AGL

amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase, the group of Glycoside hydrolases

Basic information

Region (hg38): 1:99850360-99924023

Links

ENSG00000162688 ∙ NCBI:178 ∙ OMIM:610860 ∙ HGNC:321 ∙ Uniprot:P35573 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glycogen storage disease III (Definitive), mode of inheritance: AR
• glycogen storage disease III (Definitive), mode of inheritance: AR
• glycogen storage disease III (Strong), mode of inheritance: AR
• glycogen storage disease III (Definitive), mode of inheritance: AR
• glycogen storage disease III (Definitive), mode of inheritance: AR
• glycogen storage disease III (Strong), mode of inheritance: AR
• glycogen storage disease III (Supportive), mode of inheritance: AR
• glycogen storage disease III (Strong), mode of inheritance: AR
• glycogen storage disease III (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycogen storage disease III	AR	Biochemical; Pharmacogenomic	Dietary measures (eg, high-protein diet with frequent feeding, including cornstarch) to maintain glucose levels is beneficial; Certain medications should be avoided or used with caution; Experimental treatment (eg, with synthetic ketone bodies) has been described as additionally beneficial; Liver transplantation has been described	Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic	5235982; 5285455; 288318; 6572629; 2792130; 2295969; 1293383; 1632441; 8253364; 8273986; 8755644; 8990006; 10472540; 10982190; 10655153; 11977176; 17047887; 18541889; 18924225; 19834502; 21073127; 21857385; 22138524; 22089644; 23207808; 23430490; 23649758; 23688858

ClinVar

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

• Glycogen storage disease type III (2206 variants)
• not provided (272 variants)
• not specified (89 variants)
• Inborn genetic diseases (88 variants)
• Glycogen storage disease IIIa (18 variants)
• Glycogen storage disease IIIb (5 variants)
• AGL-related condition (4 variants)
• Abnormality of metabolism/homeostasis (1 variants)
• Glycogen storage disease (1 variants)
• - (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AGL 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			11	485	5	501
missense	2	9	763	12	6	792
nonsense	56	100	2			158
start loss		1				1
frameshift	104	103	2			209
inframe indel		1	17			18
splice donor/acceptor (+/-2bp)	23	64	1			88
splice region	6	8	60	84	5	163
non coding		2	45	253	69	369
Total	185	280	841	750	80

Highest pathogenic variant AF is 0.0000723

Variants in AGL

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

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

Position	Type	Phenotype	Significance	ClinVar
1-99850380-C-T		Glycogen storage disease type III	Uncertain significance (Jan 13, 2018)
1-99850389-A-G		Glycogen storage disease type III	Uncertain significance (Jan 12, 2018)
1-99850402-A-G		Glycogen storage disease type III	Uncertain significance (Jan 12, 2018)
1-99850408-C-G		not specified	Likely benign (Nov 07, 2016)
1-99850416-G-C		Glycogen storage disease type III	Uncertain significance (Apr 11, 2023)
1-99850426-G-C		not specified	Likely benign (Sep 26, 2016)
1-99851033-A-G		not specified • Glycogen storage disease type III	Benign (Jul 15, 2021)
1-99851045-G-C		Glycogen storage disease type III	Likely pathogenic (May 08, 2017)
1-99851046-G-A		Glycogen storage disease type III	Uncertain significance (Jul 21, 2022)
1-99851048-A-C		Glycogen storage disease type III	Likely benign (Mar 27, 2023)
1-99851048-A-G		Glycogen storage disease type III	Likely benign (May 05, 2023)
1-99851050-A-G		Glycogen storage disease type III	Uncertain significance (Sep 24, 2021)
1-99851053-G-A		Glycogen storage disease type III	Uncertain significance (Aug 24, 2021)
1-99851054-T-C		Glycogen storage disease type III	Likely benign (Oct 13, 2022)
1-99851058-C-T		Glycogen storage disease IIIb • Glycogen storage disease type III	Pathogenic/Likely pathogenic (Sep 08, 2023)
1-99851058-CAG-C		Glycogen storage disease IIIb • Glycogen storage disease type III	Pathogenic/Likely pathogenic (Jan 16, 2024)
1-99851060-G-A		Glycogen storage disease type III	Likely benign (Sep 22, 2023)
1-99851063-TC-T		Glycogen storage disease type III	Pathogenic/Likely pathogenic (Jul 22, 2023)
1-99851064-C-T		Glycogen storage disease type III	Pathogenic/Likely pathogenic (Nov 17, 2023)
1-99851065-GAA-G		Glycogen storage disease type III	Pathogenic (Jun 09, 2020)
1-99851067-A-G		Glycogen storage disease type III	Uncertain significance (Aug 30, 2021)
1-99851072-A-G		Glycogen storage disease type III	Likely benign (Oct 03, 2023)
1-99851072-A-T		Glycogen storage disease type III	Uncertain significance (Jan 16, 2024)
1-99851077-T-TGC		Glycogen storage disease type III	Pathogenic/Likely pathogenic (Dec 24, 2022)
1-99851081-C-T		not specified • Glycogen storage disease type III	Benign/Likely benign (Jan 31, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AGL	protein_coding	protein_coding	ENST00000294724	33	73940

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.76e-27	0.993	125479	0	269	125748	0.00107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.461	830	793	1.05	0.0000397	10061
Missense in Polyphen		257	260.22	0.98764		3215
Synonymous	-0.199	268	264	1.02	0.0000128	2830
Loss of Function	3.17	57	89.4	0.638	0.00000479	1068

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00268	0.00268
Ashkenazi Jewish	0.000399	0.000397
East Asian	0.000816	0.000816
Finnish	0.000277	0.000277
European (Non-Finnish)	0.00132	0.00132
Middle Eastern	0.000816	0.000816
South Asian	0.000915	0.000915
Other	0.000654	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Multifunctional enzyme acting as 1,4-alpha-D-glucan:1,4- alpha-D-glucan 4-alpha-D-glycosyltransferase and amylo-1,6- glucosidase in glycogen degradation.
• Disease: DISEASE: Glycogen storage disease 3 (GSD3) [MIM:232400]: A metabolic disorder associated with an accumulation of abnormal glycogen with short outer chains. It is clinically characterized by hepatomegaly, hypoglycemia, short stature, and variable myopathy. Glycogen storage disease type 3 includes different forms: GSD type 3A patients lack glycogen debrancher enzyme activity in both liver and muscle, while GSD type 3B patients are enzyme-deficient in liver only. In rare cases, selective loss of only 1 of the 2 debranching activities, glucosidase or transferase, results in GSD type 3C or type 3D, respectively. {ECO:0000269|PubMed:10571954, ECO:0000269|PubMed:17908927}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Starch and sucrose metabolism - 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;Glycogen Metabolism;Neutrophil degranulation;Metabolism of carbohydrates;glycogenolysis;Innate Immune System;Immune System;Metabolism;Glycogen breakdown (glycogenolysis);Glycogen metabolism (Consensus)

Recessive Scores

• pRec: 0.248

Intolerance Scores

• loftool: 0.0357
• rvis_EVS: 1.86
• rvis_percentile_EVS: 97.16

Haploinsufficiency Scores

• pHI: 0.443
• hipred: Y
• hipred_score: 0.706
• ghis: 0.454

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.871

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Agl
• Phenotype: muscle phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system 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); vision/eye phenotype; limbs/digits/tail phenotype; skeleton phenotype

Gene ontology

• Biological process: glycogen biosynthetic process;glycogen catabolic process;response to nutrient;neutrophil degranulation;response to glucocorticoid
• Cellular component: extracellular region;nucleus;cytoplasm;cytosol;inclusion body;sarcoplasmic reticulum;secretory granule lumen;isoamylase complex;ficolin-1-rich granule lumen
• Molecular function: glycogen debranching enzyme activity;4-alpha-glucanotransferase activity;amylo-alpha-1,6-glucosidase activity;protein binding;polysaccharide binding;polyubiquitin modification-dependent protein binding;beta-maltose 4-alpha-glucanotransferase activity