GYS2

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

Basic information

Region (hg38): 12:21536107-21604847

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 (182 variants)
Inborn_genetic_diseases (79 variants)
not_provided (56 variants)
not_specified (46 variants)
GYS2-related_disorder (22 variants)
Glycogen_storage_disease (2 variants)
See_cases (2 variants)
Schizophrenia (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. These statistics are base on transcript: NM_000021957.4. 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			9 clinvar	48 clinvar	5 clinvar	62
missense	1 clinvar	9 clinvar	115 clinvar	15 clinvar	5 clinvar	145
nonsense	4 clinvar	7 clinvar				11
start loss						0
frameshift	5 clinvar	12 clinvar	2 clinvar			19
splice donor/acceptor (+/-2bp)	2 clinvar	7 clinvar	1 clinvar			10
Total	12	35	127	63	10

Highest pathogenic variant AF is 0.000252293

Loading clinvar variants...

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