PHKB

Summary

PHKB (phosphorylase kinase regulatory subunit beta, HGNC:8927) is a protein-coding gene on chromosome 16q12.1, encoding Phosphorylase b kinase regulatory subunit beta (Q93100). Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I.

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, encoded by this gene, which is a member of the phosphorylase b kinase regulatory subunit family. The gamma subunit also includes the skeletal muscle and hepatic isoforms, encoded by two different genes. 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 9B, also known as phosphorylase kinase deficiency of liver and muscle. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene. Two pseudogenes have been found on chromosomes 14 and 20, respectively.

Source: NCBI Gene 5257 — RefSeq curated summary.

At a glance

• Gene–disease (curated): glycogen storage disease IXb (Definitive, ClinGen)
• Clinical variants (ClinVar): 1,197 total — 90 pathogenic, 57 likely-pathogenic
• Phenotypes (HPO): 54
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_000293

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8927
Approved symbol	PHKB
Name	phosphorylase kinase regulatory subunit beta
Location	16q12.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000102893
Ensembl biotype	protein_coding
OMIM	172490
Entrez	5257

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 23 protein_coding, 3 retained_intron, 3 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000299167, ENST00000323584, ENST00000563376, ENST00000564711, ENST00000564873, ENST00000565424, ENST00000566037, ENST00000566044, ENST00000566275, ENST00000566319, ENST00000566436, ENST00000566721, ENST00000567200, ENST00000567402, ENST00000568171, ENST00000568439, ENST00000570047, ENST00000696809, ENST00000699276, ENST00000868352, ENST00000868353, ENST00000868354, ENST00000940565, ENST00000970598, ENST00000970599, ENST00000970600, ENST00000970601, ENST00000970602, ENST00000970603, ENST00000970604, ENST00000970605, ENST00000970606

RefSeq mRNA: 3 — MANE Select: NM_000293 NM_000293, NM_001031835, NM_001363837

CCDS: CCDS10729, CCDS42161, CCDS92152

Canonical transcript exons

ENST00000323584 — 31 exons

Exon	Start	End
ENSE00000682879	47610826	47610920
ENSE00000945141	47641035	47641090
ENSE00000945142	47641599	47641692
ENSE00000945143	47648533	47648616
ENSE00000945144	47649100	47649204
ENSE00000945145	47650544	47650626
ENSE00000945146	47650831	47650921
ENSE00000945150	47663677	47663734
ENSE00001020454	47593500	47593557
ENSE00001020458	47594137	47594214
ENSE00001869768	47461331	47461426
ENSE00003471588	47515521	47515601
ENSE00003482622	47596373	47596531
ENSE00003488043	47511665	47511772
ENSE00003496924	47497399	47497488
ENSE00003500705	47580295	47580358
ENSE00003501358	47587668	47587763
ENSE00003508838	47661719	47661800
ENSE00003548820	47693378	47693507
ENSE00003549101	47669215	47669417
ENSE00003558634	47660506	47660567
ENSE00003560023	47698448	47698588
ENSE00003571180	47689041	47689175
ENSE00003577000	47696381	47696488
ENSE00003584924	47547433	47547548
ENSE00003623463	47502991	47503090
ENSE00003628105	47588905	47589102
ENSE00003658560	47660657	47660819
ENSE00003693186	47499756	47499894
ENSE00003976136	47699229	47701523
ENSE00003976138	47664885	47664975

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 97.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.9340 / max 155.8396, expressed in 1811 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153937	18.3007	1805
153936	1.4929	998
153939	0.7322	287
153938	0.2642	103
153940	0.0796	32
153941	0.0643	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	97.86	gold quality
vastus lateralis	UBERON:0001379	97.23	gold quality
quadriceps femoris	UBERON:0001377	96.56	gold quality
muscle organ	UBERON:0001630	96.15	gold quality
skeletal muscle organ	UBERON:0014892	96.15	gold quality
biceps brachii	UBERON:0001507	96.14	gold quality
muscle of leg	UBERON:0001383	96.12	gold quality
sperm	CL:0000019	96.10	gold quality
gastrocnemius	UBERON:0001388	96.10	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.99	gold quality
skeletal muscle tissue	UBERON:0001134	95.53	gold quality
male germ cell	CL:0000015	95.46	gold quality
renal medulla	UBERON:0000362	95.44	gold quality
right adrenal gland cortex	UBERON:0035827	95.28	gold quality
superior surface of tongue	UBERON:0007371	95.25	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.22	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.17	gold quality
rectum	UBERON:0001052	95.16	gold quality
right adrenal gland	UBERON:0001233	94.99	gold quality
adrenal gland	UBERON:0002369	94.97	gold quality
synovial joint	UBERON:0002217	94.96	gold quality
adrenal cortex	UBERON:0001235	94.87	gold quality
left adrenal gland	UBERON:0001234	94.81	gold quality
cardia of stomach	UBERON:0001162	94.78	gold quality
monocyte	CL:0000576	94.75	gold quality
jejunum	UBERON:0002115	94.74	gold quality
muscle tissue	UBERON:0002385	94.69	gold quality
left adrenal gland cortex	UBERON:0035825	94.61	gold quality
ganglionic eminence	UBERON:0004023	94.51	gold quality
mononuclear cell	CL:0000842	94.42	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-135	yes	1666.52
E-ANND-3	yes	9.21
E-CURD-112	no	2.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

70 targeting PHKB, 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-3925-3P	100.00	69.95	1237
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-448	99.79	72.37	2103

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 4)

• alpha- and beta-subunits possess amino-terminal glucoamylase-like domains and suggests that they might possess a previously overlooked amylase activity (PMID:12876330)
• Analysis showed that the glycogen phosphorylase kinase beta-subunit (PHKB) interacted with the C-terminal region of KIAA1199 protein. (PMID:25051373)
• PHKb affects colorectal cancer cell growth and represents a novel prognostic biomarker. (PMID:28275865)
• PHKB acts as a novel prognostic indicator for HCC, which exerts its suppression function via inactivating AKT and STAT3. (PMID:31754332)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	phkb	ENSDARG00000078284
mus_musculus	Phkb	ENSMUSG00000036879
rattus_norvegicus	Phkb	ENSRNOG00000024101
drosophila_melanogaster	CG8475	FBGN0031995
caenorhabditis_elegans		WBGENE00022059

Paralogs (2): PHKA2 (ENSG00000044446), PHKA1 (ENSG00000067177)

Protein

Protein identifiers

Phosphorylase b kinase regulatory subunit beta — Q93100 (reviewed: Q93100)

All UniProt accessions (11): Q93100, A0A0G2JLB9, A0A8Q3WM21, A0A8V8TNH3, H3BQ89, H3BV13, I3L0Z1, I3L1N3, I3L213, I3L3F2, I3NHZ9

UniProt curated annotations — full annotation on UniProt →

Function. Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I. The beta chain acts as a regulatory unit and modulates the activity of the holoenzyme in response to phosphorylation.

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.

Subcellular location. Cell membrane.

Post-translational modifications. Ser-701 is probably phosphorylated by PKA. Although the final Cys may be farnesylated, the terminal tripeptide is probably not removed, and the C-terminus is not methylated.

Disease relevance. Glycogen storage disease 9B (GSD9B) [MIM:261750] A metabolic disorder characterized by hepatomegaly, only slightly elevated transaminases and plasma lipids, clinical improvement with increasing age, and remarkably no clinical muscle involvement. Biochemical observations suggest that this mild phenotype is caused by an incomplete holoenzyme that lacks the beta subunit, but that may possess residual activity. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. By phosphorylation of various serine residues.

Pathway. Glycan biosynthesis; glycogen metabolism.

Similarity. Belongs to the phosphorylase b kinase regulatory chain family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q93100-1	1	yes
Q93100-2	2
Q93100-3	3
Q93100-4	4

RefSeq proteins (3): NP_000284, NP_001027005, NP_001350766 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008734	PHK_A/B_su	Family
IPR008928	6-hairpin_glycosidase_sf	Homologous_superfamily
IPR011613	GH15-like	Domain
IPR045583	KPBA/B_C	Domain

Pfam: PF00723, PF19292

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 (124 total): helix 48, strand 32, turn 19, modified residue 8, sequence variant 6, region of interest 4, initiator methionine 3, splice variant 2, chain 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
8XYA	ELECTRON MICROSCOPY	2.7
8JFK	ELECTRON MICROSCOPY	2.9
8JFL	ELECTRON MICROSCOPY	2.9
8Z5P	ELECTRON MICROSCOPY	3.41
8Z5T	ELECTRON MICROSCOPY	3.74
8Z5Q	ELECTRON MICROSCOPY	4.24

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q93100-F1	87.06	0.64

Functional residue map

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

Post-translational modifications (9): 1090, 2, 4, 2, 4, 2, 12, 27, 701

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-70221	Glycogen breakdown (glycogenolysis)
R-HSA-1430728	Metabolism
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives
R-HSA-8982491	Glycogen metabolism

MSigDB gene sets: 241 (showing top): PAX4_01, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_POLYSACCHARIDE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, DOUGLAS_BMI1_TARGETS_DN, FUJII_YBX1_TARGETS_DN, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, GOBP_CARBOHYDRATE_CATABOLIC_PROCESS, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN, NRF2_01, REACTOME_METABOLISM_OF_CARBOHYDRATES_AND_CARBOHYDRATE_DERIVATIVES, GOCC_TRANSFERASE_COMPLEX_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS, GOCC_TRANSFERASE_COMPLEX

GO Biological Process (3): glycogen metabolic process (GO:0005977), generation of precursor metabolites and energy (GO:0006091), carbohydrate metabolic process (GO:0005975)

GO Molecular Function (2): calmodulin binding (GO:0005516), protein binding (GO:0005515)

GO Cellular Component (4): cytosol (GO:0005829), plasma membrane (GO:0005886), phosphorylase kinase complex (GO:0005964), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Glycogen metabolism	1
Metabolism	1
Metabolism of carbohydrates and carbohydrate derivatives	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
cellular anatomical structure	2
energy reserve metabolic process	1
glucan metabolic process	1
metabolic process	1
primary metabolic process	1
protein binding	1
binding	1
membrane	1
cell periphery	1
serine/threonine protein kinase complex	1

Protein interactions and networks

STRING

900 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PHKB	PHKG2	P11800	978
PHKB	PHKG1	Q16816	946
PHKB	PRKAG3	Q9UGI9	815
PHKB	PYGM	P11217	726
PHKB	PYGL	P06737	658
PHKB	CALM1	P02593	647
PHKB	A0A590UK56	A0A590UK56	646
PHKB	AGL	P35573	610
PHKB	GBE1	Q04446	588
PHKB	SLC37A4	O43826	576
PHKB	GYS2	P54840	560
PHKB	CEMIP	Q8WUJ3	538
PHKB	ITFG1	Q8TB96	503
PHKB	PYGB	P11216	493
PHKB	PHKA1	P46020	491

IntAct

52 interactions, top by confidence:

A	B	Type	Score
PHKG2	PHKA2	psi-mi:“MI:0914”(association)	0.920
MPPED1	TXNDC9	psi-mi:“MI:0914”(association)	0.640
VBP1	PFDN6	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
PHKB	CAMK2B	psi-mi:“MI:0915”(physical association)	0.560
PHKB	PASK	psi-mi:“MI:0217”(phosphorylation reaction)	0.560
PASK	PHKB	psi-mi:“MI:0217”(phosphorylation reaction)	0.560
CEMIP	COPA	psi-mi:“MI:0914”(association)	0.500
CEMIP	PHKB	psi-mi:“MI:0915”(physical association)	0.500
PHKB	VARS1	psi-mi:“MI:0915”(physical association)	0.400
PHKB	ADISSP	psi-mi:“MI:0915”(physical association)	0.370
HNRNPC	PHKB	psi-mi:“MI:0915”(physical association)	0.370
PPP1R3C	MYO1C	psi-mi:“MI:0914”(association)	0.350
BRAF	HSPA1A	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
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
C2CD4B	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
LGALS3BP	HECTD4	psi-mi:“MI:0914”(association)	0.350
FGF12	SUPT5H	psi-mi:“MI:0914”(association)	0.350
DOK4	SUPT5H	psi-mi:“MI:0914”(association)	0.350
SLU7	SUPT5H	psi-mi:“MI:0914”(association)	0.350

BioGRID (83): PHKB (Two-hybrid), PHKB (Reconstituted Complex), PHKB (Affinity Capture-MS), PHKB (Affinity Capture-MS), C20orf27 (Two-hybrid), PHKB (Two-hybrid), CORO1B (Co-fractionation), CORO1C (Co-fractionation), PHKB (Affinity Capture-MS), PHKB (Affinity Capture-MS), PHKB (Affinity Capture-MS), PHKB (Affinity Capture-Western), PHKB (Affinity Capture-MS), PHKB (Affinity Capture-MS), PHKB (Proximity Label-MS)

ESM2 similar proteins: A0A0B4K7J2, A1ZAK1, A6NKT7, F4J8D3, G5ED39, H2QII6, O01510, O14715, O48767, P0DJD0, P0DJD1, P12798, P33144, P40358, P42286, P49792, Q00416, Q0IEK6, Q18508, Q18892, Q20937, Q291E4, Q2U639, Q4WVM7, Q5B8K7, Q61CW2, Q61WP7, Q6C9G0, Q6CXL5, Q6FUS3, Q6FVG5, Q70PP2, Q751J3, Q754V0, Q759B7, Q759Y1, Q75B70, Q75CM2, Q7TSH2, Q7Z3J3

Diamond homologs: P12798, P18688, P18826, P34335, P46018, P46019, P46020, Q64649, Q7TSH2, Q8BWJ3, Q93100, Q9VLS1, Q9W391, Q9W6R1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 69 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
Glycogen breakdown (glycogenolysis)	5	82.8×	9e-07

GO biological processes:

GO term	Partners	Fold	FDR
regulation of cytokinesis	5	33.4×	8e-05
long-term synaptic potentiation	5	22.3×	4e-04
protein phosphorylation	6	6.5×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1197 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	90
Likely pathogenic	57
Uncertain significance	368
Likely benign	548
Benign	35

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070588	NM_000293.3(PHKB):c.2427+1045del	Pathogenic
1070610	NC_000016.9:g.(?47545556)(47581479_?)del	Pathogenic
13617	NM_000293.3(PHKB):c.1265dup (p.Asn422fs)	Pathogenic
13620	NM_000293.3(PHKB):c.1257T>A (p.Tyr419Ter)	Pathogenic
1433722	NC_000016.9:g.(?47495262)(47644851_?)del	Pathogenic
1455940	NM_000293.3(PHKB):c.2048dup (p.Ser684fs)	Pathogenic
1457393	NC_000016.9:g.(?47614186)(47644851_?)del	Pathogenic
1683502	NM_000293.3(PHKB):c.573_577del (p.Gln191fs)	Pathogenic
1686061	NM_000293.3(PHKB):c.1688C>A (p.Ser563Ter)	Pathogenic
1699565	NM_000293.3(PHKB):c.1285C>T (p.Arg429Ter)	Pathogenic
2035718	NM_000293.3(PHKB):c.341dup (p.Glu115fs)	Pathogenic
2078619	NM_000293.3(PHKB):c.1805_1808dup (p.Gln603fs)	Pathogenic
2422824	NC_000016.9:g.(?47531290)(47581479_?)del	Pathogenic
242718	NM_000293.3(PHKB):c.2926G>T (p.Glu976Ter)	Pathogenic
2501064	NM_000293.3(PHKB):c.2839C>T (p.Gln947Ter)	Pathogenic
2634850	NM_000293.3(PHKB):c.3124del (p.Arg1041_Leu1042insTer)	Pathogenic
2637056	NM_000293.3(PHKB):c.2896-1G>T	Pathogenic
2692944	NM_000293.3(PHKB):c.369_370del (p.Gly124fs)	Pathogenic
2693660	NM_000293.3(PHKB):c.1622dup (p.Ile543fs)	Pathogenic
2694652	NM_000293.3(PHKB):c.127G>T (p.Glu43Ter)	Pathogenic
2697311	NM_000293.3(PHKB):c.80C>G (p.Ser27Ter)	Pathogenic
2709953	NM_000293.3(PHKB):c.1320del (p.Leu442fs)	Pathogenic
2713914	NM_000293.3(PHKB):c.3038del (p.Asn1013fs)	Pathogenic
2715371	NC_000016.10:g.47499755GTCAA[1]	Pathogenic
2721383	NM_000293.3(PHKB):c.2332del (p.Leu778fs)	Pathogenic
2744454	NM_000293.3(PHKB):c.856G>T (p.Glu286Ter)	Pathogenic
2751289	NM_000293.3(PHKB):c.2345_2355del (p.Val782fs)	Pathogenic
2755522	NM_000293.3(PHKB):c.2817dup (p.Gly940fs)	Pathogenic
2770440	NM_000293.3(PHKB):c.566del (p.Gly189fs)	Pathogenic
2772728	NM_000293.3(PHKB):c.1089T>A (p.Cys363Ter)	Pathogenic

SpliceAI

5637 predictions. Top by Δscore:

Variant	Effect	Δscore
16:47497396:TA:T	acceptor_loss	1.0000
16:47497396:TAGG:T	acceptor_gain	1.0000
16:47497397:A:AG	acceptor_gain	1.0000
16:47497397:A:AT	acceptor_loss	1.0000
16:47497397:AGGCT:A	acceptor_gain	1.0000
16:47497398:G:GT	acceptor_gain	1.0000
16:47497398:GGCTC:G	acceptor_gain	1.0000
16:47497484:AATTG:A	donor_gain	1.0000
16:47497485:ATTG:A	donor_gain	1.0000
16:47497486:TTG:T	donor_gain	1.0000
16:47497487:TG:T	donor_gain	1.0000
16:47497488:GG:G	donor_gain	1.0000
16:47497488:GGTG:G	donor_loss	1.0000
16:47497489:G:GG	donor_gain	1.0000
16:47497489:G:T	donor_loss	1.0000
16:47497492:AGTAA:A	donor_loss	1.0000
16:47499754:A:AG	acceptor_gain	1.0000
16:47499755:G:GG	acceptor_gain	1.0000
16:47499755:GTC:G	acceptor_gain	1.0000
16:47506686:G:GT	donor_gain	1.0000
16:47511658:A:AG	acceptor_gain	1.0000
16:47511659:T:G	acceptor_gain	1.0000
16:47511662:TAGG:T	acceptor_loss	1.0000
16:47511663:A:AC	acceptor_loss	1.0000
16:47511664:G:A	acceptor_loss	1.0000
16:47511768:TTCAG:T	donor_loss	1.0000
16:47511769:TCAGG:T	donor_loss	1.0000
16:47511770:CAG:C	donor_loss	1.0000
16:47511771:AGGTA:A	donor_loss	1.0000
16:47511772:GGT:G	donor_loss	1.0000

AlphaMissense

7194 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:47503026:T:C	L114P	1.000
16:47547452:T:C	L205P	0.999
16:47580326:G:C	A248P	0.999
16:47580345:T:A	L254H	0.999
16:47587680:T:C	S263P	0.999
16:47587687:T:A	I265K	0.999
16:47589020:G:A	G329E	0.999
16:47589038:G:C	R335T	0.999
16:47589038:G:T	R335I	0.999
16:47499872:T:A	W95R	0.998
16:47499872:T:C	W95R	0.998
16:47503026:T:A	L114Q	0.998
16:47515552:T:C	L182P	0.998
16:47547499:T:A	W221R	0.998
16:47547499:T:C	W221R	0.998
16:47580303:G:A	G240D	0.998
16:47580317:G:C	A245P	0.998
16:47580318:C:A	A245D	0.998
16:47580321:T:C	L246P	0.998
16:47580343:C:A	N253K	0.998
16:47580343:C:G	N253K	0.998
16:47587714:G:C	R274P	0.998
16:47587752:T:C	S287P	0.998
16:47589028:C:A	R332S	0.998
16:47589031:T:C	F333L	0.998
16:47589033:C:A	F333L	0.998
16:47589033:C:G	F333L	0.998
16:47589039:A:C	R335S	0.998
16:47589039:A:T	R335S	0.998
16:47589041:A:T	D336V	0.998

dbSNP variants (sampled 300 via entrez): RS1000008508 (16:47557950 T>C), RS1000008556 (16:47555435 A>G), RS1000037395 (16:47633540 C>G), RS1000039273 (16:47607402 A>T), RS1000041170 (16:47514053 C>G), RS1000067421 (16:47614508 A>C), RS1000077686 (16:47603748 G>T), RS1000087023 (16:47695952 A>G), RS1000088822 (16:47467401 A>G), RS1000110091 (16:47552579 G>A,C), RS1000115361 (16:47508577 G>A), RS1000127106 (16:47663585 G>A), RS1000161847 (16:47492179 C>A,T), RS1000165655 (16:47552805 A>G), RS1000170855 (16:47506976 G>A,C)

Disease associations

OMIM: gene MIM:172490 | disease phenotypes: MIM:261750, MIM:232200

GenCC curated gene-disease

Disease	Classification	Inheritance
glycogen storage disease IXb	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
glycogen storage disease IXb	Definitive	AR

Mondo (4): glycogen storage disease IXb (MONDO:0009868), glycogen storage disease IX (MONDO:0700291), mitochondrial disease (MONDO:0044970), disorder of glycogen metabolism (MONDO:0002412)

Orphanet (4): Glycogen storage disease due to liver and muscle phosphorylase kinase deficiency (Orphanet:79240), Glycogen storage disease due to phosphorylase kinase deficiency (Orphanet:370), Mitochondrial disease (Orphanet:68380), Glycogen storage disease (Orphanet:79201)

HPO phenotypes

54 total (30 of 54 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000147	Polycystic ovaries
HP:0000750	Delayed speech and language development
HP:0000858	Irregular menstruation
HP:0000876	Oligomenorrhea
HP:0000939	Osteoporosis
HP:0001252	Hypotonia
HP:0001324	Muscle weakness
HP:0001394	Cirrhosis
HP:0001395	Hepatic fibrosis
HP:0001402	Hepatocellular carcinoma
HP:0001510	Growth delay
HP:0001744	Splenomegaly
HP:0001903	Anemia
HP:0001943	Hypoglycemia
HP:0001947	Renal tubular acidosis
HP:0001988	Recurrent hypoglycemia
HP:0002013	Vomiting
HP:0002014	Diarrhea
HP:0002018	Nausea
HP:0002149	Hyperuricemia
HP:0002155	Hypertriglyceridemia
HP:0002194	Delayed gross motor development
HP:0002240	Hepatomegaly
HP:0002719	Recurrent infections
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0002913	Myoglobinuria
HP:0003124	Hypercholesterolemia
HP:0003128	Lactic acidosis
HP:0003162	Fasting hypoglycemia

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D006008	Glycogen Storage Disease	C16.320.565.202.449; C18.452.648.202.449
C563008	Glycogen Storage Disease IXB (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), CHEMBL3844 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
9.30	IC50	0.5	nM	STAUROSPORINE
8.77	IC50	1.7	nM	K-252A
6.42	Kd	383.7	nM	CHEMBL5653589
6.42	ED50	383.7	nM	CHEMBL5653589
5.77	IC50	1688	nM	CHEMBL538718
5.42	IC50	3800	nM	CHEMBL538718

PubChem BioAssay actives

4 with measured affinity, of 49 total; 3 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	159258: Inhibition of phosphorylase kinase.	ic50	0.0005	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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148998: Binding affinity to human PHKB incubated for 45 mins by Kinobead based pull down assay	kd	0.3837	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
Acetaminophen	decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	decreases expression	1
S-1,2-dichlorovinyl-N-acetylcysteine	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
abrine	decreases expression	1
bisphenol S	increases expression	1
picoxystrobin	decreases expression	1
Bortezomib	increases expression	1
Sunitinib	decreases expression	1
Vorinostat	affects expression	1
Air Pollutants	decreases expression	1
Antimycin A	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	increases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Nickel	decreases expression	1

ChEMBL screening assays

21 unique, capped per target: 21 binding

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

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7WY	Ubigene A-549 PHKB KO	Cancer cell line	Male
CVCL_D8SA	Ubigene HCT 116 PHKB KO	Cancer cell line	Male
CVCL_D9MS	Ubigene HEK293 PHKB KO	Transformed cell line	Female
CVCL_E0K6	Ubigene HeLa PHKB KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03351998	PHASE4	COMPLETED	Impact of Statin Therapy on Muscle Mitochondrial Function and Aerobic Capacity
NCT00432744	PHASE3	COMPLETED	Phase III Trial of Coenzyme Q10 in Mitochondrial Disease
NCT05162768	PHASE3	COMPLETED	Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)
NCT06451757	PHASE3	RECRUITING	KHENERFIN Study: A Trial to Evaluate the Efficacy and Safety of Sonlicromanol in Primary Mitochondrial Diseases
NCT02782741	PHASE3	COMPLETED	Study to Compare the Efficacy and Safety of Enzyme Replacement Therapies Avalglucosidase Alfa and Alglucosidase Alfa Administered Every Other Week in Patients With Late-onset Pompe Disease Who Have Not Been Previously Treated for Pompe Disease
NCT04808505	PHASE3	RECRUITING	A Study to Evaluate the Safety, Efficacy, PK, PD and Immunogenicity of Cipaglucosidase Alfa/Miglustat in IOPD Subjects Aged 0 to <18
NCT02398201	PHASE2	COMPLETED	A Study of Bezafibrate in Mitochondrial Myopathy
NCT02473445	PHASE2	TERMINATED	A Long-term Extension of Study RP103-MITO-001 (NCT02023866) to Assess Cysteamine Bitartrate Delayed-release Capsules (RP103) in Children With Inherited Mitochondrial Disease
NCT02500628	PHASE2	COMPLETED	Heart Rate Variability in Response to Metformin Challenge
NCT02805790	PHASE2	COMPLETED	Safety, Tolerability, Efficacy of MTP-131 for Treatment of Mitochondrial Disease in Subjects From the MMPOWER Study
NCT02909400	PHASE2	COMPLETED	The KHENERGY Study
NCT02976038	PHASE2	TERMINATED	Open-Label Extension Trial to Characterize the Long-term Safety and Tolerability of Elamipretide in Subjects With Genetically Confirmed Primary Mitochondrial Myopathy (PMM)
NCT03177798	PHASE2	COMPLETED	Mitochondria and Chronic Kidney Disease
NCT03866954	PHASE2	WITHDRAWN	Trial of Erythrocyte Encapsulated Thymidine Phosphorylase In Mitochondrial Neurogastrointestinal Encephalomyopathy
NCT04165239	PHASE2	COMPLETED	The KHENERGYZE Study
NCT04604548	PHASE2	COMPLETED	The KHENEREXT Study
NCT04802707	PHASE2	RECRUITING	Deoxynucleosides Pyrimidines as Treatment for Mitochondrial Depletion Syndrome
NCT04846036	PHASE2	SUSPENDED	The KHENERGYC Study
NCT05650229	PHASE2	RECRUITING	Efficacy of KL1333 in Adult Patients With Primary Mitochondrial Disease
NCT05972954	PHASE2	COMPLETED	OMT-28 in Patients With Primary Mitochondrial Disease (PMD) (PMD-OPTION)
NCT06017869	PHASE2	RECRUITING	Evaluate the Safety and Therapeutic Effects of a Single Intravenous Infusion (IV) of Autologous CD34+ Cells Enriched With Allogenic Placenta-derived Mitochondria in Patients With a Diagnosis of Pearson Syndrome (PS)
NCT07514338	PHASE2	NOT_YET_RECRUITING	Open Label Extension to Assess Long Term Safety and Efficacy of KL1333 in Patients With Primary Mitochondrial Disease
NCT00765414	PHASE2	COMPLETED	Extension Study of Long-term Safety and Efficacy of Myozyme for a Single Patient With Pompe Disease Who Were Previously Enrolled in Genzyme Sponsored ERT Studies.
NCT02032524	PHASE2	COMPLETED	Avalglucosidase Alfa Extension Study
NCT03019406	PHASE2	ACTIVE_NOT_RECRUITING	A Study to Assess Safety and Efficacy of Avalglucosidase Alfa Administered Every Other Week in Pediatric Patients With Infantile-onset Pompe Disease Previously Treated With Alglucosidase Alfa
NCT06130228	PHASE2	UNKNOWN	Nutritional Therapy in Late-onset Pompe Disease
NCT00060515	PHASE1	TERMINATED	RG2133 (2’,3’,5’-Tri-O-Acetyluridine) in Mitochondrial Disease
NCT02348125	PHASE1	UNKNOWN	Does Clinical Treatment of Mitochondrial Dysfunction Impact Autism Spectrum Disorder (ASD)?
NCT02544217	PHASE1	COMPLETED	A Dose-escalating Clinical Trial With KH176
NCT03888716	PHASE1	COMPLETED	A Phase Ia/Ib, SAD and MAD Study of of KL1333 in Healthy Subjects and Patients With Primary Mitochondrial Disease
NCT04086329	PHASE1	RECRUITING	Validation of Oxygen Nanosensor in Mitochondrial Myopathy
NCT04643249	PHASE1	COMPLETED	Drug-drug Interaction Study of KL1333 in Healthy Subjects
NCT05241262	PHASE1	RECRUITING	Study of N-acetylcysteine in the Treatment of Patients With the m.3243A>G Mutation and Low Brain Glutathione Levels
NCT05569122	PHASE1	RECRUITING	Applying pGz in Mitochondrial Disease
NCT06819683	PHASE1	RECRUITING	Validation of Nanosensor Oxygen Measurement
NCT07258667	PHASE1	NOT_YET_RECRUITING	Pilot Study of the Efficacy of Nicotinamide (Vitamin B3) in Leber’s Hereditary Optic Neuropathy
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
NCT04378075	PHASE2/PHASE3	TERMINATED	A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy