GYS1

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

Basic information

Region (hg38): 19:48968130-48993310

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 (546 variants)
Inborn_genetic_diseases (110 variants)
not_provided (101 variants)
not_specified (30 variants)
GYS1-related_disorder (23 variants)
Hereditary_hyperferritinemia_with_congenital_cataracts (7 variants)
Neuroferritinopathy (7 variants)
Glycogen_storage_disease (1 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. These statistics are base on transcript: NM_000002103.5. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	1 clinvar		9 clinvar	144 clinvar	5 clinvar	159
missense			275 clinvar	3 clinvar	1 clinvar	279
nonsense	9 clinvar	2 clinvar	2 clinvar			13
start loss		1	1			2
frameshift	11 clinvar	5 clinvar	4 clinvar			20
splice donor/acceptor (+/-2bp)	4 clinvar	9 clinvar	1 clinvar			14
Total	25	17	292	147	6

Highest pathogenic variant AF is 0.0000470882

Loading clinvar variants...

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