GYG1

Summary

GYG1 (glycogenin 1, HGNC:4699) is a protein-coding gene on chromosome 3q24, encoding Glycogenin-1 (P46976). Glycogenin participates in the glycogen biosynthetic process along with glycogen synthase and glycogen branching enzyme.

This gene encodes a member of the glycogenin family. Glycogenin is a glycosyltransferase that catalyzes the formation of a short glucose polymer from uridine diphosphate glucose in an autoglucosylation reaction. This reaction is followed by elongation and branching of the polymer, catalyzed by glycogen synthase and branching enzyme, to form glycogen. This gene is expressed in muscle and other tissues. Mutations in this gene result in glycogen storage disease XV. This gene has pseudogenes on chromosomes 1, 8 and 13 respectively. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 2992 — RefSeq curated summary.

At a glance

• Gene–disease (curated): polyglucosan body myopathy type 2 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 365 total — 24 pathogenic, 13 likely-pathogenic
• Phenotypes (HPO): 47
• MANE Select transcript: NM_004130

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4699
Approved symbol	GYG1
Name	glycogenin 1
Location	3q24
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000163754
Ensembl biotype	protein_coding
OMIM	603942
Entrez	2992

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 12 protein_coding, 6 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000296048, ENST00000345003, ENST00000461191, ENST00000465547, ENST00000469873, ENST00000473005, ENST00000478067, ENST00000479119, ENST00000483267, ENST00000484197, ENST00000488851, ENST00000492285, ENST00000497528, ENST00000627418, ENST00000852397, ENST00000852398, ENST00000942925, ENST00000942926, ENST00000942927

RefSeq mRNA: 3 — MANE Select: NM_004130 NM_001184720, NM_001184721, NM_004130

CCDS: CCDS3139, CCDS54654, CCDS54655

Canonical transcript exons

ENST00000345003 — 8 exons

Exon	Start	End
ENSE00001077952	149026452	149026502
ENSE00001077958	148996742	148996904
ENSE00001906035	148991540	148991647
ENSE00003264502	149024053	149024272
ENSE00003586773	149009276	149009402
ENSE00003616909	148994142	148994277
ENSE00003790942	148996302	148996476
ENSE00003898249	149026760	149031775

Expression profiles

Bgee: expression breadth ubiquitous, 304 present calls, max score 99.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.0662 / max 539.8263, expressed in 1819 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
39134	33.6146	1812
39133	4.9380	1716
202967	1.8509	1235
202968	0.6627	425

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
biceps brachii	UBERON:0001507	99.62	gold quality
deltoid	UBERON:0001476	99.58	gold quality
gluteal muscle	UBERON:0002000	99.56	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.56	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.50	gold quality
tibialis anterior	UBERON:0001385	99.47	gold quality
oocyte	CL:0000023	99.38	gold quality
triceps brachii	UBERON:0001509	99.37	gold quality
body of tongue	UBERON:0011876	99.36	gold quality
skeletal muscle tissue	UBERON:0001134	99.34	gold quality
vastus lateralis	UBERON:0001379	99.34	gold quality
quadriceps femoris	UBERON:0001377	99.32	gold quality
secondary oocyte	CL:0000655	99.20	gold quality
gastrocnemius	UBERON:0001388	99.17	gold quality
diaphragm	UBERON:0001103	99.15	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.12	gold quality
male germ cell	CL:0000015	99.02	gold quality
sperm	CL:0000019	99.00	gold quality
muscle organ	UBERON:0001630	98.96	gold quality
skeletal muscle organ	UBERON:0014892	98.96	gold quality
adult organism	UBERON:0007023	98.84	gold quality
heart right ventricle	UBERON:0002080	98.83	gold quality
muscle of leg	UBERON:0001383	98.81	gold quality
muscle tissue	UBERON:0002385	98.76	gold quality
parotid gland	UBERON:0001831	98.54	gold quality
saphenous vein	UBERON:0007318	98.52	gold quality
trabecular bone tissue	UBERON:0002483	98.50	gold quality
left ventricle myocardium	UBERON:0006566	98.38	gold quality
endothelial cell	CL:0000115	98.26	gold quality
type B pancreatic cell	CL:0000169	98.26	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	33.87
E-MTAB-9801	yes	6.59
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting GYG1, 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-3065-5P	99.97	71.56	3281
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-190A-5P	99.54	71.45	933
HSA-MIR-190B-5P	99.54	71.40	925
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-505-3P	99.19	69.71	896
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-194-5P	99.01	69.65	1465
HSA-MIR-4764-5P	98.88	65.53	894
HSA-MIR-4724-5P	98.87	67.75	1324
HSA-MIR-3149	98.77	67.13	1639
HSA-MIR-11399	98.71	65.69	869
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-6882-3P	98.23	67.01	1119
HSA-MIR-1301-5P	98.09	66.62	495
HSA-MIR-6502-5P	98.09	66.73	495
HSA-MIR-6730-5P	98.03	68.12	1299
HSA-MIR-3159	97.94	66.79	1098
HSA-MIR-1285-3P	97.72	67.02	1932

Literature-anchored findings (GeneRIF, showing 13)

• Results show that glycogenin becomes inactivated with glycogen catabolism and that this event coincides with an increase in glycogenin gene expression as exercise and glycogenolysis progress. (PMID:15860684)
• during recovery from prolonged exhaustive exercise, glycogenin mRNA and protein content and activity increase in muscle (PMID:15870102)
• GN-1 is conserved, possibly as very small, or nascent, granules when glycogen concentration is low. This would provide the ability to rapidly restore glycogen during early recovery. (PMID:17311895)
• results explain the glycogen depletion in the patient expressing only Thr83Met glycogenin-1 and why heterozygous carriers without clinical symptoms show a small proportion of unglucosylated glycogenin-1 (PMID:22198226)
• The glucosylation of glycogenin-2 was enhanced to 2-4 glucose units by the co-presence of enzymatically active glycogenin-1. (PMID:24239874)
• Depletion of glycogenin-1 and impaired interaction with glycogen synthase underlies a new form of glycogen storage disease. (PMID:25272951)
• This study found a single homozygous intronic mutation of GYG1 harbored by five patients, who, except for two siblings, appear to be unrelated but all five live in central or south Sardinian villages. (PMID:26652229)
• We present functional evidence for the pathogenicity of a novel GYG1 missense mutation located in the substrate binding domain. (PMID:29143313)
• we screened the susceptibility loci for Myocardial infarction (MI) using exome sequencing and validated candidate variants in replication sets. We identified that three genes (GYG1, DIS3L and DDRGK1) were associated with MI at the discovery and replication stages. (PMID:29321365)
• palladium-mediated enzyme activation suggests multiphase initiation of glycogenesis (PMID:30356213)
• Glycogenin is at the core of glycogen’s structure and initiates its glucopolymerization.[review] (PMID:31689353)
• Crystal structure and mutational analysis of the human TRIM7 B30.2 domain provide insights into the molecular basis of its binding to glycogenin-1. (PMID:33989636)
• The structural mechanism of human glycogen synthesis by the GYS1-GYG1 complex. (PMID:35793618)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gyg1a	ENSDARG00000011934
danio_rerio	gyg1b	ENSDARG00000059391
mus_musculus	Gyg1	ENSMUSG00000019528
rattus_norvegicus	Gyg1	ENSRNOG00000011146
drosophila_melanogaster	Gyg	FBGN0265191

Paralogs (1): GYG2 (ENSG00000056998)

Protein

Protein identifiers

Glycogenin-1 — P46976 (reviewed: P46976)

All UniProt accessions (5): C9J7C7, C9J8R8, C9JQ42, P46976, G5E9W8

UniProt curated annotations — full annotation on UniProt →

Function. Glycogenin participates in the glycogen biosynthetic process along with glycogen synthase and glycogen branching enzyme. It catalyzes the formation of a short alpha (1,4)-glucosyl chain covalently attached via a glucose 1-O-tyrosyl linkage to internal tyrosine residues and these chains act as primers for the elongation reaction catalyzed by glycogen synthase.

Subunit / interactions. Part of the GYS1-GYG1 complex, a heterooctamer composed of a tetramer of GYS1 and 2 dimers of GYG1, where each GYS1 protomer binds to one GYG1 subunit (via GYG1 C-terminus); the GYS1 tetramer may dissociate from GYG1 dimers to continue glycogen polymerization on its own. May also form a heterooctamer complex with GYS2 (via GYG1 C-terminus).

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Highly expressed in skeletal muscle and heart, with lower levels in brain, lung, kidney and pancreas.

Post-translational modifications. Self-glycosylated by the transfer of glucose residues from UDP-glucose to itself, forming an alpha-1,4-glycan of around 10 residues attached to Tyr-195. Phosphorylated.

Disease relevance. Glycogen storage disease 15 (GSD15) [MIM:613507] A metabolic disorder resulting in muscle weakness, associated with the glycogen depletion in skeletal muscle, and cardiac arrhythmia, associated with the accumulation of abnormal storage material in the heart. The skeletal muscle shows a marked predominance of slow-twitch, oxidative muscle fibers and mitochondrial proliferation. The disease is caused by variants affecting the gene represented in this entry. Polyglucosan body myopathy 2 (PGBM2) [MIM:616199] A glycogen storage disease characterized by polyglucosan accumulation in muscle, and skeletal myopathy without cardiac involvement. Most patients manifest slowly progressive, hip girdle, shoulder girdle, and/or hand and leg muscle weakness. Polyglucosan contains abnormally long and poorly branched glucosyl chains and is variably resistant to digestion by alpha-amylase. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by palladium ions.

Cofactor. Divalent metal ions. Required for self-glucosylation. Manganese is the most effective.

Pathway. Glycan biosynthesis; glycogen biosynthesis.

Similarity. Belongs to the glycosyltransferase 8 family. Glycogenin subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P46976-1	GN-1L	yes
P46976-2	GN-1
P46976-3	GN-1S

RefSeq proteins (3): NP_001171649, NP_001171650, NP_004121* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002495	Glyco_trans_8	Family
IPR029044	Nucleotide-diphossugar_trans	Homologous_superfamily
IPR050587	GNT1/Glycosyltrans_8	Family

Pfam: PF01501

Enzyme classification (BRENDA):

• EC 2.4.1.186 — glycogenin glucosyltransferase (BRENDA: 13 organisms, 50 substrates, 15 inhibitors, 5 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
UDP-GLUCOSE	0.002–0.0044	2
N-DODECYL-BETA-D-MALTOSIDE	0.1	1
P-NITROPHENYL-ALPHA-MALTOSIDE	3	1

Catalyzed reactions (Rhea), 2 shown:

• L-tyrosyl-[glycogenin] + UDP-alpha-D-glucose = alpha-D-glucosyl-L-tyrosyl-[glycogenin] + UDP + H(+) (RHEA:23360)
• 1,4-alpha-D-glucosyl-L-tyrosyl-[glycogenin] + UDP-alpha-D-glucose = 1,4-alpha-D-glucosyl-L-tyrosyl-[glycogenin] + UDP + H(+) (RHEA:56560)

UniProt features (78 total): binding site 30, helix 18, strand 14, sequence variant 3, turn 3, modified residue 2, splice variant 2, initiator methionine 1, chain 1, region of interest 1, site 1, glycosylation site 1, mutagenesis site 1

Structure

Experimental structures (PDB)

23 structures.

PDB	Method	Resolution (Å)
3U2U	X-RAY DIFFRACTION	1.45
3U2V	X-RAY DIFFRACTION	1.5
3U2W	X-RAY DIFFRACTION	1.68
7OVX	X-RAY DIFFRACTION	1.7
3U2X	X-RAY DIFFRACTION	1.77
3T7M	X-RAY DIFFRACTION	1.8
3RMV	X-RAY DIFFRACTION	1.82
3T7O	X-RAY DIFFRACTION	1.85
3RMW	X-RAY DIFFRACTION	1.93
3Q4S	X-RAY DIFFRACTION	1.98
3T7N	X-RAY DIFFRACTION	1.98
3U2T	X-RAY DIFFRACTION	2.05
6EQJ	X-RAY DIFFRACTION	2.18
3QVB	X-RAY DIFFRACTION	2.26
6EQL	X-RAY DIFFRACTION	2.38
7ZBN	ELECTRON MICROSCOPY	2.62
7Q0B	ELECTRON MICROSCOPY	3
7Q13	ELECTRON MICROSCOPY	3
8CVX	ELECTRON MICROSCOPY	3.5
8CVZ	ELECTRON MICROSCOPY	3.52
8CVY	ELECTRON MICROSCOPY	3.6
7Q12	ELECTRON MICROSCOPY	3.7
7Q0S	ELECTRON MICROSCOPY	4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P46976-F1	84.90	0.59

Functional residue map

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

Catalytic / active sites (1): 86 (important for catalytic activity)

Ligand- & substrate-binding residues (30): 15; 77; 77; 86; 102; 102; 102; 103; 103; 104; 104; 104 …

Post-translational modifications (2): 2, 44

Glycosylation sites (1): 195

Mutagenesis-validated functional residues (1):

Position	Phenotype
195	loss of glucosylation.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-3322077	Glycogen synthesis
R-HSA-3785653	Myoclonic epilepsy of Lafora
R-HSA-3814836	Glycogen storage disease type XV (GYG1)
R-HSA-3828062	Glycogen storage disease type 0 (muscle GYS1)
R-HSA-5357609	Glycogen storage disease type II (GAA)
R-HSA-6798695	Neutrophil degranulation
R-HSA-70221	Glycogen breakdown (glycogenolysis)

MSigDB gene sets: 326 (showing top): ELVIDGE_HYPOXIA_DN, MODULE_52, SHEPARD_BMYB_MORPHOLINO_UP, chr3q24, REACTOME_INNATE_IMMUNE_SYSTEM, MOOTHA_GLYCOGEN_METABOLISM, GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS, GOCC_SECRETORY_GRANULE, MODULE_151, MEF2_02, MODULE_16, USF_C, CEBPB_01, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, MODULE_118

GO Biological Process (2): glycogen biosynthetic process (GO:0005978), obsolete glycogen biosynthetic process via UDP-glucose (GO:0160249)

GO Molecular Function (7): glycogenin glucosyltransferase activity (GO:0008466), glycosyltransferase activity (GO:0016757), manganese ion binding (GO:0030145), protein homodimerization activity (GO:0042803), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (8): extracellular region (GO:0005576), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), secretory granule lumen (GO:0034774), lysosomal lumen (GO:0043202), ficolin-1-rich granule lumen (GO:1904813)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Glycogen storage diseases	4
Glycogen metabolism	2
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
glycogen metabolic process	1
glucan biosynthetic process	1
UDP-glucosyltransferase activity	1
transferase activity	1
transition metal ion binding	1
identical protein binding	1
protein dimerization activity	1
binding	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
secretory granule	1
cytoplasmic vesicle lumen	1
lysosome	1
vacuolar lumen	1
intracellular organelle lumen	1
ficolin-1-rich granule	1

Protein interactions and networks

STRING

1167 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GYG1	TRIM7	Q9C029	938
GYG1	AMY1B	P04745	886
GYG1	AMY2A	P04746	884
GYG1	GYS1	P13807	838
GYG1	AMY2B	P19961	838
GYG1	GBE1	Q04446	793
GYG1	AGL	P35573	724
GYG1	PYGM	P11217	677
GYG1	GYS2	P54840	677
GYG1	PYGL	P06737	666
GYG1	PYGB	P11216	656
GYG1	TRAT1	Q6PIZ9	601
GYG1	EPM2A	O95278	566
GYG1	UGP2	Q16851	563
GYG1	ENGASE	Q8NFI3	541

IntAct

58 interactions, top by confidence:

A	B	Type	Score
PIK3CB	PIK3R2	psi-mi:“MI:0914”(association)	0.860
GYS1	GYG1	psi-mi:“MI:0915”(physical association)	0.840
GYG1	GYS1	psi-mi:“MI:0915”(physical association)	0.840
STBD1	GABARAP	psi-mi:“MI:0914”(association)	0.760
PRKAB2	GYS1	psi-mi:“MI:0914”(association)	0.730
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
GYG2	GYS1	psi-mi:“MI:0914”(association)	0.660
GYS1	GYG2	psi-mi:“MI:0914”(association)	0.660
PRKAB2	PRKAB2	psi-mi:“MI:0914”(association)	0.550
PRKCA	PRKCB	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
STBD1	MID1	psi-mi:“MI:0914”(association)	0.530
GBE1	GYS1	psi-mi:“MI:0914”(association)	0.530
PYGB	STBD1	psi-mi:“MI:0914”(association)	0.530
GYG1	Gys1	psi-mi:“MI:0915”(physical association)	0.400
GYG1	GYS1	psi-mi:“MI:0915”(physical association)	0.370
CD6	GYG1	psi-mi:“MI:0915”(physical association)	0.370
GYG1	CMSS1	psi-mi:“MI:0915”(physical association)	0.370
GYG1	POM121	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
SDCCAG8	MYO1C	psi-mi:“MI:0914”(association)	0.350
ULK1	HNRNPCL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (75): GYS1 (Two-hybrid), GYG1 (Affinity Capture-MS), GYG1 (Affinity Capture-MS), GYG1 (Affinity Capture-MS), GYG1 (Affinity Capture-MS), GYS1 (Two-hybrid), GYG1 (Affinity Capture-MS), POM121 (Two-hybrid), ESD (Co-fractionation), GGT1 (Co-fractionation), GYG1 (Co-fractionation), GYG1 (Co-fractionation), GYG1 (Affinity Capture-MS), GYG1 (Affinity Capture-MS), GYG1 (Affinity Capture-MS)

ESM2 similar proteins: A6ZPQ2, A6ZQE9, A6ZQJ2, B3LQ40, C4R360, C4R941, C7G304, F4KED2, H2KYQ5, O08730, O15488, O22693, O22893, O43061, O43062, O80518, P12954, P13280, P15938, P25569, P36090, P38274, P40360, P46976, P46982, P47011, P53059, P53745, P87056, Q09679, Q09680, Q09681, Q4PSY4, Q59KJ7, Q59R28, Q59YS7, Q59ZI3, Q5A687, Q5AD72, Q5AP90

Diamond homologs: A6ZQJ2, A7A018, C4R941, H2KYQ5, J9VPM2, O08730, O15488, P13280, P36143, P46976, P47011, Q9LSB1, Q9R062, V5ILS6, Q8GWW4, F4HZC3, F4JMI5, Q8GWB7, Q8VZP6, Q9FZ37, Q8W4A7, O43062, O43061, Q09680, Q6CT96, Q9XGN3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 61 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
VEGFA-VEGFR2 Pathway	5	17.4×	1e-03
Macroautophagy	6	17.3×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	24
Likely pathogenic	13
Uncertain significance	145
Likely benign	127
Benign	33

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
162664	NM_004130.4(GYG1):c.749G>A (p.Trp250Ter)	Pathogenic
162665	NM_004130.4(GYG1):c.487del (p.Asp163fs)	Pathogenic
1879594	NM_004130.4(GYG1):c.646C>T (p.Arg216Ter)	Pathogenic
1906288	NM_004130.4(GYG1):c.683del (p.Thr228fs)	Pathogenic
1946636	NM_004130.4(GYG1):c.10C>T (p.Gln4Ter)	Pathogenic
2007595	NM_004130.4(GYG1):c.844dup (p.Tyr282fs)	Pathogenic
2045936	NM_004130.4(GYG1):c.82C>T (p.Gln28Ter)	Pathogenic
2048341	NM_004130.4(GYG1):c.352_353del (p.Glu118fs)	Pathogenic
2081385	NC_000003.12:g.148996742del	Pathogenic
2926005	NM_004130.4(GYG1):c.26dup (p.Thr10fs)	Pathogenic
2927980	NM_004130.4(GYG1):c.844_845insG (p.Tyr282Ter)	Pathogenic
2929759	NM_004130.4(GYG1):c.384G>A (p.Trp128Ter)	Pathogenic
2949894	NM_004130.4(GYG1):c.93dup (p.Thr32fs)	Pathogenic
2952434	NM_004130.4(GYG1):c.221T>A (p.Leu74Ter)	Pathogenic
2953065	NM_004130.4(GYG1):c.490C>T (p.Gln164Ter)	Pathogenic
3246935	NC_000003.11:g.(?148709428)(148709454_?)del	Pathogenic
3754301	NM_004130.4(GYG1):c.773dup (p.Leu258fs)	Pathogenic
3763958	NM_004130.4(GYG1):c.438C>A (p.Tyr146Ter)	Pathogenic
4784695	NM_004130.4(GYG1):c.561T>G (p.Tyr187Ter)	Pathogenic
4785162	NM_004130.4(GYG1):c.797_798dup (p.Val267fs)	Pathogenic
4788300	NM_004130.4(GYG1):c.35del (p.Asn12fs)	Pathogenic
569450	NM_004130.4(GYG1):c.154G>T (p.Glu52Ter)	Pathogenic
850059	NM_004130.4(GYG1):c.819T>A (p.Tyr273Ter)	Pathogenic
855451	NM_004130.4(GYG1):c.631del (p.Val211fs)	Pathogenic
1477393	NM_004130.4(GYG1):c.3G>C (p.Met1Ile)	Likely pathogenic
1516792	NM_004130.4(GYG1):c.481+2T>C	Likely pathogenic
2637494	NM_004130.4(GYG1):c.7+2T>C	Likely pathogenic
2935601	NM_004130.4(GYG1):c.482-1G>C	Likely pathogenic
3763584	NM_004130.4(GYG1):c.319-2_319-1insC	Likely pathogenic
3779717	NM_004130.4(GYG1):c.164_165del (p.Val54_Phe55insTer)	Likely pathogenic

SpliceAI

1232 predictions. Top by Δscore:

Variant	Effect	Δscore
3:148994133:T:TA	acceptor_gain	1.0000
3:148994136:A:AG	acceptor_gain	1.0000
3:148994137:T:G	acceptor_gain	1.0000
3:148994139:A:AG	acceptor_gain	1.0000
3:148994140:A:AG	acceptor_gain	1.0000
3:148994141:G:GG	acceptor_gain	1.0000
3:148994141:GATCA:G	acceptor_gain	1.0000
3:149009401:GT:G	donor_gain	1.0000
3:149009403:G:GG	donor_gain	1.0000
3:149024045:C:G	acceptor_gain	1.0000
3:149024270:GTG:G	donor_gain	1.0000
3:149024273:G:GA	donor_loss	1.0000
3:148994137:TTAA:T	acceptor_loss	0.9900
3:148994138:TAAGA:T	acceptor_loss	0.9900
3:148994139:AAG:A	acceptor_loss	0.9900
3:148994141:GAT:G	acceptor_gain	0.9900
3:148994276:AG:A	donor_loss	0.9900
3:148994277:GG:G	donor_loss	0.9900
3:148994279:T:A	donor_loss	0.9900
3:148996301:GAAAA:G	acceptor_gain	0.9900
3:148996901:GATG:G	donor_gain	0.9900
3:149009270:TTTTA:T	acceptor_loss	0.9900
3:149009271:TTTAG:T	acceptor_loss	0.9900
3:149009272:TTAGG:T	acceptor_loss	0.9900
3:149009273:TA:T	acceptor_loss	0.9900
3:149009274:A:AT	acceptor_loss	0.9900
3:149009274:AGGT:A	acceptor_gain	0.9900
3:149009275:GGT:G	acceptor_gain	0.9900
3:149009275:GGTG:G	acceptor_gain	0.9900
3:149024044:A:AG	acceptor_gain	0.9900

AlphaMissense

2293 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:148996416:G:C	K86N	0.999
3:148996416:G:T	K86N	0.999
3:148996469:A:T	D104V	0.999
3:148996805:T:A	W128R	0.999
3:148996805:T:C	W128R	0.999
3:148996822:T:A	N133K	0.999
3:148996822:T:G	N133K	0.999
3:149024078:C:G	H212D	0.999
3:149024102:T:A	W220R	0.999
3:149024102:T:C	W220R	0.999
3:149026855:G:C	W325C	0.999
3:149026855:G:T	W325C	0.999
3:148996426:T:A	W90R	0.998
3:148996426:T:C	W90R	0.998
3:148996463:A:T	D102V	0.998
3:148996468:G:C	D104H	0.998
3:148996818:T:C	F132S	0.998
3:149024096:A:G	K218E	0.998
3:149024098:A:C	K218N	0.998
3:149024098:A:T	K218N	0.998
3:149026853:T:A	W325R	0.998
3:149026853:T:C	W325R	0.998
3:148994186:G:C	G18R	0.997
3:148996452:T:G	C98W	0.997
3:148996470:T:A	D104E	0.997
3:148996470:T:G	D104E	0.997
3:148996788:C:A	A122E	0.997
3:148996807:G:C	W128C	0.997
3:148996807:G:T	W128C	0.997
3:148996809:C:A	P129H	0.997

dbSNP variants (sampled 300 via entrez): RS1000038641 (3:149003764 T>G), RS1000175190 (3:149028260 C>A), RS1000188219 (3:148995468 T>C), RS1000310753 (3:148997416 A>G), RS1000374919 (3:148990566 A>G), RS1000377479 (3:149013674 A>G), RS1000405725 (3:148991960 G>A,T), RS1000419903 (3:149017788 A>G,T), RS1000425379 (3:149030745 C>T), RS1000509323 (3:149029686 T>A,C), RS1000549374 (3:149009946 T>C), RS1000559674 (3:148997054 T>TG,TGTG,TGTGTG,TGTGTGTG), RS1000580928 (3:148996550 A>G), RS1000623875 (3:149029341 C>A,T), RS1000689648 (3:148993312 G>A,C)

Disease associations

OMIM: gene MIM:603942 | disease phenotypes: MIM:613507, MIM:616199, MIM:232200

GenCC curated gene-disease

Disease	Classification	Inheritance
polyglucosan body myopathy type 2	Definitive	Autosomal recessive
glycogen storage disease XV	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
polyglucosan body myopathy type 2	Definitive	AR

Mondo (3): glycogen storage disease XV (MONDO:0013291), polyglucosan body myopathy type 2 (MONDO:0014526), disorder of glycogen metabolism (MONDO:0002412)

Orphanet (3): Glycogen storage disease with severe cardiomyopathy due to glycogenin deficiency (Orphanet:263297), Polyglucosan body myopathy type 2 (Orphanet:456369), Glycogen storage disease (Orphanet:79201)

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000819	Diabetes mellitus
HP:0000821	Hypothyroidism
HP:0001288	Gait disturbance
HP:0001324	Muscle weakness
HP:0001638	Cardiomyopathy
HP:0001663	Ventricular fibrillation
HP:0001714	Ventricular hypertrophy
HP:0001962	Palpitations
HP:0002321	Vertigo
HP:0002460	Distal muscle weakness
HP:0002875	Exertional dyspnea
HP:0003199	Decreased muscle mass
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003325	Limb-girdle muscle weakness
HP:0003458	EMG: myopathic abnormalities
HP:0003484	Upper limb muscle weakness
HP:0003547	Shoulder girdle muscle weakness
HP:0003584	Late onset
HP:0003596	Middle age onset
HP:0003677	Slowly progressive
HP:0003691	Scapular winging
HP:0003722	Neck flexor weakness
HP:0003749	Pelvic girdle muscle weakness
HP:0003803	Type 1 muscle fiber predominance
HP:0004751	Paroxysmal ventricular tachycardia
HP:0004756	Ventricular tachycardia
HP:0005144	Ventricular septal hypertrophy
HP:0008946	Pelvic girdle amyotrophy
HP:0009023	Abdominal wall muscle weakness

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006479_32	Diverticular disease	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009959	diverticular disease

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D006008	Glycogen Storage Disease	C16.320.565.202.449; C18.452.648.202.449

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	6
bisphenol A	decreases expression, increases expression	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
Acetaminophen	increases expression, affects cotreatment	2
Doxorubicin	affects expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	increases expression	2
Cyclosporine	increases expression	2
2,4,6-tribromophenol	decreases expression	1
arsenite	affects binding, increases reaction	1
tetrabromobisphenol A	decreases expression	1
gossypol acetic acid	decreases expression	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases methylation	1
jinfukang	decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Dactinomycin	affects cotreatment, increases secretion	1
Dexamethasone	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02782741	PHASE3	COMPLETED	Study to Compare the Efficacy and Safety of Enzyme Replacement Therapies Avalglucosidase Alfa and Alglucosidase Alfa Administered Every Other Week in Patients With Late-onset Pompe Disease Who Have Not Been Previously Treated for Pompe Disease
NCT04808505	PHASE3	RECRUITING	A Study to Evaluate the Safety, Efficacy, PK, PD and Immunogenicity of Cipaglucosidase Alfa/Miglustat in IOPD Subjects Aged 0 to <18
NCT00765414	PHASE2	COMPLETED	Extension Study of Long-term Safety and Efficacy of Myozyme for a Single Patient With Pompe Disease Who Were Previously Enrolled in Genzyme Sponsored ERT Studies.
NCT02032524	PHASE2	COMPLETED	Avalglucosidase Alfa Extension Study
NCT03019406	PHASE2	ACTIVE_NOT_RECRUITING	A Study to Assess Safety and Efficacy of Avalglucosidase Alfa Administered Every Other Week in Pediatric Patients With Infantile-onset Pompe Disease Previously Treated With Alglucosidase Alfa
NCT06130228	PHASE2	UNKNOWN	Nutritional Therapy in Late-onset Pompe Disease
NCT06795152	Not specified	RECRUITING	Rare Glycogen Storage Diseases Natural History Study
NCT05095727	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study of mRNA-3745 in Adult and Pediatric Participants With Glycogen Storage Disease Type 1a (GSD1a)
NCT00001342	Not specified	COMPLETED	Study of Glycogen Storage Disease and Associated Disorders
NCT00566878	Not specified	COMPLETED	Pompe Lactation Sub-Registry
NCT01461304	Not specified	NO_LONGER_AVAILABLE	Compassionate Use of Triheptanoin (C7) for Inherited Disorders of Energy Metabolism
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT02057731	Not specified	COMPLETED	Study of Glycogen Storage Disease Expression in Carriers
NCT02176096	Not specified	COMPLETED	Comparison of the Effect of a Novel Starch (Glycosade) Versus Gastrostomy Tube-Dextrose Infusion on Overnight Euglycaemia Control in Children With Glycogen Storage Disease Type I: Open Label Demonstration Trial
NCT02318966	Not specified	COMPLETED	Glycosade v UCCS in the Dietary Management of Hepatic GSD
NCT02338817	Not specified	TERMINATED	Clinical Evaluation of a Non-Invasive Hypoglycemia Detector in a Glycogen Storage Disease Population
NCT02385162	Not specified	WITHDRAWN	Biomarker for Glycogen Storage Diseases (BioGlycogen)
NCT03255213	Not specified	COMPLETED	Lingual Muscle Training in Late-Onset Pompe Disease (LOPD)
NCT03564561	Not specified	RECRUITING	Natural History of Pompe Disease
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT04292938	Not specified	COMPLETED	McArdle Disease Treatment by Ketogenic Diet
NCT04399694	Not specified	COMPLETED	Identification and Characterization of Novel Non-Coding Variants That Contribute to Genetic Disorders
NCT04929002	Not specified	ACTIVE_NOT_RECRUITING	Carbon-13 Magnetic Resonance Spectroscopy in Glycogen Storage Diseases
NCT05199246	Not specified	COMPLETED	Assessment of Safety and Acute Effects of a Lower-limb Powered Dermoskeleton in Patients With Neuromuscular Disorders
NCT05200702	Not specified	COMPLETED	Assessment of Safety and Acute Effects of a Knee-hip Powered Soft Exoskeleton in Patients With Neuromuscular Disorders
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT06396546	Not specified	RECRUITING	‘Glycogen Storage Diseases (GSDs) in Indian Children- Establishing an Indian GSD (I-GSD) Registry’
NCT06813443	Not specified	RECRUITING	Characterization of Patients With Cardiomyopathy to Identify Critical Patients Candidates for Cardiac Transplantation
NCT07136844	Not specified	RECRUITING	Gait Analysis Parameter and Upper Limb Evaluation in Adult Patients With Neurological or Metabolic Pathology
NCT07336394	Not specified	RECRUITING	Precision Diagnosis and Risk Stratification of Rare Cardiomyopathies Based on Novel Cardiac Magnetic Resonance Techniques
NCT07614139	Not specified	COMPLETED	Continuous Glucose Monitoring Alerts, Accuracy, and Patient Outcomes in Adults With Inherited Metabolic Disorders