GBE1

1,4-alpha-glucan branching enzyme 1

Basic information

Region (hg38): 3:81489702-81761645

Links

ENSG00000114480 ∙ NCBI:2632 ∙ OMIM:607839 ∙ HGNC:4180 ∙ Uniprot:Q04446 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glycogen storage disease due to glycogen branching enzyme deficiency (Strong), mode of inheritance: AR
• glycogen storage disease due to glycogen branching enzyme deficiency (Definitive), mode of inheritance: AR
• adult polyglucosan body disease (Moderate), mode of inheritance: AR
• glycogen storage disease due to glycogen branching enzyme deficiency (Strong), mode of inheritance: AR
• adult polyglucosan body disease (Supportive), mode of inheritance: AR
• glycogen storage disease due to glycogen branching enzyme deficiency (Definitive), mode of inheritance: AR
• glycogen storage disease due to glycogen branching enzyme deficiency (Definitive), mode of inheritance: AR
• glycogen storage disease due to glycogen branching enzyme deficiency (Strong), mode of inheritance: AR
• glycogen storage disease due to glycogen branching enzyme deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycogen storage disease IV; Polyglucosan body neuropathy, adult form	AR	Biochemical; Cardiovascular	In some forms of Glycogen storage disease IV, management to decrease morbidity and mortality related to cardiac sequalae may be beneficial; Liver transplant may be beneficial in some individuals with Glycogen storage disease IV; In Polyglucosan body neuropathy, adult form, surveillance for cardiac sequelae such as cardiomyopathy has been recommended	Biochemical; Cardiovascular; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic	13279125; 5229990; 4502299; 284761; 6579239; 3464425; 3474393; 3162725; 1984162; 1375445; 7683169; 8437594; 8059607; 8494336; 8613547; 8830177; 9851430; 10384399; 10545044; 10449659; 10603098; 10762170; 12913206; 15452297; 15520786; 14755501; 15019703; 16007674; 16528737; 17662246; 17915577; 17994551; 18661138; 18230843; 20301758; 19813197; 20058079; 20833045; 20531024; 21917543; 22305237; 23218673; 36796138

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GBE1 gene.

• Glycogen storage disease, type IV;Glycogen storage disease IV, classic hepatic (349 variants)
• Glycogen storage disease IV, classic hepatic;Glycogen storage disease, type IV (216 variants)
• Glycogen storage disease, type IV (204 variants)
• not provided (148 variants)
• Adult polyglucosan body disease (86 variants)
• not specified (46 variants)
• Inborn genetic diseases (26 variants)
• GBE1-related condition (10 variants)
• Adult polyglucosan body disease;Glycogen storage disease, type IV (8 variants)
• Glycogen storage disease, type IV;Adult polyglucosan body disease (7 variants)
• GBE1-Related Disorders (7 variants)
• Adult polyglucosan body neuropathy (5 variants)
• Glycogen storage disease due to glycogen branching enzyme deficiency, congenital neuromuscular form (5 variants)
• See cases (3 variants)
• Glycogen storage disease IV, classic hepatic (3 variants)
• Glycogen storage disease IV, nonprogressive hepatic (2 variants)
• Glycogen storage disease due to glycogen branching enzyme deficiency, childhood neuromuscular form (2 variants)
• Arthrogryposis multiplex congenita;Fetal akinesia deformation sequence 1 (1 variants)
• Glycogen storage disease (1 variants)
• Polyneuropathy (1 variants)
• Glycogen storage disease IV, combined hepatic and myopathic (1 variants)
• Glycogen storage disease due to glycogen branching enzyme deficiency, fatal perinatal neuromuscular form (1 variants)
• Osteogenesis imperfecta type 15 (1 variants)
• Cutis laxa, autosomal recessive, type 1B (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GBE1 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				205	3	208
missense	2	17	165	8	6	198
nonsense	16	17				33
start loss						0
frameshift	14	21				35
inframe indel			1			1
splice donor/acceptor (+/-2bp)	4	23				27
splice region		1	9	36	1	47
non coding		2	15	83	27	127
Total	36	80	181	296	36

Highest pathogenic variant AF is 0.000756

Variants in GBE1

This is a list of pathogenic ClinVar variants found in the GBE1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-81489809-C-G		Glycogen storage disease, type IV • Adult polyglucosan body disease	Uncertain significance (Jan 12, 2018)
3-81489849-A-G		Glycogen storage disease, type IV • Adult polyglucosan body disease	Uncertain significance (Jan 12, 2018)
3-81489852-C-T		Glycogen storage disease, type IV • Adult polyglucosan body disease	Uncertain significance (Jan 13, 2018)
3-81489862-C-G		Adult polyglucosan body disease • Glycogen storage disease, type IV	Uncertain significance (Jan 12, 2018)
3-81489884-A-T		Glycogen storage disease, type IV • Adult polyglucosan body disease	Benign (Apr 27, 2017)
3-81489913-T-A		Adult polyglucosan body disease • Glycogen storage disease, type IV	Benign (Jan 13, 2018)
3-81489913-T-G		Glycogen storage disease, type IV • Adult polyglucosan body disease	Uncertain significance (Jan 12, 2018)
3-81489939-C-T		Adult polyglucosan body disease • Glycogen storage disease, type IV	Uncertain significance (Jan 12, 2018)
3-81489941-C-T		Glycogen storage disease, type IV • Adult polyglucosan body disease	Uncertain significance (Jan 13, 2018)
3-81489947-G-A		Glycogen storage disease, type IV • Adult polyglucosan body disease	Uncertain significance (Jan 13, 2018)
3-81490012-T-C		Adult polyglucosan body disease • Glycogen storage disease, type IV	Uncertain significance (Jan 13, 2018)
3-81490019-A-T		Glycogen storage disease, type IV • Adult polyglucosan body disease	Uncertain significance (Mar 30, 2018)
3-81490099-G-A		Adult polyglucosan body disease • Glycogen storage disease, type IV	Likely benign (Aug 17, 2018)
3-81490181-A-G		Adult polyglucosan body disease • Glycogen storage disease, type IV	Uncertain significance (Jan 13, 2018)
3-81490231-C-T		Adult polyglucosan body disease • Glycogen storage disease, type IV	Benign (Jun 26, 2018)
3-81490255-G-T		Adult polyglucosan body disease • Glycogen storage disease, type IV	Benign (Jun 23, 2018)
3-81490363-A-T		Adult polyglucosan body disease • Glycogen storage disease, type IV	Uncertain significance (Jan 12, 2018)
3-81490395-A-G		Glycogen storage disease, type IV	Uncertain significance (Sep 19, 2022)
3-81490402-C-T		not specified	Likely benign (May 20, 2016)
3-81490409-A-C		Glycogen storage disease IV, classic hepatic;Glycogen storage disease, type IV • not specified	Uncertain significance (Feb 01, 2023)
3-81490410-A-G		Glycogen storage disease IV, classic hepatic;Glycogen storage disease, type IV	Likely benign (Apr 23, 2022)
3-81490413-C-T		Glycogen storage disease IV, classic hepatic;Glycogen storage disease, type IV • Glycogen storage disease, type IV	Likely benign (Dec 29, 2023)
3-81490414-G-A		Polyneuropathy	Uncertain significance (Mar 11, 2022)
3-81490421-C-A		Glycogen storage disease, type IV	Uncertain significance (Aug 14, 2020)
3-81490423-A-G		Glycogen storage disease IV, classic hepatic;Glycogen storage disease, type IV	Uncertain significance (Jul 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GBE1	protein_coding	protein_coding	ENST00000429644	16	272463

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.15e-12	0.728	124549	0	109	124658	0.000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0919	352	357	0.986	0.0000185	4595
Missense in Polyphen		123	157.13	0.78281		2061
Synonymous	0.726	117	127	0.918	0.00000678	1255
Loss of Function	1.69	24	34.7	0.691	0.00000168	473

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00204	0.00204
Ashkenazi Jewish	0.00	0.00
East Asian	0.000237	0.000223
Finnish	0.0000938	0.0000928
European (Non-Finnish)	0.000291	0.000283
Middle Eastern	0.000237	0.000223
South Asian	0.000151	0.000131
Other	0.00107	0.000991

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for normal glycogen accumulation (PubMed:8463281, PubMed:26199317, PubMed:8613547). The alpha 1-6 branches of glycogen play an important role in increasing the solubility of the molecule (Probable). {ECO:0000269|PubMed:26199317, ECO:0000269|PubMed:8463281, ECO:0000269|PubMed:8613547, ECO:0000305}.
• Disease: DISEASE: Glycogen storage disease 4 (GSD4) [MIM:232500]: A metabolic disorder characterized by the accumulation of an amylopectin-like polysaccharide. The typical clinical manifestation is liver disease of childhood, progressing to lethal hepatic cirrhosis. Most children with this condition die before two years of age. However, the liver disease is not always progressive. No treatment apart from liver transplantation has been found to prevent progression of the disease. There is also a neuromuscular form of glycogen storage disease type 4 that varies in onset (perinatal, congenital, juvenile, or adult) and severity. {ECO:0000269|PubMed:10545044, ECO:0000269|PubMed:15452297, ECO:0000269|PubMed:8613547}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Neuromuscular perinatal glycogen storage disease type 4 is associated with non-immune hydrops fetalis, a generalized edema of the fetus with fluid accumulation in the body cavities due to non-immune causes. Non-immune hydrops fetalis is not a diagnosis in itself but a symptom, a feature of many genetic disorders, and the end-stage of a wide variety of disorders. {ECO:0000269|PubMed:15452297}.; DISEASE: Polyglucosan body neuropathy, adult form (APBN) [MIM:263570]: A late-onset, slowly progressive disorder affecting the central and peripheral nervous systems. Patients typically present after age 40 years with a variable combination of cognitive impairment, pyramidal tetraparesis, peripheral neuropathy, and neurogenic bladder. Other manifestations include cerebellar dysfunction and extrapyramidal signs. The pathologic hallmark of APBN is the widespread accumulation of round, intracellular polyglucosan bodies throughout the nervous system, which are confined to neuronal and astrocytic processes. {ECO:0000269|PubMed:10762170}. 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;Metabolism of carbohydrates;Metabolism;glycogen biosynthesis;Glycogen synthesis;Glycogen metabolism (Consensus)

Recessive Scores

• pRec: 0.455

Intolerance Scores

• loftool: 0.116
• rvis_EVS: 0.62
• rvis_percentile_EVS: 83.53

Haploinsufficiency Scores

• pHI: 0.336
• hipred: N
• hipred_score: 0.174
• ghis: 0.457

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.776

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gbe1
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); 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); 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); liver/biliary system phenotype; respiratory system phenotype

Gene ontology

• Biological process: carbohydrate metabolic process;glycogen metabolic process;glycogen biosynthetic process;generation of precursor metabolites and energy
• Cellular component: cytosol;extracellular exosome
• Molecular function: 1,4-alpha-glucan branching enzyme activity;hydrolase activity, hydrolyzing O-glycosyl compounds;protein binding;cation binding;1,4-alpha-glucan branching enzyme activity (using a glucosylated glycogenin as primer for glycogen synthesis)