PYGB

Summary

PYGB (glycogen phosphorylase B, HGNC:9723) is a protein-coding gene on chromosome 20p11.21, encoding Glycogen phosphorylase, brain form (P11216). Glycogen phosphorylase that regulates glycogen mobilization.

The protein encoded by this gene is a glycogen phosphorylase found predominantly in the brain. The encoded protein forms homodimers which can associate into homotetramers, the enzymatically active form of glycogen phosphorylase. The activity of this enzyme is positively regulated by AMP and negatively regulated by ATP, ADP, and glucose-6-phosphate. This enzyme catalyzes the rate-determining step in glycogen degradation.

Source: NCBI Gene 5834 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 165 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002862

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9723
Approved symbol	PYGB
Name	glycogen phosphorylase B
Location	20p11.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000100994
Ensembl biotype	protein_coding
OMIM	138550
Entrez	5834

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 22 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000216962, ENST00000428458, ENST00000471359, ENST00000896648, ENST00000896649, ENST00000896650, ENST00000896651, ENST00000896652, ENST00000896653, ENST00000896654, ENST00000896655, ENST00000896656, ENST00000923184, ENST00000923185, ENST00000944638, ENST00000944639, ENST00000944640, ENST00000944641, ENST00000944642, ENST00000944643, ENST00000944644, ENST00000944645, ENST00000944646

RefSeq mRNA: 1 — MANE Select: NM_002862 NM_002862

CCDS: CCDS13171

Canonical transcript exons

ENST00000216962 — 20 exons

Exon	Start	End
ENSE00000661004	25259237	25259338
ENSE00000661012	25280266	25280412
ENSE00000859498	25248085	25248421
ENSE00001140305	25294158	25294292
ENSE00001140318	25290481	25290622
ENSE00001140326	25288425	25288483
ENSE00001140340	25283176	25283277
ENSE00001140348	25282033	25282147
ENSE00001140359	25280949	25281112
ENSE00001140376	25278319	25278462
ENSE00001140385	25277244	25277326
ENSE00001140397	25274592	25274723
ENSE00001140403	25271383	25271486
ENSE00001140409	25269129	25269207
ENSE00001597985	25276646	25276757
ENSE00001767518	25284104	25284251
ENSE00001779306	25279057	25279149
ENSE00001786057	25292406	25292613
ENSE00001860485	25296370	25298012
ENSE00003460504	25295604	25295670

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 98.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 67.5914 / max 732.0354, expressed in 1816 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183925	65.8236	1816
183926	1.2044	829
183927	0.5634	307

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus muscularis layer	UBERON:0035833	98.93	gold quality
lower esophagus	UBERON:0013473	98.92	gold quality
apex of heart	UBERON:0002098	98.70	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.33	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.23	gold quality
cerebellar hemisphere	UBERON:0002245	98.19	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.15	gold quality
cerebellar cortex	UBERON:0002129	98.14	gold quality
transverse colon	UBERON:0001157	98.07	gold quality
right coronary artery	UBERON:0001625	98.06	gold quality
popliteal artery	UBERON:0002250	97.88	gold quality
tibial artery	UBERON:0007610	97.87	gold quality
mucosa of transverse colon	UBERON:0004991	97.73	gold quality
minor salivary gland	UBERON:0001830	97.69	gold quality
right atrium auricular region	UBERON:0006631	97.68	gold quality
heart left ventricle	UBERON:0002084	97.53	gold quality
cerebellum	UBERON:0002037	97.52	gold quality
aorta	UBERON:0000947	97.48	gold quality
sigmoid colon	UBERON:0001159	97.35	gold quality
cardiac atrium	UBERON:0002081	97.35	gold quality
cardiac ventricle	UBERON:0002082	97.35	gold quality
skin of leg	UBERON:0001511	97.18	gold quality
thoracic aorta	UBERON:0001515	97.10	gold quality
ascending aorta	UBERON:0001496	97.07	gold quality
stromal cell of endometrium	CL:0002255	96.97	gold quality
heart	UBERON:0000948	96.96	gold quality
right frontal lobe	UBERON:0002810	96.95	gold quality
left coronary artery	UBERON:0001626	96.88	gold quality
descending thoracic aorta	UBERON:0002345	96.85	gold quality
rectum	UBERON:0001052	96.84	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6819	yes	899.24
E-CURD-114	yes	31.12
E-MTAB-7381	no	2465.91
E-GEOD-36552	no	112.84
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

61 targeting PYGB, 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-5193	100.00	67.26	1744
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-451B	99.55	68.28	1380

Literature-anchored findings (GeneRIF, showing 16)

• Brain-type glycogen phosphorylase is expressed in non-small-cell lung carcinoma, particularly adenocarcinomas, and is an independent poor prognostic factor. (PMID:17393985)
• This protein has been found differentially expressed in thalami from patients with schizophrenia. (PMID:20471030)
• Significant increase in plasma glycoprotein BB in patients with hypertrophic cardiomyopathy. (PMID:20482380)
• GPBB is a valuable biological marker to predict the prognosis in patient with acute coronary syndrome. (PMID:22818785)
• H-FABP and GPBB can contribute to early acute myocardial infarction diagnosis and can distinguish acute myocardial infarction from acute coronary syndrome (PMID:22838188)
• the bGP structures reveal molecular features unique to the brain isozyme that provide a deeper understanding of the differences in the activation properties of these allosteric enzymes by the allosteric effector AMP. (PMID:27402852)
• disulfide bond acts as a redox switch that precludes the allosteric activation of the enzyme by AMP without affecting its activation by phosphorylation. This unique regulatory feature of bGP sheds new light on the isoform-specific regulation of glycogen phosphorylase and glycogen metabolism. (PMID:27660393)
• Using cysteine chemical labeling, mass spectrometry, and site-directed mutagenesis approaches, we show that thiram (and certain of its metabolites) alters the activity of bGP through the formation of an intramolecular disulfide bond (Cys(318)-Cys(326)), known to act as a redox switch that precludes the allosteric activation of bGP by AMP. (PMID:27965358)
• The mean plasma GPBB levels were higher in acute ischemic stroke cases than in controls. (PMID:29030420)
• PYGB siRNA exerted an inhibitory effect on the cell viability of the human osteosarcoma cells MG63 and HOS by blocking the Caspase/Bcl and CDK1 signaling pathway, highlighting novel potential therapeutic methods for treating osteosarcoma. (PMID:29845265)
• PYGB silencing suppressed the growth and promoted the apoptosis of prostate cancer cells by affecting the NFkappaB/Nrf2 signaling pathway. (PMID:30106110)
• we identify PYGB as a novel metabolic target with potential applications in the management and/or prevention of metastasis in breast cancer. (PMID:31536495)
• Authors showed that PYGB was upregulated in ovarian cancer tissue and high level of PYGB expression is markedly correlated with poor prognosis of ovarian cancer patients. PYGB knockdown significantly suppressed ovarian cancer cell proliferation, invasion and migration. (PMID:31627092)
• This method allows absolute quantitative measurement when conventional calibration curve fails to provide accurate estimation of cardiac biomarkers, especially at low and high concentration ranges. Under an optimised condition, the LOD of our SERS-based muPAD was identified at 8, 10, and 1pgmL(-1), for GPBB, CK-MB and cTnT, respectively, which is well below the clinical cutoff values. (PMID:31678828)
• PYGB Promoted Tumor Progression by Regulating Wnt/beta-Catenin Pathway in Gastric Cancer. (PMID:32462986)
• Unveiling the role of PYGB in pancreatic cancer: a novel diagnostic biomarker and gene therapy target. (PMID:38483604)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pygb	ENSDARG00000002021
mus_musculus	Pygb	ENSMUSG00000033059
rattus_norvegicus	Pygb	ENSRNOG00000007583
drosophila_melanogaster	Glyp	FBGN0004507
caenorhabditis_elegans		WBGENE00020696

Paralogs (2): PYGM (ENSG00000068976), PYGL (ENSG00000100504)

Protein

Protein identifiers

Glycogen phosphorylase, brain form — P11216 (reviewed: P11216)

All UniProt accessions (2): P11216, H0Y4Z6

UniProt curated annotations — full annotation on UniProt →

Function. Glycogen phosphorylase that regulates glycogen mobilization. Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties.

Subunit / interactions. Homodimer. Dimers associate into a tetramer to form the enzymatically active phosphorylase A.

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

Activity regulation. Activity of phosphorylase is controlled both by allosteric means (through the non-covalent binding of metabolites) and by covalent modification. Thus AMP allosterically activates, whereas ATP, ADP, and glucose-6-phosphate allosterically inhibit, phosphorylase B. Activated upon phosphorylation.

Similarity. Belongs to the glycogen phosphorylase family.

RefSeq proteins (1): NP_002853* (*=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 (99 total): helix 44, strand 25, turn 8, modified residue 5, site 4, sequence conflict 4, binding site 4, sequence variant 2, initiator methionine 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5IKO	X-RAY DIFFRACTION	2.5
5IKP	X-RAY DIFFRACTION	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11216-F1	93.71	0.88

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 (4): 156 (may be involved in allosteric control); 76 (participates in a stacking interaction with the adenine ring of amp); 109 (involved in the association of subunits); 143 (involved in the association of subunits)

Ligand- & substrate-binding residues (4): 43; 197 (in other chain); 310 (in other chain); 569

Post-translational modifications (5): 2, 15, 197, 473, 681

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: 176 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, REACTOME_INNATE_IMMUNE_SYSTEM, MODULE_255, GOCC_SECRETORY_GRANULE, ZHAN_MULTIPLE_MYELOMA_MF_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_317, PATIL_LIVER_CANCER, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_POLYSACCHARIDE_CATABOLIC_PROCESS, JOHANSSON_BRAIN_CANCER_EARLY_VS_LATE_DN, WATANABE_RECTAL_CANCER_RADIOTHERAPY_RESPONSIVE_UP, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM3, ROZANOV_MMP14_TARGETS_UP

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

GO Molecular Function (7): 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 (5): extracellular region (GO:0005576), cytoplasm (GO:0005737), membrane (GO:0016020), azurophil granule lumen (GO:0035578), extracellular exosome (GO:0070062)

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
glycogen metabolic process	1
glucan catabolic process	1
primary metabolic process	1
energy reserve metabolic process	1
glucan metabolic process	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
vacuolar lumen	1
secretory granule lumen	1
azurophil granule	1
extracellular vesicle	1

Protein interactions and networks

STRING

2411 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PYGB	GYS2	P54840	908
PYGB	AGL	P35573	792
PYGB	G6PC3	Q9BUM1	789
PYGB	G6PC1	P35575	786
PYGB	UGP2	Q16851	783
PYGB	GCK	P35557	782
PYGB	G6PC2	Q9NQR9	782
PYGB	GYS1	P13807	774
PYGB	SSTR4	P31391	748
PYGB	GBE1	Q04446	721
PYGB	H6PD	O95479	719
PYGB	G6PD	P11413	668
PYGB	GYG2	O15488	665
PYGB	GYG1	P46976	656
PYGB	LIPE	Q05469	637

IntAct

104 interactions, top by confidence:

A	B	Type	Score
PYGB	PYGL	psi-mi:“MI:0915”(physical association)	0.850
PYGL	PYGB	psi-mi:“MI:0915”(physical association)	0.850
KIF24	CCP110	psi-mi:“MI:0914”(association)	0.810
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
PYGB	PPP1R3B	psi-mi:“MI:0915”(physical association)	0.670
PYGB	PYGM	psi-mi:“MI:0915”(physical association)	0.670
PYGB	SIAH1	psi-mi:“MI:0915”(physical association)	0.560
PYGB	FKBP5	psi-mi:“MI:0915”(physical association)	0.560
CD69	PALM3	psi-mi:“MI:0914”(association)	0.530
GJB7	PALM3	psi-mi:“MI:0914”(association)	0.530
STBD1	MID1	psi-mi:“MI:0914”(association)	0.530
CYP1A1	SNX3	psi-mi:“MI:0914”(association)	0.530
PRKAB2	STBD1	psi-mi:“MI:0914”(association)	0.530
HSPB8	VWA8	psi-mi:“MI:0914”(association)	0.530

BioGRID (186): PYGB (Two-hybrid), PYGL (Two-hybrid), SIAH1 (Two-hybrid), PYGB (Affinity Capture-MS), PYGB (Affinity Capture-MS), PYGB (Affinity Capture-MS), PYGB (Affinity Capture-MS), PYGB (Affinity Capture-MS), PYGB (Affinity Capture-MS), PYGB (Affinity Capture-MS), PYGB (Affinity Capture-MS), PYGB (Affinity Capture-MS), PYGB (Affinity Capture-MS), ACLY (Co-fractionation), APOA1BP (Co-fractionation)

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

4 interactions.

A	Effect	B	Mechanism
PYGB	“down-regulates quantity”	glycogen	“chemical modification”
PYGB	“up-regulates quantity”	“alpha-D-glucose 1-phosphate(2-)”	“chemical modification”
glycogen	“up-regulates activity”	PYGB	“chemical activation”
PYGB	“up-regulates quantity”	α-D-glucose	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	120
Likely benign	3
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

3694 predictions. Top by Δscore:

Variant	Effect	Δscore
20:25248418:CAAGG:C	donor_loss	1.0000
20:25248420:AGGTG:A	donor_loss	1.0000
20:25248422:GTGAG:G	donor_loss	1.0000
20:25259235:A:AG	acceptor_gain	1.0000
20:25259236:G:GG	acceptor_gain	1.0000
20:25259236:GCGC:G	acceptor_gain	1.0000
20:25259256:T:TA	acceptor_gain	1.0000
20:25269124:TGCA:T	acceptor_loss	1.0000
20:25269125:GCA:G	acceptor_loss	1.0000
20:25269126:CA:C	acceptor_loss	1.0000
20:25269127:A:AG	acceptor_gain	1.0000
20:25269127:AG:A	acceptor_loss	1.0000
20:25269127:AGTT:A	acceptor_gain	1.0000
20:25269127:AGTTG:A	acceptor_gain	1.0000
20:25269128:G:GG	acceptor_gain	1.0000
20:25269128:GT:G	acceptor_gain	1.0000
20:25269128:GTT:G	acceptor_gain	1.0000
20:25269128:GTTG:G	acceptor_gain	1.0000
20:25269128:GTTGG:G	acceptor_gain	1.0000
20:25269205:CAGG:C	donor_loss	1.0000
20:25269206:AGGT:A	donor_loss	1.0000
20:25269207:GGTAA:G	donor_loss	1.0000
20:25269208:GT:G	donor_loss	1.0000
20:25269209:T:G	donor_loss	1.0000
20:25271378:TTCA:T	acceptor_loss	1.0000
20:25271380:CAGC:C	acceptor_loss	1.0000
20:25271381:A:AG	acceptor_gain	1.0000
20:25271381:AGC:A	acceptor_gain	1.0000
20:25271381:AGCGT:A	acceptor_gain	1.0000
20:25271382:G:GC	acceptor_gain	1.0000

AlphaMissense

5581 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:25269180:G:T	G133W	1.000
20:25269181:G:A	G133E	1.000
20:25271451:G:T	G165W	1.000
20:25271452:G:A	G165E	1.000
20:25271457:T:C	F167L	1.000
20:25271459:T:A	F167L	1.000
20:25271459:T:G	F167L	1.000
20:25274610:T:A	W183R	1.000
20:25274610:T:C	W183R	1.000
20:25276718:T:A	W245R	1.000
20:25276718:T:C	W245R	1.000
20:25278338:T:C	L292P	1.000
20:25278351:G:C	Q296H	1.000
20:25278351:G:T	Q296H	1.000
20:25279076:A:C	D340A	1.000
20:25279076:A:T	D340V	1.000
20:25280305:C:G	H378D	1.000
20:25280307:C:A	H378Q	1.000
20:25280307:C:G	H378Q	1.000
20:25284192:G:T	R570M	1.000
20:25284207:A:T	K575M	1.000
20:25284208:G:C	K575N	1.000
20:25284208:G:T	K575N	1.000
20:25259258:G:A	E89K	0.999
20:25259270:G:C	G93R	0.999
20:25269175:G:A	G131D	0.999
20:25269178:T:C	L132P	0.999
20:25269180:G:A	G133R	0.999
20:25269180:G:C	G133R	0.999
20:25269181:G:T	G133V	0.999

dbSNP variants (sampled 300 via entrez): RS1000004955 (20:25254633 TA>T,TAA), RS1000008499 (20:25251253 A>G), RS1000079877 (20:25249916 C>A,T), RS1000137671 (20:25265007 T>C), RS1000231445 (20:25292326 C>T), RS1000288218 (20:25296611 G>A), RS1000332715 (20:25264306 C>T), RS1000410140 (20:25264515 T>C), RS1000435831 (20:25275569 T>G), RS1000439934 (20:25254775 G>T), RS1000522178 (20:25266344 C>T), RS1000575252 (20:25272070 G>A), RS1000831800 (20:25256246 G>A), RS1000889733 (20:25256003 G>A), RS1000962463 (20:25255566 C>T)

Disease associations

OMIM: gene MIM:138550 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001276_7	Liver enzyme levels (alkaline phosphatase)	7.000000e-10
GCST002201_13	Calcium levels	5.000000e-06
GCST002875_96	Diisocyanate-induced asthma	2.000000e-06
GCST006485_12	Telomere length	1.000000e-06
GCST009652_32	Serum alkaline phosphatase levels	7.000000e-10
GCST010346_1	TPE interval (resting)	3.000000e-10
GCST010346_62	TPE interval (resting)	2.000000e-10
GCST010703_48	Brain morphology (MOSTest)	1.000000e-08
GCST90002401_318	Platelet distribution width	5.000000e-17
GCST90013406_75	Liver enzyme levels (alkaline phosphatase)	6.000000e-63

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004533	alkaline phosphatase measurement
EFO:0004838	calcium measurement
EFO:0006995	response to diisocyanate
EFO:0004644	TPE interval measurement
EFO:0004346	neuroimaging measurement
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3856 (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

13 potent at pChembl≥5 of 44 total, top 13 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.50	Ki	31.62	nM	CHEMBL335077
7.40	Kd	39.46	nM	CHEMBL3752910
7.40	ED50	39.46	nM	CHEMBL3752910
6.80	Ki	158.5	nM	CHEMBL3351153
5.52	Ki	3000	nM	CHEMBL3351144
5.51	Ki	3100	nM	CHEMBL97548
5.50	Ki	3162	nM	CHEMBL3351144
5.45	Kd	3569	nM	ALVOCIDIB
5.38	Ki	4200	nM	CHEMBL97548
5.29	Ki	5100	nM	CHEMBL489798
5.16	Ki	7000	nM	CHEMBL489798
5.16	Kd	6996	nM	CHEMBL5653589
5.16	ED50	6996	nM	CHEMBL5653589

PubChem BioAssay actives

11 with measured affinity, of 476 total; 8 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
(2S)-N-[(1S)-1-(dioxiran-3-yl)-2-(1H-indol-3-yl)ethyl]-2-[[(1S)-1-(dioxiran-3-yl)-3-phenylpropyl]amino]-4-methylpentanamide	73824: Inhibitory activity against Pig Skeletal Glycogen Phosphorylase b	ki	0.0316	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149159: Binding affinity to human PYGB incubated for 45 mins by Kinobead based pull down assay	kd	0.0395	uM
(5S,7S,8S,9S,10S)-3-amino-8,9,10-trihydroxy-7-(hydroxymethyl)-6-oxa-1,3-diazaspiro[4.5]decane-2,4-dione	73824: Inhibitory activity against Pig Skeletal Glycogen Phosphorylase b	ki	0.1585	uM
(5S,7S,8S,9S,10S)-8,9,10-trihydroxy-7-(hydroxymethyl)-6-oxa-1,3-diazaspiro[4.5]decane-2,4-dione	73815: Inhibition of rabbit glycogen phosphorylase B enzyme	ki	3.0000	uM
(5S,8S,9S)-8,9,10-trihydroxy-7-(hydroxymethyl)-6-oxa-1,3-diazaspiro[4.5]decane-2,4-dione	141119: Inhibitory activity against muscle Glycogen Phosphorylase b	ki	3.1000	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	1425145: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	3.5690	uM
(5S,7R,8S,9S,10R)-8,9,10-trihydroxy-7-(hydroxymethyl)-2-sulfanylidene-6-oxa-1,3-diazaspiro[4.5]decan-4-one	141119: Inhibitory activity against muscle Glycogen Phosphorylase b	ki	5.1000	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149159: Binding affinity to human PYGB incubated for 45 mins by Kinobead based pull down assay	kd	6.9958	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects binding, increases reaction, decreases expression (+1 more)	6
bisphenol A	affects expression, decreases expression, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Cyclosporine	increases expression	3
(+)-JQ1 compound	increases expression	2
Smoke	decreases expression	2
Tobacco Smoke Pollution	increases expression, affects expression	2
sotorasib	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
baicalein	decreases activity	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects localization, increases expression, affects cotreatment	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
perfluorooctanoic acid	increases expression	1
doxifluridine	increases response to substance	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
nickel sulfate	decreases expression	1
1-UFT protocol	increases response to substance	1
hydroquinone	increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
alvocidib	affects binding	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
K 7174	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
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1

ChEMBL screening assays

14 unique, capped per target: 14 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3991858	Binding	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by ma	The target landscape of clinical kinase drugs. — Science

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1YN	Abcam A-549 PYGB KO	Cancer cell line	Male
CVCL_D2CS	Abcam HCT 116 PYGB KO	Cancer cell line	Male

Clinical trials (associated diseases)

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