GYS2

glycogen synthase 2, the group of Glycosyl transferases group 1 domain containing

Basic information

Region (hg38): 12:21536106-21604847

Links

ENSG00000111713 ∙ NCBI:2998 ∙ OMIM:138571 ∙ HGNC:4707 ∙ Uniprot:P54840 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glycogen storage disorder due to hepatic glycogen synthase deficiency (Strong), mode of inheritance: AR
• glycogen storage disorder due to hepatic glycogen synthase deficiency (Strong), mode of inheritance: AR
• glycogen storage disorder due to hepatic glycogen synthase deficiency (Strong), mode of inheritance: AR
• glycogen storage disorder due to hepatic glycogen synthase deficiency (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycogen storage disease, type 0, liver	AR	Biochemical	Dietary management (eg, with frequent and overnight feeds) can be beneficial	Biochemical; Gastrointestinal; Neurologic	21032403; 4505568; 8831078; 9691087; 11483824; 12794686; 18341095; 20051115; 23426827

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GYS2 gene.

• Glycogen storage disorder due to hepatic glycogen synthase deficiency (169 variants)
• not provided (87 variants)
• not specified (51 variants)
• Inborn genetic diseases (21 variants)
• Glycogen storage disease (2 variants)
• See cases (2 variants)
• GYS2-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GYS2 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			9	31	5	45
missense		5	64	11	7	87
nonsense	4	3				7
start loss						0
frameshift	5	3	1			9
inframe indel						0
splice donor/acceptor (+/-2bp)	2	6	1			9
splice region			5	2		7
non coding			16	23	40	79
Total	11	17	91	65	52

Highest pathogenic variant AF is 0.000204

Variants in GYS2

This is a list of pathogenic ClinVar variants found in the GYS2 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-21536211-GTTTA-G		Glycogen storage disorder due to hepatic glycogen synthase deficiency	Uncertain significance (Jun 14, 2016)
12-21536270-G-A		Glycogen storage disorder due to hepatic glycogen synthase deficiency	Uncertain significance (Jan 13, 2018)
12-21536300-C-T		Glycogen storage disorder due to hepatic glycogen synthase deficiency	Uncertain significance (Jan 13, 2018)
12-21536322-AC-A		Glycogen storage disorder due to hepatic glycogen synthase deficiency	Uncertain significance (Jun 14, 2016)
12-21536386-AT-A		Glycogen storage disorder due to hepatic glycogen synthase deficiency	Uncertain significance (Jun 14, 2016)
12-21536409-C-T		Glycogen storage disorder due to hepatic glycogen synthase deficiency	Uncertain significance (Jan 13, 2018)
12-21536434-T-C		Glycogen storage disorder due to hepatic glycogen synthase deficiency	Uncertain significance (Jan 12, 2018)
12-21536486-A-G		Glycogen storage disorder due to hepatic glycogen synthase deficiency	Uncertain significance (Jan 13, 2018)
12-21536496-T-A		Glycogen storage disorder due to hepatic glycogen synthase deficiency	Uncertain significance (Jan 12, 2018)
12-21536516-T-TA		Glycogen storage disorder due to hepatic glycogen synthase deficiency	Likely benign (Jun 14, 2016)
12-21536546-T-C		Glycogen storage disorder due to hepatic glycogen synthase deficiency	Uncertain significance (Jan 13, 2018)
12-21536548-A-C		Glycogen storage disorder due to hepatic glycogen synthase deficiency	Uncertain significance (Jan 13, 2018)
12-21536595-G-A		Glycogen storage disorder due to hepatic glycogen synthase deficiency	Uncertain significance (Jan 12, 2018)
12-21536664-C-A		Glycogen storage disorder due to hepatic glycogen synthase deficiency	Benign (Apr 27, 2017)
12-21536695-A-T		Glycogen storage disorder due to hepatic glycogen synthase deficiency	Uncertain significance (Jan 12, 2018)
12-21536717-A-G		Glycogen storage disorder due to hepatic glycogen synthase deficiency	Uncertain significance (Jan 12, 2018)
12-21536802-G-A		Glycogen storage disorder due to hepatic glycogen synthase deficiency	Benign (Jun 29, 2018)
12-21536948-T-A		not specified • Glycogen storage disorder due to hepatic glycogen synthase deficiency	Benign (Aug 10, 2021)
12-21536966-T-C			Likely benign (Oct 23, 2015)
12-21536994-G-A		Glycogen storage disorder due to hepatic glycogen synthase deficiency	Likely benign (Oct 29, 2018)
12-21536998-C-A		Glycogen storage disorder due to hepatic glycogen synthase deficiency	Likely benign (Jan 15, 2024)
12-21536998-C-T		Glycogen storage disorder due to hepatic glycogen synthase deficiency	Uncertain significance (Nov 19, 2023)
12-21536999-G-A		not specified • Glycogen storage disorder due to hepatic glycogen synthase deficiency	Benign (Jan 22, 2024)
12-21537006-A-T		Inborn genetic diseases	Uncertain significance (Jan 16, 2024)
12-21537011-A-G		Glycogen storage disorder due to hepatic glycogen synthase deficiency	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GYS2	protein_coding	protein_coding	ENST00000261195	16	68659

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.79e-22	0.0146	125463	1	284	125748	0.00113

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.138	374	382	0.980	0.0000203	4615
Missense in Polyphen		169	175.2	0.9646		2166
Synonymous	-1.79	166	139	1.19	0.00000769	1329
Loss of Function	0.890	36	42.2	0.852	0.00000248	456

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00155	0.00155
Ashkenazi Jewish	0.000104	0.0000992
East Asian	0.000326	0.000326
Finnish	0.000139	0.000139
European (Non-Finnish)	0.00122	0.00121
Middle Eastern	0.000326	0.000326
South Asian	0.00330	0.00327
Other	0.000816	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transfers the glycosyl residue from UDP-Glc to the non- reducing end of alpha-1,4-glucan.
• Disease: DISEASE: Glycogen storage disease 0 (GSD0) [MIM:240600]: A metabolic disorder characterized by fasting hypoglycemia presenting in infancy or early childhood, high blood ketones and low alanine and lactate concentrations. Although feeding relieves symptoms, it often results in postprandial hyperglycemia and hyperlactatemia. {ECO:0000269|PubMed:9691087}. 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);Glycogen synthetase deficiency;Glycogenosis, Type III. Cori disease, Debrancher glycogenosis;Mucopolysaccharidosis VI. Sly syndrome;Sucrase-isomaltase deficiency;Glycogenosis, Type IV. Amylopectinosis, Anderson disease;Glycogenosis, Type VI. Hers disease;Starch and Sucrose Metabolism;AMP-activated Protein Kinase (AMPK) Signaling;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Insulin Signaling;Glycogen Metabolism;Metabolism of carbohydrates;Metabolism;insulin Mam;glycogen biosynthesis;Glycogen synthesis;insulin;Glycogen metabolism (Consensus)

Recessive Scores

• pRec: 0.573

Intolerance Scores

• loftool: 0.874
• rvis_EVS: 0.32
• rvis_percentile_EVS: 72.8

Haploinsufficiency Scores

• pHI: 0.132
• hipred: Y
• hipred_score: 0.553
• ghis: 0.402

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.821

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gys2
• Phenotype: 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype

Gene ontology

• Biological process: glycogen biosynthetic process;generation of precursor metabolites and energy;response to glucose
• Cellular component: cytoplasm;cytosol;cytoskeleton;cell cortex;cortical actin cytoskeleton;ectoplasm
• Molecular function: glycogen (starch) synthase activity;protein homodimerization activity;glycogen synthase activity, transferring glucose-1-phosphate