PYGM

Summary

PYGM (glycogen phosphorylase, muscle associated, HGNC:9726) is a protein-coding gene on chromosome 11q13.1, encoding Glycogen phosphorylase, muscle form (P11217). Allosteric enzyme that catalyzes the rate-limiting step in glycogen catabolism, the phosphorolytic cleavage of glycogen to produce glucose-1-phosphate, and plays a central role in maintaining cellular and organismal glucose homeostasis.

This gene encodes a muscle enzyme involved in glycogenolysis. Highly similar enzymes encoded by different genes are found in liver and brain. Mutations in this gene are associated with McArdle disease (myophosphorylase deficiency), a glycogen storage disease of muscle. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 5837 — RefSeq curated summary.

At a glance

• Gene–disease (curated): glycogen storage disease V (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 1,602 total — 110 pathogenic, 128 likely-pathogenic
• Phenotypes (HPO): 34
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005609

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9726
Approved symbol	PYGM
Name	glycogen phosphorylase, muscle associated
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	GSD5
Ensembl gene	ENSG00000068976
Ensembl biotype	protein_coding
OMIM	608455
Entrez	5837

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000164139, ENST00000377432, ENST00000460413, ENST00000462303, ENST00000483742, ENST00000938870, ENST00000967737

RefSeq mRNA: 2 — MANE Select: NM_005609 NM_001164716, NM_005609

CCDS: CCDS53659, CCDS8079

Canonical transcript exons

ENST00000164139 — 20 exons

Exon	Start	End
ENSE00000730789	64747224	64747358
ENSE00000730792	64750376	64750583
ENSE00000730794	64751325	64751466
ENSE00000730806	64753519	64753682
ENSE00000730810	64754253	64754345
ENSE00000863650	64752403	64752504
ENSE00000863651	64753073	64753187
ENSE00000863655	64754693	64754836
ENSE00000863658	64757779	64757910
ENSE00001171774	64758246	64758349
ENSE00001171784	64758437	64758515
ENSE00001171792	64758603	64758704
ENSE00001621025	64755447	64755558
ENSE00001722365	64751924	64752071
ENSE00001879584	64759656	64759974
ENSE00002460194	64755273	64755355
ENSE00003535111	64746921	64746987
ENSE00003566811	64751597	64751655
ENSE00003642960	64753879	64754025
ENSE00003850850	64746398	64746808

Expression profiles

Bgee: expression breadth ubiquitous, 227 present calls, max score 99.87.

FANTOM5 (CAGE): breadth broad, TPM avg 23.0219 / max 6302.9580, expressed in 465 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120443	22.3868	426
120441	0.2308	117
120442	0.1669	71
120440	0.1232	26
120438	0.0625	15
120439	0.0430	9
120437	0.0087	5

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.87	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.86	gold quality
gastrocnemius	UBERON:0001388	99.82	gold quality
triceps brachii	UBERON:0001509	99.82	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.82	gold quality
biceps brachii	UBERON:0001507	99.80	gold quality
gluteal muscle	UBERON:0002000	99.80	gold quality
skeletal muscle tissue	UBERON:0001134	99.77	gold quality
quadriceps femoris	UBERON:0001377	99.75	gold quality
vastus lateralis	UBERON:0001379	99.75	gold quality
tibialis anterior	UBERON:0001385	99.59	gold quality
deltoid	UBERON:0001476	99.59	gold quality
diaphragm	UBERON:0001103	99.58	gold quality
body of tongue	UBERON:0011876	99.35	gold quality
muscle organ	UBERON:0001630	98.98	gold quality
skeletal muscle organ	UBERON:0014892	98.98	gold quality
muscle of leg	UBERON:0001383	98.67	gold quality
apex of heart	UBERON:0002098	97.66	gold quality
muscle tissue	UBERON:0002385	96.00	gold quality
heart left ventricle	UBERON:0002084	93.92	gold quality
heart right ventricle	UBERON:0002080	93.66	gold quality
cardiac ventricle	UBERON:0002082	93.64	gold quality
tongue	UBERON:0001723	91.36	gold quality
right atrium auricular region	UBERON:0006631	91.12	gold quality
heart	UBERON:0000948	90.84	gold quality
cardiac atrium	UBERON:0002081	89.83	gold quality
left ventricle myocardium	UBERON:0006566	89.79	gold quality
popliteal artery	UBERON:0002250	89.08	gold quality
tibial artery	UBERON:0007610	89.05	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	88.67	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR2F2

miRNA regulators (miRDB)

21 targeting PYGM, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-5572	98.55	65.84	970
HSA-MIR-6529-5P	97.85	66.47	673
HSA-MIR-10398-5P	97.12	64.94	1051
HSA-MIR-3162-5P	95.67	67.53	794
HSA-MIR-4693-3P	95.23	65.92	735
HSA-MIR-6741-5P	93.86	63.06	437

Literature-anchored findings (GeneRIF, showing 39)

• McArdle disease may be caused by a R269X nonsense mutation in this gene. (PMID:11749054)
• two new mutations in the myophosphorylase gene in Italian patients with McArdle’s disease; both were compound heterozygous, with the common mutation at codon 49 (R49X) on the other allele (PMID:12031624)
• molecular genetic study of McArdle’s disease in Yemenite-Jewish patients expands the already remarkable genetic heterogeneity of McArdle’s disease and suggests the existence of ethnic or private mutations within this group. (PMID:12398832)
• In Mcardle’s disease (deficiency of this enzyme) efferent muscle sympathetic nerve activity (MSNA) is attenuated. (PMID:12640006)
• the muscle subtype of glycogen phosphorylase mRNA level is up-regulated in preeclampsia in placenta (PMID:14662163)
• A new autosomal dominant gene mutation in McArdle disease. (PMID:15979037)
• We report a Spanish family with muscle glycogen phosphorylase (PYGM) deficiency (McArdle’s disease) harbouring a novel compound genotype (A659D/L586P). (PMID:16154688)
• muscle isoform of human glycogen phosphorylase has structural differences that are consistent with the long-known kinetic differences between the liver and muscle enzymes (PMID:16523484)
• 19 novel mutations within the PYGM gene are associated with McArdle disease. (PMID:16786513)
• findings further demonstrate molecular heterogeneity of myophosphorylase deficiency, absence of genotype-phenotype correlation and expand the already crowded map of mutations within the myophosphorylase gene (PMID:17324573)
• The study further extends the genetic heterogeneity of myophosphorylase gene mutations showing no mutational hotspot and no genotype-phenotype correlation. (PMID:17404776)
• This unique case of a false negative myophosphorylase histochemical reaction is apparently related to sepsis. (PMID:17719780)
• Glycogenosis type V is an autosomal recessive metabolic disorder caused by a deficiency of the muscle isoform of glycogen phosphorylase (myophosphorylase, PYGM. [REVIEW] (PMID:17915571)
• To investigate if nonsense mediated decay affects the levels of transcripts containing PYGM mutations, 28 Spanish patients with McArdle disease, harboring 17 different mutations with premature termination codons in 77% of their alleles, were studied. (PMID:17994553)
• Defect in glycogen breakdown is due to mutations of the gene for myophosphorylase in McArdle disease (gycogenosis type V). (PMID:18808785)
• Different PYGM mutations and mutant molecular mechanisms are described in patients with McArdle disease. (PMID:19251976)
• study of two patients with atypical McArdle disease who carried common mutations on one allele (R50X and G205S), and novel splice mutations in introns 3 [IVS3-26A>G (c.425-26A>G)] and 5 [IVS5-601G>A (c.856-601G>A)] on the other allele (PMID:19433441)
• Nine novel mutations of PYGM were identified in patients with McArdle disease. (PMID:19472443)
• indicate that in both patients’ and controls’ cell cultures, unlike in skeletal muscle tissue, most of the protein and GP activities result from the expression of brain GP and liver GP genes (PMID:20957198)
• This study demonistrated that PYGM mutation in McArdle disease. (PMID:21658951)
• No genotype-phenotype correlation is evident and that no gender effect is related to the phenotype of McArdle’s disease (PYGM gene) in a cohort of 123 European McArdle’s disease patients. (PMID:21802952)
• The current data add to the list of pathogenic mutations in the PYGM gene associated with McArdle disease (PMID:21880526)
• a new role for Rac1 in cell signaling, showing that this GTPase triggers T-cell proliferation upon IL-2 stimulation by associating with PYGM and modulating its enzymatic activity. (PMID:22337875)
• a novel mutation, in the PYGM gene c.632delG, in three unrelated families of Jewish descent originating from the Caucasus region (PMID:22608882)
• 5 different PYGM mutations were found in 8 Brazilian families: 4 previously described (p.R50X, p.T692kfs30, p.K609K, and p.G455R), and one, pI513V, a novel heterozygous mutation. (PMID:23653251)
• study found that T lymphocytes expressed myophosphorylase in healthy donors, but expression was significantly lower in McArdle patients (p<0.001); PYGM mRNA levels were also lower in white blood cells from McArdle patients (PMID:25240406)
• biological significance of this PKCtheta;/alphaPIX/Rac 1 GTPase/PYGM signaling pathway seems to be the control of different cellular responses such as migration and proliferation (PMID:25694429)
• update of the reported mutations and polymorphisms in the PYGM gene [review] (PMID:25914343)
• Because the NMD mechanism does not seem to operate in nonspecific cells, PBMCs were more suitable than muscle biopsies for detecting the pathogenicity of some PYGM mutations, notably the silent mutation whose effect in the splicing of intron 6 was unnoticed in previous muscle transcriptomic studies (PMID:26913921)
• Results show that PYGM and RAC1 are altered in the dorsolateral prefrontal cortex in chronic schizophrenia and are controlled by NMDA signaling in the rodent cortex and cortical astrocytes suggesting an altered NMDA-dependent glycogenolysis in astrocytes in schizophrenia. (PMID:27156240)
• Variations in AMPD1, CPT2, and PGYM genes are not associated with the onset, susceptibility, or severity of chronic fatigue syndrome. (PMID:27525900)
• This report expands the phenotype and genotype of McArdle disease and suggests that PYGM mutations should be looked for in patients with very late-onset myopathy with no previous history of exercise intolerance (PMID:28120463)
• These findings explain the lack of PYGM genotype-phenotype correlation and have important implications for the design of molecular-based therapeutic approaches. (PMID:30011114)
• Bioinformatics-based discovery of PYGM and TNNC2 as potential biomarkers of head and neck squamous cell carcinoma. (PMID:31324732)
• The effect of muscle glycogen phosphorylase (Pygm) knockdown on zebrafish morphology. (PMID:31747538)
• A New Glycogen Storage Disease Caused by a Dominant PYGM Mutation. (PMID:32386344)
• PYGM mRNA expression in McArdle disease: Demographic, clinical, morphological and genetic features. (PMID:32735634)
• Muscle Glycogen Phosphorylase and Its Functional Partners in Health and Disease. (PMID:33924466)
• Whole-exome sequencing detects PYGM variants in two adults with McArdle disease. (PMID:35022222)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pygmb	ENSDARG00000013317
danio_rerio	pygma	ENSDARG00000055518
mus_musculus	Pygm	ENSMUSG00000032648
rattus_norvegicus	Pygm	ENSRNOG00000021090
drosophila_melanogaster	Glyp	FBGN0004507
caenorhabditis_elegans		WBGENE00020696

Paralogs (2): PYGL (ENSG00000100504), PYGB (ENSG00000100994)

Protein

Protein identifiers

Glycogen phosphorylase, muscle form — P11217 (reviewed: P11217)

Alternative names: Myophosphorylase

All UniProt accessions (1): P11217

UniProt curated annotations — full annotation on UniProt →

Function. Allosteric enzyme that catalyzes the rate-limiting step in glycogen catabolism, the phosphorolytic cleavage of glycogen to produce glucose-1-phosphate, and plays a central role in maintaining cellular and organismal glucose homeostasis.

Subunit / interactions. Homodimer. Homotetramer; to form the enzymatically active phosphorylase A.

Post-translational modifications. Phosphorylation of Ser-15 converts phosphorylase B (unphosphorylated) to phosphorylase A.

Disease relevance. Glycogen storage disease 5 (GSD5) [MIM:232600] A metabolic disorder resulting in myopathy characterized by exercise intolerance, cramps, muscle weakness and recurrent myoglobinuria. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Allosterically regulated through the non-covalent binding of metabolites, being activated by AMP and inhibited by ATP, ADP, and glucose-6-phosphate. The activity is also controlled by post-translational modifications including phosphorylation.

Similarity. Belongs to the glycogen phosphorylase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P11217-1	1	yes
P11217-2	2

RefSeq proteins (2): NP_001158188, NP_005600* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000811	Glyco_trans_35	Family
IPR011833	Glycg_phsphrylas	Family
IPR035090	Pyridoxal_P_attach_site	Conserved_site

Pfam: PF00343

Catalyzed reactions (Rhea), 1 shown:

• (1->4)-alpha-D-glucosyl + phosphate = (1->4)-alpha-D-glucosyl + alpha-D-glucose 1-phosphate (RHEA:41732)

UniProt features (118 total): helix 43, strand 24, sequence variant 20, turn 11, modified residue 10, binding site 3, site 3, initiator methionine 1, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1Z8D	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11217-F1	94.41	0.89

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 109 (involved in the association of subunits); 143 (involved in the association of subunits); 156 (may be involved in allosteric control)

Ligand- & substrate-binding residues (3): 43; 76; 310–319

Post-translational modifications (10): 204, 227, 430, 473, 514, 681, 747, 748, 2, 15

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-70221	Glycogen breakdown (glycogenolysis)

MSigDB gene sets: 222 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, MODY_HIPPOCAMPUS_POSTNATAL, MOOTHA_GLYCOGEN_METABOLISM, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, TGACCTY_ERR1_Q2, GGGTGGRR_PAX4_03, chr11q13, CAGCTG_AP4_Q5, HUMMERICH_SKIN_CANCER_PROGRESSION_DN, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_POLYSACCHARIDE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, TGACATY_UNKNOWN, KEGG_STARCH_AND_SUCROSE_METABOLISM, GOBP_CARBOHYDRATE_CATABOLIC_PROCESS

GO Biological Process (3): glycogen metabolic process (GO:0005977), glycogen catabolic process (GO:0005980), carbohydrate metabolic process (GO:0005975)

GO Molecular Function (8): nucleotide binding (GO:0000166), glycogen phosphorylase activity (GO:0008184), pyridoxal phosphate binding (GO:0030170), catalytic activity (GO:0003824), 1,4-alpha-oligoglucan phosphorylase activity (GO:0004645), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glycogen metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
energy reserve metabolic process	1
glucan metabolic process	1
glycogen metabolic process	1
glucan catabolic process	1
primary metabolic process	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
1,4-alpha-oligoglucan phosphorylase activity	1
anion binding	1
vitamin B6 binding	1
molecular_function	1
hexosyltransferase activity	1
binding	1
catalytic activity	1
transferase activity	1
intracellular anatomical structure	1
cytoplasm	1
extracellular vesicle	1

Protein interactions and networks

STRING

2380 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PYGM	GYS2	P54840	856
PYGM	MEN1	O00255	830
PYGM	SF1	Q15637	800
PYGM	AGL	P35573	799
PYGM	PLCB3	Q01970	792
PYGM	G6PC1	P35575	789
PYGM	G6PC3	Q9BUM1	789
PYGM	CAPN1	P07384	786
PYGM	ROM1	Q03395	786
PYGM	FTH1	P02794	784
PYGM	GYS1	P13807	784
PYGM	UGP2	Q16851	784
PYGM	GCK	P35557	782
PYGM	G6PC2	Q9NQR9	781
PYGM	MARK2	Q7KZI7	778

IntAct

95 interactions, top by confidence:

A	B	Type	Score
PRKAB2	PYGM	psi-mi:“MI:0915”(physical association)	0.780
PYGM	PRKAB2	psi-mi:“MI:0915”(physical association)	0.780
STBD1	GABARAP	psi-mi:“MI:0914”(association)	0.760
PYGM	NTAQ1	psi-mi:“MI:0915”(physical association)	0.670
NTAQ1	PYGM	psi-mi:“MI:0915”(physical association)	0.670
PYGB	PYGM	psi-mi:“MI:0915”(physical association)	0.670
PYGL	PYGM	psi-mi:“MI:0915”(physical association)	0.560
rep	PYGM	psi-mi:“MI:0915”(physical association)	0.560
HSPB8	VWA8	psi-mi:“MI:0914”(association)	0.530
DNAJC30	NDUFS8	psi-mi:“MI:0914”(association)	0.530
TAF6L	SUPT3H	psi-mi:“MI:0914”(association)	0.530
PYGB	STBD1	psi-mi:“MI:0914”(association)	0.530
Ccdc15		psi-mi:“MI:0915”(physical association)	0.400
TRIM31	PYGM	psi-mi:“MI:0915”(physical association)	0.400
TLE3	ATP2A1	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
HCN1	USP27X	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ABTB2	IFT56	psi-mi:“MI:0914”(association)	0.350
MECOM	ATP2A1	psi-mi:“MI:0914”(association)	0.350
RSPH6A	ATP2A1	psi-mi:“MI:0914”(association)	0.350
GPRASP2	GYG2	psi-mi:“MI:0914”(association)	0.350

BioGRID (90): PYGM (Two-hybrid), WDYHV1 (Two-hybrid), PYGM (Biochemical Activity), GBE1 (Co-fractionation), PYGM (Affinity Capture-MS), PYGM (Affinity Capture-MS), PYGM (Affinity Capture-MS), PYGM (Affinity Capture-MS), PYGM (Biochemical Activity), PYGM (Affinity Capture-MS), PYGM (Affinity Capture-MS), PYGM (Affinity Capture-Western), PYGM (Affinity Capture-MS), PYGL (Two-hybrid), PYGB (Two-hybrid)

ESM2 similar proteins: A2RRU1, A7MB78, F4IAG2, F4J8C6, J9VTK7, O08739, O09178, O18751, O43314, O80452, O93869, P09812, P0C644, P11216, P11217, P13807, P13834, P17625, P23337, P27472, P32811, P53534, P53537, P54840, P79334, P91309, Q00766, Q01432, Q10003, Q2WF59, Q3B7M9, Q5K2C4, Q5MIB6, Q5R5M6, Q5R9H0, Q5REW0, Q84NP7, Q84WW3, Q8CI94, Q8CIG3

Diamond homologs: O18751, O84250, P00489, P00490, P04045, P06737, P06738, P09811, P09812, P0AC86, P0AC87, P11216, P11217, P27598, P29849, P32811, P34114, P39123, P45180, P53534, P53535, P53536, P53537, P73511, P79334, Q00766, Q0VCM4, Q3B7M9, Q5MIB5, Q5MIB6, Q5R5M6, Q8CI94, Q8HXW4, Q9CN90, Q9ET01, Q9LIB2, Q9LKJ3, Q9PKE6, Q9SD76, Q9WUB3

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
PYGM	“down-regulates quantity”	glycogen	“chemical modification”
PYGM	“up-regulates quantity”	“alpha-D-glucose 1-phosphate(2-)”	“chemical modification”
PHKG1	“up-regulates activity”	PYGM	phosphorylation
PHKG2	“up-regulates activity”	PYGM	phosphorylation
PP1	“down-regulates activity”	PYGM	dephosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

1602 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	110
Likely pathogenic	128
Uncertain significance	473
Likely benign	671
Benign	34

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1066872	NM_005609.4(PYGM):c.2385_2386del (p.Glu797fs)	Pathogenic
1069632	NM_005609.4(PYGM):c.1353dup (p.Ala452fs)	Pathogenic
1069821	NM_005609.4(PYGM):c.493_514del (p.Gly165fs)	Pathogenic
1069823	NM_005609.4(PYGM):c.1159del (p.Arg387fs)	Pathogenic
1070312	NM_005609.4(PYGM):c.1403+1G>A	Pathogenic
1070313	NM_005609.4(PYGM):c.225C>A (p.Tyr75Ter)	Pathogenic
1070372	NM_005609.4(PYGM):c.1523del (p.Ile508fs)	Pathogenic
1073391	NM_005609.4(PYGM):c.681C>A (p.Tyr227Ter)	Pathogenic
1076041	NC_000011.9:g.(?64525241)(64527380_?)del	Pathogenic
1076857	NM_005609.4(PYGM):c.521del (p.Gly174fs)	Pathogenic
1299506	NM_005609.4(PYGM):c.2113_2114del (p.Gly705fs)	Pathogenic
1323510	NM_005609.4(PYGM):c.1774A>T (p.Lys592Ter)	Pathogenic
1332748	NM_005609.4(PYGM):c.2448dup (p.Thr817fs)	Pathogenic
1351367	NM_005609.4(PYGM):c.2154del (p.Asp718fs)	Pathogenic
1355803	NM_005609.4(PYGM):c.1138_1144del (p.Val380fs)	Pathogenic
1377601	NM_005609.4(PYGM):c.157del (p.Tyr53fs)	Pathogenic
139608	NM_005609.4(PYGM):c.255C>A (p.Tyr85Ter)	Pathogenic
1410779	NM_005609.4(PYGM):c.1853dup (p.Met619fs)	Pathogenic
1449350	NC_000011.9:g.(?64517838)(64522318_?)del	Pathogenic
1451644	NM_005609.4(PYGM):c.1358_1364del (p.Val453fs)	Pathogenic
1451837	NM_005609.4(PYGM):c.734G>A (p.Trp245Ter)	Pathogenic
1452391	NM_005609.4(PYGM):c.1239_1239+1delinsAT	Pathogenic
1452880	NM_005609.4(PYGM):c.632del (p.Ser211fs)	Pathogenic
1453638	NM_005609.4(PYGM):c.569G>A (p.Trp190Ter)	Pathogenic
1454148	NM_005609.4(PYGM):c.1009C>T (p.Gln337Ter)	Pathogenic
1457488	NM_005609.4(PYGM):c.730del (p.Leu244fs)	Pathogenic
1460419	NC_000011.9:g.(?64514121)(64518065_?)del	Pathogenic
156341	NM_005609.4(PYGM):c.1A>C (p.Met1Leu)	Pathogenic
1678578	NM_005609.4(PYGM):c.373del (p.Glu125fs)	Pathogenic
188778	NM_005609.4(PYGM):c.78_79del (p.Glu27fs)	Pathogenic

SpliceAI

2625 predictions. Top by Δscore:

Variant	Effect	Δscore
11:64746807:TTC:T	acceptor_loss	1.0000
11:64746808:TCT:T	acceptor_loss	1.0000
11:64746809:C:CC	acceptor_gain	1.0000
11:64746915:CCTCA:C	donor_loss	1.0000
11:64746916:CTCAC:C	donor_loss	1.0000
11:64746917:TCACC:T	donor_loss	1.0000
11:64746918:CAC:C	donor_loss	1.0000
11:64746919:ACC:A	donor_loss	1.0000
11:64746920:C:T	donor_loss	1.0000
11:64746983:TAAAC:T	acceptor_gain	1.0000
11:64746984:AAAC:A	acceptor_gain	1.0000
11:64746985:AAC:A	acceptor_gain	1.0000
11:64746986:AC:A	acceptor_gain	1.0000
11:64746987:CC:C	acceptor_gain	1.0000
11:64746988:C:CC	acceptor_gain	1.0000
11:64746988:CTGG:C	acceptor_loss	1.0000
11:64747219:CTCA:C	donor_loss	1.0000
11:64747222:A:AC	donor_gain	1.0000
11:64747223:C:CC	donor_gain	1.0000
11:64747223:CCGG:C	donor_loss	1.0000
11:64747223:CCGGT:C	donor_gain	1.0000
11:64747300:G:C	donor_gain	1.0000
11:64747356:TACCT:T	acceptor_loss	1.0000
11:64747357:ACCTG:A	acceptor_loss	1.0000
11:64747360:T:A	acceptor_loss	1.0000
11:64750374:AC:A	donor_gain	1.0000
11:64750375:CC:C	donor_gain	1.0000
11:64750375:CCCT:C	donor_gain	1.0000
11:64750393:AT:A	donor_gain	1.0000
11:64750400:T:TA	donor_gain	1.0000

AlphaMissense

5569 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:64751967:T:A	K575N	1.000
11:64751967:T:G	K575N	1.000
11:64751968:T:A	K575I	1.000
11:64753136:G:C	N485K	1.000
11:64753136:G:T	N485K	1.000
11:64753984:G:C	H378Q	1.000
11:64753984:G:T	H378Q	1.000
11:64753986:G:C	H378D	1.000
11:64754326:T:A	D340V	1.000
11:64754804:C:A	Q296H	1.000
11:64754804:C:G	Q296H	1.000
11:64754817:A:G	L292P	1.000
11:64755486:A:G	W245R	1.000
11:64755486:A:T	W245R	1.000
11:64757892:A:G	W183R	1.000
11:64757892:A:T	W183R	1.000
11:64758273:A:C	F167L	1.000
11:64758273:A:T	F167L	1.000
11:64758275:A:G	F167L	1.000
11:64746712:A:G	W826R	0.999
11:64746712:A:T	W826R	0.999
11:64746746:A:C	S814R	0.999
11:64746746:A:T	S814R	0.999
11:64746748:T:G	S814R	0.999
11:64746752:G:C	F812L	0.999
11:64746752:G:T	F812L	0.999
11:64746754:A:G	F812L	0.999
11:64750469:C:T	G695E	0.999
11:64750471:G:C	D694E	0.999
11:64750471:G:T	D694E	0.999

dbSNP variants (sampled 300 via entrez): RS1000039653 (11:64748180 G>A), RS1000782176 (11:64759207 T>A), RS1000808186 (11:64759590 T>A), RS1001220282 (11:64748251 C>T), RS1001315143 (11:64748584 T>C), RS1002252713 (11:64759240 G>A), RS1002320347 (11:64747933 C>T), RS1002586741 (11:64760499 C>T), RS1002638948 (11:64760733 T>C), RS1002833550 (11:64755034 G>A), RS1002890691 (11:64749469 C>G,T), RS1002986961 (11:64749921 C>T), RS1003000532 (11:64749538 A>C), RS1003169944 (11:64756614 C>A), RS1003317651 (11:64751080 C>T)

Disease associations

OMIM: gene MIM:608455 | disease phenotypes: MIM:232600, MIM:232200, MIM:145600

GenCC curated gene-disease

Disease	Classification	Inheritance
glycogen storage disease V	Strong	Autosomal recessive
disorder of glycogen metabolism	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
glycogen storage disease V	Definitive	AR

Mondo (6): glycogen storage disease V (MONDO:0009293), disorder of glycogen metabolism (MONDO:0002412), retinal disorder (MONDO:0005283), hereditary skeletal muscle disorder (MONDO:0700223), malignant hyperthermia, susceptibility to, 1 (MONDO:0007783), myopathy (MONDO:0005336)

Orphanet (3): Glycogen storage disease due to muscle glycogen phosphorylase deficiency (Orphanet:368), Glycogen storage disease (Orphanet:79201), Malignant hyperthermia of anesthesia (Orphanet:423)

HPO phenotypes

34 total (30 of 34 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001324	Muscle weakness
HP:0001639	Hypertrophic cardiomyopathy
HP:0001649	Tachycardia
HP:0001919	Acute kidney injury
HP:0002015	Dysphagia
HP:0002149	Hyperuricemia
HP:0002875	Exertional dyspnea
HP:0002913	Myoglobinuria
HP:0003201	Rhabdomyolysis
HP:0003202	Skeletal muscle atrophy
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003546	Exercise intolerance
HP:0003596	Middle age onset
HP:0003621	Juvenile onset
HP:0003652	Recurrent myoglobinuria
HP:0003710	Exercise-induced muscle cramps
HP:0003738	Exercise-induced myalgia
HP:0005216	Impaired mastication
HP:0008305	Exercise-induced myoglobinuria
HP:0008967	Exercise-induced muscle stiffness
HP:0009045	Exercise-induced rhabdomyolysis
HP:0009051	Increased muscle glycogen content
HP:0009073	Progressive proximal muscle weakness
HP:0011463	Childhood onset
HP:0012378	Fatigue
HP:0012622	Chronic kidney disease
HP:0030231	Glycogen accumulation in muscle fiber lysosomes
HP:0030234	Highly elevated creatine kinase
HP:0030973	Postexertional symptom exacerbation

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001163_5	Urate levels	6.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D006008	Glycogen Storage Disease	C16.320.565.202.449; C18.452.648.202.449
D006012	Glycogen Storage Disease Type V	C16.320.565.202.449.560; C18.452.648.202.449.560
D012164	Retinal Diseases	C11.768
C535694	Malignant hyperthermia susceptibility type 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3526 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 27,781 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL428690	ALVOCIDIB	3	27,781

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

100 potent at pChembl≥5 of 109 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.80	Ki	1.6	nM	CHEMBL3322297
8.52	IC50	3	nM	CHEMBL134802
8.22	IC50	6	nM	CHEMBL115651
8.08	IC50	8.28	nM	CHEMBL113736
8.05	IC50	9	nM	CHEMBL133911
8.00	IC50	10	nM	CHEMBL423509
7.97	IC50	10.61	nM	CHEMBL326950
7.96	Ki	11	nM	CHEMBL324288
7.96	IC50	11	nM	CHEMBL115341
7.92	IC50	12	nM	CHEMBL440528
7.92	IC50	12	nM	CHEMBL133832
7.89	IC50	12.9	nM	CHEMBL114226
7.85	IC50	14	nM	CHEMBL139472
7.70	IC50	19.9	nM	CHEMBL114846
7.60	IC50	25	nM	CHEMBL132191
7.58	IC50	26	nM	CHEMBL114731
7.54	IC50	29	nM	CHEMBL133274
7.54	IC50	29	nM	CHEMBL113762
7.50	IC50	32	nM	CHEMBL337332
7.43	IC50	37	nM	CHEMBL115441
7.42	IC50	38	nM	CHEMBL139461
7.41	IC50	39	nM	CHEMBL134854
7.39	IC50	41	nM	CHEMBL334272
7.28	IC50	52	nM	CHEMBL114271
7.26	IC50	55	nM	CHEMBL136327
7.26	IC50	55	nM	CHEMBL342880
7.25	IC50	56	nM	CHEMBL136218
7.24	IC50	57	nM	CHEMBL337012
7.24	IC50	58	nM	CHEMBL136182
7.24	IC50	57	nM	CHEMBL133923
7.22	IC50	60	nM	CHEMBL132640
7.16	IC50	69	nM	CHEMBL422632
7.14	IC50	73	nM	CHEMBL134793
7.10	IC50	80	nM	CHEMBL337224
7.08	IC50	83	nM	CHEMBL134797
7.06	IC50	88	nM	CHEMBL136168
7.05	IC50	89	nM	CHEMBL136573
7.04	IC50	91	nM	CHEMBL117483
7.01	IC50	98	nM	CHEMBL136572
6.98	IC50	105	nM	CHEMBL342364
6.96	IC50	110	nM	CHEMBL194177
6.96	IC50	110	nM	CHEMBL194356
6.96	IC50	110	nM	CHEMBL137196
6.96	IC50	109	nM	CHEMBL133114
6.96	IC50	110	nM	CHEMBL133603
6.92	IC50	120	nM	CHEMBL194807
6.92	IC50	120	nM	CHEMBL138822
6.86	IC50	138	nM	CHEMBL114950
6.85	IC50	140	nM	CHEMBL193734
6.85	IC50	140	nM	CHEMBL442404

PubChem BioAssay actives

100 with measured affinity, of 197 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1,4-dihydropyridine-2,3-dicarboxylic acid	1186738: Inhibition of glycogen phosphorylase b (unknown origin)	ki	0.0016	uM
4-[3-[(4-nitropyridine-2-carbonyl)amino]naphthalen-2-yl]oxyphthalic acid	73812: Inhibitory activity against HMGP(human muscle glycogen phosphorylase)	ic50	0.0030	uM
4-(2-chlorophenyl)-1-[(4-chlorophenyl)methyl]-6-methyl-5-propan-2-yloxycarbonyl-4H-pyridine-2,3-dicarboxylic acid	141122: In vitro inhibitory activity against human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0060	uM
4-(2-chlorophenyl)-1-ethyl-6-methyl-5-(2-methylpropylcarbamoyl)-4H-pyridine-2,3-dicarboxylic acid	141122: In vitro inhibitory activity against human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0083	uM
4-[3-fluoro-2-[(4-nitropyridine-2-carbonyl)amino]phenoxy]phthalic acid	73812: Inhibitory activity against HMGP(human muscle glycogen phosphorylase)	ic50	0.0090	uM
4-(2-chlorophenyl)-6-methyl-1-[(3-nitrophenyl)methyl]-5-propan-2-yloxycarbonyl-4H-pyridine-2,3-dicarboxylic acid	141122: In vitro inhibitory activity against human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0100	uM
5-(benzylcarbamoyl)-4-(2-chlorophenyl)-1-ethyl-6-methyl-4H-pyridine-2,3-dicarboxylic acid	141122: In vitro inhibitory activity against human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0106	uM
(4S)-1-ethyl-6-methyl-4-phenyl-5-propan-2-yloxycarbonyl-4H-pyridine-2,3-dicarboxylic acid	141123: Inhibitory activity against rabbit muscle glycogen phosphorylase a in the absence of AMP	ki	0.0110	uM
4-(2-chlorophenyl)-1-[(3,4-dimethoxyphenyl)methyl]-6-methyl-5-propan-2-yloxycarbonyl-4H-pyridine-2,3-dicarboxylic acid	141122: In vitro inhibitory activity against human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0110	uM
4-[3-[(4-chloropyridine-2-carbonyl)amino]naphthalen-2-yl]oxyphthalic acid	73812: Inhibitory activity against HMGP(human muscle glycogen phosphorylase)	ic50	0.0120	uM
4-[3-[(4-methoxypyridine-2-carbonyl)amino]naphthalen-2-yl]oxyphthalic acid	73812: Inhibitory activity against HMGP(human muscle glycogen phosphorylase)	ic50	0.0120	uM
4-(2-chlorophenyl)-1-ethyl-6-methyl-5-(propan-2-ylcarbamoyl)-4H-pyridine-2,3-dicarboxylic acid	141122: In vitro inhibitory activity against human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0129	uM
5-chloro-N-[(3R)-2-oxo-3,4-dihydro-1H-quinolin-3-yl]-1H-indole-2-carboxamide	73823: Inhibitory concentration against recombinant human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0140	uM
4-(2-chlorophenyl)-1-ethyl-5-(ethylcarbamoyl)-6-methyl-4H-pyridine-2,3-dicarboxylic acid	141122: In vitro inhibitory activity against human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0199	uM
4-[2-[(4-nitropyridine-2-carbonyl)amino]phenoxy]phthalic acid	73812: Inhibitory activity against HMGP(human muscle glycogen phosphorylase)	ic50	0.0250	uM
1-benzyl-4-(2-chlorophenyl)-6-methyl-5-propan-2-yloxycarbonyl-4H-pyridine-2,3-dicarboxylic acid	141122: In vitro inhibitory activity against human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0260	uM
4-(2-chlorophenyl)-1-[(3-chlorophenyl)methyl]-6-methyl-5-propan-2-yloxycarbonyl-4H-pyridine-2,3-dicarboxylic acid	141122: In vitro inhibitory activity against human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0290	uM
4-[3-[(4-ethylpyridine-2-carbonyl)amino]naphthalen-2-yl]oxyphthalic acid	73812: Inhibitory activity against HMGP(human muscle glycogen phosphorylase)	ic50	0.0290	uM
5-chloro-N-(1-methyl-2-oxo-3,4-dihydroquinolin-3-yl)-1H-indole-2-carboxamide	73823: Inhibitory concentration against recombinant human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0320	uM
4-(2-chlorophenyl)-1-[(3,5-dichlorophenyl)methyl]-6-methyl-5-propan-2-yloxycarbonyl-4H-pyridine-2,3-dicarboxylic acid	141122: In vitro inhibitory activity against human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0370	uM
5-chloro-N-(2-oxo-3,4-dihydro-1H-quinolin-3-yl)-1H-indole-2-carboxamide	73823: Inhibitory concentration against recombinant human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0380	uM
5-chloro-N-[(3S)-2-oxo-3,4-dihydro-1H-quinolin-3-yl]-1H-indole-2-carboxamide	73823: Inhibitory concentration against recombinant human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0390	uM
4-(2-chlorophenyl)-1-[(3,4-dichlorophenyl)methyl]-6-methyl-5-propan-2-yloxycarbonyl-4H-pyridine-2,3-dicarboxylic acid	141122: In vitro inhibitory activity against human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0410	uM
4-(2-chlorophenyl)-6-methyl-5-propan-2-yloxycarbonyl-1-(2,2,2-trifluoroethyl)-4H-pyridine-2,3-dicarboxylic acid	141122: In vitro inhibitory activity against human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0520	uM
5-chloro-N-(2-oxo-1,3,4,5-tetrahydro-1-benzazepin-3-yl)-1H-indole-2-carboxamide	73823: Inhibitory concentration against recombinant human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0550	uM
5-chloro-7-fluoro-N-(1-methyl-2-oxo-3,4-dihydroquinolin-3-yl)-1H-indole-2-carboxamide	73823: Inhibitory concentration against recombinant human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0550	uM
N-(1-methyl-2-oxo-3,4-dihydroquinolin-3-yl)-1H-indole-2-carboxamide	73823: Inhibitory concentration against recombinant human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0560	uM
4-[3-[(4-methylpyridine-2-carbonyl)amino]naphthalen-2-yl]oxyphthalic acid	73812: Inhibitory activity against HMGP(human muscle glycogen phosphorylase)	ic50	0.0570	uM
5-chloro-N-[(3S)-1-methyl-2-oxo-3,4-dihydroquinolin-3-yl]-1H-indole-2-carboxamide	73823: Inhibitory concentration against recombinant human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0570	uM
5-chloro-N-[(3R)-1-methyl-2-oxo-3,4-dihydroquinolin-3-yl]-1H-indole-2-carboxamide	73823: Inhibitory concentration against recombinant human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0580	uM
4-[2-[(4-chloropyridine-2-carbonyl)amino]-3-fluorophenoxy]phthalic acid	73812: Inhibitory activity against HMGP(human muscle glycogen phosphorylase)	ic50	0.0600	uM
6-chloro-N-(1-methyl-2-oxo-3,4-dihydroquinolin-3-yl)-1H-indole-2-carboxamide	73823: Inhibitory concentration against recombinant human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0690	uM
5-bromo-N-(1-methyl-2-oxo-3,4-dihydroquinolin-3-yl)-1H-indole-2-carboxamide	73823: Inhibitory concentration against recombinant human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0730	uM
4-[3-[[4-(trifluoromethyl)pyridine-2-carbonyl]amino]naphthalen-2-yl]oxyphthalic acid	73812: Inhibitory activity against HMGP(human muscle glycogen phosphorylase)	ic50	0.0800	uM
5-chloro-N-[(3R)-2-oxo-1,3,4,5-tetrahydro-1-benzazepin-3-yl]-1H-indole-2-carboxamide	73823: Inhibitory concentration against recombinant human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0830	uM
7-chloro-N-(1-methyl-2-oxo-3,4-dihydroquinolin-3-yl)-1H-indole-2-carboxamide	73823: Inhibitory concentration against recombinant human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0880	uM
5-fluoro-N-(1-methyl-2-oxo-3,4-dihydroquinolin-3-yl)-1H-indole-2-carboxamide	73823: Inhibitory concentration against recombinant human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0890	uM
4-(2-chlorophenyl)-1-[(2,5-dichlorophenyl)methyl]-6-methyl-5-propan-2-yloxycarbonyl-4H-pyridine-2,3-dicarboxylic acid	141122: In vitro inhibitory activity against human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0910	uM
5-methyl-N-(1-methyl-2-oxo-3,4-dihydroquinolin-3-yl)-1H-indole-2-carboxamide	73823: Inhibitory concentration against recombinant human muscle glycogen phosphorylase a (HMGPa)	ic50	0.0980	uM
5-chloro-N-(1-methyl-2-oxo-4,5-dihydro-3H-1-benzazepin-3-yl)-1H-indole-2-carboxamide	73823: Inhibitory concentration against recombinant human muscle glycogen phosphorylase a (HMGPa)	ic50	0.1050	uM
4-[4-fluoro-2-[(4-nitropyridine-2-carbonyl)amino]phenoxy]phthalic acid	73812: Inhibitory activity against HMGP(human muscle glycogen phosphorylase)	ic50	0.1090	uM
4-[(4-methyl-3-oxoquinoxalin-2-yl)amino]-N-(1,2-oxazol-3-yl)benzamide	254905: Inhibitory concentration against glycogen phosphorylase of rabbit muscle	ic50	0.1100	uM
4-[(4-methyl-3-oxoquinoxalin-2-yl)amino]-N-(thiophen-2-ylmethyl)benzamide	254905: Inhibitory concentration against glycogen phosphorylase of rabbit muscle	ic50	0.1100	uM
4-[3-fluoro-2-[(4-methoxypyridine-2-carbonyl)amino]phenoxy]phthalic acid	73812: Inhibitory activity against HMGP(human muscle glycogen phosphorylase)	ic50	0.1100	uM
5-cyano-N-(1-methyl-2-oxo-3,4-dihydroquinolin-3-yl)-1H-indole-2-carboxamide	73823: Inhibitory concentration against recombinant human muscle glycogen phosphorylase a (HMGPa)	ic50	0.1100	uM
N-(furan-2-ylmethyl)-4-[(4-methyl-3-oxoquinoxalin-2-yl)amino]benzamide	254905: Inhibitory concentration against glycogen phosphorylase of rabbit muscle	ic50	0.1200	uM
N-(1-methyl-2-oxo-3,4-dihydroquinolin-3-yl)-7-nitro-1H-indole-2-carboxamide	73823: Inhibitory concentration against recombinant human muscle glycogen phosphorylase a (HMGPa)	ic50	0.1200	uM
4-(2-chlorophenyl)-1-ethyl-6-methyl-5-propan-2-yloxycarbonyl-4H-pyridine-2,3-dicarboxylic acid	141122: In vitro inhibitory activity against human muscle glycogen phosphorylase a (HMGPa)	ic50	0.1380	uM
4-[(7-fluoro-4-methyl-3-oxoquinoxalin-2-yl)amino]-N-(thiophen-2-ylmethyl)benzamide	254905: Inhibitory concentration against glycogen phosphorylase of rabbit muscle	ic50	0.1400	uM
4-[3-[(3-nitrobenzoyl)amino]naphthalen-2-yl]oxyphthalic acid	73812: Inhibitory activity against HMGP(human muscle glycogen phosphorylase)	ic50	0.1400	uM

CTD chemical–gene interactions

52 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Doxorubicin	decreases expression	4
bisphenol A	decreases expression, increases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
Daunorubicin	decreases expression	2
Mitoxantrone	decreases expression	2
Silicon Dioxide	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
titanium dioxide	increases expression	1
decabromobiphenyl ether	decreases expression	1
sodium bichromate	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
tetrabromobisphenol A	increases expression	1
perfluorooctanoic acid	decreases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
2,7-dihydroxynaphthalene	decreases expression	1
corosolic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
bromovanin	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1

ChEMBL screening assays

18 unique, capped per target: 18 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1285511	Binding	Inhibition of glycogen phosphorylase b	The binding of β-d-glucopyranosyl-thiosemicarbazone derivatives to glycogen phosphorylase: A new class of inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

5 cell lines: 4 induced pluripotent stem cell, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1L24	GM23505	Transformed cell line	Male
CVCL_A4DB	IISHDOi007-A	Induced pluripotent stem cell	Female
CVCL_C7T5	IISHDOi001-B	Induced pluripotent stem cell	Female
CVCL_C7T7	IISHDOi001-A-1	Induced pluripotent stem cell	Female
CVCL_QX71	IISHDOi001-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

117 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01955135	PHASE4	COMPLETED	Anesthesia for Retinopathy of Prematurity
NCT00120055	PHASE4	COMPLETED	Association Between Systemic Exposure of Atorvastatin and Metabolites and Atorvastatin-induced Myotoxicity
NCT03633565	PHASE4	UNKNOWN	Comparative Study of Strategies for Management of Duchenne Myopathy (DM)
NCT02782741	PHASE3	COMPLETED	Study to Compare the Efficacy and Safety of Enzyme Replacement Therapies Avalglucosidase Alfa and Alglucosidase Alfa Administered Every Other Week in Patients With Late-onset Pompe Disease Who Have Not Been Previously Treated for Pompe Disease
NCT04808505	PHASE3	RECRUITING	A Study to Evaluate the Safety, Efficacy, PK, PD and Immunogenicity of Cipaglucosidase Alfa/Miglustat in IOPD Subjects Aged 0 to <18
NCT01225614	PHASE3	UNKNOWN	Efficacy and Tolerance of Early Launching of Nocturnal Non Invasive
NCT02432768	PHASE2	COMPLETED	The Effect of Triheptanoin in Adults With McArdle Disease (Glycogen Storage Disease Type V)
NCT02919631	PHASE2	COMPLETED	Triheptanoin in Mc Ardle
NCT03112889	PHASE2	COMPLETED	Sodium Valproate for GSDV
NCT00765414	PHASE2	COMPLETED	Extension Study of Long-term Safety and Efficacy of Myozyme for a Single Patient With Pompe Disease Who Were Previously Enrolled in Genzyme Sponsored ERT Studies.
NCT02032524	PHASE2	COMPLETED	Avalglucosidase Alfa Extension Study
NCT03019406	PHASE2	ACTIVE_NOT_RECRUITING	A Study to Assess Safety and Efficacy of Avalglucosidase Alfa Administered Every Other Week in Pediatric Patients With Infantile-onset Pompe Disease Previously Treated With Alglucosidase Alfa
NCT06130228	PHASE2	UNKNOWN	Nutritional Therapy in Late-onset Pompe Disease
NCT01373476	PHASE2	COMPLETED	Multicentre, Randomized, Controlled Trial of Qideng Mingmu Capsule in The Treatment of Diabetic Retinopathy
NCT01793090	PHASE2	COMPLETED	EPI-743 in Cobalamin C Defect: Effects on Visual and Neurological Impairment
NCT04226274	PHASE1	COMPLETED	A Study of the Safety of REN001 in Patients With McArdle Disease
NCT00278564	PHASE1	TERMINATED	Stem Cell Transplantation in Idiopathic Inflammatory Myopathy Diseases
NCT02385162	Not specified	WITHDRAWN	Biomarker for Glycogen Storage Diseases (BioGlycogen)
NCT02635269	Not specified	UNKNOWN	Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy
NCT03211923	Not specified	UNKNOWN	Muscle Relaxation in Myopathies With Positive Muscle Phenomena
NCT03843606	Not specified	COMPLETED	Modified Ketogenic Diet in Patients With McArdle Disease Part A
NCT03844022	Not specified	COMPLETED	MRI in McArdle Disease (GSDV)
NCT03945370	Not specified	COMPLETED	Oral Ketone Body Supplementation in Patients With McArdle Disease
NCT04044508	Not specified	COMPLETED	Modified Ketogenic Diet in Patients With McArdle Disease Part B
NCT04349566	Not specified	COMPLETED	Fast Troponin as a Biomarker to Assess Exercise-induced Muscle Damage in Muscle Diseases
NCT04694547	Not specified	COMPLETED	Ketogenic Diet Survey in Patients With McArdle Disease (GSDV)
NCT04929002	Not specified	ACTIVE_NOT_RECRUITING	Carbon-13 Magnetic Resonance Spectroscopy in Glycogen Storage Diseases
NCT05943678	Not specified	ACTIVE_NOT_RECRUITING	Novel Metabolic Muscular Biomarkers in Pompe Disease - a Non-invasive Magnetic Resonance Exploratory Pilot Study.
NCT05095727	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study of mRNA-3745 in Adult and Pediatric Participants With Glycogen Storage Disease Type 1a (GSD1a)
NCT00001342	Not specified	COMPLETED	Study of Glycogen Storage Disease and Associated Disorders
NCT00566878	Not specified	COMPLETED	Pompe Lactation Sub-Registry
NCT01461304	Not specified	NO_LONGER_AVAILABLE	Compassionate Use of Triheptanoin (C7) for Inherited Disorders of Energy Metabolism
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT02057731	Not specified	COMPLETED	Study of Glycogen Storage Disease Expression in Carriers
NCT02176096	Not specified	COMPLETED	Comparison of the Effect of a Novel Starch (Glycosade) Versus Gastrostomy Tube-Dextrose Infusion on Overnight Euglycaemia Control in Children With Glycogen Storage Disease Type I: Open Label Demonstration Trial
NCT02318966	Not specified	COMPLETED	Glycosade v UCCS in the Dietary Management of Hepatic GSD
NCT02338817	Not specified	TERMINATED	Clinical Evaluation of a Non-Invasive Hypoglycemia Detector in a Glycogen Storage Disease Population
NCT03255213	Not specified	COMPLETED	Lingual Muscle Training in Late-Onset Pompe Disease (LOPD)
NCT03564561	Not specified	RECRUITING	Natural History of Pompe Disease
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns