GYS1

glycogen synthase 1, the group of Glycosyl transferases group 1 domain containing

Basic information

Region (hg38): 19:48968129-48993310

Previous symbols: [ "GYS" ]

Links

ENSG00000104812 ∙ NCBI:2997 ∙ OMIM:138570 ∙ HGNC:4706 ∙ Uniprot:P13807 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glycogen storage disease due to muscle and heart glycogen synthase deficiency (Strong), mode of inheritance: AR
• glycogen storage disease due to muscle and heart glycogen synthase deficiency (Strong), mode of inheritance: AR
• glycogen storage disease due to muscle and heart glycogen synthase deficiency (Strong), mode of inheritance: AR
• glycogen storage disease due to muscle and heart glycogen synthase deficiency (Supportive), mode of inheritance: AR
• glycogen storage disease due to muscle and heart glycogen synthase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycogen storage disease, type 0, muscle	AR	Cardiovascular	Individuals may manifest with findings such as hypertrophic cardiomyopathy and sudden cardiac arrest and death, and treatment with cardioprotective medications (eg, beta-blockers) has been reported as beneficial	Biochemical; Cardiovascular; Musculoskeletal; Neurologic	17928598; 21958591
An individual with seizures has been described, but it is not clear if this finding was primarily related to the underlying condition

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GYS1 gene.

• Glycogen storage disease due to muscle and heart glycogen synthase deficiency (17 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GYS1 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			7	109	6	122
missense			242	1	1	244
nonsense	7	2	2			11
start loss			1			1
frameshift	8	3	4			15
inframe indel			2			2
splice donor/acceptor (+/-2bp)	2	8	1			11
splice region			10	23	1	34
non coding			22	106	29	157
Total	17	13	281	216	36

Highest pathogenic variant AF is 0.0000197

Variants in GYS1

This is a list of pathogenic ClinVar variants found in the GYS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-48968167-G-C		FTL-related disorder	Benign (Jun 28, 2022)
19-48968171-ACACT-A		Neuroferritinopathy • Glycogen storage disease due to muscle and heart glycogen synthase deficiency • Hereditary hyperferritinemia with congenital cataracts	Conflicting classifications of pathogenicity (Sep 16, 2021)
19-48968244-A-C		Glycogen storage disease due to muscle and heart glycogen synthase deficiency	Uncertain significance (Jan 12, 2018)
19-48968319-G-A		Glycogen storage disease due to muscle and heart glycogen synthase deficiency	Uncertain significance (Jan 12, 2018)
19-48968380-C-T		Hereditary hyperferritinemia with congenital cataracts • Glycogen storage disease due to muscle and heart glycogen synthase deficiency • Neuroferritinopathy	Likely benign (May 20, 2021)
19-48968420-T-C		Neuroferritinopathy • Glycogen storage disease due to muscle and heart glycogen synthase deficiency • Hereditary hyperferritinemia with congenital cataracts • FTL-related disorder	Conflicting classifications of pathogenicity (Jun 17, 2021)
19-48968447-T-C		Hereditary hyperferritinemia with congenital cataracts • Neuroferritinopathy • Glycogen storage disease due to muscle and heart glycogen synthase deficiency	Likely benign (May 12, 2021)
19-48968463-TA-T		Glycogen storage disease due to muscle and heart glycogen synthase deficiency	Uncertain significance (Jun 14, 2016)
19-48968563-G-A		Neuroferritinopathy • Glycogen storage disease due to muscle and heart glycogen synthase deficiency • Hereditary hyperferritinemia with congenital cataracts	Benign/Likely benign (May 12, 2021)
19-48968629-G-A		Neuroferritinopathy • Hereditary hyperferritinemia with congenital cataracts • Glycogen storage disease due to muscle and heart glycogen synthase deficiency • FTL-related disorder	Conflicting classifications of pathogenicity (May 02, 2022)
19-48968677-G-A		Hereditary hyperferritinemia with congenital cataracts • Neuroferritinopathy • Glycogen storage disease due to muscle and heart glycogen synthase deficiency	Likely benign (Jan 12, 2018)
19-48968816-C-T		Glycogen storage disease due to muscle and heart glycogen synthase deficiency	Uncertain significance (Jan 12, 2018)
19-48968823-C-T		Glycogen storage disease due to muscle and heart glycogen synthase deficiency	Uncertain significance (Mar 23, 2018)
19-48968838-C-T		Neuroferritinopathy • Glycogen storage disease due to muscle and heart glycogen synthase deficiency • Hereditary hyperferritinemia with congenital cataracts	Likely benign (May 24, 2021)
19-48968867-T-C		Neuroferritinopathy • Hereditary hyperferritinemia with congenital cataracts • Glycogen storage disease due to muscle and heart glycogen synthase deficiency	Likely benign (Jan 13, 2018)
19-48968875-C-T		Glycogen storage disease due to muscle and heart glycogen synthase deficiency	Uncertain significance (Jan 12, 2018)
19-48968893-G-A		Glycogen storage disease due to muscle and heart glycogen synthase deficiency	Uncertain significance (Jan 13, 2018)
19-48968901-C-T			Likely benign (May 26, 2021)
19-48968918-T-G		Hereditary hyperferritinemia with congenital cataracts • Neuroferritinopathy • Glycogen storage disease due to muscle and heart glycogen synthase deficiency	Conflicting classifications of pathogenicity (Jun 14, 2016)
19-48968921-G-A		FTL-related disorder	Likely benign (Aug 06, 2023)
19-48968931-C-T		Glycogen storage disease due to muscle and heart glycogen synthase deficiency	Uncertain significance (Jan 13, 2018)
19-48968987-C-T		Glycogen storage disease due to muscle and heart glycogen synthase deficiency • Hereditary hyperferritinemia with congenital cataracts • Neuroferritinopathy	Conflicting classifications of pathogenicity (Jun 14, 2016)
19-48969032-C-T		Glycogen storage disease due to muscle and heart glycogen synthase deficiency	Likely benign (Jun 08, 2021)
19-48969059-G-A		Glycogen storage disease due to muscle and heart glycogen synthase deficiency	Uncertain significance (Jan 12, 2018)
19-48969145-G-C		Glycogen storage disease due to muscle and heart glycogen synthase deficiency	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GYS1	protein_coding	protein_coding	ENST00000323798	16	25186

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000291	1.00	125686	0	62	125748	0.000247

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.84	360	472	0.762	0.0000329	4788
Missense in Polyphen		139	181.16	0.76727		1856
Synonymous	0.922	183	200	0.917	0.0000150	1445
Loss of Function	3.96	14	41.5	0.337	0.00000242	422

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000843	0.000843
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.000327	0.000323
European (Non-Finnish)	0.000244	0.000220
Middle Eastern	0.000218	0.000217
South Asian	0.000229	0.000229
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transfers the glycosyl residue from UDP-Glc to the non- reducing end of alpha-1,4-glucan.
• Disease: DISEASE: Muscle glycogen storage disease 0 (GSD0b) [MIM:611556]: Metabolic disorder characterized by fasting hypoglycemia presenting in infancy or early childhood. The role of muscle glycogen is to provide critical energy during bursts of activity and sustained muscle work. {ECO:0000269|PubMed:17928598}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Insulin resistance - Homo sapiens (human);Starch and sucrose metabolism - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);AMP-activated Protein Kinase (AMPK) Signaling;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in squamous cell - TarBase;Angiopoietin Like Protein 8 Regulatory Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Insulin Signaling;Glycogen Metabolism;Metabolism of carbohydrates;Metabolism;KitReceptor;insulin Mam;glycogen biosynthesis;Insulin-mediated glucose transport;Glycogen synthesis;insulin;Glycogen metabolism (Consensus)

Recessive Scores

• pRec: 0.724

Intolerance Scores

• loftool: 0.800
• rvis_EVS: -1.18
• rvis_percentile_EVS: 5.97

Haploinsufficiency Scores

• pHI: 0.325
• hipred: Y
• hipred_score: 0.766
• ghis: 0.600

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.994

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gys1
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs 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); 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); liver/biliary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype

Gene ontology

• Biological process: glycogen biosynthetic process;heart development
• Cellular component: cytoplasm;cytosol;membrane;inclusion body
• Molecular function: glycogen (starch) synthase activity;protein binding;glucose binding;protein kinase binding;glycogen synthase activity, transferring glucose-1-phosphate