GYG1

glycogenin 1, the group of Glycosyltransferase family 8

Basic information

Region (hg38): 3:148991407-149031775

Previous symbols: [ "GYG" ]

Links

ENSG00000163754 ∙ NCBI:2992 ∙ OMIM:603942 ∙ HGNC:4699 ∙ Uniprot:P46976 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glycogen storage disease XV (Strong), mode of inheritance: AR
• polyglucosan body myopathy type 2 (Definitive), mode of inheritance: AR
• glycogen storage disease XV (Strong), mode of inheritance: AR
• polyglucosan body myopathy type 2 (Strong), mode of inheritance: AR
• glycogen storage disease XV (Supportive), mode of inheritance: AR
• polyglucosan body myopathy type 2 (Supportive), mode of inheritance: AR
• glycogen storage disease XV (Strong), mode of inheritance: AR
• polyglucosan body myopathy type 2 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycogen storage disease XV	AR	Cardiovascular	Surveillance to allow early diagnosis and treatment of cardiac complications (eg, treatment of heart failure and arrhythmias via medical management and ICD placement) may be beneficial	Biochemical; Cardiovascular; Musculoskeletal	20357282; 25272951

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GYG1 gene.

• Glycogen storage disease XV;Polyglucosan body myopathy type 2 (9 variants)
• Polyglucosan body myopathy type 2;Glycogen storage disease XV (8 variants)
• not provided (2 variants)
• Glycogen storage disease XV (1 variants)
• Polyglucosan body myopathy type 2 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GYG1 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	40	4	45
missense			103	11	1	115
nonsense	9	1	3			13
start loss		1	1			2
frameshift	8	3				11
inframe indel			3			3
splice donor/acceptor (+/-2bp)		4	1			5
splice region		1	3	5		9
non coding			1	42	23	66
Total	17	9	113	93	28

Highest pathogenic variant AF is 0.000420

Variants in GYG1

This is a list of pathogenic ClinVar variants found in the GYG1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-148991479-A-G			Likely benign (May 19, 2019)
3-148991537-G-A			Benign (Sep 18, 2018)
3-148991568-C-G			Likely benign (May 15, 2019)
3-148991599-CA-C		not specified	Likely benign (Nov 18, 2016)
3-148991642-T-A		Glycogen storage disease XV;Polyglucosan body myopathy type 2	Uncertain significance (Oct 13, 2022)
3-148991643-G-C		Polyglucosan body myopathy type 2;Glycogen storage disease XV	Likely pathogenic (Jun 30, 2021)
3-148991645-C-G		Glycogen storage disease XV;Polyglucosan body myopathy type 2	Uncertain significance (Mar 14, 2022)
3-148991648-G-A		Polyglucosan body myopathy type 2 • Polyglucosan body myopathy type 2;Glycogen storage disease XV	Likely pathogenic (Dec 09, 2023)
3-148991649-T-C		Polyglucosan body myopathy type 2 • Glycogen storage disease XV;Polyglucosan body myopathy type 2	Likely pathogenic (Oct 26, 2023)
3-148991655-C-T		Polyglucosan body myopathy type 2;Glycogen storage disease XV	Likely benign (Nov 14, 2022)
3-148991664-C-G		Glycogen storage disease XV;Polyglucosan body myopathy type 2	Likely benign (Sep 08, 2023)
3-148991743-C-G			Benign (Jun 14, 2018)
3-148991963-G-A			Benign (Jun 14, 2018)
3-148994127-T-C		Glycogen storage disease XV;Polyglucosan body myopathy type 2	Likely benign (Jul 04, 2021)
3-148994129-T-C		Glycogen storage disease XV;Polyglucosan body myopathy type 2	Likely benign (Nov 22, 2022)
3-148994144-C-T		Glycogen storage disease XV;Polyglucosan body myopathy type 2	Pathogenic (Apr 03, 2023)
3-148994148-C-T			Uncertain significance (Jun 01, 2024)
3-148994159-C-G		Polyglucosan body myopathy type 2;Glycogen storage disease XV	Uncertain significance (Jun 10, 2021)
3-148994159-C-T		Polyglucosan body myopathy type 2;Glycogen storage disease XV	Likely benign (Oct 17, 2023)
3-148994159-C-CT		Polyglucosan body myopathy type 2;Glycogen storage disease XV	Pathogenic (Oct 17, 2023)
3-148994170-C-G		Glycogen storage disease XV;Polyglucosan body myopathy type 2	Uncertain significance (Dec 02, 2021)
3-148994179-C-T		Polyglucosan body myopathy type 2;Glycogen storage disease XV	Likely benign (Jul 22, 2022)
3-148994180-G-A		Polyglucosan body myopathy type 2;Glycogen storage disease XV • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 06, 2024)
3-148994189-G-T		Inborn genetic diseases • Glycogen storage disease XV;Polyglucosan body myopathy type 2	Uncertain significance (Jul 06, 2022)
3-148994190-C-T		Polyglucosan body myopathy type 2;Glycogen storage disease XV	Uncertain significance (Feb 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GYG1	protein_coding	protein_coding	ENST00000345003	8	36292

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.83e-12	0.0553	125568	0	180	125748	0.000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0645	185	187	0.987	0.00000949	2283
Missense in Polyphen		79	76.446	1.0334		968
Synonymous	0.703	68	75.8	0.897	0.00000435	680
Loss of Function	0.211	18	19.0	0.948	0.00000101	211

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000797	0.000795
Ashkenazi Jewish	0.00	0.00
East Asian	0.000435	0.000435
Finnish	0.000554	0.000554
European (Non-Finnish)	0.00103	0.00103
Middle Eastern	0.000435	0.000435
South Asian	0.000490	0.000490
Other	0.000816	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Self-glucosylates, via an inter-subunit mechanism, to form an oligosaccharide primer that serves as substrate for glycogen synthase.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:20357282}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:25272951}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Starch and sucrose metabolism - Homo sapiens (human);Insulin Signaling;Glycogen Metabolism;Neutrophil degranulation;Metabolism of carbohydrates;Innate Immune System;Immune System;Metabolism;glycogen biosynthesis;Glycogen breakdown (glycogenolysis);Glycogen synthesis;Glycogen metabolism (Consensus)

Recessive Scores

• pRec: 0.164

Intolerance Scores

• loftool: 0.977
• rvis_EVS: -0.07
• rvis_percentile_EVS: 48.54

Haploinsufficiency Scores

• pHI: 0.173
• hipred: N
• hipred_score: 0.396
• ghis: 0.471

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.399

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gyg
• Phenotype: 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Gene ontology

• Biological process: glycogen biosynthetic process;neutrophil degranulation
• Cellular component: extracellular region;cytosol;membrane;secretory granule lumen;lysosomal lumen;ficolin-1-rich granule lumen
• Molecular function: protein binding;glycogenin glucosyltransferase activity;metal ion binding;UDP-alpha-D-glucose:glucosyl-glycogenin alpha-D-glucosyltransferase activity