PYGL

Summary

PYGL (glycogen phosphorylase L, HGNC:9725) is a protein-coding gene on chromosome 14q22.1, encoding Glycogen phosphorylase, liver form (P06737). 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 homodimeric protein that catalyses the cleavage of alpha-1,4-glucosidic bonds to release glucose-1-phosphate from liver glycogen stores. This protein switches from inactive phosphorylase B to active phosphorylase A by phosphorylation of serine residue 15. Activity of this enzyme is further regulated by multiple allosteric effectors and hormonal controls. Humans have three glycogen phosphorylase genes that encode distinct isozymes that are primarily expressed in liver, brain and muscle, respectively. The liver isozyme serves the glycemic demands of the body in general while the brain and muscle isozymes supply just those tissues. In glycogen storage disease type VI, also known as Hers disease, mutations in liver glycogen phosphorylase inhibit the conversion of glycogen to glucose and results in moderate hypoglycemia, mild ketosis, growth retardation and hepatomegaly. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 5836 — RefSeq curated summary.

At a glance

• Gene–disease (curated): glycogen storage disease VI (Definitive, ClinGen)
• GWAS associations: 4
• Clinical variants (ClinVar): 452 total — 43 pathogenic, 27 likely-pathogenic
• Phenotypes (HPO): 34
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002863

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9725
Approved symbol	PYGL
Name	glycogen phosphorylase L
Location	14q22.1
Locus type	gene with protein product
Status	Approved
Aliases	GSD6
Ensembl gene	ENSG00000100504
Ensembl biotype	protein_coding
OMIM	613741
Entrez	5836

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 19 protein_coding, 4 retained_intron

ENST00000216392, ENST00000528757, ENST00000530336, ENST00000532107, ENST00000532462, ENST00000544180, ENST00000553872, ENST00000874286, ENST00000874287, ENST00000874288, ENST00000874289, ENST00000874290, ENST00000874291, ENST00000924121, ENST00000924122, ENST00000924123, ENST00000924124, ENST00000924125, ENST00000941158, ENST00000941159, ENST00000941160, ENST00000941161, ENST00000941162

RefSeq mRNA: 2 — MANE Select: NM_002863 NM_001163940, NM_002863

CCDS: CCDS32080, CCDS53894

Canonical transcript exons

ENST00000216392 — 20 exons

Exon	Start	End
ENSE00000657191	50920956	50921067
ENSE00000657192	50923969	50924100
ENSE00001507082	50916962	50917105
ENSE00002175022	50944161	50944483
ENSE00002201324	50905217	50905556
ENSE00003499601	50914701	50914815
ENSE00003503537	50915825	50915971
ENSE00003513330	50908821	50908955
ENSE00003545313	50911730	50911871
ENSE00003554617	50935107	50935185
ENSE00003579352	50931673	50931776
ENSE00003584178	50911978	50912036
ENSE00003586911	50909895	50910102
ENSE00003594453	50920541	50920623
ENSE00003612549	50915336	50915499
ENSE00003614745	50913029	50913130
ENSE00003625852	50908271	50908337
ENSE00003642482	50916642	50916734
ENSE00003647602	50912156	50912303
ENSE00003689518	50937736	50937837

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 97.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 58.4449 / max 4611.1911, expressed in 1758 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143183	35.4838	1735
143182	18.0625	1714
143181	3.8982	1372
143180	1.0003	556

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	97.79	gold quality
monocyte	CL:0000576	97.59	gold quality
mononuclear cell	CL:0000842	97.17	gold quality
leukocyte	CL:0000738	97.07	gold quality
right lobe of liver	UBERON:0001114	96.71	gold quality
bone marrow	UBERON:0002371	96.28	gold quality
adipose tissue	UBERON:0001013	96.18	gold quality
adipose tissue of abdominal region	UBERON:0007808	95.99	gold quality
bone marrow cell	CL:0002092	95.90	gold quality
omental fat pad	UBERON:0010414	95.85	gold quality
connective tissue	UBERON:0002384	95.83	gold quality
peritoneum	UBERON:0002358	95.80	gold quality
gingival epithelium	UBERON:0001949	95.78	gold quality
bone element	UBERON:0001474	95.60	gold quality
palpebral conjunctiva	UBERON:0001812	95.25	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.20	gold quality
gingiva	UBERON:0001828	95.16	gold quality
liver	UBERON:0002107	95.15	gold quality
esophagus mucosa	UBERON:0002469	95.11	gold quality
trabecular bone tissue	UBERON:0002483	95.00	gold quality
amniotic fluid	UBERON:0000173	94.06	gold quality
granulocyte	CL:0000094	94.01	gold quality
ectocervix	UBERON:0012249	93.95	gold quality
esophagus squamous epithelium	UBERON:0006920	93.91	gold quality
right lung	UBERON:0002167	93.79	gold quality
spleen	UBERON:0002106	93.61	gold quality
vagina	UBERON:0000996	93.05	gold quality
squamous epithelium	UBERON:0006914	92.66	gold quality
lower esophagus mucosa	UBERON:0035834	92.48	gold quality
epithelium of esophagus	UBERON:0001976	92.47	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	230.90
E-MTAB-6701	yes	46.25
E-GEOD-135922	yes	19.87
E-MTAB-9067	yes	10.14
E-MTAB-9801	yes	9.81
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting PYGL, 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-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-1257	98.97	68.02	1133
HSA-MIR-6796-3P	98.68	65.49	689
HSA-MIR-3613-5P	98.40	68.91	604
HSA-MIR-5000-5P	97.40	66.11	1055
HSA-MIR-514A-3P	96.43	67.77	1048
HSA-MIR-514B-3P	96.43	67.77	1048

Literature-anchored findings (GeneRIF, showing 12)

• A novel role for Strip/Cka in JNK pathway regulation during spermatogenesis within the developing Drosophila testis. (PMID:31164352)
• Mob4/Cka/Mts functions as an intrinsic molecular switch coordinating Hippo and InR/PI3K/Akt pathways and enabling neural stem cells reactivation. (PMID:31167138)
• Susceptibility to excessive liver glycogen storage in patients with type 1 diabetes. (PMID:15223230)
• Deficiency of liver glycogen phosphorylase is predominantly the result of missense mutations affecting enzyme activity. There are no common mutations and the severity of clinical symptoms varies significantly. (PMID:17705025)
• The vitamin B6-regulated enzymes PYGL and G6PD fuel NADPH oxidases to promote skin inflammation. (PMID:32126244)
• Description of two GSD VI patients expanding the spectrum of PYGL mutations. (PMID:32268899)
• Glycogen storage disease type VI can progress to cirrhosis: ten Chinese patients with GSD VI and a literature review. (PMID:32892177)
• Glycogen storage disease type VI with a novel PYGL mutation: Two case reports and literature review. (PMID:33879691)
• Long noncoding RNA KCNMB2-AS1 promotes the development of esophageal cancer by modulating the miR-3194-3p/PYGL axis. (PMID:34516362)
• Human hair follicles operate an internal Cori cycle and modulate their growth via glycogen phosphorylase. (PMID:34675331)
• Identification of PYGL as a key prognostic gene of glioma by integrated bioinformatics analysis. (PMID:35037470)
• miR-155-5p regulates hypoxia-induced pulmonary artery smooth muscle cell function by targeting PYGL. (PMID:35611851)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pygl	ENSDARG00000002197
mus_musculus	Pygl	ENSMUSG00000021069
rattus_norvegicus	Pygl	ENSRNOG00000006388
drosophila_melanogaster	Glyp	FBGN0004507
caenorhabditis_elegans		WBGENE00020696

Paralogs (2): PYGM (ENSG00000068976), PYGB (ENSG00000100994)

Protein

Protein identifiers

Glycogen phosphorylase, liver form — P06737 (reviewed: P06737)

All UniProt accessions (2): P06737, E9PK47

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; enzymatically active. Interacts with PPP1R3B; recruits the phosphatase PP1 which dephosphorylates and inactivates PYGL/glycogen phosphorylase.

Subcellular location. Cytoplasm. Cytosol.

Post-translational modifications. Acetylation, which is up-regulated by glucose and insulin and down-regulated by glucagon, inhibits the glycogen phosphorylase activity by promoting PPP1R3B-mediated recruitment of phosphatase PP1 and Ser-15 dephosphorylation. Phosphorylation at Ser-15 converts inactive phosphorylase b into active phosphorylase a. Dephosphorylation of Ser-15 by phosphatase PP1 inactivates the enzyme.

Disease relevance. 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. 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 and acetylation.

Similarity. Belongs to the glycogen phosphorylase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P06737-1	1	yes
P06737-2	2

RefSeq proteins (2): NP_001157412, NP_002854* (*=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

Enzyme classification (BRENDA):

• EC 2.4.1.1 — glycogen phosphorylase (BRENDA: 72 organisms, 328 substrates, 721 inhibitors, 318 Km, 78 kcat entries)

Substrate kinetics (BRENDA)

31 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
PHOSPHATE	0.45–100	53
GLUCOSE 1-PHOSPHATE	0.05–20	39
GLYCOGEN	0.0138–40	23
MALTOHEPTAOSE	0.08–39.86	22
MALTOTETRAOSE	0.28–53	22
MALTOPENTAOSE	0.11–280	19
STARCH	0.013–15.5	16
ALPHA-D-GLUCOSE 1-PHOSPHATE	0.054–22	14
MALTOHEXAOSE	0.16–32	12
MALTOTRIOSE	0.3–70	11
AMP	—	9
D-GLUCOSE-1-PHOSPHATE	0.33–0.96	8
AMYLOSE	0.71–20	6
AMYLOPECTIN	0.0046–0.03	5
SOLUBLE STARCH	0.0106–0.15	4

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 (128 total): helix 48, strand 32, modified residue 9, turn 9, sequence variant 9, sequence conflict 8, mutagenesis site 4, binding site 3, site 3, initiator methionine 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

19 structures.

PDB	Method	Resolution (Å)
3DDS	X-RAY DIFFRACTION	1.8
2ATI	X-RAY DIFFRACTION	1.9
3DDW	X-RAY DIFFRACTION	1.9
1L5R	X-RAY DIFFRACTION	2.1
1L5S	X-RAY DIFFRACTION	2.1
1XOI	X-RAY DIFFRACTION	2.1
1EM6	X-RAY DIFFRACTION	2.2
1L5Q	X-RAY DIFFRACTION	2.25
1L7X	X-RAY DIFFRACTION	2.3
1EXV	X-RAY DIFFRACTION	2.4
1FA9	X-RAY DIFFRACTION	2.4
1FC0	X-RAY DIFFRACTION	2.4
2ZB2	X-RAY DIFFRACTION	2.45
3CEM	X-RAY DIFFRACTION	2.47
2QLL	X-RAY DIFFRACTION	2.56
3DD1	X-RAY DIFFRACTION	2.57
8EMS	ELECTRON MICROSCOPY	2.65
3CEH	X-RAY DIFFRACTION	2.8
3CEJ	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P06737-F1	92.87	0.87

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): 43–45; 76; 310

Post-translational modifications (9): 364, 470, 524, 561, 639, 681, 796, 2, 15

Mutagenesis-validated functional residues (4):

Position	Phenotype
470	decreased glycogen phosphorylase activity.
470	decreased acetylation; when associated with r-796.
796	decreased glycogen phosphorylase activity.
796	decreased acetylation; when associated with r-470.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-70221	Glycogen breakdown (glycogenolysis)

MSigDB gene sets: 307 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, MOOTHA_GLYCOGEN_METABOLISM, GOCC_SECRETORY_GRANULE, MODULE_151, MODULE_45, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_16, DOANE_BREAST_CANCER_CLASSES_DN, SHEPARD_BMYB_MORPHOLINO_DN, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_POLYSACCHARIDE_CATABOLIC_PROCESS, HSIAO_LIVER_SPECIFIC_GENES, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, KEGG_STARCH_AND_SUCROSE_METABOLISM, BROWN_MYELOID_CELL_DEVELOPMENT_UP

GO Biological Process (6): glycogen metabolic process (GO:0005977), glycogen catabolic process (GO:0005980), response to bacterium (GO:0009617), glucose homeostasis (GO:0042593), necroptotic process (GO:0070266), carbohydrate metabolic process (GO:0005975)

GO Molecular Function (15): purine nucleobase binding (GO:0002060), ATP binding (GO:0005524), D-glucose binding (GO:0005536), glycogen phosphorylase activity (GO:0008184), AMP binding (GO:0016208), vitamin binding (GO:0019842), pyridoxal phosphate binding (GO:0030170), bile acid binding (GO:0032052), identical protein binding (GO:0042802), nucleotide binding (GO:0000166), 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 (6): extracellular region (GO:0005576), cytoplasm (GO:0005737), cytosol (GO:0005829), secretory granule lumen (GO:0034774), extracellular exosome (GO:0070062), ficolin-1-rich granule lumen (GO:1904813)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
Glycogen metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
adenyl ribonucleotide binding	2
anion binding	2
energy reserve metabolic process	1
glucan metabolic process	1
glycogen metabolic process	1
glucan catabolic process	1
response to other organism	1
carbohydrate homeostasis	1
programmed necrotic cell death	1
primary metabolic process	1
nucleobase binding	1
purine ribonucleoside triphosphate binding	1
monosaccharide binding	1
1,4-alpha-oligoglucan phosphorylase activity	1
cation binding	1
small molecule binding	1
vitamin B6 binding	1
monocarboxylic acid binding	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
hexosyltransferase activity	1
binding	1
catalytic activity	1
transferase activity	1
intracellular anatomical structure	1
cytoplasm	1
secretory granule	1
cytoplasmic vesicle lumen	1
extracellular vesicle	1
intracellular organelle lumen	1
ficolin-1-rich granule	1

Protein interactions and networks

STRING

2499 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PYGL	GYS2	P54840	960
PYGL	AGL	P35573	801
PYGL	UGP2	Q16851	800
PYGL	G6PC1	P35575	791
PYGL	G6PC3	Q9BUM1	789
PYGL	GCK	P35557	782
PYGL	G6PC2	Q9NQR9	782
PYGL	GYS1	P13807	778
PYGL	GBE1	Q04446	763
PYGL	INS	P01308	760
PYGL	H6PD	O95479	717
PYGL	PPP1R3B	Q86XI6	682
PYGL	LIPE	Q05469	675
PYGL	GYG1	P46976	666
PYGL	G6PD	P11413	664

IntAct

81 interactions, top by confidence:

A	B	Type	Score
IKBKB	CHUK	psi-mi:“MI:0914”(association)	0.960
PYGB	PYGL	psi-mi:“MI:0915”(physical association)	0.850
PYGL	PYGB	psi-mi:“MI:0915”(physical association)	0.850
STBD1	GABARAP	psi-mi:“MI:0914”(association)	0.760
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
PYGL	PYGM	psi-mi:“MI:0915”(physical association)	0.560
DCAF4L2	CLUH	psi-mi:“MI:0914”(association)	0.530
HSPB8	VWA8	psi-mi:“MI:0914”(association)	0.530
ZFP41	LRP4	psi-mi:“MI:0914”(association)	0.530
PYGB	STBD1	psi-mi:“MI:0914”(association)	0.530
PYGL	LRRFIP2	psi-mi:“MI:0915”(physical association)	0.400
PYGL	BAG1	psi-mi:“MI:0915”(physical association)	0.370
PYGL	IDH2	psi-mi:“MI:0915”(physical association)	0.370
PYGL	HSD3B7	psi-mi:“MI:0915”(physical association)	0.370
STAT1	KPNA6	psi-mi:“MI:0914”(association)	0.350
APBB1	SSPOP	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (153): PYGL (Affinity Capture-MS), PYGL (Two-hybrid), PYGL (Affinity Capture-MS), PYGL (Affinity Capture-MS), PYGL (Affinity Capture-MS), GBE1 (Co-fractionation), PFKL (Co-fractionation), PFKP (Co-fractionation), PGK1 (Co-fractionation), PYGL (Co-fractionation), PYGL (Co-fractionation), PYGL (Co-fractionation), PYGL (Proximity Label-MS), PYGL (Proximity Label-MS), PYGL (Proximity Label-MS)

ESM2 similar proteins: A0A061AE05, A0QQV6, A1D858, A4YKV0, A5ETE1, A5VSQ0, A9CKA8, A9ILN1, A9M8Q9, B0CIS7, B2S877, B3QBB7, B6IUW0, B6JAC3, C0RFG8, O05877, P06737, P09811, P09824, P11216, P53534, P56862, Q07VC7, Q0V6P9, Q13EF2, Q1QQX2, Q21BY5, Q2J2R9, Q2YLS2, Q3B7M9, Q57AX5, Q5LSN8, Q5LU04, Q5LX16, Q5MIB6, Q5R5M6, Q6NCG2, Q83XD3, Q886D9, Q89XV1

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

9 interactions.

A	Effect	B	Mechanism
RIPK3	up-regulates	PYGL	binding
CP-91149	down-regulates	PYGL	“chemical inhibition”
PYGL	“down-regulates quantity”	glycogen	“chemical modification”
PYGL	“up-regulates quantity”	“alpha-D-glucose 1-phosphate(2-)”	“chemical modification”
PHKG1	“up-regulates activity”	PYGL	phosphorylation
PHKG2	“up-regulates activity”	PYGL	phosphorylation
PP1	“down-regulates activity”	PYGL	dephosphorylation
OGT	“up-regulates activity”	PYGL	glycosylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 86 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of NF-kappaB in B cells	5	16.4×	1e-03
FCERI mediated NF-kB activation	6	15.6×	8e-04
CLEC7A (Dectin-1) signaling	6	14.3×	8e-04
Downstream TCR signaling	6	12.8×	9e-04
Interleukin-1 signaling	6	12.4×	9e-04
PKR-mediated signaling	5	11.8×	2e-03
ER-Phagosome pathway	5	10.8×	3e-03
SARS-CoV-2 activates/modulates innate and adaptive immune responses	6	8.9×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
autophagy	8	12.1×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	43
Likely pathogenic	27
Uncertain significance	185
Likely benign	94
Benign	46

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1029651	NM_002863.5(PYGL):c.528+2T>C	Pathogenic
1070486	NC_000014.8:g.(?51372090)(51411141_?)del	Pathogenic
1076414	NM_002863.5(PYGL):c.1726C>T (p.Arg576Ter)	Pathogenic
11992	NM_002863.5(PYGL):c.1768+1G>A	Pathogenic
11993	NM_002863.5(PYGL):c.529-1G>C	Pathogenic
11995	NM_002863.5(PYGL):c.1131C>G (p.Asn377Lys)	Pathogenic
1298581	NM_002863.5(PYGL):c.1099G>T (p.Glu367Ter)	Pathogenic
1319173	NM_002863.5(PYGL):c.1518+1del	Pathogenic
1686118	NM_002863.5(PYGL):c.1404-1G>A	Pathogenic
1799523	NM_002863.5(PYGL):c.198del (p.Arg67fs)	Pathogenic
189242	NM_002863.5(PYGL):c.25_44dup (p.Ser15fs)	Pathogenic
1935779	NM_002863.5(PYGL):c.1475G>A (p.Trp492Ter)	Pathogenic
194379	NM_002863.5(PYGL):c.1648dup (p.Leu550fs)	Pathogenic
1987284	NM_002863.5(PYGL):c.647G>A (p.Trp216Ter)	Pathogenic
1988522	NM_002863.5(PYGL):c.514C>T (p.Arg172Ter)	Pathogenic
2075738	NM_002863.5(PYGL):c.179_197del (p.Val60fs)	Pathogenic
21327	NM_002863.5(PYGL):c.1195C>T (p.Arg399Ter)	Pathogenic
21337	NM_002863.5(PYGL):c.280C>T (p.Arg94Ter)	Pathogenic
21339	NM_002863.5(PYGL):c.698G>A (p.Gly233Asp)	Pathogenic
2148422	NM_002863.5(PYGL):c.1964_1969+4delinsGAAAAA	Pathogenic
2627510	NM_002863.5(PYGL):c.528+1G>A	Pathogenic
2815716	NM_002863.5(PYGL):c.1228A>T (p.Lys410Ter)	Pathogenic
3252330	NM_002863.5(PYGL):c.773-2A>G	Pathogenic
3346255	NM_002863.5(PYGL):c.856dup (p.Glu288Ter)	Pathogenic
3385228	NM_002863.5(PYGL):c.730C>T (p.Leu244Phe)	Pathogenic
3701206	NM_002863.5(PYGL):c.1778_1781del (p.Lys593fs)	Pathogenic
3720984	NM_002863.5(PYGL):c.808C>T (p.Arg270Ter)	Pathogenic
3727125	NM_002863.5(PYGL):c.324del (p.Cys109fs)	Pathogenic
3772160	NM_002863.5(PYGL):c.702C>G (p.Tyr234Ter)	Pathogenic
38367	NM_002863.5(PYGL):c.1016A>G (p.Asn339Ser)	Pathogenic

SpliceAI

4910 predictions. Top by Δscore:

Variant	Effect	Δscore
14:50872274:CTGCG:C	donor_gain	1.0000
14:50872275:TGCG:T	donor_gain	1.0000
14:50872276:GCG:G	donor_gain	1.0000
14:50872276:GCGG:G	donor_gain	1.0000
14:50872277:CG:C	donor_gain	1.0000
14:50872277:CGGT:C	donor_loss	1.0000
14:50872278:GG:G	donor_gain	1.0000
14:50872278:GGT:G	donor_loss	1.0000
14:50872279:G:GG	donor_gain	1.0000
14:50872279:GTGA:G	donor_loss	1.0000
14:50872280:T:G	donor_loss	1.0000
14:50872281:GAGTA:G	donor_loss	1.0000
14:50881581:A:AG	acceptor_gain	1.0000
14:50881582:A:G	acceptor_gain	1.0000
14:50888816:A:AG	acceptor_gain	1.0000
14:50888817:T:G	acceptor_gain	1.0000
14:50888821:A:AG	acceptor_gain	1.0000
14:50888821:AAG:A	acceptor_gain	1.0000
14:50888822:A:G	acceptor_gain	1.0000
14:50888875:TTGC:T	donor_gain	1.0000
14:50888899:TAAAG:T	donor_loss	1.0000
14:50888900:AAAG:A	donor_loss	1.0000
14:50888901:AAGG:A	donor_loss	1.0000
14:50888902:AGGTG:A	donor_loss	1.0000
14:50888903:GG:G	donor_loss	1.0000
14:50888905:T:A	donor_loss	1.0000
14:50901826:TAG:T	acceptor_loss	1.0000
14:50901827:A:AG	acceptor_gain	1.0000
14:50901827:AGA:A	acceptor_loss	1.0000
14:50901828:G:GG	acceptor_gain	1.0000

AlphaMissense

5630 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:50912199:C:A	K575N	1.000
14:50912199:C:G	K575N	1.000
14:50912200:T:A	K575M	1.000
14:50914745:A:G	W492R	1.000
14:50914745:A:T	W492R	1.000
14:50915902:A:G	W388R	1.000
14:50915902:A:T	W388R	1.000
14:50931700:G:C	F167L	1.000
14:50931700:G:T	F167L	1.000
14:50931702:A:G	F167L	1.000
14:50905460:A:G	W826R	0.999
14:50905460:A:T	W826R	0.999
14:50905489:C:G	R816P	0.999
14:50905494:A:C	S814R	0.999
14:50905494:A:T	S814R	0.999
14:50905496:T:G	S814R	0.999
14:50905500:G:C	F812L	0.999
14:50905500:G:T	F812L	0.999
14:50905502:A:G	F812L	0.999
14:50910015:C:T	G686E	0.999
14:50910016:C:A	G686W	0.999
14:50910029:C:A	K681N	0.999
14:50910029:C:G	K681N	0.999
14:50910031:T:C	K681E	0.999
14:50910035:A:C	N679K	0.999
14:50910035:A:T	N679K	0.999
14:50910046:C:A	G676W	0.999
14:50911867:G:T	A611D	0.999
14:50911870:G:T	A610D	0.999
14:50912197:C:G	R576P	0.999

dbSNP variants (sampled 300 via entrez): RS1000072939 (14:50943652 C>G,T), RS1000119603 (14:50930773 A>C), RS1000146278 (14:50943468 G>A), RS1000152292 (14:50934671 ATG>A,ATGTG), RS1000160174 (14:50925125 G>A), RS1000173865 (14:50930410 G>T), RS1000257515 (14:50934483 T>A), RS1000346242 (14:50925160 C>T), RS1000347948 (14:50928420 C>A), RS1000399635 (14:50921537 G>A), RS1000504546 (14:50919114 C>T), RS1000576563 (14:50921704 A>C), RS1000628784 (14:50922002 T>C), RS1000711044 (14:50937383 A>T), RS1000740925 (14:50912810 C>A,T)

Disease associations

OMIM: gene MIM:613741 | disease phenotypes: MIM:232700, MIM:232200

GenCC curated gene-disease

Disease	Classification	Inheritance
glycogen storage disease VI	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
glycogen storage disease VI	Definitive	AR

Mondo (2): glycogen storage disease VI (MONDO:0009294), disorder of glycogen metabolism (MONDO:0002412)

Orphanet (2): Glycogen storage disease due to liver glycogen phosphorylase deficiency (Orphanet:369), Glycogen storage disease (Orphanet:79201)

HPO phenotypes

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

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000077	Abnormality of the kidney
HP:0000093	Proteinuria
HP:0000737	Irritability
HP:0000823	Delayed puberty
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0001252	Hypotonia
HP:0001270	Motor delay
HP:0001394	Cirrhosis
HP:0001395	Hepatic fibrosis
HP:0001402	Hepatocellular carcinoma
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001531	Failure to thrive in infancy
HP:0001639	Hypertrophic cardiomyopathy
HP:0001943	Hypoglycemia
HP:0001946	Ketosis
HP:0002155	Hypertriglyceridemia
HP:0002240	Hepatomegaly
HP:0002360	Sleep disturbance
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003077	Hyperlipidemia
HP:0003124	Hypercholesterolemia
HP:0003270	Abdominal distention
HP:0003710	Exercise-induced muscle cramps
HP:0004322	Short stature
HP:0004913	Intermittent lactic acidemia
HP:0006568	Increased hepatic glycogen content
HP:0006580	Portal fibrosis

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001693_4	Acute lymphoblastic leukemia (childhood)	7.000000e-09
GCST002211_4	Psychosis (atypical)	8.000000e-07
GCST006585_2675	Blood protein levels	3.000000e-06
GCST012204_1	Rectal cancer	5.000000e-09

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D006008	Glycogen Storage Disease	C16.320.565.202.449; C18.452.648.202.449
D006013	Glycogen Storage Disease Type VI	C16.320.565.202.449.580; C18.452.648.202.449.580

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2568 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 102,674 (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
CHEMBL50	QUERCETIN	3	74,559
CHEMBL206468	AFEGOSTAT	2	334

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs7142143	Efficacy	3	asparaginase;dexamethasone;methotrexate	Acute lymphoblastic leukemia

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7142143	PYGL	3	0.00	1	asparaginase;dexamethasone;methotrexate

Binding affinities (BindingDB)

99 measured of 104 human assays (104 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
2,3-dichloro-N-{1-[(2R)-2,3-dihydroxypropyl]-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl}-4H-thieno[3,2-b]pyrrole-5-carboxamide	IC50	2 nM
(2S,3R)-3-(tert-butoxy)-2-{[4-(4-methoxyphenyl)-2-{[(2,4,6-trimethylphenyl)carbamoyl]amino}phenyl]formamido}butanoic acid	IC50	3 nM
(2S,3R)-3-(tert-butoxy)-2-{[2-({[4-(cyclopropylmethyl)-2,6-dimethylphenyl]carbamoyl}amino)-4-(3-fluorophenyl)phenyl]formamido}butanoic acid	IC50	3 nM
(2S,3R)-3-(tert-butoxy)-2-{[2-({[4-(cyclopropylmethyl)-2,6-dimethylphenyl]carbamoyl}amino)-4-fluorophenyl]formamido}butanoic acid	IC50	4 nM
(2S,3R)-3-(tert-butoxy)-2-[(2-{[(2,6-dimethyl-4-propylphenyl)carbamoyl]amino}-4-(4-methoxyphenyl)phenyl)formamido]butanoic acid	IC50	4 nM
(2S,3R)-3-(tert-butoxy)-2-[(2-{[(2,6-dimethyl-4-propylphenyl)carbamoyl]amino}-4-(3-fluorophenyl)phenyl)formamido]butanoic acid	IC50	4 nM
CP-526,423	IC50	6 nM
2,3-dichloro-N-[1-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]-4H-thieno[3,2-b]pyrrole-5-carboxamide	IC50	7 nM
(2S,3R)-3-(tert-butoxy)-2-[(3-{[(2,4,6-trimethylphenyl)carbamoyl]amino}naphthalen-2-yl)formamido]butanoic acid	IC50	7 nM
(2S,3R)-3-(tert-butoxy)-2-{[4-(4-fluorophenyl)-2-{[(2,4,6-trimethylphenyl)carbamoyl]amino}phenyl]formamido}butanoic acid	IC50	7 nM
(2S,3R)-3-(tert-butoxy)-2-{[4-(3,4-difluorophenyl)-2-{[(2,6-dimethyl-4-propylphenyl)carbamoyl]amino}phenyl]formamido}butanoic acid	IC50	7 nM
(2S,3R)-3-(tert-butoxy)-2-{[4-(3-methoxyphenyl)-2-{[(2,4,6-trimethylphenyl)carbamoyl]amino}phenyl]formamido}butanoic acid	IC50	8 nM
(2S,3R)-3-(tert-butoxy)-2-[(4-phenyl-2-{[(2,4,6-trimethylphenyl)carbamoyl]amino}phenyl)formamido]butanoic acid	IC50	10 nM
(2S,3R)-3-(tert-butoxy)-2-[(2-{[(2,6-dimethyl-4-propylphenyl)carbamoyl]amino}-4-fluorophenyl)formamido]butanoic acid	IC50	10 nM
2-chloro-N-[(3S)-1-[(2S)-2,3-dihydroxypropyl]-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]-6H-thieno[2,3-b]pyrrole-5-carboxamide	IC50	12 nM
(2S,3R)-3-(tert-butoxy)-2-{[4-(3,4-difluorophenyl)-2-{[(2,4,6-trimethylphenyl)carbamoyl]amino}phenyl]formamido}butanoic acid	IC50	13 nM
(2S)-2-cyclohexyl-2-{[2-({[4-(cyclopropylmethyl)-2,6-dimethylphenyl]carbamoyl}amino)-4-fluorophenyl]formamido}acetic acid	IC50	13 nM
(2S,3R)-3-(tert-butoxy)-2-{[4-(3-fluorophenyl)-2-{[(2,4,6-trimethylphenyl)carbamoyl]amino}phenyl]formamido}butanoic acid	IC50	15 nM
5-chloro-N-[1-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]-1H-indole-2-carboxamide	IC50	17 nM
(2S)-2-cyclohexyl-2-[(2-{[(2,6-dimethyl-4-propylphenyl)carbamoyl]amino}-4-fluorophenyl)formamido]acetic acid	IC50	19 nM
indole-2-carboxamide derivative, 25e (R-isomer)	IC50	20 nM
2-chloro-N-[1-(3-hydroxypropyl)-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]-6H-thieno[2,3-b]pyrrole-5-carboxamide	IC50	21 nM
2-chloro-N-[(3R)-1-[(2S)-2,3-dihydroxypropyl]-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]-6H-thieno[2,3-b]pyrrole-5-carboxamide	IC50	21 nM
2-chloro-N-[1-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]-6H-thieno[2,3-b]pyrrole-5-carboxamide	IC50	26 nM
2-chloro-N-[(3S)-1-[(2R)-2,3-dihydroxypropyl]-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]-6H-thieno[2,3-b]pyrrole-5-carboxamide	IC50	27 nM
2-chloro-N-[1-(cyanomethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]-6H-thieno[2,3-b]pyrrole-5-carboxamide	IC50	28 nM
(2S,3R)-3-(tert-butoxy)-2-{[4-(2-methoxyphenyl)-2-{[(2,4,6-trimethylphenyl)carbamoyl]amino}phenyl]formamido}butanoic acid	IC50	28 nM
2-chloro-N-{1-[(2R)-2,3-dihydroxypropyl]-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl}-6H-thieno[2,3-b]pyrrole-5-carboxamide	IC50	29 nM
indole-2-carboxamide derivative, 25e	IC50	36 nM
2,3-dichloro-N-{1-[3-hydroxy-2-(hydroxymethyl)propyl]-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl}-4H-thieno[3,2-b]pyrrole-5-carboxamide	IC50	38 nM
2-chloro-N-[(3R)-1-[(2R)-2,3-dihydroxypropyl]-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]-6H-thieno[2,3-b]pyrrole-5-carboxamide	IC50	40 nM
2-chloro-N-(2-oxo-1,2,3,4-tetrahydroquinolin-3-yl)-6H-thieno[2,3-b]pyrrole-5-carboxamide	IC50	41 nM
2-chloro-N-[1-(2-hydroxybutyl)-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]-6H-thieno[2,3-b]pyrrole-5-carboxamide	IC50	44 nM
5-chloro-N-{1-[(2R)-2,3-dihydroxypropyl]-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl}-1H-indole-2-carboxamide	IC50	44 nM
1-{(S)-2-[(5-Chloro-1H-indole-2-carbonyl)-amino]-3-phenyl-propionyl}-azetidine-3-carboxylic acid	IC50	45 nM
2-chloro-N-[1-(2-methanesulfinylethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]-6H-thieno[2,3-b]pyrrole-5-carboxamide	IC50	48 nM
indole-2-carboxamide derivative, 25d	IC50	48 nM
(2S)-2-[(2-{[(4-butyl-2,6-dimethylphenyl)carbamoyl]amino}-4-fluorophenyl)formamido]-2-cyclohexylacetic acid	IC50	49 nM
2-chloro-N-[1-(2-methoxyethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]-6H-thieno[2,3-b]pyrrole-5-carboxamide	IC50	50 nM
2-chloro-N-{1-[3-hydroxy-2-(hydroxymethyl)propyl]-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl}-6H-thieno[2,3-b]pyrrole-5-carboxamide	IC50	60 nM
2-chloro-N-[1-(2-methanesulfonylethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]-6H-thieno[2,3-b]pyrrole-5-carboxamide	IC50	63 nM
2-[3-({2,3-dichloro-4H-thieno[3,2-b]pyrrole-5-}amido)-2-oxo-1,2,3,4-tetrahydroquinolin-1-yl]acetic acid	IC50	63 nM
indole-2-carboxamide derivative, 25c	IC50	63 nM
5-chloro-N-{1-[3-hydroxy-2-(hydroxymethyl)propyl]-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl}-1H-indole-2-carboxamide	IC50	66 nM
indole-2-carboxamide derivative, 15	IC50	68 nM
(2S)-2-[(3-{[(2-chloro-6-methylphenyl)carbamoyl]amino}naphthalen-2-yl)formamido]-2-cyclohexylacetic acid	IC50	73 nM
2-chloro-N-{1-[(N’-hydroxycarbamimidoyl)methyl]-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl}-6H-thieno[2,3-b]pyrrole-5-carboxamide	IC50	75 nM
2-chloro-N-{1-[(methylcarbamoyl)methyl]-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl}-6H-thieno[2,3-b]pyrrole-5-carboxamide	IC50	79 nM
2-chloro-N-[2-oxo-1-(2-oxobutyl)-1,2,3,4-tetrahydroquinolin-3-yl]-6H-thieno[2,3-b]pyrrole-5-carboxamide	IC50	84 nM
methyl 2-[3-({2-chloro-6H-thieno[2,3-b]pyrrole-5-}amido)-2-oxo-1,2,3,4-tetrahydroquinolin-1-yl]acetate	IC50	84 nM

ChEMBL bioactivities

666 potent at pChembl≥5 of 715 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	IC50	1	nM	CHEMBL134802
9.00	IC50	1	nM	CHEMBL133911
8.70	IC50	2	nM	CHEMBL394526
8.70	IC50	2	nM	CHEMBL440528
8.70	IC50	2	nM	CHEMBL133832
8.70	IC50	2	nM	CHEMBL115651
8.62	Kd	2.394	nM	CHEMBL3752910
8.62	ED50	2.394	nM	CHEMBL3752910
8.52	IC50	3	nM	CHEMBL471266
8.52	IC50	3	nM	CHEMBL458655
8.52	IC50	3	nM	CHEMBL132191
8.40	IC50	4	nM	CHEMBL459792
8.40	IC50	4	nM	CHEMBL506011
8.40	IC50	4	nM	CHEMBL449986
8.40	IC50	4	nM	CHEMBL133274
8.40	IC50	4	nM	CHEMBL115341
8.30	IC50	5	nM	CHEMBL217994
8.30	IC50	5	nM	CHEMBL480195
8.30	IC50	5	nM	CHEMBL481534
8.30	IC50	5	nM	CHEMBL423509
8.22	IC50	6	nM	CHEMBL434025
8.22	IC50	6	nM	CHEMBL472140
8.22	IC50	6	nM	CHEMBL474193
8.15	IC50	7	nM	CHEMBL395733
8.15	IC50	7	nM	CHEMBL473851
8.15	IC50	7	nM	CHEMBL472292
8.15	IC50	7	nM	CHEMBL443938
8.10	IC50	8	nM	CHEMBL479920
8.10	IC50	7.88	nM	CHEMBL113736
8.10	IC50	8	nM	CHEMBL113762
8.05	IC50	9	nM	CHEMBL219059
8.05	IC50	9	nM	CHEMBL516081
8.04	IC50	9.1	nM	CHEMBL114226
8.00	IC50	10	nM	CHEMBL482146
8.00	IC50	10	nM	CHEMBL471469
8.00	IC50	10	nM	CHEMBL473486
8.00	IC50	10	nM	CHEMBL133923
8.00	IC50	10	nM	CHEMBL132640
7.96	IC50	11	nM	CHEMBL133603
7.96	IC50	11	nM	CHEMBL114731
7.96	IC50	10.9	nM	CHEMBL326950
7.92	IC50	12	nM	CHEMBL179485
7.92	IC50	12	nM	CHEMBL396724
7.92	IC50	12	nM	CHEMBL488273
7.92	IC50	12	nM	CHEMBL337224
7.91	IC50	12.4	nM	CHEMBL114846
7.89	IC50	13	nM	CHEMBL519796
7.89	IC50	13	nM	CHEMBL512725
7.89	IC50	13	nM	CHEMBL474098
7.89	IC50	13	nM	CHEMBL133114

PubChem BioAssay actives

762 with measured affinity, of 1146 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
4-[3-fluoro-2-[(4-nitropyridine-2-carbonyl)amino]phenoxy]phthalic acid	73811: Inhibitory activity against HLGP(human liver glycogen phosphorylase)	ic50	0.0010	uM
4-[3-[(4-nitropyridine-2-carbonyl)amino]naphthalen-2-yl]oxyphthalic acid	73811: Inhibitory activity against HLGP(human liver glycogen phosphorylase)	ic50	0.0010	uM
2,3-dichloro-N-[1-[(2R)-2,3-dihydroxypropyl]-2-oxo-3,4-dihydroquinolin-3-yl]-4H-thieno[3,2-b]pyrrole-5-carboxamide	1798432: Enzyme Inhibition Assay from Article 10.1016/j.bmcl.2006.10.037: “Development of potent, orally active 1-substituted-3,4-dihydro-2-quinolone glycogen phosphorylase inhibitors.”	ic50	0.0020	uM
4-(2-chlorophenyl)-1-[(4-chlorophenyl)methyl]-6-methyl-5-propan-2-yloxycarbonyl-4H-pyridine-2,3-dicarboxylic acid	101848: In vitro inhibitory activity against human liver glycogen phosphorylase a (HLGPa)	ic50	0.0020	uM
4-[3-[(4-chloropyridine-2-carbonyl)amino]naphthalen-2-yl]oxyphthalic acid	73811: Inhibitory activity against HLGP(human liver glycogen phosphorylase)	ic50	0.0020	uM
4-[3-[(4-methoxypyridine-2-carbonyl)amino]naphthalen-2-yl]oxyphthalic acid	73811: Inhibitory activity against HLGP(human liver glycogen phosphorylase)	ic50	0.0020	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149160: Binding affinity to human PYGL incubated for 45 mins by Kinobead based pull down assay	kd	0.0024	uM
(2S,3R)-2-[[2-[[4-(cyclopropylmethyl)-2,6-dimethylphenyl]carbamoylamino]-4-(3-fluorophenyl)benzoyl]amino]-3-[(2-methylpropan-2-yl)oxy]butanoic acid	1798827: Human Liver GPa Enzymatic Activity Assay from Article 10.1016/j.bmcl.2008.12.085: “Anthranilimide based glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. Part 3: X-ray crystallographic characterization, core and urea optimization and in vivo efficacy.”	ic50	0.0030	uM
(2S,3R)-2-[[4-(4-methoxyphenyl)-2-[(2,4,6-trimethylphenyl)carbamoylamino]benzoyl]amino]-3-[(2-methylpropan-2-yl)oxy]butanoic acid	1798827: Human Liver GPa Enzymatic Activity Assay from Article 10.1016/j.bmcl.2008.12.085: “Anthranilimide based glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. Part 3: X-ray crystallographic characterization, core and urea optimization and in vivo efficacy.”	ic50	0.0030	uM
4-[2-[(4-nitropyridine-2-carbonyl)amino]phenoxy]phthalic acid	73811: Inhibitory activity against HLGP(human liver glycogen phosphorylase)	ic50	0.0030	uM
(2S,3R)-2-[[2-[[4-(cyclopropylmethyl)-2,6-dimethylphenyl]carbamoylamino]-4-fluorobenzoyl]amino]-3-[(2-methylpropan-2-yl)oxy]butanoic acid	1798827: Human Liver GPa Enzymatic Activity Assay from Article 10.1016/j.bmcl.2008.12.085: “Anthranilimide based glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. Part 3: X-ray crystallographic characterization, core and urea optimization and in vivo efficacy.”	ic50	0.0040	uM
(2S,3R)-2-[[2-[(2,6-dimethyl-4-propylphenyl)carbamoylamino]-4-(4-methoxyphenyl)benzoyl]amino]-3-[(2-methylpropan-2-yl)oxy]butanoic acid	1798827: Human Liver GPa Enzymatic Activity Assay from Article 10.1016/j.bmcl.2008.12.085: “Anthranilimide based glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. Part 3: X-ray crystallographic characterization, core and urea optimization and in vivo efficacy.”	ic50	0.0040	uM
(2S,3R)-2-[[2-[(2,6-dimethyl-4-propylphenyl)carbamoylamino]-4-(3-fluorophenyl)benzoyl]amino]-3-[(2-methylpropan-2-yl)oxy]butanoic acid	1798827: Human Liver GPa Enzymatic Activity Assay from Article 10.1016/j.bmcl.2008.12.085: “Anthranilimide based glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. Part 3: X-ray crystallographic characterization, core and urea optimization and in vivo efficacy.”	ic50	0.0040	uM
4-[3-[(4-ethylpyridine-2-carbonyl)amino]naphthalen-2-yl]oxyphthalic acid	73811: Inhibitory activity against HLGP(human liver glycogen phosphorylase)	ic50	0.0040	uM
4-(2-chlorophenyl)-1-[(3,4-dimethoxyphenyl)methyl]-6-methyl-5-propan-2-yloxycarbonyl-4H-pyridine-2,3-dicarboxylic acid	101848: In vitro inhibitory activity against human liver glycogen phosphorylase a (HLGPa)	ic50	0.0040	uM
1-[[3-[(2,4,6-trimethylphenyl)carbamoylamino]naphthalene-2-carbonyl]amino]cyclooctane-1-carboxylic acid	367021: Inhibition of human liver glycogen phosphorylase A by fluorescence intensity endpoint assay in presence of glucose	ic50	0.0050	uM
4-(2-chlorophenyl)-6-methyl-1-[(3-nitrophenyl)methyl]-5-propan-2-yloxycarbonyl-4H-pyridine-2,3-dicarboxylic acid	101848: In vitro inhibitory activity against human liver glycogen phosphorylase a (HLGPa)	ic50	0.0050	uM
2,3-dichloro-N-[(2S)-1-(dimethylamino)-1-oxo-3-phenylpropan-2-yl]-4H-thieno[3,2-b]pyrrole-5-carboxamide	276334: Inhibition of recombinant human liver GPa by multienzyme coupled assay	ic50	0.0050	uM
(2S)-2-cyclohexyl-2-[[3-[[2,6-dichloro-4-(trifluoromethoxy)phenyl]carbamoylamino]naphthalene-2-carbonyl]amino]acetic acid	367021: Inhibition of human liver glycogen phosphorylase A by fluorescence intensity endpoint assay in presence of glucose	ic50	0.0050	uM
5-chloro-N-[2-[2-[2-[(5-chloro-1H-indole-2-carbonyl)amino]ethoxy]ethoxy]ethyl]-1H-indole-2-carboxamide	1186739: Inhibition of glycogen phosphorylase a (unknown origin)	ic50	0.0060	uM
(2S)-2-cyclohexyl-2-[[3-[(2,4,6-trimethylphenyl)carbamoylamino]naphthalene-2-carbonyl]amino]acetic acid	367021: Inhibition of human liver glycogen phosphorylase A by fluorescence intensity endpoint assay in presence of glucose	ic50	0.0060	uM
(2S,3R)-3-(1-methylcyclopentyl)oxy-2-[[3-[(2,4,6-trimethylphenyl)carbamoylamino]naphthalene-2-carbonyl]amino]butanoic acid	367036: Inhibition of human liver glycogen phosphorylase A by fluorescence plate reader assay	ic50	0.0060	uM
N-[2-[2-[2-[(5-chloro-1H-indole-2-carbonyl)amino]ethoxy]ethoxy]ethyl]-5-methyl-1H-indole-2-carboxamide	1799470: Inhibition Activity Assay from Article 10.1016/S1074-5521(00)00004-1: “Human liver glycogen phosphorylase inhibitors bind at a new allosteric site.”	ic50	0.0060	uM
2,3-dichloro-N-[1-(2-hydroxyethyl)-2-oxo-3,4-dihydroquinolin-3-yl]-4H-thieno[3,2-b]pyrrole-5-carboxamide	1798432: Enzyme Inhibition Assay from Article 10.1016/j.bmcl.2006.10.037: “Development of potent, orally active 1-substituted-3,4-dihydro-2-quinolone glycogen phosphorylase inhibitors.”	ic50	0.0070	uM
(2S,3R)-3-[(2-methylpropan-2-yl)oxy]-2-[[3-[(2,4,6-trimethylphenyl)carbamoylamino]naphthalene-2-carbonyl]amino]butanoic acid	1798827: Human Liver GPa Enzymatic Activity Assay from Article 10.1016/j.bmcl.2008.12.085: “Anthranilimide based glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. Part 3: X-ray crystallographic characterization, core and urea optimization and in vivo efficacy.”	ic50	0.0070	uM
(2S,3R)-2-[[4-(4-fluorophenyl)-2-[(2,4,6-trimethylphenyl)carbamoylamino]benzoyl]amino]-3-[(2-methylpropan-2-yl)oxy]butanoic acid	1798827: Human Liver GPa Enzymatic Activity Assay from Article 10.1016/j.bmcl.2008.12.085: “Anthranilimide based glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. Part 3: X-ray crystallographic characterization, core and urea optimization and in vivo efficacy.”	ic50	0.0070	uM
(2S,3R)-2-[[4-(3,4-difluorophenyl)-2-[(2,6-dimethyl-4-propylphenyl)carbamoylamino]benzoyl]amino]-3-[(2-methylpropan-2-yl)oxy]butanoic acid	1798827: Human Liver GPa Enzymatic Activity Assay from Article 10.1016/j.bmcl.2008.12.085: “Anthranilimide based glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. Part 3: X-ray crystallographic characterization, core and urea optimization and in vivo efficacy.”	ic50	0.0070	uM
4-(2-chlorophenyl)-1-ethyl-6-methyl-5-(2-methylpropylcarbamoyl)-4H-pyridine-2,3-dicarboxylic acid	101848: In vitro inhibitory activity against human liver glycogen phosphorylase a (HLGPa)	ic50	0.0079	uM
(2S,3R)-2-[[4-(3-methoxyphenyl)-2-[(2,4,6-trimethylphenyl)carbamoylamino]benzoyl]amino]-3-[(2-methylpropan-2-yl)oxy]butanoic acid	1798827: Human Liver GPa Enzymatic Activity Assay from Article 10.1016/j.bmcl.2008.12.085: “Anthranilimide based glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. Part 3: X-ray crystallographic characterization, core and urea optimization and in vivo efficacy.”	ic50	0.0080	uM
4-(2-chlorophenyl)-1-[(3-chlorophenyl)methyl]-6-methyl-5-propan-2-yloxycarbonyl-4H-pyridine-2,3-dicarboxylic acid	101848: In vitro inhibitory activity against human liver glycogen phosphorylase a (HLGPa)	ic50	0.0080	uM
(2S)-5-methyl-2-[[3-[(2,4,6-trimethylphenyl)carbamoylamino]naphthalene-2-carbonyl]amino]hexanoic acid	367036: Inhibition of human liver glycogen phosphorylase A by fluorescence plate reader assay	ic50	0.0090	uM
2,3-dichloro-N-[(1R,2R)-1-hydroxy-2,3-dihydro-1H-inden-2-yl]-4H-thieno[3,2-b]pyrrole-5-carboxamide	276334: Inhibition of recombinant human liver GPa by multienzyme coupled assay	ic50	0.0090	uM
4-(2-chlorophenyl)-1-ethyl-6-methyl-5-(propan-2-ylcarbamoyl)-4H-pyridine-2,3-dicarboxylic acid	101848: In vitro inhibitory activity against human liver glycogen phosphorylase a (HLGPa)	ic50	0.0091	uM
(2S)-2-cyclohexyl-2-[[3-[(2,4,6-trimethylphenyl)carbamoylamino]naphthalene-2-carbonyl]amino]propanoic acid	367021: Inhibition of human liver glycogen phosphorylase A by fluorescence intensity endpoint assay in presence of glucose	ic50	0.0100	uM
(2S,3R)-3-[(2-methylpropan-2-yl)oxy]-2-[[4-phenyl-2-[(2,4,6-trimethylphenyl)carbamoylamino]benzoyl]amino]butanoic acid	1798827: Human Liver GPa Enzymatic Activity Assay from Article 10.1016/j.bmcl.2008.12.085: “Anthranilimide based glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. Part 3: X-ray crystallographic characterization, core and urea optimization and in vivo efficacy.”	ic50	0.0100	uM
(2S,3R)-2-[[2-[(2,6-dimethyl-4-propylphenyl)carbamoylamino]-4-fluorobenzoyl]amino]-3-[(2-methylpropan-2-yl)oxy]butanoic acid	1798827: Human Liver GPa Enzymatic Activity Assay from Article 10.1016/j.bmcl.2008.12.085: “Anthranilimide based glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. Part 3: X-ray crystallographic characterization, core and urea optimization and in vivo efficacy.”	ic50	0.0100	uM
4-[3-[(4-methylpyridine-2-carbonyl)amino]naphthalen-2-yl]oxyphthalic acid	73811: Inhibitory activity against HLGP(human liver glycogen phosphorylase)	ic50	0.0100	uM
4-[2-[(4-chloropyridine-2-carbonyl)amino]-3-fluorophenoxy]phthalic acid	73811: Inhibitory activity against HLGP(human liver glycogen phosphorylase)	ic50	0.0100	uM
5-(benzylcarbamoyl)-4-(2-chlorophenyl)-1-ethyl-6-methyl-4H-pyridine-2,3-dicarboxylic acid	101848: In vitro inhibitory activity against human liver glycogen phosphorylase a (HLGPa)	ic50	0.0109	uM
1-benzyl-4-(2-chlorophenyl)-6-methyl-5-propan-2-yloxycarbonyl-4H-pyridine-2,3-dicarboxylic acid	101848: In vitro inhibitory activity against human liver glycogen phosphorylase a (HLGPa)	ic50	0.0110	uM
4-[3-fluoro-2-[(4-methoxypyridine-2-carbonyl)amino]phenoxy]phthalic acid	73811: Inhibitory activity against HLGP(human liver glycogen phosphorylase)	ic50	0.0110	uM
2-chloro-N-[(3S)-1-[(2S)-2,3-dihydroxypropyl]-2-oxo-3,4-dihydroquinolin-3-yl]-6H-thieno[2,3-b]pyrrole-5-carboxamide	1798432: Enzyme Inhibition Assay from Article 10.1016/j.bmcl.2006.10.037: “Development of potent, orally active 1-substituted-3,4-dihydro-2-quinolone glycogen phosphorylase inhibitors.”	ic50	0.0120	uM
4-[3-[[4-(trifluoromethyl)pyridine-2-carbonyl]amino]naphthalen-2-yl]oxyphthalic acid	73811: Inhibitory activity against HLGP(human liver glycogen phosphorylase)	ic50	0.0120	uM
5-chloro-N-[2-[(1,1-dioxothian-4-yl)-(2-hydroxyethyl)amino]-2-oxoethyl]-1H-indole-2-carboxamide	240837: Inhibitory concentration against glycogen phosphorylase	ic50	0.0120	uM
(E)-3-(3,4-dichlorophenyl)-N-[2-[2-[[(E)-3-(3,4-dichlorophenyl)prop-2-enoyl]amino]ethylsulfanyl]ethyl]prop-2-enamide	409747: Inhibition of human liver glycogen phosphorylase a in presence of glucose	ic50	0.0120	uM
4-(2-chlorophenyl)-1-ethyl-5-(ethylcarbamoyl)-6-methyl-4H-pyridine-2,3-dicarboxylic acid	101848: In vitro inhibitory activity against human liver glycogen phosphorylase a (HLGPa)	ic50	0.0124	uM
(2S,3R)-2-[[4-(3,4-difluorophenyl)-2-[(2,4,6-trimethylphenyl)carbamoylamino]benzoyl]amino]-3-[(2-methylpropan-2-yl)oxy]butanoic acid	1798827: Human Liver GPa Enzymatic Activity Assay from Article 10.1016/j.bmcl.2008.12.085: “Anthranilimide based glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. Part 3: X-ray crystallographic characterization, core and urea optimization and in vivo efficacy.”	ic50	0.0130	uM
(2S)-2-cyclohexyl-2-[[2-[[4-(cyclopropylmethyl)-2,6-dimethylphenyl]carbamoylamino]-4-fluorobenzoyl]amino]acetic acid	1798827: Human Liver GPa Enzymatic Activity Assay from Article 10.1016/j.bmcl.2008.12.085: “Anthranilimide based glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. Part 3: X-ray crystallographic characterization, core and urea optimization and in vivo efficacy.”	ic50	0.0130	uM
4-(2-chlorophenyl)-1-[(3,4-dichlorophenyl)methyl]-6-methyl-5-propan-2-yloxycarbonyl-4H-pyridine-2,3-dicarboxylic acid	101848: In vitro inhibitory activity against human liver glycogen phosphorylase a (HLGPa)	ic50	0.0130	uM
4-[4-fluoro-2-[(4-nitropyridine-2-carbonyl)amino]phenoxy]phthalic acid	73811: Inhibitory activity against HLGP(human liver glycogen phosphorylase)	ic50	0.0130	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
Cisplatin	decreases expression, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
methylmercuric chloride	decreases expression	2
bisphenol A	decreases expression, increases expression	2
chloropicrin	increases expression, decreases expression	2
Vorinostat	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Cyclosporine	decreases expression	2
bisphenol F	increases expression	1
chloroacetaldehyde	affects expression	1
triphenyl phosphate	affects expression	1
baicalein	decreases activity	1
sodium arsenate	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression, decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	increases expression	1
benzamide	decreases activity	1
di-n-butylphosphoric acid	affects expression	1
alvocidib	affects binding	1
vanillin	affects binding	1
acyline	increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
procyanidin B1	affects cotreatment, decreases activity	1
nutlin 3	affects cotreatment, increases expression, increases secretion	1
bisphenol B	increases expression	1
p-coumaric acid	affects cotreatment, decreases activity	1
abrine	decreases expression	1

ChEMBL screening assays

58 unique, capped per target: 58 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1027304	Binding	Inhibition of human liver glycogen phosphorylase a by coupled kinetic fluorescent intensity assay	Anthranilimide based glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. Part 3: X-ray crystallographic characterization, core and urea optimization and in vivo efficacy. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
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
NCT02385162	Not specified	WITHDRAWN	Biomarker for Glycogen Storage Diseases (BioGlycogen)
NCT04454216	Not specified	RECRUITING	GSD VI and GSD IX Natural History
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
NCT04292938	Not specified	COMPLETED	McArdle Disease Treatment by Ketogenic Diet
NCT04399694	Not specified	COMPLETED	Identification and Characterization of Novel Non-Coding Variants That Contribute to Genetic Disorders
NCT04929002	Not specified	ACTIVE_NOT_RECRUITING	Carbon-13 Magnetic Resonance Spectroscopy in Glycogen Storage Diseases
NCT05199246	Not specified	COMPLETED	Assessment of Safety and Acute Effects of a Lower-limb Powered Dermoskeleton in Patients With Neuromuscular Disorders
NCT05200702	Not specified	COMPLETED	Assessment of Safety and Acute Effects of a Knee-hip Powered Soft Exoskeleton in Patients With Neuromuscular Disorders
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT06396546	Not specified	RECRUITING	‘Glycogen Storage Diseases (GSDs) in Indian Children- Establishing an Indian GSD (I-GSD) Registry’
NCT06795152	Not specified	RECRUITING	Rare Glycogen Storage Diseases Natural History Study
NCT06813443	Not specified	RECRUITING	Characterization of Patients With Cardiomyopathy to Identify Critical Patients Candidates for Cardiac Transplantation
NCT07136844	Not specified	RECRUITING	Gait Analysis Parameter and Upper Limb Evaluation in Adult Patients With Neurological or Metabolic Pathology
NCT07336394	Not specified	RECRUITING	Precision Diagnosis and Risk Stratification of Rare Cardiomyopathies Based on Novel Cardiac Magnetic Resonance Techniques
NCT07614139	Not specified	COMPLETED	Continuous Glucose Monitoring Alerts, Accuracy, and Patient Outcomes in Adults With Inherited Metabolic Disorders