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PHKG1

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Summary

PHKG1 (phosphorylase kinase catalytic subunit gamma 1, HGNC:8930) is a protein-coding gene on chromosome 7p11.2, encoding Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform (Q16816). Catalytic subunit of the phosphorylase b kinase (PHK), which mediates the neural and hormonal regulation of glycogen breakdown (glycogenolysis) by phosphorylating and thereby activating glycogen phosphorylase.

This gene is a member of the Ser/Thr protein kinase family and encodes a protein with one protein kinase domain and two calmodulin-binding domains. This protein is the catalytic member of a 16 subunit protein kinase complex which contains equimolar ratios of 4 subunit types. The complex is a crucial glycogenolytic regulatory enzyme. This gene has two pseudogenes at chromosome 7q11.21 and one at chromosome 11p11.12. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5260 — RefSeq curated summary.

At a glance

  • GWAS associations: 5
  • Clinical variants (ClinVar): 107 total
  • Phenotypes (HPO): 16
  • Druggable target: yes — 20 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_006213

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:8930
Approved symbolPHKG1
Namephosphorylase kinase catalytic subunit gamma 1
Location7p11.2
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000164776
Ensembl biotypeprotein_coding
OMIM172470
Entrez5260

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 12 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000297373, ENST00000395428, ENST00000432123, ENST00000446428, ENST00000452681, ENST00000467726, ENST00000471665, ENST00000489604, ENST00000492124, ENST00000911172, ENST00000911173, ENST00000911174, ENST00000966258, ENST00000966259, ENST00000966260, ENST00000966261, ENST00000966262

RefSeq mRNA: 3 — MANE Select: NM_006213 NM_001258459, NM_001258460, NM_006213

CCDS: CCDS5525, CCDS59057

Canonical transcript exons

ENST00000297373 — 10 exons

ExonStartEnd
ENSE000010873775608189356082046
ENSE000010873805608029556081299
ENSE000011202145608216356082253
ENSE000011202205608327856083441
ENSE000017414455608163056081755
ENSE000018034845609283656092952
ENSE000035269705608885956088975
ENSE000035926115608365056083715
ENSE000036864145608697056087024
ENSE000037483185608759856087776

Expression profiles

Bgee: expression breadth ubiquitous, 181 present calls, max score 97.11.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3294 / max 149.4558, expressed in 219 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
841791.2231207
841800.106372

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
gastrocnemiusUBERON:000138897.11gold quality
muscle of legUBERON:000138396.66gold quality
hindlimb stylopod muscleUBERON:000425296.29gold quality
triceps brachiiUBERON:000150996.12gold quality
muscle organUBERON:000163094.49gold quality
skeletal muscle tissue of rectus abdominisUBERON:000451191.30gold quality
biceps brachiiUBERON:000150790.36gold quality
skeletal muscle tissueUBERON:000113489.58gold quality
gluteal muscleUBERON:000200088.78gold quality
skeletal muscle tissue of biceps brachiiUBERON:000450288.73gold quality
apex of heartUBERON:000209888.05gold quality
quadriceps femorisUBERON:000137787.97gold quality
vastus lateralisUBERON:000137987.85gold quality
muscle tissueUBERON:000238586.52gold quality
right atrium auricular regionUBERON:000663186.08gold quality
diaphragmUBERON:000110385.97silver quality
tibialis anteriorUBERON:000138584.91silver quality
cardiac atriumUBERON:000208184.37gold quality
heart left ventricleUBERON:000208483.56gold quality
cardiac ventricleUBERON:000208282.87gold quality
right hemisphere of cerebellumUBERON:001489081.13gold quality
heartUBERON:000094880.90gold quality
cerebellar hemisphereUBERON:000224579.98gold quality
muscle layer of sigmoid colonUBERON:003580579.88gold quality
cerebellar cortexUBERON:000212979.84gold quality
deltoidUBERON:000147679.63gold quality
caudate nucleusUBERON:000187379.54gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047379.31gold quality
calcaneal tendonUBERON:000370179.28gold quality
body of tongueUBERON:001187678.76gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-MTAB-8271yes531.68
E-ANND-3no2.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting PHKG1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-6783-3P99.8967.922059
HSA-MIR-197699.7465.481127
HSA-MIR-445299.5068.451493
HSA-MIR-584-3P99.3567.691082
HSA-MIR-532-3P99.3465.761195
HSA-MIR-431199.3170.473041
HSA-MIR-939-3P98.9765.072347
HSA-MIR-367-5P98.8467.18902
HSA-MIR-1227-5P98.6565.321549
HSA-MIR-6784-3P98.3964.88662
HSA-MIR-59998.3266.991037
HSA-MIR-6862-3P97.9264.86531
HSA-MIR-1224-3P97.2465.92851
HSA-MIR-6762-5P96.5564.62972
HSA-MIR-6845-5P96.5564.65969
HSA-MIR-797396.4865.54502
HSA-MIR-120489.5065.56109

Literature-anchored findings (GeneRIF, showing 1)

  • Lung adenocarcinoma-derived vWF promotes tumor metastasis by regulating PHKG1-mediated glycogen metabolism. (PMID:35150045)

Cross-species orthologs

4 orthologs

OrganismSymbolGene ID
danio_reriophkg1aENSDARG00000030604
danio_reriophkg1bENSDARG00000069498
mus_musculusPhkg1ENSMUSG00000025537
rattus_norvegicusPhkg1ENSRNOG00000000920

Paralogs (22): CAMKK1 (ENSG00000004660), CAMK1G (ENSG00000008118), CAMK2B (ENSG00000058404), CAMK2A (ENSG00000070808), MYLK2 (ENSG00000101306), CAMKK2 (ENSG00000110931), STK11 (ENSG00000118046), STK33 (ENSG00000130413), PNCK (ENSG00000130822), DCLK1 (ENSG00000133083), CAMK1 (ENSG00000134072), MYLK3 (ENSG00000140795), CAMK2D (ENSG00000145349), MYLK4 (ENSG00000145949), PSKH2 (ENSG00000147613), CAMK2G (ENSG00000148660), PHKG2 (ENSG00000156873), PSKH1 (ENSG00000159792), DCLK3 (ENSG00000163673), CAMKV (ENSG00000164076), DCLK2 (ENSG00000170390), CAMK1D (ENSG00000183049)

Protein

Protein identifiers

Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform — Q16816 (reviewed: Q16816)

Alternative names: Phosphorylase kinase subunit gamma-1, Serine/threonine-protein kinase PHKG1

All UniProt accessions (4): C9J2Q6, C9JME8, Q16816, F8WD25

UniProt curated annotations — full annotation on UniProt →

Function. Catalytic subunit of the phosphorylase b kinase (PHK), which mediates the neural and hormonal regulation of glycogen breakdown (glycogenolysis) by phosphorylating and thereby activating glycogen phosphorylase. In vitro, phosphorylates PYGM, TNNI3, MAPT/TAU, GAP43 and NRGN/RC3.

Subunit / interactions. Hexadecamer of 4 heterotetramers, each composed of alpha, beta, gamma, and delta subunits. Alpha (PHKA1 or PHKA2) and beta (PHKB) are regulatory subunits, gamma (PHKG1 or PHKG2) is the catalytic subunit, and delta is calmodulin.

Domain organisation. The two calmodulin-binding domains appear to act in concert to bind a single molecule of calmodulin and are pseudosubstrate/autoinhibitory domains.

Similarity. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.

Isoforms (2)

UniProt IDNamesCanonical?
Q16816-11yes
Q16816-22

RefSeq proteins (3): NP_001245388, NP_001245389, NP_006204* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000719Prot_kinase_domDomain
IPR002291Phosph_kin_gammaFamily
IPR008271Ser/Thr_kinase_ASActive_site
IPR011009Kinase-like_dom_sfHomologous_superfamily
IPR017441Protein_kinase_ATP_BSBinding_site

Pfam: PF00069

Enzyme classification (BRENDA):

  • EC 2.7.11.19 — phosphorylase kinase (BRENDA: 23 organisms, 150 substrates, 165 inhibitors, 89 Km, 8 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
ATP0.018–0.9516
PHOSPHORYLASE B0.01–0.3716
MGATP2-0.07–0.19
S-PEPTIDE0.21–0.282
SER-ASP-GLN-GLU-LYS-ARG-LYS-GLN-ILE-SER-VAL-ASP-1.2–3.52
TETRADECAPEPTIDE0.3085–0.472
GLYCOGEN PHOSPHORYLASE B0.00931
GTP0.61
MELITTIN0.00981
SER-ASP-GLN-GLU-LYS-ARG-LYS-GLN-ILE-SER-VAL-ASP21
UTP1.41

Catalyzed reactions (Rhea), 4 shown:

  • L-seryl-[tau protein] + ATP = O-phospho-L-seryl-[tau protein] + ADP + H(+) (RHEA:12801)
  • L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
  • L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)
  • L-threonyl-[tau protein] + ATP = O-phospho-L-threonyl-[tau protein] + ADP + H(+) (RHEA:53904)

UniProt features (44 total): helix 21, strand 10, turn 2, region of interest 2, binding site 2, sequence variant 2, chain 1, domain 1, sequence conflict 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

10 structures.

PDBMethodResolution (Å)
8XYAELECTRON MICROSCOPY2.7
8JFKELECTRON MICROSCOPY2.9
8JFLELECTRON MICROSCOPY2.9
8XY7ELECTRON MICROSCOPY2.9
8XYBELECTRON MICROSCOPY3.1
8Z5PELECTRON MICROSCOPY3.41
8Z5RELECTRON MICROSCOPY3.52
8Z5MELECTRON MICROSCOPY3.66
8Z5TELECTRON MICROSCOPY3.74
8Z5QELECTRON MICROSCOPY4.24

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q16816-F187.110.67

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 (1): 150 (proton acceptor)

Ligand- & substrate-binding residues (2): 26–34; 49

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

IDPathway
R-HSA-70221Glycogen breakdown (glycogenolysis)

MSigDB gene sets: 131 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, ENK_UV_RESPONSE_KERATINOCYTE_UP, MODULE_45, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_POLYSACCHARIDE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, MODULE_157, GOBP_CARBOHYDRATE_CATABOLIC_PROCESS, MODULE_48, MODULE_95, P53_DECAMER_Q2, REACTOME_METABOLISM_OF_CARBOHYDRATES_AND_CARBOHYDRATE_DERIVATIVES, GOCC_TRANSFERASE_COMPLEX_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS, GOCC_TRANSFERASE_COMPLEX

GO Biological Process (5): carbohydrate metabolic process (GO:0005975), glycogen metabolic process (GO:0005977), glycogen catabolic process (GO:0005980), signal transduction (GO:0007165), protein phosphorylation (GO:0006468)

GO Molecular Function (11): phosphorylase kinase activity (GO:0004689), calmodulin binding (GO:0005516), ATP binding (GO:0005524), enzyme binding (GO:0019899), tau-protein kinase activity (GO:0050321), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), phosphorylase kinase complex (GO:0005964)

Reactome top-level categories

Rollup of top-1 pathways:

CategoryPathways
Glycogen metabolism1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
protein binding2
protein kinase activity2
cellular anatomical structure2
cytoplasm2
primary metabolic process1
energy reserve metabolic process1
glucan metabolic process1
glycogen metabolic process1
glucan catabolic process1
cell communication1
cellular process1
signaling1
regulation of cellular process1
cellular response to stimulus1
phosphorylation1
protein modification process1
calcium/calmodulin-dependent protein kinase activity1
adenyl ribonucleotide binding1
purine ribonucleoside triphosphate binding1
protein serine/threonine kinase activity1
nucleoside phosphate binding1
heterocyclic compound binding1
kinase activity1
phosphotransferase activity, alcohol group as acceptor1
catalytic activity, acting on a protein1
transferase activity, transferring phosphorus-containing groups1
catalytic activity1
intracellular anatomical structure1
serine/threonine protein kinase complex1

Protein interactions and networks

STRING

714 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
PHKG1PHKBQ93100946
PHKG1PHKA1P46020928
PHKG1PHKA2P46019919
PHKG1CALM1P02593642
PHKG1SUMF2Q8NBJ7642
PHKG1PRKAG3Q9UGI9600
PHKG1PYGMP11217584
PHKG1ZNF713Q8N859495
PHKG1AGLP35573464
PHKG1PYGLP06737461
PHKG1GYS1P13807451
PHKG1NIPSNAP2O75323436
PHKG1PDPRQ8NCN5426
PHKG1GBE1Q04446424
PHKG1PGAM2P15259414

IntAct

6 interactions, top by confidence:

ABTypeScore
PHKG2PHKA2psi-mi:“MI:0914”(association)0.920
RPS6KA1RPS6KA3psi-mi:“MI:0914”(association)0.790
PHKG2PRKAB2psi-mi:“MI:0914”(association)0.640
PHKA2GYG2psi-mi:“MI:0914”(association)0.350

BioGRID (5): PHKG1 (Affinity Capture-MS), PHKG1 (Affinity Capture-MS), PHKG1 (Affinity Capture-MS), PHKG1 (Affinity Capture-MS), PHKG1 (Affinity Capture-MS)

ESM2 similar proteins: A1Z9X0, A8WUG4, A8XWC4, F1M7Y5, O13310, O19111, O74536, O97627, P00518, P07934, P09217, P13286, P23443, P26817, P26818, P26819, P31325, P34722, P35626, P41743, P54645, P54646, P67998, P67999, P83099, Q02111, Q02956, Q04759, Q05513, Q09137, Q12706, Q13131, Q16816, Q19266, Q21734, Q28948, Q2KJ16, Q3UYH7, Q5EG47, Q5R4K9

Diamond homologs: A0A5K1K8H0, A4IFM7, A7SNN5, A8C984, A8WRV1, A8XQD5, D3ZHP7, E9PT87, F1M0Z1, O01761, O02827, O14936, O15865, O43293, O44997, O45818, O54784, O55005, O65554, O70150, O70589, O75962, O88764, O94768, O94806, P00518, P05986, P07313, P0C5E3, P11275, P11798, P20689, P25323, P29294, P34099, P53355, P70193, Q0KHT7, Q0KL02, Q12263

SIGNOR signaling

12 interactions.

AEffectBMechanism
PHKG1“up-regulates activity”PYGMphosphorylation
PHKG1“up-regulates activity”PYGLphosphorylation
PHKA2“down-regulates activity”PHKG1binding
PHKA1“down-regulates activity”PHKG1binding
PHKG1“up-regulates activity”PYGphosphorylation
PHKG1“down-regulates activity”MAPTphosphorylation
PHKG1unknownPHKG1phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance97
Likely benign2
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1912 predictions. Top by Δscore:

VariantEffectΔscore
7:56081299:CCT:Cacceptor_loss1.0000
7:56081301:T:Aacceptor_loss1.0000
7:56081624:TAGTA:Tdonor_loss1.0000
7:56081625:AGTAC:Adonor_gain1.0000
7:56081626:GTA:Gdonor_loss1.0000
7:56081627:TAC:Tdonor_loss1.0000
7:56081628:ACC:Adonor_loss1.0000
7:56081638:T:TAdonor_gain1.0000
7:56081639:C:Adonor_gain1.0000
7:56081664:T:TAdonor_gain1.0000
7:56081751:GAGAC:Gacceptor_gain1.0000
7:56081752:AGAC:Aacceptor_gain1.0000
7:56081753:GAC:Gacceptor_gain1.0000
7:56081754:AC:Aacceptor_gain1.0000
7:56081755:CC:Cacceptor_gain1.0000
7:56081756:C:CCacceptor_gain1.0000
7:56081758:G:Cacceptor_gain1.0000
7:56081887:TCTCA:Tdonor_loss1.0000
7:56081888:CTCAC:Cdonor_loss1.0000
7:56081889:TCA:Tdonor_loss1.0000
7:56081890:CA:Cdonor_loss1.0000
7:56081891:A:ACdonor_gain1.0000
7:56081891:A:Gdonor_loss1.0000
7:56081892:C:CAdonor_loss1.0000
7:56081892:C:CCdonor_gain1.0000
7:56081897:T:TAdonor_gain1.0000
7:56082046:CCT:Cacceptor_loss1.0000
7:56082161:A:ACdonor_gain1.0000
7:56082162:C:CCdonor_gain1.0000
7:56083438:CTTT:Cacceptor_gain1.0000

AlphaMissense

2534 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
7:56083321:G:CD168E1.000
7:56083321:G:TD168E1.000
7:56083376:T:GD150A1.000
7:56083379:C:GR149P1.000
7:56087713:C:AK49N1.000
7:56087713:C:GK49N1.000
7:56081995:G:CF230L0.999
7:56081995:G:TF230L0.999
7:56081997:A:GF230L0.999
7:56081999:G:TP229H0.999
7:56082017:A:GL223P0.999
7:56082035:C:TG217D0.999
7:56082040:G:CS215R0.999
7:56082040:G:TS215R0.999
7:56082042:T:GS215R0.999
7:56082043:C:AW214C0.999
7:56082043:C:GW214C0.999
7:56082045:A:GW214R0.999
7:56082045:A:TW214R0.999
7:56082244:C:TG186E0.999
7:56083322:T:AD168V0.999
7:56083322:T:CD168G0.999
7:56083322:T:GD168A0.999
7:56083323:C:GD168H0.999
7:56083360:G:CN155K0.999
7:56083360:G:TN155K0.999
7:56083369:C:AK152N0.999
7:56083369:C:GK152N0.999
7:56083371:T:CK152E0.999
7:56083375:G:CD150E0.999

dbSNP variants (sampled 300 via entrez): RS1000339358 (7:56094278 G>A), RS1000385302 (7:56081391 G>A), RS1000681720 (7:56079853 A>G), RS1000776892 (7:56080079 C>T), RS1000831888 (7:56085417 G>A), RS1000956411 (7:56088151 C>T), RS1001037078 (7:56091056 A>G,T), RS1001384556 (7:56091298 C>T), RS1001668431 (7:56080770 T>A), RS1001689290 (7:56088315 C>A), RS1001707312 (7:56088727 G>T), RS1001764386 (7:56086164 T>A), RS1002049410 (7:56084976 G>T), RS1002213389 (7:56090644 A>G), RS1002704252 (7:56094851 C>T)

Disease associations

OMIM: gene MIM:172470 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

16 total (16 of 16 shown, HPO-id order):

HPOTerm
HP:0001265Hyporeflexia
HP:0001288Gait disturbance
HP:0002913Myoglobinuria
HP:0003202Skeletal muscle atrophy
HP:0003236Elevated circulating creatine kinase concentration
HP:0003323Progressive muscle weakness
HP:0003326Myalgia
HP:0003391Gowers sign
HP:0003394Muscle spasm
HP:0003458EMG: myopathic abnormalities
HP:0003546Exercise intolerance
HP:0003551Difficulty climbing stairs
HP:0009051Increased muscle glycogen content
HP:0012378Fatigue
HP:0100595Camptocormia
HP:6000198Reduced muscle phosphorylase kinase activity

GWAS associations

5 associations (top):

StudyTraitp-value
GCST007382_33Plasma free amino acid levels (adjusted for twenty other PFAAs)1.000000e-25
GCST007385_23Plasma free amino acid levels2.000000e-21
GCST009597_51Multiple sclerosis3.000000e-07
GCST012251_16Macular telangiectasia type 23.000000e-07
GCST012252_7Macular telangiectasia type 26.000000e-09

EFO canonical traits (3, from GWAS)

EFO IDTrait name
EFO:0005134amino acid measurement
EFO:0009774serine measurement
EFO:1002009macular telangiectasia type 2

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2111324 (PROTEIN COMPLEX GROUP), CHEMBL4004 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

20 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 346,306 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL1173655AFATINIB415,144
CHEMBL1287853FEDRATINIB43,554
CHEMBL1789941RUXOLITINIB411,547
CHEMBL24828VANDETANIB442,230
CHEMBL288441BOSUTINIB412,255
CHEMBL502835NINTEDANIB48,545
CHEMBL535SUNITINIB479,020
CHEMBL608533MIDOSTAURIN47,259
CHEMBL939GEFITINIB4117,814
CHEMBL300138ENZASTAURIN33,209
CHEMBL428690ALVOCIDIB327,781
CHEMBL522892DOVITINIB34,944
CHEMBL603469LESTAURTINIB3
CHEMBL91829RUBOXISTAURIN377
CHEMBL1721885SU-0148132363
CHEMBL572878TOZASERTIB22,998
CHEMBL607707PELITINIB26,340
CHEMBL1908397KW-24491622
CHEMBL296468BMS-38703212,075
CHEMBL4169078SRA-7371529

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Phosphorylase kinase (PHK) family

Binding affinities (BindingDB)

12 measured of 12 human assays (12 total across all organisms); most potent 12 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
StaurosporineKD1.7 nM
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amineKD150 nM
PKC-412KD190 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyrilKD520 nM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.1^{7,14}.0^{2,6}.0^{8,13}.0^{22,27}]nonacosa-1(28),2(6),7(29),8(13),9,11,22(27),23,25-nonaene-3,5-dioneKD700 nM
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamideKD1100 nM
BMS-387072KD1800 nM
GEFITINIBIC502300 nMUS-9416123: Kinase modulators for the treatment of cancer
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamideKD2600 nM
(E)-N-[4-(3-chloro-4-fluoro-anilino)-3-cyano-7-ethoxy-6-quinolyl]-4-(dimethylamino)but-2-enamideKD3500 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamideKD3500 nM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S)-3-hydroxy-1-methyl-4-piperidinyl]-1-benzopyran-4-oneKD5300 nM

ChEMBL bioactivities

65 potent at pChembl≥5 of 66 total, top 49 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
9.41Kd0.39nMLESTAURTINIB
9.30IC500.5nMSTAUROSPORINE
9.30Kd0.5nMSTAUROSPORINE
9.19Kd0.65nMSTAUROSPORINE
9.00Kd1nMCHEMBL4465866
8.77IC501.7nMK-252A
8.72IC501.92nMSTAUROSPORINE
8.59IC502.58nMSTAUROSPORINE
8.54IC502.89nMSTAUROSPORINE
8.52Kd3nMCHEMBL4576489
8.26Kd5.5nMSUNITINIB
7.92Kd12nMCHEMBL4792981
7.77Kd17nMTAE-684
7.16Kd70nMSUNITINIB
7.11IC5078nMCHEMBL3815054
7.08Kd83nMSU-014813
6.87IC50136nMCHEMBL4062218
6.85Kd140nMNINTEDANIB
6.72Kd190nMMIDOSTAURIN
6.68Kd210nMKW-2449
6.48Kd330nMFEDRATINIB
6.47Kd340nMBOSUTINIB
6.23Kd590nMCHEMBL1908395
6.19Kd640nMDOVITINIB
6.05Kd900nMMIDOSTAURIN
6.00IC501000nMTP-030-1
6.00IC501000nMTP-030-2
6.00IC501000nMTP-030n
5.96Kd1100nMVANDETANIB
5.96Kd1100nMCGP-52421
5.96Kd1100nMCHEMBL464552
5.92Kd1200nMCHEMBL379218
5.89Kd1300nMAFATINIB
5.82Kd1500nMPELITINIB
5.77IC501688nMCHEMBL538718
5.72Kd1900nMPHA-665752
5.66Kd2200nMALVOCIDIB
5.66Kd2200nMTOZASERTIB
5.57Kd2700nMRUBOXISTAURIN
5.46IC503470nMSRA-737
5.46Kd3500nMPELITINIB
5.43Kd3700nMGEFITINIB
5.43Kd3700nMRUBOXISTAURIN
5.42Kd3800nMBMS-387032
5.42IC503800nMCHEMBL538718
5.38Kd4200nMENZASTAURIN
5.24Kd5700nMRUXOLITINIB
5.20IC506310nMCHEMBL5549980
5.15Kd7100nMVANDETANIB

PubChem BioAssay actives

59 with measured affinity, of 383 total; 34 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one507670: Binding affinity to PHKG1kd0.0004uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one159258: Inhibition of phosphorylase kinase.ic500.0005uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide1526158: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged PHKG1 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assaykd0.0010uM
methyl (15S,16R,18R)-16-hydroxy-15-methyl-3-oxo-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaene-16-carboxylate1405290: Inhibition of phosphorylase kinase (unknown origin)ic500.0017uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-methylamino]ethoxy]ethoxy]ethoxy]ethyl]propanamide1526158: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged PHKG1 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assaykd0.0030uM
Sunitinib436042: Binding constant for full-length PHKG1kd0.0055uM
N-[(1R)-1-(3,5-difluorophenyl)ethyl]-3-[(E)-2-pyridin-2-ylethenyl]-2H-indazol-5-amine1741258: Binding affinity to wild-type human full length PHKG1 (M1 to Y387 residues) expressed in bacterial expression system by Kinomescan method relative to controlkd0.0120uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine625035: Binding constant for PHKG1 kinase domainkd0.0170uM
3-[1-[3-(dimethylamino)propyl]pyrazol-4-yl]-7-(1H-pyrazol-4-yl)-5H-indeno[1,2-b]indol-10-one1305295: Inhibition of PHKGI (unknown origin) by kinomescan analysisic500.0780uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide436042: Binding constant for full-length PHKG1kd0.0830uM
4-[[4-cyclopentyloxy-5-(2-methyl-1,3-benzoxazol-6-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-3-methoxy-N-methylbenzamide1476576: Inhibition of full length human GST-tagged PHKG1 expressed in baculovirus by Z’-LYTE assayic500.1360uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate625035: Binding constant for PHKG1 kinase domainkd0.1400uM
Midostaurin507670: Binding affinity to PHKG1kd0.1900uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone625035: Binding constant for PHKG1 kinase domainkd0.2100uM
Fedratinib625035: Binding constant for PHKG1 kinase domainkd0.3300uM
Bosutinib625035: Binding constant for PHKG1 kinase domainkd0.3400uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride625035: Binding constant for PHKG1 kinase domainkd0.5900uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one436042: Binding constant for full-length PHKG1kd0.6400uM
2-[[2-[[1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydroindol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluoro-N-methylbenzamide625035: Binding constant for PHKG1 kinase domainkd1.1000uM
Vandetanib436042: Binding constant for full-length PHKG1kd1.1000uM
N-[(2S,3R,4R,6R,18S)-18-hydroxy-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-N-methylbenzamide507670: Binding affinity to PHKG1kd1.1000uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine625035: Binding constant for PHKG1 kinase domainkd1.2000uM
Afatinib625035: Binding constant for PHKG1 kinase domainkd1.3000uM
(E)-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide256639: Average Binding Constant for PHkg1; NA=Not Active at 10 uMkd1.5000uM
(3Z)-5-[(2,6-dichlorophenyl)methylsulfonyl]-3-[[3,5-dimethyl-4-[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl]-1H-pyrrol-2-yl]methylidene]-1H-indol-2-one625035: Binding constant for PHKG1 kinase domainkd1.9000uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one436042: Binding constant for full-length PHKG1kd2.2000uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide436042: Binding constant for full-length PHKG1kd2.2000uM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.17,14.02,6.08,13.022,27]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione256639: Average Binding Constant for PHkg1; NA=Not Active at 10 uMkd2.7000uM
5-[[4-[[(2R)-morpholin-2-yl]methylamino]-5-(trifluoromethyl)-2-pyridinyl]amino]pyrazine-2-carbonitrile2154712: Inhibition of PHKG1 (unknown origin) by FRET based Z-LYTE kinase assayic503.4700uM
Gefitinib436042: Binding constant for full-length PHKG1kd3.7000uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide436042: Binding constant for full-length PHKG1kd3.8000uM
3-(1-methylindol-3-yl)-4-[1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]indol-3-yl]pyrrole-2,5-dione625035: Binding constant for PHKG1 kinase domainkd4.2000uM
Ruxolitinib625035: Binding constant for PHKG1 kinase domainkd5.7000uM
5-[4-[2-aminoethyl(ethyl)amino]-3-(1,2,4-triazol-4-yl)anilino]-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile2066658: Inhibition of human PHKG1 expressed in HEK293 cells incubated for 2 hrs by NanoBRET assayic506.3096uM

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

ChemicalActions (top 5)PubMed papers
aristolochic acid Iincreases expression1
bisphenol Fincreases expression1
fluorene-9-bisphenoldecreases expression1
triphenyl phosphateaffects expression1
sodium arseniteincreases expression1
potassium chromate(VI)affects cotreatment, increases expression1
epigallocatechin gallateaffects cotreatment, increases expression1
abrineincreases expression1
licochalcone Bincreases expression1
bisphenol Sincreases expression1
prothioconazoleincreases expression1
bisphenol AFincreases expression1
Benzo(a)pyreneincreases methylation1
Phthalic Acidsincreases methylation1
Smokedecreases expression1
Tobacco Smoke Pollutiondecreases expression1
Fatty Acids, Omega-3increases expression1
Fatty Acids, Omega-6decreases expression1

ChEMBL screening assays

209 unique, capped per target: 209 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1020729BindingInhibition of human PHK at 10 umol/LDesign, synthesis, and evaluation of indolinones as triple angiokinase inhibitors and the discovery of a highly specific 6-methoxycarbonyl-substituted indolinone (BIBF 1120). — J Med Chem

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 transformed cell line

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

CellosaurusNameCategorySex
CVCL_D8SBUbigene HCT 116 PHKG1 KOCancer cell lineMale
CVCL_D9MTUbigene HEK293 PHKG1 KOTransformed cell lineFemale
CVCL_TD27HAP1 PHKG1 (-) 1Cancer cell lineMale
CVCL_TD28HAP1 PHKG1 (-) 2Cancer cell lineMale
CVCL_TD29HAP1 PHKG1 (-) 3Cancer cell lineMale

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 81

This page pulls from 81 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot