ Uniprot:O14653 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• progressive myoclonic epilepsy type 6 (Supportive), mode of inheritance: AR
• progressive myoclonic epilepsy type 6 (Strong), mode of inheritance: AR
• muscular dystrophy, congenital, with or without seizures (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epilepsy, progessive myoclonic 6; Muscular dystrophy, congenital, with or without seizures	AR	General	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	Musculoskeletal; Neurologic	21549339; 23449775; 24458321; 29855340; 33639315

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GOSR2 gene.

• Progressive myoclonic epilepsy (253 variants)
• not provided (76 variants)
• Inborn genetic diseases (41 variants)
• not specified (28 variants)
• Progressive myoclonic epilepsy type 6 (12 variants)
• Muscular dystrophy, congenital, with or without seizures (3 variants)
• Muscular dystrophy (2 variants)
• GOSR2-Related Disorders (1 variants)
• Myoclonic epilepsy, progressive, X-linked (1 variants)
• Hearing loss, autosomal recessive (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GOSR2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	30		31
missense	1		122	2	2	127
nonsense	5		1			6
start loss		1	2			3
frameshift	6	1	2		1	10
inframe indel			1			1
splice donor/acceptor (+/-2bp)		5				5
splice region			5	10		15
non coding			27	30	23	80
Total	12	7	156	62	26

Highest pathogenic variant AF is 0.0000788

Variants in GOSR2

This is a list of pathogenic ClinVar variants found in the GOSR2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-46923129-G-T		Progressive myoclonic epilepsy	Uncertain significance (Jun 14, 2016)
17-46923155-A-AAGCCAG			Benign (Apr 15, 2015)
17-46923159-C-T		not specified	Likely benign (Sep 21, 2016)
17-46923163-G-C		not specified • Progressive myoclonic epilepsy • Progressive myoclonic epilepsy type 6	Benign (Aug 10, 2021)
17-46923164-C-T		not specified	Likely benign (Sep 03, 2016)
17-46923167-G-C		not specified	Benign (Sep 22, 2015)
17-46923170-C-A		not specified	Benign (Jul 02, 2014)
17-46923171-C-G		not specified	Likely benign (Aug 03, 2017)
17-46923173-T-G		Progressive myoclonic epilepsy	Uncertain significance (Jun 14, 2016)
17-46923177-C-G			Benign (Mar 03, 2015)
17-46923181-G-C		not specified • Progressive myoclonic epilepsy • Progressive myoclonic epilepsy type 6	Benign (Aug 10, 2021)
17-46923186-C-G		Progressive myoclonic epilepsy	Uncertain significance (Jun 14, 2016)
17-46923192-C-T		Inborn genetic diseases	Uncertain significance (Oct 27, 2020)
17-46923193-A-C		Hearing loss, autosomal recessive	Likely pathogenic (Apr 17, 2023)
17-46923193-A-G		Progressive myoclonic epilepsy • Inborn genetic diseases	Conflicting classifications of pathogenicity (Apr 25, 2022)
17-46923194-T-G		Muscular dystrophy, congenital, with or without seizures	Pathogenic (Dec 22, 2022)
17-46923195-G-A		Progressive myoclonic epilepsy	Uncertain significance (Jan 20, 2020)
17-46923195-G-T		Progressive myoclonic epilepsy	Uncertain significance (Aug 22, 2022)
17-46923196-G-A		Progressive myoclonic epilepsy	Uncertain significance (Jun 10, 2021)
17-46923197-A-C			Uncertain significance (Nov 08, 2019)
17-46923197-A-G		Inborn genetic diseases	Uncertain significance (Jun 29, 2023)
17-46923198-T-A		Progressive myoclonic epilepsy	Uncertain significance (Jun 15, 2022)
17-46923198-T-C		Progressive myoclonic epilepsy • Inborn genetic diseases	Likely benign (Oct 17, 2022)
17-46923199-C-A		not specified • Progressive myoclonic epilepsy • Inborn genetic diseases	Benign/Likely benign (Feb 01, 2024)
17-46923199-C-G		Progressive myoclonic epilepsy	Uncertain significance (Dec 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GOSR2	protein_coding	protein_coding	ENST00000225567	7	104521

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.66e-7	0.403	125697	0	50	125747	0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.489	138	123	1.12	0.00000735	1415
Missense in Polyphen		19	24.716	0.76873		305
Synonymous	-0.151	46	44.7	1.03	0.00000256	392
Loss of Function	0.632	11	13.5	0.814	8.31e-7	131

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000536	0.000535
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000256	0.000255
Middle Eastern	0.0000544	0.0000544
South Asian	0.000131	0.000131
Other	0.000327	0.000326

dbNSFP

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.
• Pathway: SNARE interactions in vesicular transport - Homo sapiens (human);XBP1(S) activates chaperone genes;Vesicle-mediated transport;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Cargo concentration in the ER;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;Arf1 pathway;Intra-Golgi traffic;COPI-mediated anterograde transport;COPII-mediated vesicle transport;ER to Golgi Anterograde Transport;Intra-Golgi and retrograde Golgi-to-ER traffic (Consensus)

Recessive Scores

• pRec: 0.119

Intolerance Scores

• loftool: 0.845
• rvis_EVS: 0.35
• rvis_percentile_EVS: 74.18

Haploinsufficiency Scores

• pHI: 0.169
• hipred: N
• hipred_score: 0.203
• ghis: 0.494

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.804

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gosr2
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• 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;retrograde transport, endosome to Golgi;COPII vesicle coating;vesicle fusion with Golgi apparatus
• Cellular component: Golgi membrane;endoplasmic reticulum membrane;Golgi apparatus;cytosol;ER to Golgi transport vesicle membrane;membrane;integral component of membrane;SNARE complex;late endosome membrane;endoplasmic reticulum-Golgi intermediate compartment membrane
• Molecular function: SNARE binding;SNAP receptor activity;protein binding