PYGM

glycogen phosphorylase, muscle associated, the group of Glycogen phosphorylases

Basic information

Region (hg38): 11:64746388-64759974

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 (1038 variants)
• not provided (183 variants)
• not specified (81 variants)
• Inborn genetic diseases (36 variants)
• Tip-toe gait (18 variants)
• PYGM-related condition (6 variants)
• See cases (3 variants)
• McArdle disease, mild (2 variants)
• Elevated circulating creatine kinase concentration (2 variants)
• Abnormality of metabolism/homeostasis (1 variants)
• Rhabdomyolysis (1 variants)
• Muscular atrophy (1 variants)
• High myopia (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.

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			2	315	3	320
missense	8	22	255	3	2	290
nonsense	16	16				32
start loss	3	2				5
frameshift	50	39				89
inframe indel	1	4	6			11
splice donor/acceptor (+/-2bp)	5	43				48
splice region		1	7	71	2	81
non coding		1	6	120	23	150
Total	83	127	269	438	28

Highest pathogenic variant AF is 0.00176

Variants in PYGM

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

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

Position	Type	Phenotype	Significance	ClinVar
11-64746579-C-T		Glycogen storage disease, type V	Uncertain significance (Jan 12, 2018)
11-64746628-C-T			Likely benign (May 11, 2020)
11-64746648-G-A		not specified	Likely benign (Aug 10, 2016)
11-64746660-C-A		Glycogen storage disease, type V	Likely pathogenic (Feb 19, 2016)
11-64746661-A-T		Glycogen storage disease, type V	Uncertain significance (May 30, 2018)
11-64746663-A-T		Glycogen storage disease, type V	Uncertain significance (Feb 18, 2022)
11-64746670-C-T		Glycogen storage disease, type V	Uncertain significance (Feb 02, 2021)
11-64746672-T-A		Glycogen storage disease, type V	Uncertain significance (Jan 13, 2018)
11-64746673-C-T		Glycogen storage disease, type V	Uncertain significance (Aug 02, 2020)
11-64746674-C-T		Glycogen storage disease, type V	Likely benign (Oct 30, 2023)
11-64746676-G-C		Glycogen storage disease, type V	Uncertain significance (Jun 13, 2022)
11-64746688-G-A		Glycogen storage disease, type V	Uncertain significance (Aug 31, 2022)
11-64746688-G-C		Glycogen storage disease, type V • Inborn genetic diseases	Uncertain significance (Jun 02, 2023)
11-64746692-G-A		Glycogen storage disease, type V	Likely benign (Jan 11, 2022)
11-64746694-G-A		Glycogen storage disease, type V • Inborn genetic diseases	Uncertain significance (Nov 18, 2023)
11-64746695-G-A		Glycogen storage disease, type V	Likely benign (Aug 23, 2022)
11-64746698-A-G		Glycogen storage disease, type V	Likely benign (Mar 18, 2023)
11-64746701-C-T		Glycogen storage disease, type V	Likely benign (Oct 28, 2022)
11-64746719-C-T		Glycogen storage disease, type V	Likely benign (Jul 11, 2023)
11-64746720-C-T		Inborn genetic diseases	Uncertain significance (Feb 05, 2024)
11-64746721-G-A		Glycogen storage disease, type V	Uncertain significance (Jun 23, 2022)
11-64746722-G-A		Glycogen storage disease, type V	Likely benign (Sep 12, 2022)
11-64746723-G-A		Glycogen storage disease, type V	Uncertain significance (Aug 27, 2020)
11-64746723-G-T		Glycogen storage disease, type V	Uncertain significance (Aug 24, 2021)
11-64746725-A-G		Glycogen storage disease, type V	Likely benign (Jan 11, 2024)

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