PYGL

glycogen phosphorylase L, the group of Glycogen phosphorylases

Basic information

Region (hg38): 14:50857891-50944483

Links

ENSG00000100504 ∙ NCBI:5836 ∙ OMIM:613741 ∙ HGNC:9725 ∙ Uniprot:P06737 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycogen storage disease VI	AR	Biochemical	The condition can include manifestations suc has hypoglycemia, ketosis, and growth retardation, and recommendations for care include laboratory-based monitoring (eg, including liver function tests, glucose, and ketones), radiological monitoring (abdominal imaging), and nutritional recommendations and avoidance of certain medications in order to help improve metabolic to control and prevent the primary complications; Specific care during pregnancy has been recommended	Biochemical	13646331; 5904467; 9529348; 9536091; 17705025; 20301788; 21646031; 25266922; 30659246

ClinVar

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

• Glycogen storage disease, type VI (26 variants)
• not provided (6 variants)
• PYGL-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PYGL 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			3	45	5	53
missense	4	11	102	6	2	125
nonsense	9	4	1			14
start loss						0
frameshift	8	5	1			14
inframe indel			2			2
splice donor/acceptor (+/-2bp)	9	5			1	15
splice region			4	9	2	15
non coding		1	31	23	38	93
Total	30	26	140	74	46

Highest pathogenic variant AF is 0.0000460

Variants in PYGL

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

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

Position	Type	Phenotype	Significance	ClinVar
14-50858108-A-T			Uncertain significance (Sep 01, 2022)
14-50872181-G-A		not specified	Uncertain significance (Apr 08, 2022)
14-50872209-C-T		not specified	Likely benign (Jan 26, 2022)
14-50872245-C-A		not specified	Uncertain significance (Jul 08, 2022)
14-50877959-C-G		not specified	Uncertain significance (Feb 22, 2023)
14-50877975-T-C		not specified	Likely benign (May 18, 2023)
14-50877979-C-T			Likely benign (Jul 01, 2022)
14-50878002-A-G		not specified	Uncertain significance (Aug 02, 2021)
14-50878059-T-C		not specified	Uncertain significance (May 31, 2024)
14-50878826-C-T		not specified	Uncertain significance (Oct 05, 2023)
14-50878846-T-C		not specified	Uncertain significance (Aug 12, 2022)
14-50880498-T-C		not specified	Likely benign (Mar 27, 2024)
14-50880523-G-C		not specified	Uncertain significance (May 06, 2022)
14-50880538-T-C		not specified	Uncertain significance (Apr 04, 2023)
14-50881610-G-C		not specified	Uncertain significance (Feb 22, 2023)
14-50881627-G-T			Benign (Feb 01, 2024)
14-50885652-C-A		not specified	Uncertain significance (Aug 14, 2023)
14-50885769-T-C		not specified	Uncertain significance (Nov 03, 2022)
14-50885769-T-G		not specified	Uncertain significance (Jun 13, 2024)
14-50885781-C-T		not specified	Uncertain significance (Feb 12, 2024)
14-50885786-A-G		not specified	Uncertain significance (Sep 06, 2022)
14-50885801-G-A		not specified	Uncertain significance (Apr 12, 2024)
14-50885808-C-T		not specified	Uncertain significance (Mar 04, 2024)
14-50885816-G-A		not specified	Uncertain significance (Mar 04, 2024)
14-50888830-C-A		not specified	Uncertain significance (Mar 15, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PYGL	protein_coding	protein_coding	ENST00000216392	20	86846

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.71e-17	0.492	41757	26796	57195	125748	0.424

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.203	478	466	1.03	0.0000254	5610
Missense in Polyphen		246	239.07	1.029		2934
Synonymous	0.297	177	182	0.972	0.0000103	1601
Loss of Function	1.74	33	45.7	0.722	0.00000259	525

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	1.31	1.31
Ashkenazi Jewish	0.338	0.335
East Asian	0.610	0.607
Finnish	0.360	0.361
European (Non-Finnish)	0.343	0.342
Middle Eastern	0.610	0.607
South Asian	0.446	0.442
Other	0.408	0.407

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties.
• Disease: DISEASE: Glycogen storage disease 6 (GSD6) [MIM:232700]: A metabolic disorder characterized by mild to moderate hypoglycemia, mild ketosis, growth retardation, and prominent hepatomegaly. Heart and skeletal muscle are not affected. {ECO:0000269|PubMed:9529348}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Insulin resistance - Homo sapiens (human);Starch and sucrose metabolism - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Necroptosis - 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;TNF alpha Signaling Pathway;Glycogen Metabolism;Neutrophil degranulation;Metabolism of carbohydrates;glycogenolysis;Innate Immune System;Immune System;Metabolism;Glycogen breakdown (glycogenolysis);Glycogen metabolism (Consensus)

Recessive Scores

• pRec: 0.423

Intolerance Scores

• loftool: 0.0522
• rvis_EVS: 0.21
• rvis_percentile_EVS: 67.5

Haploinsufficiency Scores

• pHI: 0.242
• hipred: N
• hipred_score: 0.492
• ghis: 0.496

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.992

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pygl

Gene ontology

• Biological process: glycogen metabolic process;glycogen catabolic process;5-phosphoribose 1-diphosphate biosynthetic process;response to bacterium;glucose homeostasis;neutrophil degranulation;necroptotic process
• Cellular component: extracellular region;cytoplasm;cytosol;secretory granule lumen;extracellular exosome;ficolin-1-rich granule lumen
• Molecular function: purine nucleobase binding;protein binding;ATP binding;glucose binding;drug binding;glycogen phosphorylase activity;AMP binding;vitamin binding;pyridoxal phosphate binding;bile acid binding;protein homodimerization activity;linear malto-oligosaccharide phosphorylase activity;SHG alpha-glucan phosphorylase activity