GOSR2

Summary

GOSR2 (golgi SNAP receptor complex member 2, HGNC:4431) is a protein-coding gene on chromosome 17q21.32, encoding Golgi SNAP receptor complex member 2 (O14653). Involved in transport of proteins from the cis/medial-Golgi to the trans-Golgi network. It is a common-essential gene (DepMap: required in 97.8% of cancer cell lines).

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.

Source: NCBI Gene 9570 — RefSeq curated summary.

At a glance

• Gene–disease (curated): progressive myoclonus epilepsy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 65
• Clinical variants (ClinVar): 290 total — 18 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 48
• Cancer dependency (DepMap): dependent in 97.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_004287

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4431
Approved symbol	GOSR2
Name	golgi SNAP receptor complex member 2
Location	17q21.32
Locus type	gene with protein product
Status	Approved
Aliases	GS27, Bos1
Ensembl gene	ENSG00000108433
Ensembl biotype	protein_coding
OMIM	604027
Entrez	9570

Gene structure

Transcript identifiers

Ensembl transcripts: 47 — 31 protein_coding, 11 nonsense_mediated_decay, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000225567, ENST00000393456, ENST00000415811, ENST00000570879, ENST00000571048, ENST00000571658, ENST00000572403, ENST00000573224, ENST00000575949, ENST00000576910, ENST00000623037, ENST00000638189, ENST00000638216, ENST00000638219, ENST00000638374, ENST00000638468, ENST00000638579, ENST00000638634, ENST00000638697, ENST00000638838, ENST00000638892, ENST00000639031, ENST00000639066, ENST00000639080, ENST00000639199, ENST00000639287, ENST00000639365, ENST00000639388, ENST00000639713, ENST00000639985, ENST00000640007, ENST00000640051, ENST00000640068, ENST00000640138, ENST00000640269, ENST00000640358, ENST00000640443, ENST00000640495, ENST00000640608, ENST00000640621, ENST00000640709, ENST00000640711, ENST00000640723, ENST00000640792, ENST00000640806, ENST00000640866, ENST00000640871

RefSeq mRNA: 10 — MANE Select: NM_004287 NM_001012511, NM_001321133, NM_001321134, NM_001330252, NM_001353114, NM_001353115, NM_001353116, NM_001363851, NM_004287, NM_054022

CCDS: CCDS11507, CCDS42355, CCDS45719, CCDS82148, CCDS86609, CCDS86610, CCDS86611, CCDS86612, CCDS86613

Canonical transcript exons

ENST00000640051 — 6 exons

Exon	Start	End
ENSE00003508727	46929520	46929584
ENSE00003523890	46935029	46935169
ENSE00003526728	46931099	46931207
ENSE00003545059	46932067	46932199
ENSE00003805679	46938599	46942020
ENSE00003902498	46923160	46923221

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 97.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.7404 / max 138.4966, expressed in 1819 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161330	29.7404	1819

Top tissues by expression

296 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	97.38	gold quality
left testis	UBERON:0004533	94.94	gold quality
right testis	UBERON:0004534	94.84	gold quality
stromal cell of endometrium	CL:0002255	93.30	gold quality
testis	UBERON:0000473	93.26	gold quality
colonic epithelium	UBERON:0000397	93.16	gold quality
adenohypophysis	UBERON:0002196	92.95	gold quality
islet of Langerhans	UBERON:0000006	92.70	gold quality
body of pancreas	UBERON:0001150	92.14	gold quality
pituitary gland	UBERON:0000007	92.06	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.06	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.95	gold quality
gastrocnemius	UBERON:0001388	91.75	gold quality
pancreas	UBERON:0001264	91.72	gold quality
small intestine	UBERON:0002108	91.64	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.62	gold quality
apex of heart	UBERON:0002098	91.58	gold quality
cortical plate	UBERON:0005343	91.57	gold quality
right atrium auricular region	UBERON:0006631	91.41	gold quality
prefrontal cortex	UBERON:0000451	91.40	gold quality
tendon of biceps brachii	UBERON:0008188	91.36	gold quality
muscle of leg	UBERON:0001383	91.26	gold quality
smooth muscle tissue	UBERON:0001135	91.20	gold quality
metanephros cortex	UBERON:0010533	91.17	gold quality
rectum	UBERON:0001052	91.05	gold quality
ganglionic eminence	UBERON:0004023	91.04	gold quality
right frontal lobe	UBERON:0002810	90.85	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.75	gold quality
lower esophagus	UBERON:0013473	90.74	gold quality
spleen	UBERON:0002106	90.73	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.47

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

75 targeting GOSR2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-7151-5P	99.37	67.82	613
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-449B-3P	99.20	67.24	1047

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 16)

• These studies suggest that membrin recruits Arf-1 to the early Golgi and reveal distinct kinetic cycles for Arf-1 at early and late Golgi determined by different sets of Arf regulators and effectors. (PMID:15781476)
• We found evidence that a SNP in GOSR2 is modestly associated with hypertension in whites from the ARIC study and the WGHS. (PMID:19057520)
• A homozygous mutation in GOSR2 (c.430G>T, p.Gly144Trp), was identified in five apparently unrelated families with a clinically distinct progressive myoclonic epilepsy syndrome. (PMID:21549339)
• This p.Gly144Trp mutation is equivalent to a loss of function and results in failure of GOSR2 protein to localize to the cis-Golgi. (PMID:21549339)
• Single nucleotide polymorphisms in the GOSR2 gene are associated with essential hypertension in Japanese men. (PMID:23313660)
• Golgi vesicles, presumably with COPI, serve to inhibit intra-Golgi transport by the extraction of GS27 and GS28 from the Golgi cisternae, which blocks the formation of inter-cisternal connections (PMID:23387339)
• GOSR2 gene mutation is associated with progressive myoclonus epilepsy cases, all of whom came from countries bounding the North Sea, extending to the coastal region of Northern Norway. (PMID:23449775)
• A haplotype of the GOSR2 gene is associated with myocardial infarction in Japanese men (PMID:23675987)
• Based on the presented phenotype, we would advise movement disorder specialists to consider mutation analysis of GOSR2 in patients with Ramsay Hunt syndrome, especially when they also have areflexia. (PMID:24458321)
• The SNAREs(Soluble N-ethylmaleimide-sensitive factor attachment protein receptors), that regulate both the biogenesis and secretion of multiple lysosome-related organelles(LROs). (PMID:26760525)
• review of the phenotype/genotype of GOSR2-associated progressive myoclonus epilepsy [review] (PMID:27618868)
• Mutations in GOSR2 reveal stringent secretory pathway demands of dendritic growth and synaptic integrity. (PMID:28978487)
• Molecular dynamics (MD) simulations showed that the hydrophobic core, which triggers SNARE complex formation, is compromised due to the glycine-to-tryptophan substitution in both GOSR2 and Bos1. (PMID:28982678)
• Recessive mutations in TRAPPC11 and GOSR2 are associated with congenital muscular dystrophy and hypoglycosylation of alpha-dystroglycan. (PMID:29855340)
• Computational estimates of annular diameter reveal genetic determinants of mitral valve function and disease. (PMID:35132965)
• Novel Genetic and Phenotypic Expansion in GOSR2-Related Progressive Myoclonus Epilepsy. (PMID:37895210)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gosr2	ENSDARG00000053070
mus_musculus	Gosr2	ENSMUSG00000020946
rattus_norvegicus	Gosr2	ENSRNOG00000003506

Paralogs (2): VTI1B (ENSG00000100568), VTI1A (ENSG00000151532)

Protein

Protein identifiers

Golgi SNAP receptor complex member 2 — O14653 (reviewed: O14653)

Alternative names: 27 kDa Golgi SNARE protein, Membrin

All UniProt accessions (34): O14653, A0A1W2PNV3, A0A1W2PP28, A0A1W2PPE0, A0A1W2PPG1, A0A1W2PPG5, A0A1W2PPJ0, A0A1W2PPP5, A0A1W2PPW8, A0A1W2PQ06, A0A1W2PQ12, A0A1W2PQ38, A0A1W2PQ77, A0A1W2PQE0, A0A1W2PQM3, A0A1W2PQP2, A0A1W2PQQ4, A0A1W2PQS3, A0A1W2PR02, A0A1W2PR23, A0A1W2PRC2, A0A1W2PRD0, A0A1W2PRE6, A0A1W2PRH7, A0A1W2PRL0, A0A1W2PRP7, A0A1W2PRV0, A0A1W2PS12, A0A1W2PS81, A0A1X7SBU8, I3L0K1, I3L1K7, I3L4Z6, I3NI02

UniProt curated annotations — full annotation on UniProt →

Function. Involved in transport of proteins from the cis/medial-Golgi to the trans-Golgi network.

Subunit / interactions. Part of a unique SNARE complex composed of the Golgi SNAREs GOSR1, STX5 and YKT6. Interacts (via IxM motif) with SEC24C and SEC24D; mediates GOSR2 packaging into COPII-coated vesicles. Interacts with BET1.

Subcellular location. Golgi apparatus. cis-Golgi network membrane. Golgi apparatus membrane. Endoplasmic reticulum membrane.

Disease relevance. Epilepsy, progressive myoclonic 6 (EPM6) [MIM:614018] A form of progressive myoclonic epilepsy, a clinically and genetically heterogeneous group of disorders defined by the combination of action and reflex myoclonus, other types of epileptic seizures, and progressive neurodegeneration and neurocognitive impairment. EPM6 is an autosomal recessive form 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. The disease is caused by variants affecting the gene represented in this entry. Muscular dystrophy, congenital, with or without seizures (MYOS) [MIM:620166] An autosomal recessive muscular dystrophy characterized by hypotonia and elevated serum creatine kinase levels apparent from birth. Patients have progressive muscle weakness, areflexia, and may develop seizures in early childhood or have abnormal epileptiform findings on electroencephalogram studies. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the GOSR2 family.

Isoforms (3)

UniProt ID	Names	Canonical?
O14653-1	A	yes
O14653-2	B
O14653-3	3

RefSeq proteins (10): NP_001012529, NP_001308062, NP_001308063, NP_001317181, NP_001340043, NP_001340044, NP_001340045, NP_001350780, NP_004278, NP_473363 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010989	SNARE	Homologous_superfamily
IPR027027	GOSR2/Membrin/Bos1	Family
IPR038407	v-SNARE_N_sf	Homologous_superfamily

Pfam: PF12352

UniProt features (19 total): sequence variant 4, sequence conflict 3, topological domain 2, mutagenesis site 2, splice variant 2, chain 1, strand 1, transmembrane region 1, coiled-coil region 1, short sequence motif 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3EG9	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14653-F1	83.30	0.25

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 1

Mutagenesis-validated functional residues (2):

Position	Phenotype
118	loss of interaction with sec24c.
120	loss of interaction with sec24c.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-204005	COPII-mediated vesicle transport
R-HSA-381038	XBP1(S) activates chaperone genes
R-HSA-5694530	Cargo concentration in the ER
R-HSA-6807878	COPI-mediated anterograde transport
R-HSA-6811438	Intra-Golgi traffic

MSigDB gene sets: 315 (showing top): TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, BROWNE_HCMV_INFECTION_6HR_DN, GOBP_VESICLE_ORGANIZATION, MENSE_HYPOXIA_UP, GOBP_MEMBRANE_FUSION, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_INTRA_GOLGI_VESICLE_MEDIATED_TRANSPORT, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, WEI_MYCN_TARGETS_WITH_E_BOX, MARTINEZ_RB1_TARGETS_UP, GOBP_ENDOPLASMIC_RETICULUM_TO_GOLGI_VESICLE_MEDIATED_TRANSPORT, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_ORGANELLE_MEMBRANE_FUSION

GO Biological Process (5): intra-Golgi vesicle-mediated transport (GO:0006891), vesicle fusion (GO:0006906), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192), membrane fusion (GO:0061025)

GO Molecular Function (3): SNARE binding (GO:0000149), SNAP receptor activity (GO:0005484), protein binding (GO:0005515)

GO Cellular Component (13): Golgi membrane (GO:0000139), nucleoplasm (GO:0005654), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), cytosol (GO:0005829), ER to Golgi transport vesicle membrane (GO:0012507), membrane (GO:0016020), SNARE complex (GO:0031201), late endosome membrane (GO:0031902), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), endomembrane system (GO:0012505)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
ER to Golgi Anterograde Transport	3
IRE1alpha activates chaperones	1
Intra-Golgi and retrograde Golgi-to-ER traffic	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	4
transport	2
bounding membrane of organelle	2
endomembrane system	2
intracellular membrane-bounded organelle	2
Golgi vesicle transport	1
vesicle organization	1
vesicle-mediated transport	1
organelle membrane fusion	1
intracellular protein localization	1
establishment of protein localization	1
cellular process	1
membrane organization	1
protein binding	1
protein-macromolecule adaptor activity	1
membrane fusion	1
fusogenic activity	1
binding	1
Golgi apparatus	1
nuclear lumen	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
COPII-coated ER to Golgi transport vesicle	1
transport vesicle membrane	1
coated vesicle membrane	1
membrane protein complex	1
late endosome	1
endosome membrane	1
endoplasmic reticulum-Golgi intermediate compartment	1
intracellular anatomical structure	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

1768 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GOSR2	STX5	Q13190	999
GOSR2	SEC22B	O75396	999
GOSR2	BET1	O15155	998
GOSR2	GOSR1	O95249	972
GOSR2	SCFD1	Q8WVM8	957
GOSR2	VTI1B	Q9UEU0	956
GOSR2	SEC22A	Q96IW7	924
GOSR2	SEC22C	Q9BRL7	876
GOSR2	COG3	Q96JB2	814
GOSR2	COG8	Q96MW5	798
GOSR2	COG6	Q9Y2V7	778
GOSR2	YKT6	O15498	760
GOSR2	BET1L	Q9NYM9	747
GOSR2	SEC24D	O94855	739
GOSR2	ARF1	P10947	731

IntAct

230 interactions, top by confidence:

A	B	Type	Score
GOSR2	BET1	psi-mi:“MI:0915”(physical association)	0.810
GOSR2	BET1	psi-mi:“MI:0914”(association)	0.810
STX4	GOSR2	psi-mi:“MI:0915”(physical association)	0.720
GOSR2	KASH5	psi-mi:“MI:0915”(physical association)	0.720
GOSR2	STX4	psi-mi:“MI:0915”(physical association)	0.720
KASH5	GOSR2	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
GOSR2	STX6	psi-mi:“MI:0915”(physical association)	0.670
STX6	GOSR2	psi-mi:“MI:0915”(physical association)	0.670
GOSR2	STX5	psi-mi:“MI:0915”(physical association)	0.670
STX5	GOSR2	psi-mi:“MI:0914”(association)	0.670
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
GOSR2	GOLGA8F	psi-mi:“MI:0915”(physical association)	0.560
GOLGA8DP	GOSR2	psi-mi:“MI:0915”(physical association)	0.560
GOLGA8F	GOSR2	psi-mi:“MI:0915”(physical association)	0.560
GOSR2	GOLGA8DP	psi-mi:“MI:0915”(physical association)	0.560
GOSR2	HIBADH	psi-mi:“MI:0915”(physical association)	0.560
GOSR2	CYB561	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (198): GOSR2 (Two-hybrid), STX6 (Two-hybrid), CCDC155 (Two-hybrid), GOLGA8EP (Two-hybrid), GOLGA8F (Two-hybrid), GOSR2 (Affinity Capture-MS), GOSR2 (Affinity Capture-MS), GOSR2 (Affinity Capture-MS), GOSR2 (Affinity Capture-MS), PHB (Co-fractionation), GOSR2 (Proximity Label-MS), GOSR2 (Proximity Label-MS), GOSR2 (Proximity Label-MS), GOSR2 (Affinity Capture-MS), GOSR2 (Affinity Capture-MS)

ESM2 similar proteins: A8XLW0, A8XP14, O04378, O13644, O14653, O35165, O35166, O65359, O89116, O94531, O94651, P25385, P38736, P41941, P59277, P78768, P93654, Q01590, Q04338, Q09835, Q12981, Q20797, Q39233, Q54CK6, Q54IX6, Q6BVM4, Q6BZQ6, Q6CRX0, Q6FKA1, Q6QD59, Q75CY3, Q8VHI8, Q95ZW1, Q96AJ9, Q9FFK1, Q9FK28, Q9HGN3, Q9JI51, Q9LK09, Q9LMP7

Diamond homologs: A8XP14, O14653, O35165, O35166, P41941, Q6BZQ6, Q75CY3, Q9FK28, Q9P7G5, Q9VRL2, Q9SJL6, P25385, Q6BVM4, Q6CRX0, Q6FKA1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 86 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
COPII-mediated vesicle transport	5	16.3×	2e-04
ER to Golgi Anterograde Transport	5	13.3×	4e-04
Intra-Golgi and retrograde Golgi-to-ER traffic	5	10.5×	7e-04
Transport to the Golgi and subsequent modification	5	10.3×	7e-04
Membrane Trafficking	11	8.2×	7e-06
Vesicle-mediated transport	11	7.7×	9e-06
Asparagine N-linked glycosylation	6	7.2×	8e-04

GO biological processes:

GO term	Partners	Fold	FDR
obsolete vesicle docking	5	51.1×	2e-05
vesicle fusion	5	40.1×	3e-05
endoplasmic reticulum to Golgi vesicle-mediated transport	6	10.9×	2e-03
intracellular protein transport	8	6.9×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

290 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	18
Likely pathogenic	5
Uncertain significance	129
Likely benign	80
Benign	28

Top pathogenic / likely-pathogenic (23)

Variant ID	HGVS	Classification
1073493	NM_004287.5(GOSR2):c.89_90del (p.Val30fs)	Pathogenic
1324496	NM_004287.5(GOSR2):c.2T>G (p.Met1Arg)	Pathogenic
1372090	NM_004287.5(GOSR2):c.301C>T (p.Arg101Ter)	Pathogenic
1410870	NM_004287.5(GOSR2):c.16C>T (p.Gln6Ter)	Pathogenic
1451722	NM_004287.5(GOSR2):c.161del (p.Leu54fs)	Pathogenic
1458379	NC_000017.10:g.(?44845686)(45016126_?)del	Pathogenic
208982	NM_004287.5(GOSR2):c.485AGA[2] (p.Lys164del)	Pathogenic
2123629	NM_004287.5(GOSR2):c.262C>T (p.Gln88Ter)	Pathogenic
2234799	NM_004287.5(GOSR2):c.341_342del (p.Asp113_Ser114insTer)	Pathogenic
2748845	NM_004287.5(GOSR2):c.186_187del (p.Arg63fs)	Pathogenic
2797676	NM_004287.5(GOSR2):c.221dup (p.Tyr75fs)	Pathogenic
30406	NM_004287.5(GOSR2):c.430G>T (p.Gly144Trp)	Pathogenic
3683794	NM_004287.5(GOSR2):c.241C>T (p.Gln81Ter)	Pathogenic
3712404	NM_004287.5(GOSR2):c.179dup (p.Pro60_Asn61insTer)	Pathogenic
831185	NC_000017.11:g.(?46923173)(46940633_?)del	Pathogenic
859319	NM_004287.5(GOSR2):c.262del (p.Gln88fs)	Pathogenic
983499	NM_004287.5(GOSR2):c.82C>T (p.Gln28Ter)	Pathogenic
997028	NM_004287.5(GOSR2):c.319C>T (p.Arg107Ter)	Pathogenic
2501009	NM_004287.5(GOSR2):c.1A>C (p.Met1Leu)	Likely pathogenic
265531	NM_004287.5(GOSR2):c.29+1G>A	Likely pathogenic
4737197	NM_004287.5(GOSR2):c.95-2A>G	Likely pathogenic
4772388	NM_004287.5(GOSR2):c.2T>C (p.Met1Thr)	Likely pathogenic
578675	NM_004287.5(GOSR2):c.337-2A>G	Likely pathogenic

SpliceAI

1453 predictions. Top by Δscore:

Variant	Effect	Δscore
17:46923222:G:GG	donor_gain	1.0000
17:46929519:GGCA:G	acceptor_gain	1.0000
17:46929580:GCACA:G	donor_gain	1.0000
17:46929585:GTGA:G	donor_gain	1.0000
17:46931097:A:AG	acceptor_gain	1.0000
17:46931098:G:GG	acceptor_gain	1.0000
17:46931098:GT:G	acceptor_gain	1.0000
17:46931098:GTA:G	acceptor_gain	1.0000
17:46931098:GTAGT:G	acceptor_gain	1.0000
17:46931203:AGACT:A	donor_gain	1.0000
17:46931204:GACT:G	donor_gain	1.0000
17:46931204:GACTG:G	donor_gain	1.0000
17:46931205:ACT:A	donor_gain	1.0000
17:46931206:CT:C	donor_gain	1.0000
17:46931208:G:GG	donor_gain	1.0000
17:46932057:T:G	acceptor_gain	1.0000
17:46932065:A:AG	acceptor_gain	1.0000
17:46932065:AGTC:A	acceptor_gain	1.0000
17:46932065:AGTCG:A	acceptor_gain	1.0000
17:46932066:G:GG	acceptor_gain	1.0000
17:46932066:G:GT	acceptor_gain	1.0000
17:46932066:GT:G	acceptor_gain	1.0000
17:46932066:GTC:G	acceptor_gain	1.0000
17:46932066:GTCG:G	acceptor_gain	1.0000
17:46932066:GTCGG:G	acceptor_gain	1.0000
17:46932198:AC:A	donor_gain	1.0000
17:46932200:G:GG	donor_gain	1.0000
17:46935226:GTTTA:G	donor_gain	1.0000
17:46935227:T:G	donor_gain	1.0000
17:46938581:T:TA	acceptor_gain	1.0000

AlphaMissense

1411 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:46932102:T:C	L80P	0.991
17:46938663:T:C	L181P	0.987
17:46938645:C:T	S175F	0.986
17:46932165:G:C	R101P	0.985
17:46932188:T:C	F109L	0.985
17:46932190:C:A	F109L	0.985
17:46932190:C:G	F109L	0.985
17:46938627:C:A	A169D	0.982
17:46932114:T:C	L84P	0.981
17:46938645:C:A	S175Y	0.979
17:46935165:T:C	L158S	0.978
17:46938722:T:C	C201R	0.978
17:46938686:G:C	D189H	0.977
17:46935144:T:C	L151P	0.976
17:46938626:G:C	A169P	0.975
17:46938687:A:C	D189A	0.975
17:46938707:G:A	G196R	0.975
17:46938707:G:C	G196R	0.975
17:46932110:G:C	A83P	0.973
17:46935111:T:C	L140P	0.973
17:46938688:C:A	D189E	0.973
17:46938688:C:G	D189E	0.973
17:46932174:T:C	L104P	0.970
17:46938642:T:C	L174S	0.970
17:46931156:T:C	L51P	0.969
17:46938660:G:C	R180P	0.969
17:46938732:T:G	M204R	0.969
17:46935169:G:C	K159N	0.968
17:46935169:G:T	K159N	0.968
17:46938666:T:A	I182N	0.968

dbSNP variants (sampled 300 via entrez): RS1000011317 (17:46944119 C>T), RS1000021652 (17:46934847 T>G), RS1000068419 (17:46956015 C>T), RS1000130393 (17:46941394 T>G), RS1000275456 (17:46959438 A>G), RS1000319845 (17:46941623 G>A,T), RS1000474497 (17:46964839 G>GA,GAA), RS1000481244 (17:46941066 T>A,C), RS1000489720 (17:46946444 A>C,G), RS1000579672 (17:46971980 G>A), RS1000616716 (17:46943207 G>A), RS1000670523 (17:46941952 AGAT>A), RS1000719840 (17:46921905 C>G), RS1000738902 (17:46951858 C>T), RS1000761148 (17:46952642 A>T)

Disease associations

OMIM: gene MIM:604027 | disease phenotypes: MIM:254800, MIM:620166, MIM:614018, MIM:220290, MIM:607197

GenCC curated gene-disease

Disease	Classification	Inheritance
progressive myoclonic epilepsy type 6	Strong	Autosomal recessive
muscular dystrophy, congenital, with or without seizures	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
progressive myoclonus epilepsy	Definitive	AR

Mondo (5): progressive myoclonus epilepsy (MONDO:0020074), muscular dystrophy, congenital, with or without seizures (MONDO:0859336), progressive myoclonic epilepsy type 6 (MONDO:0013526), hearing loss, autosomal recessive (MONDO:0019588), muscular dystrophy (MONDO:0020121)

Orphanet (6): Progressive myoclonic epilepsy type 1 (Orphanet:308), Progressive myoclonic epilepsy (Orphanet:98261), Progressive myoclonic epilepsy type 6 (Orphanet:280620), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Muscular dystrophy (Orphanet:98473)

HPO phenotypes

48 total (30 of 48 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000639	Nystagmus
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001268	Mental deterioration
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001324	Muscle weakness
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001558	Decreased fetal movement
HP:0001730	Progressive hearing impairment
HP:0001761	Pes cavus
HP:0002015	Dysphagia
HP:0002027	Abdominal pain
HP:0002058	Myopathic facies
HP:0002069	Bilateral tonic-clonic seizure
HP:0002098	Respiratory distress
HP:0002119	Ventriculomegaly
HP:0002121	Generalized non-motor (absence) seizure
HP:0002168	Scanning speech
HP:0002197	Generalized-onset seizure
HP:0002354	Memory impairment
HP:0002359	Frequent falls
HP:0002505	Loss of ambulation
HP:0002650	Scoliosis
HP:0002878	Respiratory failure
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003323	Progressive muscle weakness

GWAS associations

65 associations (top):

Study	Trait	p-value
GCST000872_6	QRS duration	5.000000e-10
GCST001227_11	Systolic blood pressure	1.000000e-10
GCST001235_7	Blood pressure	6.000000e-15
GCST001236_16	Blood pressure	2.000000e-07
GCST003598_16	QRS duration	2.000000e-06
GCST003598_43	QRS duration	4.000000e-07
GCST004166_52	Nonsyndromic cleft lip with cleft palate	1.000000e-11
GCST004279_2	Systolic blood pressure	3.000000e-08
GCST004651_8	Aortic root size	2.000000e-10
GCST004775_34	Pulse pressure	2.000000e-15
GCST004776_68	Systolic blood pressure	4.000000e-13
GCST004986_7	Idiopathic pulmonary fibrosis	4.000000e-06
GCST005195_118	Coronary artery disease	8.000000e-10
GCST005196_25	Coronary artery disease	6.000000e-10
GCST005951_16	Body mass index	4.000000e-08
GCST005986_26	Blood urea nitrogen levels	8.000000e-17
GCST006021_31	Systolic blood pressure	3.000000e-10
GCST006061_178	Atrial fibrillation	1.000000e-08
GCST006061_179	Atrial fibrillation	4.000000e-09
GCST006231_2	Mean arterial pressure	1.000000e-07
GCST006259_14	Systolic blood pressure	2.000000e-15
GCST006945_5	Feeling guilty	4.000000e-08
GCST006950_39	Feeling worry	2.000000e-08
GCST007095_134	Systolic blood pressure	1.000000e-08
GCST007095_135	Systolic blood pressure	8.000000e-07
GCST007096_79	Pulse pressure	3.000000e-40
GCST007097_124	Pulse pressure	7.000000e-10
GCST007097_125	Pulse pressure	2.000000e-12
GCST007099_226	Systolic blood pressure	2.000000e-27
GCST007103_24	QRS duration	9.000000e-27

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0006340	mean arterial pressure
EFO:0003959	cleft lip
EFO:0000768	idiopathic pulmonary fibrosis
EFO:0004340	body mass index
EFO:0009595	guilt measurement
EFO:0009589	worry measurement
EFO:0009930	Calcium channel blocker use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0004509	hemoglobin measurement
EFO:0004327	electrocardiography
EFO:0004682	QT interval
EFO:0004298	cardiovascular measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D009136	Muscular Dystrophies	C05.651.534.500; C10.668.491.175.500; C16.320.577
D020191	Myoclonic Epilepsies, Progressive	C10.228.140.490.375.130.650; C10.228.140.490.493.063.650
C564609	Deafness, Autosomal Recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs758391	GOSR2, LRRC37A2		0.00	0

CTD chemical–gene interactions

56 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	7
Ozone	affects cotreatment, increases expression, increases abundance, affects expression	3
Cyclosporine	increases expression	3
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Air Pollutants	increases expression, affects expression, affects cotreatment, increases abundance	2
Copper	affects binding, decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
trichostatin A	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
sodium arsenite	increases expression	1
potassium chromate(VI)	increases expression	1
hydroquinone	decreases expression	1
pentabromodiphenyl ether	increases expression	1
CGP 52608	affects binding, increases reaction	1
U 0126	affects expression, affects reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
NSC 689534	affects binding, increases expression	1
bisphenol AF	increases expression	1
Bortezomib	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Vorinostat	increases expression	1

Clinical trials (associated diseases)

132 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01882400	PHASE4	COMPLETED	Assessment of Response to Treatment of Osteoporosis With Oral Bisphosphonates in Patients With Muscular Dystrophy
NCT01254019	PHASE3	COMPLETED	A Clinical Study to Assess the Efficacy and Safety of GSK2402968 in Subjects With Duchenne Muscular Dystrophy
NCT01480245	PHASE3	TERMINATED	Open Label Study of GSK2402968 in Subjects With Duchenne Muscular Dystrophy
NCT01803412	PHASE3	TERMINATED	A Study of the Safety, Tolerability & Efficacy of Long-term Administration of Drisapersen in US & Canadian Subjects
NCT01826487	PHASE3	COMPLETED	Phase 3 Study of Ataluren in Participants With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD)
NCT01890798	PHASE3	WITHDRAWN	Drisapersen Duchenne Muscular Dystrophy (DMD) Treatment Protocol
NCT02090959	PHASE3	TERMINATED	An Extension Study of Ataluren (PTC124) in Participants With Nonsense Mutation Dystrophinopathy
NCT02432885	PHASE3	COMPLETED	Myocardial Fibrosis Progression in Duchenne and Becker Muscular Dystrophy - ACE Inhibitor Therapy Trial
NCT03179631	PHASE3	COMPLETED	Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy
NCT05126758	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Deramiocel (CAP-1002) in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy
NCT07587242	PHASE3	NOT_YET_RECRUITING	A Phase 3 Study to Evaluate the Safety and Efficacy of AOC 1044 (Also Referred to as Delpacibart Zotadirsen) in Participants With DMD With Gene Mutations Amenable to Exon 44 Skipping
NCT07608432	PHASE3	RECRUITING	Efficacy, Safety, and Tolerability of Zeleciment Rostudirsen (DYNE-251) Administered Intravenously Every 4 Weeks in Ambulatory Participants With Duchenne Muscular Dystrophy (FORZETTO)
NCT01153932	PHASE2	COMPLETED	Phase II Doubleblind Exploratory Study of GSK2402968 in Ambulant Subjects With Duchenne Muscular Dystrophy
NCT01462292	PHASE2	COMPLETED	A Clinical Study to Assess Two Doses of GSK2402968 in Subjects With Duchenne Muscular Dystrophy (DMD)
NCT01910649	PHASE2	TERMINATED	A Phase I/II, Open Label, Escalating Dose, Pilot Study to Assess Effect, Safety, Tolerability and PK of Multiple SC Doses of Drisapersen in Patients With Duchenne Muscular Dystrophy and to Assess the Potential for IV Dosing as an Alternative Route of Administration
NCT03406780	PHASE2	COMPLETED	A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy
NCT05479981	PHASE2	COMPLETED	Extension of AOC 1001-CS1 (MARINA) Study in Adult Myotonic Dystrophy Type 1 (DM1) Patients
NCT06290713	PHASE2	RECRUITING	Vasodilator and Exercise Study for DMD (VASO-REx)
NCT06547216	PHASE2	ACTIVE_NOT_RECRUITING	Phase 2 Open-label Extension Study of AOC 1020 in Participants With Facioscapulohumeral Muscular Dystrophy (FSHD)
NCT07287189	PHASE2	RECRUITING	Phase 2 Study of SAT-3247 in Pediatric Ambulatory Patients
NCT00494195	PHASE1	COMPLETED	Gene Transfer Therapy for Treating Children and Adults With Limb Girdle Muscular Dystrophy Type 2D (LGMD2D)
NCT00674843	PHASE1	UNKNOWN	The Efficacy of Using Far Infrared Radiation to Manage Muscular Dystrophies
NCT00873782	PHASE1	COMPLETED	Safety Study of Transvenous Limb Perfusion in Human Muscular Dystrophy
NCT01128855	PHASE1	COMPLETED	A Double-blind, Escalating Dose, Randomized, Placebo-controlled Study Assessing PK, Safety, Tolerability in Non-ambulant DMD Subjects
NCT02241928	PHASE1	WITHDRAWN	Stem Cell Therapy in Muscular Dystrophy
NCT03627494	PHASE1	COMPLETED	First Time in Human (FTIH) Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single and Repeat Doses of GSK3439171A in Healthy Subjects and to Assess Food Effect
NCT05492734	PHASE1	COMPLETED	A Study to Assess the Feasibility of Non-invasive Dried Blood Sampling
NCT05730842	PHASE1	COMPLETED	Absorption, Metabolism, Excretion and Absolute Bioavailability of EDG-5506 in Healthy Volunteers
NCT06593951	Not specified	RECRUITING	Registry and Natural History Study for Progressive Myoclonus Epilepsy Type 1 (EPM1)
NCT06923241	Not specified	COMPLETED	Nutri-score Labelling in a UK Restaurant Setting: a Randomised Control Trial
NCT01834040	PHASE1/PHASE2	UNKNOWN	Study Safety and Efficacy of BMMNC for the Patient With Duchenne Muscular Dystrophy
NCT01834066	PHASE1/PHASE2	UNKNOWN	Study Safety and Efficacy of Bone Marrow Derived Autologous Cells for the Treatment of Muscular Dystrophy.
NCT02515669	PHASE1/PHASE2	TERMINATED	Study of an Investigational Drug, RO7239361 (BMS-986089), in Ambulatory Boys With DMD
NCT05230459	PHASE1/PHASE2	RECRUITING	A Study to Evaluate the Safety of AB-1003 (Previously LION-101) in Subjects With Genetic Confirmation of LGMD2I/R9 (Part1)
NCT05747924	PHASE1/PHASE2	COMPLETED	Phase 1/2 Study of AOC 1020 in Participants With Facioscapulohumeral Muscular Dystrophy (FSHD)
NCT02653833	EARLY_PHASE1	TERMINATED	The Study of Skeletal Muscle Blood Flow in Becker Muscular Dystrophy
NCT00001164	Not specified	COMPLETED	Studies of Patients With Skin Disease, Patients With Neurological Degenerations, and Normal Volunteers
NCT00004568	Not specified	RECRUITING	Study of Inherited Neurological Disorders
NCT00027391	Not specified	COMPLETED	Study of Albuterol and Oxandrolone in Patients With Facioscapulohumeral Dystrophy (FSHD)
NCT00082108	Not specified	RECRUITING	Myotonic Dystrophy and Facioscapulohumeral Muscular Dystrophy Registry