PYGM

glycogen phosphorylase, muscle associated, the group of Glycogen phosphorylases

Basic information

Region (hg38): 11:64746389-64759974

Links

ENSG00000068976 ∙ NCBI:5837 ∙ OMIM:608455 ∙ HGNC:9726 ∙ Uniprot:P11217 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glycogen storage disease V (Strong), mode of inheritance: AR
• glycogen storage disease V (Limited), mode of inheritance: AD
• glycogen storage disease V (Strong), mode of inheritance: AR
• glycogen storage disease V (Strong), mode of inheritance: AR
• glycogen storage disease V (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycogen storage disease V	AR	Biochemical; Musculoskeletal; Pharmacogenomic; Renal	Avoidance of excessive exercise may be beneficial to avoid rhabdomyolysis and potential renal failure; Sucrose ingestion may be beneficial (eg, prior to exercise); Certain precautions should be taken with general anesthesia	Biochemical; Musculoskeletal; Renal	16590445; 14442994; 4502558; 1067063; 101896; 6929403; 3808314; 3466902; 3207360; 2768781; 2391551; 8408630; 8316268; 11168025; 14695410; 16924035; 17705025; 17915571; 18667317; 19251976; 19433441; 20301518; 20957198; 21802952; 21880526; 22608882; 22818872; 22899091

ClinVar

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

• Glycogen_storage_disease,_type_V (1410 variants)
• not_provided (193 variants)
• not_specified (90 variants)
• Inborn_genetic_diseases (87 variants)
• PYGM-related_disorder (30 variants)
• Tip-toe_gait (19 variants)
• See_cases (3 variants)
• Elevated_circulating_creatine_kinase_concentration (2 variants)
• Glycogen_storage_disease (2 variants)
• McArdle_disease,_mild (2 variants)
• Acute_rhabdomyolysis (2 variants)
• High_myopia (1 variants)
• Hereditary_skeletal_muscle_disorder (1 variants)
• Malignant_hyperthermia,_susceptibility_to,_1 (1 variants)
• Rhabdomyolysis (1 variants)
• EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
• Abnormality_of_metabolism/homeostasis (1 variants)
• Myopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PYGM gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005609.4. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	2	1	17	407	3	430
missense	10	67	408	17	2	504
nonsense	20	20				40
start loss	4	2				6
frameshift	63	57		1		121
splice donor/acceptor (+/-2bp)	5	54	1			60
Total	104	201	426	425	5

Highest pathogenic variant AF is 0.0028372484

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PYGM	protein_coding	protein_coding	ENST00000164139	20	13909

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.03e-13	0.948	125257	0	491	125748	0.00195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0469	519	522	0.994	0.0000387	5528
Missense in Polyphen		247	256.2	0.96409		2696
Synonymous	-0.518	221	211	1.05	0.0000154	1637
Loss of Function	2.22	27	42.6	0.634	0.00000238	479

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00335	0.00323
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.000544	0.000544
Finnish	0.000832	0.000832
European (Non-Finnish)	0.00293	0.00293
Middle Eastern	0.000544	0.000544
South Asian	0.000721	0.000719
Other	0.00261	0.00261

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 5 (GSD5) [MIM:232600]: A metabolic disorder resulting in myopathy characterized by exercise intolerance, cramps, muscle weakness and recurrent myoglobinuria. {ECO:0000269|PubMed:10382911, ECO:0000269|PubMed:10382912, ECO:0000269|PubMed:10417800, ECO:0000269|PubMed:10590419, ECO:0000269|PubMed:10681080, ECO:0000269|PubMed:10714589, ECO:0000269|PubMed:10899452, ECO:0000269|PubMed:11706962, ECO:0000269|PubMed:12031624, ECO:0000269|PubMed:7603523, ECO:0000269|PubMed:8316268, ECO:0000269|PubMed:8535454, ECO:0000269|PubMed:9506549}. 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 Metabolism;Metabolism of carbohydrates;glycogenolysis;Metabolism;Glycogen breakdown (glycogenolysis);Glycogen metabolism (Consensus)

Recessive Scores

• pRec: 0.128

Intolerance Scores

• loftool: 0.0422
• rvis_EVS: -0.19
• rvis_percentile_EVS: 39.31

Haploinsufficiency Scores

• pHI: 0.508
• hipred: N
• hipred_score: 0.414
• ghis: 0.515

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.994

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pygm
• Phenotype: renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); muscle phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: glycogen metabolic process;glycogen catabolic process
• Cellular component: cytoplasm;cytosol;extracellular exosome
• Molecular function: nucleotide binding;protein binding;glycogen phosphorylase activity;pyridoxal phosphate binding;linear malto-oligosaccharide phosphorylase activity;SHG alpha-glucan phosphorylase activity