PHKG2

Summary

PHKG2 (phosphorylase kinase catalytic subunit gamma 2, HGNC:8931) is a protein-coding gene on chromosome 16p11.2, encoding Phosphorylase b kinase gamma catalytic chain, liver/testis isoform (P15735). 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.

Phosphorylase kinase is a polymer of 16 subunits, four each of alpha, beta, gamma and delta. The alpha subunit includes the skeletal muscle and hepatic isoforms, encoded by two different genes. The beta subunit is the same in both the muscle and hepatic isoforms, and encoded by one gene. The gamma subunit also includes the skeletal muscle and hepatic isoforms, and the hepatic isoform is encoded by this gene. The delta subunit is a calmodulin and can be encoded by three different genes. The gamma subunits contain the active site of the enzyme, whereas the alpha and beta subunits have regulatory functions controlled by phosphorylation. The delta subunit mediates the dependence of the enzyme on calcium concentration. Mutations in this gene cause glycogen storage disease type 9C, also known as autosomal liver glycogenosis. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene.

Source: NCBI Gene 5261 — RefSeq curated summary.

At a glance

• Gene–disease (curated): glycogen storage disease IXc (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 433 total — 37 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 62
• Druggable target: yes — 36 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_000294

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8931
Approved symbol	PHKG2
Name	phosphorylase kinase catalytic subunit gamma 2
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000156873
Ensembl biotype	protein_coding
OMIM	172471
Entrez	5261

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 15 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000328273, ENST00000424889, ENST00000561712, ENST00000563588, ENST00000563607, ENST00000563913, ENST00000564838, ENST00000565897, ENST00000565924, ENST00000569684, ENST00000569762, ENST00000866453, ENST00000866454, ENST00000866455, ENST00000866456, ENST00000915462, ENST00000915463, ENST00000915464, ENST00000958863, ENST00000958864

RefSeq mRNA: 2 — MANE Select: NM_000294 NM_000294, NM_001172432

CCDS: CCDS10690, CCDS54002

Canonical transcript exons

ENST00000563588 — 10 exons

Exon	Start	End
ENSE00001306312	30751106	30751281
ENSE00001418385	30748425	30748490
ENSE00002578850	30756804	30761176
ENSE00003467298	30753394	30753557
ENSE00003484107	30753232	30753297
ENSE00003508884	30748803	30748915
ENSE00003575993	30756182	30756272
ENSE00003624736	30751549	30751603
ENSE00003633325	30756590	30756715
ENSE00003637906	30756367	30756520

Expression profiles

Bgee: expression breadth ubiquitous, 204 present calls, max score 98.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.8025 / max 507.9217, expressed in 1816 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153722	26.4693	1816
153723	1.6779	355
153721	0.3094	122
153724	0.1778	84
153720	0.0960	37
153725	0.0721	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	98.79	gold quality
right testis	UBERON:0004534	98.67	gold quality
granulocyte	CL:0000094	95.61	gold quality
testis	UBERON:0000473	95.56	gold quality
mucosa of transverse colon	UBERON:0004991	94.65	gold quality
right lobe of liver	UBERON:0001114	94.43	gold quality
adenohypophysis	UBERON:0002196	94.39	gold quality
right uterine tube	UBERON:0001302	94.14	gold quality
right lobe of thyroid gland	UBERON:0001119	93.98	gold quality
left lobe of thyroid gland	UBERON:0001120	93.86	gold quality
metanephros cortex	UBERON:0010533	93.77	gold quality
lower esophagus mucosa	UBERON:0035834	93.53	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.40	gold quality
transverse colon	UBERON:0001157	92.96	gold quality
cerebellar hemisphere	UBERON:0002245	92.94	gold quality
cerebellar cortex	UBERON:0002129	92.65	gold quality
right frontal lobe	UBERON:0002810	92.59	gold quality
thyroid gland	UBERON:0002046	92.52	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.40	gold quality
body of stomach	UBERON:0001161	92.29	gold quality
pituitary gland	UBERON:0000007	92.16	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.13	gold quality
right adrenal gland cortex	UBERON:0035827	92.05	gold quality
right adrenal gland	UBERON:0001233	91.96	gold quality
monocyte	CL:0000576	91.93	gold quality
minor salivary gland	UBERON:0001830	91.90	gold quality
left adrenal gland cortex	UBERON:0035825	91.83	gold quality
skin of abdomen	UBERON:0001416	91.57	gold quality
left adrenal gland	UBERON:0001234	91.56	gold quality
skin of leg	UBERON:0001511	91.52	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.41

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

129 targeting PHKG2, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-4487	99.96	64.58	1252
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-6845-3P	99.94	66.88	1439
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-4728-5P	99.85	69.39	4718

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 5)

• PHKG2 mutations are associated with Glycogen storage disease type IX (PMID:17689125)
• Patients with PHKG2 mutations have a severe hepatic phenotype within the heterogeneous GSD IX disorder. A defect in PHKG2 should be considered in patients with suspected glycogenosis associated with significant liver fibrosis and cirrhosis. (PMID:24326380)
• These cases add to the current knowledge of clinical variability in patients with PHKG2 mutations. Long term studies, involving follow-up of these patients into adulthood, are needed (PMID:24389071)
• Variability of clinical and biochemical phenotype in liver phosphorylase kinase deficiency with variants in the phosphorylase kinase (PHKG2) gene. (PMID:32697758)
• PHKG2 regulates RSL3-induced ferroptosis in Helicobacter pylori related gastric cancer. (PMID:36948350)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	phkg2	ENSDARG00000054208
mus_musculus	Phkg2	ENSMUSG00000030815
rattus_norvegicus	Phkg2	ENSRNOG00000018725

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), PSKH1 (ENSG00000159792), DCLK3 (ENSG00000163673), CAMKV (ENSG00000164076), PHKG1 (ENSG00000164776), DCLK2 (ENSG00000170390), CAMK1D (ENSG00000183049)

Protein

Protein identifiers

Phosphorylase b kinase gamma catalytic chain, liver/testis isoform — P15735 (reviewed: P15735)

Alternative names: PSK-C3, Phosphorylase kinase subunit gamma-2

All UniProt accessions (6): P15735, H3BN16, H3BP07, H3BTI9, H3BTW6, J3KNN3

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. May regulate glycogeneolysis in the testis. In vitro, phosphorylates PYGM.

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.

Disease relevance. Glycogen storage disease 9C (GSD9C) [MIM:613027] A metabolic disorder manifesting in infancy with hepatomegaly, growth retardation, hypotonia, liver dysfunction, and elevated plasma aminotransferases and lipids. These symptoms improve with age in most cases; however, some patients may develop hepatic fibrosis or cirrhosis. The disease is caused by variants affecting the gene represented in this entry.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P15735-1	1	yes
P15735-2	2

RefSeq proteins (2): NP_000285, NP_001165903 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR002291	Phosph_kin_gamma	Family
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_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.

Substrate	Km (mM)	Measurements
ATP	0.018–0.95	16
PHOSPHORYLASE B	0.01–0.37	16
MGATP2-	0.07–0.1	9
S-PEPTIDE	0.21–0.28	2
SER-ASP-GLN-GLU-LYS-ARG-LYS-GLN-ILE-SER-VAL-ASP-	1.2–3.5	2
TETRADECAPEPTIDE	0.3085–0.47	2
GLYCOGEN PHOSPHORYLASE B	0.0093	1
GTP	0.6	1
MELITTIN	0.0098	1
SER-ASP-GLN-GLU-LYS-ARG-LYS-GLN-ILE-SER-VAL-ASP	2	1
UTP	1.4	1

UniProt features (45 total): helix 13, sequence variant 8, strand 7, sequence conflict 5, region of interest 2, turn 2, binding site 2, splice variant 2, chain 1, domain 1, active site 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2Y7J	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P15735-F1	83.77	0.60

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): 153 (proton acceptor)

Ligand- & substrate-binding residues (2): 30–38; 53

Post-translational modifications (1): 345

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 262 (showing top): ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, RIZKI_TUMOR_INVASIVENESS_3D_DN, GGGTGGRR_PAX4_03, GOBP_POSITIVE_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_POLYSACCHARIDE_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_GLYCOGEN_METABOLIC_PROCESS, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, chr16p11, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_REGULATION_OF_GLUCOSE_METABOLIC_PROCESS

GO Biological Process (6): glycogen metabolic process (GO:0005977), glycogen catabolic process (GO:0005980), generation of precursor metabolites and energy (GO:0006091), protein phosphorylation (GO:0006468), signal transduction (GO:0007165), positive regulation of glycogen catabolic process (GO:0045819)

GO Molecular Function (11): protein serine/threonine kinase activity (GO:0004674), phosphorylase kinase activity (GO:0004689), calmodulin binding (GO:0005516), ATP binding (GO:0005524), enzyme binding (GO:0019899), tau-protein kinase activity (GO:0050321), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), 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:

Category	Pathways
Glycogen metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	2
cellular anatomical structure	2
cytoplasm	2
energy reserve metabolic process	1
glucan metabolic process	1
glycogen metabolic process	1
glucan catabolic process	1
metabolic process	1
phosphorylation	1
protein modification process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
glycogen catabolic process	1
regulation of glycogen catabolic process	1
positive regulation of catabolic process	1
positive regulation of glycogen metabolic process	1
protein kinase activity	1
calcium/calmodulin-dependent protein kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein serine/threonine kinase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular anatomical structure	1
serine/threonine protein kinase complex	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

52 interactions, top by confidence:

A	B	Type	Score
PHKG2	PHKA2	psi-mi:“MI:0915”(physical association)	0.920
PHKG2	PHKA2	psi-mi:“MI:0914”(association)	0.920
MAPK8	WDR62	psi-mi:“MI:0914”(association)	0.730
MPPED1	TXNDC9	psi-mi:“MI:0914”(association)	0.640
PHKG2	PRKAB2	psi-mi:“MI:0914”(association)	0.640
MPPED1	CLUH	psi-mi:“MI:0914”(association)	0.640
PHKG2	MAGEA2	psi-mi:“MI:0915”(physical association)	0.560
SCGN	SNAP23	psi-mi:“MI:0914”(association)	0.550
COMTD1	IFRD1	psi-mi:“MI:0914”(association)	0.530
PHKG2	DAPK1	psi-mi:“MI:0407”(direct interaction)	0.440
Ppp1r3b		psi-mi:“MI:0914”(association)	0.350
PHKG2	PEX10	psi-mi:“MI:0914”(association)	0.350
	SGK1	psi-mi:“MI:0914”(association)	0.350
	AURKA	psi-mi:“MI:0914”(association)	0.350
PPP1R3C	MYO1C	psi-mi:“MI:0914”(association)	0.350
HERC2	EIF3F	psi-mi:“MI:0914”(association)	0.350
SCGN	SNAP23	psi-mi:“MI:0914”(association)	0.350
TCEANC2	ANKHD1	psi-mi:“MI:0914”(association)	0.350
DOK4	SUPT5H	psi-mi:“MI:0914”(association)	0.350
MED23	PGRMC1	psi-mi:“MI:0914”(association)	0.350
PHKG2	N4BP1	psi-mi:“MI:0914”(association)	0.350
CALM1	MYO1C	psi-mi:“MI:0914”(association)	0.350
CALM2	MYO1C	psi-mi:“MI:0914”(association)	0.350
CALM3	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
PHKG2	PRPF40A	psi-mi:“MI:0914”(association)	0.350
CTCFL	TARS3	psi-mi:“MI:0914”(association)	0.350

BioGRID (138): PHKG2 (Affinity Capture-MS), PHKG2 (Affinity Capture-MS), PHKG2 (Affinity Capture-MS), PHKG2 (Affinity Capture-MS), PHKG2 (Synthetic Lethality), PHKG2 (Affinity Capture-MS), PHKG2 (Affinity Capture-MS), PHKG2 (Affinity Capture-Western), GAK (Affinity Capture-MS), LAMC1 (Affinity Capture-MS), PEX10 (Affinity Capture-MS), PHKA1 (Affinity Capture-MS), PHKA2 (Affinity Capture-MS), PHKB (Affinity Capture-MS), GTF3C5 (Affinity Capture-MS)

ESM2 similar proteins: A0AAR7, A1A699, A4IGM9, D0N4E2, O08605, O80673, P15735, P31325, P53681, Q10KY3, Q13555, Q21734, Q2KJ16, Q2QQR2, Q2QVG8, Q43531, Q4G050, Q58D94, Q5NTH4, Q5U2N4, Q66JF3, Q6AVM3, Q6F3A6, Q6GPL3, Q6H5L4, Q6I5I8, Q6RET7, Q76L34, Q7XJR9, Q7XSQ5, Q852N6, Q8GVC7, Q8LPZ7, Q8S9F2, Q96GD4, Q96QS6, Q9BUB5, Q9DB30, Q9FIM9, Q9FKW4

Diamond homologs: A0A509AFG4, A0A5K1K8H0, A2AAJ9, A2ZVI7, A4IFM7, A8C984, A8WXF6, B9FKW9, C0HKC8, C0HKC9, E9PT87, O02827, O43293, O44997, O54784, O62305, O70150, O75147, O80673, O88764, O94768, P07313, P08414, P11801, P13234, P15735, P18653, P20689, P29294, P31325, P34101, P43292, P53355, P53681, Q00168, Q00771, Q0KHT7, Q0V7M1, Q10KY3, Q14012

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
PHKG2	“up-regulates activity”	PYGM	phosphorylation
PHKG2	“up-regulates activity”	PYGL	phosphorylation
PHKA2	“down-regulates activity”	PHKG2	binding
PHKA1	“down-regulates activity”	PHKG2	binding
PHKG2	“up-regulates activity”	PYG	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 57 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
Translocation of SLC2A4 (GLUT4) to the plasma membrane	5	22.1×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
regulation of cytokinesis	6	50.6×	8e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	37
Likely pathogenic	10
Uncertain significance	113
Likely benign	212
Benign	14

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1072144	NM_000294.3(PHKG2):c.557-1_557delinsAG	Pathogenic
13625	NM_000294.3(PHKG2):c.265dup (p.His89fs)	Pathogenic
13626	NM_000294.3(PHKG2):c.566G>A (p.Gly189Glu)	Pathogenic
13627	NM_000294.3(PHKG2):c.317T>A (p.Val106Glu)	Pathogenic
13628	NM_000294.3(PHKG2):c.130C>T (p.Arg44Ter)	Pathogenic
13629	NM_000294.3(PHKG2):c.277del (p.Leu93fs)	Pathogenic
13630	NM_000294.3(PHKG2):c.433C>T (p.His145Tyr)	Pathogenic
13631	NM_000294.3(PHKG2):c.677T>G (p.Leu226Arg)	Pathogenic
1453300	NM_000294.3(PHKG2):c.226C>T (p.Arg76Ter)	Pathogenic
1459077	NM_000294.3(PHKG2):c.502C>T (p.Arg168Ter)	Pathogenic
1686062	NM_000294.3(PHKG2):c.927+1G>A	Pathogenic
1705670	NM_000294.3(PHKG2):c.802-2A>C	Pathogenic
2023569	NM_000294.3(PHKG2):c.648-2_648del	Pathogenic
2023570	NM_000294.3(PHKG2):c.827del (p.Pro276fs)	Pathogenic
2126568	NM_000294.3(PHKG2):c.767del (p.Glu256fs)	Pathogenic
2736338	NM_000294.3(PHKG2):c.900G>A (p.Trp300Ter)	Pathogenic
2752978	NM_000294.3(PHKG2):c.385G>T (p.Glu129Ter)	Pathogenic
2769867	NM_000294.3(PHKG2):c.905_909del (p.Leu302fs)	Pathogenic
2834443	NM_000294.3(PHKG2):c.53_54del (p.Lys18fs)	Pathogenic
2862845	NM_000294.3(PHKG2):c.72C>A (p.Tyr24Ter)	Pathogenic
3000582	NM_000294.3(PHKG2):c.850C>T (p.Gln284Ter)	Pathogenic
3243489	NC_000016.9:g.(?30760142)(30768418_?)del	Pathogenic
3243490	NC_000016.9:g.(?30762850)(30762944_?)del	Pathogenic
3721908	NM_000294.3(PHKG2):c.679del (p.Leu227fs)	Pathogenic
3722164	NM_000294.3(PHKG2):c.859C>T (p.Gln287Ter)	Pathogenic
3931692	NM_000294.3(PHKG2):c.528C>A (p.Cys176Ter)	Pathogenic
4813543	NM_000294.3(PHKG2):c.455G>A (p.Arg152Gln)	Pathogenic
538172	NM_000294.3(PHKG2):c.671_672delinsAA (p.Phe224Ter)	Pathogenic
538173	NM_000294.3(PHKG2):c.318_319del (p.Val106_Phe107insTer)	Pathogenic
566399	NM_000294.3(PHKG2):c.250del (p.Val84fs)	Pathogenic

SpliceAI

2726 predictions. Top by Δscore:

Variant	Effect	Δscore
16:30748912:GCAG:G	donor_gain	1.0000
16:30748916:G:GA	donor_loss	1.0000
16:30751094:C:CA	acceptor_gain	1.0000
16:30751101:TGCAG:T	acceptor_gain	1.0000
16:30751103:CAG:C	acceptor_gain	1.0000
16:30751104:A:AG	acceptor_gain	1.0000
16:30751104:AGA:A	acceptor_gain	1.0000
16:30751105:G:GG	acceptor_gain	1.0000
16:30751105:GA:G	acceptor_gain	1.0000
16:30751105:GAG:G	acceptor_gain	1.0000
16:30751105:GAGGA:G	acceptor_gain	1.0000
16:30751215:G:GT	donor_gain	1.0000
16:30751224:G:GT	donor_gain	1.0000
16:30751282:G:GG	donor_gain	1.0000
16:30751287:G:GT	donor_gain	1.0000
16:30753390:CCA:C	acceptor_loss	1.0000
16:30753391:CAGG:C	acceptor_loss	1.0000
16:30753392:A:AG	acceptor_gain	1.0000
16:30753392:AG:A	acceptor_gain	1.0000
16:30753393:G:GT	acceptor_gain	1.0000
16:30753393:GG:G	acceptor_gain	1.0000
16:30753393:GGT:G	acceptor_gain	1.0000
16:30753393:GGTC:G	acceptor_gain	1.0000
16:30753393:GGTCC:G	acceptor_gain	1.0000
16:30753555:GAG:G	donor_gain	1.0000
16:30753558:G:GA	donor_loss	1.0000
16:30753558:G:GG	donor_gain	1.0000
16:30753559:T:A	donor_loss	1.0000
16:30756262:G:GT	donor_gain	1.0000
16:30756273:G:GG	donor_gain	1.0000

AlphaMissense

2641 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:30751169:G:C	K53N	1.000
16:30751169:G:T	K53N	1.000
16:30753456:G:C	R152P	1.000
16:30753459:A:C	D153A	1.000
16:30753459:A:G	D153G	1.000
16:30753459:A:T	D153V	1.000
16:30753460:T:A	D153E	1.000
16:30753460:T:G	D153E	1.000
16:30753513:A:C	D171A	1.000
16:30753513:A:G	D171G	1.000
16:30753513:A:T	D171V	1.000
16:30753514:T:A	D171E	1.000
16:30753514:T:G	D171E	1.000
16:30756368:T:A	W217R	1.000
16:30756368:T:C	W217R	1.000
16:30756416:T:C	F233L	1.000
16:30756418:C:A	F233L	1.000
16:30756418:C:G	F233L	1.000
16:30751107:G:A	G33R	0.999
16:30751107:G:C	G33R	0.999
16:30751108:G:A	G33E	0.999
16:30751123:T:A	V38D	0.999
16:30751126:G:C	R39P	0.999
16:30751132:G:A	C41Y	0.999
16:30751133:T:G	C41W	0.999
16:30751162:C:A	A51E	0.999
16:30751167:A:C	K53Q	0.999
16:30751167:A:G	K53E	0.999
16:30751252:T:C	L81P	0.999
16:30753462:T:C	L154P	0.999

dbSNP variants (sampled 300 via entrez): RS1000351483 (16:30751836 G>A), RS1000644591 (16:30749408 C>A,G), RS1000764019 (16:30756606 A>G), RS1000931738 (16:30748814 C>T), RS1000948798 (16:30750680 A>G), RS1001044332 (16:30755640 T>C), RS1001075788 (16:30761500 C>G,T), RS1001191906 (16:30760863 A>C,G), RS1001233777 (16:30750339 G>A), RS1001256267 (16:30754670 A>G), RS1001365886 (16:30755367 C>T), RS1002297629 (16:30749999 G>A,T), RS1002489716 (16:30749842 C>T), RS1002584684 (16:30759380 G>A), RS1002788904 (16:30753922 T>A)

Disease associations

OMIM: gene MIM:172471 | disease phenotypes: MIM:613027

GenCC curated gene-disease

Disease	Classification	Inheritance
glycogen storage disease IXc	Strong	Autosomal recessive
glycogen storage disease due to liver phosphorylase kinase deficiency	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
glycogen storage disease IXc	Definitive	AR

Mondo (4): glycogen storage disease IXc (MONDO:0013091), glycogen storage disease IX (MONDO:0700291), Mauriac syndrome (MONDO:0022435), glycogen storage disease due to liver phosphorylase kinase deficiency (MONDO:0020693)

Orphanet (2): Glycogen storage disease due to liver phosphorylase kinase deficiency (Orphanet:264580), Glycogen storage disease due to phosphorylase kinase deficiency (Orphanet:370)

HPO phenotypes

62 total (30 of 62 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000147	Polycystic ovaries
HP:0000750	Delayed speech and language development
HP:0000823	Delayed puberty
HP:0000858	Irregular menstruation
HP:0000876	Oligomenorrhea
HP:0000939	Osteoporosis
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001394	Cirrhosis
HP:0001395	Hepatic fibrosis
HP:0001396	Cholestasis
HP:0001397	Hepatic steatosis
HP:0001408	Bile duct proliferation
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001638	Cardiomyopathy
HP:0001744	Splenomegaly
HP:0001903	Anemia
HP:0001943	Hypoglycemia
HP:0001946	Ketosis
HP:0001947	Renal tubular acidosis
HP:0002013	Vomiting
HP:0002014	Diarrhea
HP:0002018	Nausea
HP:0002040	Esophageal varix
HP:0002151	Increased circulating lactate concentration
HP:0002155	Hypertriglyceridemia

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C567809	Glycogen Storage Disease IXC (supp.)
C580130	Glycogen Storage Disease Type Ix (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2111324 (PROTEIN COMPLEX GROUP), CHEMBL2349 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

36 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 389,818 (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
CHEMBL1173655	AFATINIB	4	15,144
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1738797	ALECTINIB	4	6,731
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL2105712	AFATINIB DIMALEATE	4	3,215
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL939	GEFITINIB	4	117,814
CHEMBL2105728	CRENOLANIB	3	2,167
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230165	SILMITASERTIB	2	593
CHEMBL1721885	SU-014813	2	363
CHEMBL253969	OSI-632	2
CHEMBL3545396	BMS-690514	2
CHEMBL3979920	MIVAVOTINIB	2
CHEMBL402548	DANUSERTIB	2
CHEMBL475251	R-406	2
CHEMBL513909	BI-2536	2
CHEMBL564829	MILCICLIB	2
CHEMBL572878	TOZASERTIB	2
CHEMBL607707	PELITINIB	2
CHEMBL1230607	PHA-793887	1

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

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
staurosporine	Inhibition	10.0	pIC50
compound 2c [PMID: 24900538]	Inhibition	8.21	pIC50

Binding affinities (BindingDB)

6 measured of 6 human assays (6 total across all organisms); most potent 6 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
PKC-412	KD	190 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
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-carboxamide	KD	2600 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-carboxamide	KD	3500 nM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S)-3-hydroxy-1-methyl-4-piperidinyl]-1-benzopyran-4-one	KD	5300 nM

ChEMBL bioactivities

215 potent at pChembl≥5 of 217 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.85	Kd	0.14	nM	STAUROSPORINE
9.47	IC50	0.336	nM	STAUROSPORINE
9.31	IC50	0.49	nM	STAUROSPORINE
9.31	IC50	0.486	nM	STAUROSPORINE
9.30	IC50	0.5	nM	STAUROSPORINE
9.21	IC50	0.62	nM	STAUROSPORINE
9.00	Kd	1	nM	STAUROSPORINE
8.77	IC50	1.7	nM	K-252A
8.77	Kd	1.7	nM	LESTAURTINIB
8.23	Kd	5.9	nM	SUNITINIB
8.21	IC50	6.1	nM	CHEMBL2151321
8.10	Ki	7.943	nM	TAE-684
7.90	Ki	12.59	nM	CHEMBL2001751
7.89	Kd	13	nM	TAE-684
7.80	Ki	15.85	nM	CHEMBL1990885
7.75	Kd	17.58	nM	CHEMBL5653589
7.74	ED50	18.13	nM	CHEMBL5653589
7.41	Kd	39	nM	SUNITINIB
7.32	Kd	48	nM	GILTERITINIB
7.30	Ki	50.12	nM	CHEMBL1993661
7.28	Kd	53	nM	PF-03758309
7.15	Kd	71	nM	CHEMBL4465866
7.14	Kd	72	nM	CHEMBL4576489
7.10	Ki	79.43	nM	CHEMBL1987034
7.00	Kd	100	nM	SU-014813
7.00	Ki	100	nM	CHEMBL1966628
6.97	IC50	108	nM	BRIGATINIB
6.91	Kd	122	nM	LESTAURTINIB
6.90	Ki	125.9	nM	CHEMBL592030
6.86	Kd	139.4	nM	CHEMBL3752910
6.85	Kd	140	nM	KW-2449
6.84	ED50	143.7	nM	CHEMBL3752910
6.80	Ki	158.5	nM	CHEMBL1995813
6.80	Ki	158.5	nM	CHEMBL1997129
6.80	Ki	158.5	nM	CHEMBL1973540
6.70	Ki	199.5	nM	CHEMBL1986943
6.70	Ki	199.5	nM	CHEMBL1982957
6.65	IC50	226	nM	MIVAVOTINIB
6.60	Ki	251.2	nM	CHEMBL210887
6.60	Ki	251.2	nM	CHEMBL1983111
6.60	Ki	251.2	nM	CHEMBL1974328
6.60	Ki	251.2	nM	CHEMBL2000393
6.60	Ki	251.2	nM	CHEMBL1992634
6.60	Ki	251.2	nM	CHEMBL1999931
6.58	Kd	260	nM	NINTEDANIB
6.50	Ki	316.2	nM	CHEMBL458997
6.50	Ki	316.2	nM	CHEMBL1991078
6.50	Ki	316.2	nM	CHEMBL2000354
6.50	Ki	316.2	nM	CHEMBL1082440
6.50	Ki	316.2	nM	CHEMBL2000345

PubChem BioAssay actives

78 with measured affinity, of 1622 total; 48 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,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-one	350287: Inhibition of PHKgamma2	ic50	0.0001	uM
(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-one	507671: Binding affinity to PHKG2	kd	0.0017	uM
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-carboxylate	1405290: Inhibition of phosphorylase kinase (unknown origin)	ic50	0.0017	uM
Sunitinib	435930: Binding constant for PHKG2 kinase domain	kd	0.0059	uM
N-[(1S)-1-(5-fluoro-2-pyridinyl)ethyl]-3-(3-propan-2-yloxy-1H-pyrazol-5-yl)imidazo[4,5-b]pyridin-5-amine	692414: Inhibition of PhKg2	ic50	0.0061	uM
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-diamine	624797: Binding constant for PHKG2 kinase domain	kd	0.0130	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148999: Binding affinity to human PHKG2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0176	uM
Gilteritinib	1425110: 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	0.0480	uM
N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methylthieno[3,2-d]pyrimidin-4-yl)amino]-1,4-dihydropyrrolo[3,4-d]pyrazole-5-carboxamide	1425110: 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	0.0530	uM
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]propanamide	1526237: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged PHKG2 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0710	uM
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]propanamide	1526237: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged PHKG2 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0720	uM
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-carboxamide	435930: Binding constant for PHKG2 kinase domain	kd	0.1000	uM
Brigatinib	2182829: Inhibition of human PHKg2 using KKLNRTLSFAEPG as substrate in presence of [gamma33P]-ATP by HotSpot assay	ic50	0.1080	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148999: Binding affinity to human PHKG2 incubated for 45 mins by Kinobead based pull down assay	kd	0.1394	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624797: Binding constant for PHKG2 kinase domain	kd	0.1400	uM
6-[[(1R,2S)-2-aminocyclohexyl]amino]-7-fluoro-4-(1-methylpyrazol-4-yl)-1,2-dihydropyrrolo[3,4-c]pyridin-3-one	1330038: Inhibition of human recombinant full length N-terminal GST-tagged PHKG2 expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.2260	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	624797: Binding constant for PHKG2 kinase domain	kd	0.2600	uM
Nilotinib	1425110: 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	0.3310	uM
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone	1425110: 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	0.3970	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide	624797: Binding constant for PHKG2 kinase domain	kd	0.4600	uM
Afatinib	624797: Binding constant for PHKG2 kinase domain	kd	0.4700	uM
14,15-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-1(15),2,4,6,9(16),10,12-heptaen-8-one	256618: Average Binding Constant for PHkg2; NA=Not Active at 10 uM	kd	0.4800	uM
(15R)-15-methyl-5-(6-methyl-3-pyridinyl)-11-thia-6,14,17-triazatetracyclo[8.8.0.02,7.012,18]octadeca-1(10),2(7),3,5,8,12(18)-hexaen-13-one	2167729: Inhibition of PhKgamma2 (unknown origin)	ic50	0.5280	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	624797: Binding constant for PHKG2 kinase domain	kd	0.7600	uM
N-[5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrol-3-yl]-3-(4-methylpiperazin-1-yl)propanamide	1155248: Binding affinity to PHKgamma2 (unknown origin)	ki	0.8400	uM
Midostaurin	507671: Binding affinity to PHKG2	kd	0.9000	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	624797: Binding constant for PHKG2 kinase domain	kd	0.9400	uM
Ruxolitinib	624797: Binding constant for PHKG2 kinase domain	kd	1.0000	uM
N-[6,6-dimethyl-5-(1-methylpiperidine-4-carbonyl)-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-3-methylbutanamide	1425110: 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	1.0020	uM
Bosutinib	624797: Binding constant for PHKG2 kinase domain	kd	1.3000	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	624797: Binding constant for PHKG2 kinase domain	kd	1.6000	uM
Fedratinib	624797: Binding constant for PHKG2 kinase domain	kd	1.6000	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	624797: Binding constant for PHKG2 kinase domain	kd	1.7000	uM
Alectinib	1425110: 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	1.7110	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	256618: Average Binding Constant for PHkg2; NA=Not Active at 10 uM	kd	2.0000	uM
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-methylbenzamide	624797: Binding constant for PHKG2 kinase domain	kd	2.1000	uM
(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-one	624797: Binding constant for PHKG2 kinase domain	kd	2.4000	uM
4-N-(5-cyclopropyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-2-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]pyrimidine-2,4-diamine	1425110: 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	2.4070	uM
(E)-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide	256618: Average Binding Constant for PHkg2; NA=Not Active at 10 uM	kd	2.5000	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	624797: Binding constant for PHKG2 kinase domain	kd	2.6000	uM
Gefitinib	624797: Binding constant for PHKG2 kinase domain	kd	2.7000	uM
5-(3-chloroanilino)benzo[c][2,6]naphthyridine-8-carboxylic acid	1425110: 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	3.5040	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	624797: Binding constant for PHKG2 kinase domain	kd	4.4000	uM
(3R,4R)-4-amino-1-[[4-(3-methoxyanilino)pyrrolo[2,1-f][1,2,4]triazin-5-yl]methyl]piperidin-3-ol	1425110: 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	4.6180	uM
1-[2-[5-[(3-methyloxetan-3-yl)methoxy]benzimidazol-1-yl]quinolin-8-yl]piperidin-4-amine	1425110: 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	5.0160	uM
N-[5-[(2R)-2-methoxy-2-phenylacetyl]-4,6-dihydro-1H-pyrrolo[3,4-d]pyrazol-3-yl]-4-(4-methylpiperazin-1-yl)benzamide	1425110: 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	7.5030	uM
Vandetanib	624797: Binding constant for PHKG2 kinase domain	kd	7.9000	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	435930: Binding constant for PHKG2 kinase domain	kd	9.0000	uM

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
titanium dioxide	decreases methylation	1
beta-lapachone	decreases expression	1
sodium arsenite	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
bisphenol S	increases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	increases abundance, affects expression	1
Atrazine	decreases expression	1
Doxorubicin	increases expression	1
Ivermectin	decreases expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Tretinoin	increases expression	1
Sodium Selenite	increases expression	1
Cadmium Chloride	increases expression	1

ChEMBL screening assays

278 unique, capped per target: 277 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1020729	Binding	Inhibition of human PHK at 10 umol/L	Design, 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
CHEMBL1963696	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: PHKG2	PubChem BioAssay data set

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_D7WZ	Ubigene A-549 PHKG2 KO	Cancer cell line	Male
CVCL_D8SC	Ubigene HCT 116 PHKG2 KO	Cancer cell line	Male
CVCL_D9MU	Ubigene HEK293 PHKG2 KO	Transformed cell line	Female
CVCL_E0K7	Ubigene HeLa PHKG2 KO	Cancer cell line	Female
CVCL_TD30	HAP1 PHKG2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT04454216	Not specified	RECRUITING	GSD VI and GSD IX Natural History
NCT02635269	Not specified	UNKNOWN	Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy