Details for: PHKG2

Gene ID: 5261

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: PHKG2

Ensembl ID: ENSG00000156873

Description: phosphorylase kinase catalytic subunit gamma 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • lung macrophage CL1001603
    CSI 6.98
    rCSI 15.6%
    PRS 84.69
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 5.84
    rCSI 5.27%
    PRS 75.53
  • dendritic cell, human CL0001056
    CSI 3.94
    rCSI 6.05%
    PRS 85.92
  • double negative thymocyte CL0002489
    CSI 3.59
    rCSI 2.5%
    PRS 88.46
  • multi-ciliated epithelial cell CL0005012
    CSI 3.58
    rCSI 3.57%
    PRS 71.09
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 3.39
    rCSI 2.58%
    PRS 89.47
  • transit amplifying cell of colon CL0009011
    CSI 3.38
    rCSI 3.97%
    PRS 79.23
  • common myeloid progenitor CL0000049
    CSI 3.32
    rCSI 2.69%
    PRS 79.8
  • precursor B cell CL0000817
    CSI 3.14
    rCSI 2.75%
    PRS 84.87
  • duct epithelial cell CL0000068
    CSI 3.07
    rCSI 4.49%
    PRS 82.26
  • epithelial cell of lung CL0000082
    CSI 2.86
    rCSI 2.37%
    PRS 77.98
  • plasmacytoid dendritic cell, human CL0001058
    CSI 2.85
    rCSI 1.99%
    PRS 80.68
  • neural crest cell CL0011012
    CSI 2.59
    rCSI 2.05%
    PRS 65.66
  • plasmablast CL0000980
    CSI 2.47
    rCSI 1.95%
    PRS 82.98
  • ciliated epithelial cell CL0000067
    CSI 2.47
    rCSI 2.17%
    PRS 66.25
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 2.37
    rCSI 3.11%
    PRS 88.15
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.37
    rCSI 2.83%
    PRS 59.05
  • ionocyte CL0005006
    CSI 2.36
    rCSI 2.53%
    PRS 78.42
  • CD4-positive, CD25-positive, alpha-beta regulatory T cell CL0000792
    CSI 2.33
    rCSI 2.29%
    PRS 90.52
  • activated type II NK T cell CL0000931
    CSI 2.25
    rCSI 2.53%
    PRS 90.27
  • secretory cell CL0000151
    CSI 2.17
    rCSI 2.27%
    PRS 76.73
  • lung ciliated cell CL1000271
    CSI 2.16
    rCSI 2.49%
    PRS 69.27
  • type B pancreatic cell CL0000169
    CSI 2.15
    rCSI 4.76%
    PRS 76.69
  • pro-B cell CL0000826
    CSI 2.03
    rCSI 1.68%
    PRS 79.95
  • activated CD8-positive, alpha-beta T cell, human CL0001049
    CSI 1.92
    rCSI 3.29%
    PRS 90.54
  • squamous epithelial cell CL0000076
    CSI 1.91
    rCSI 4.54%
    PRS 78.33
  • BEST4+ enteroycte CL4030026
    CSI 1.91
    rCSI 2.37%
    PRS 78.78
  • extravillous trophoblast CL0008036
    CSI 1.88
    rCSI 2.32%
    PRS 75.15
  • granulocyte monocyte progenitor cell CL0000557
    CSI 1.86
    rCSI 1.61%
    PRS 81.64
  • retina horizontal cell CL0000745
    CSI 1.86
    rCSI 2.83%
    PRS 74.17
  • epithelial cell of lower respiratory tract CL0002632
    CSI 1.83
    rCSI 1.42%
    PRS 80.99
  • intermediate monocyte CL0002393
    CSI 1.8
    rCSI 2.71%
    PRS 82.78
  • common dendritic progenitor CL0001029
    CSI 1.78
    rCSI 2.23%
    PRS 86.38
  • promyelocyte CL0000836
    CSI 1.75
    rCSI 2.53%
    PRS 83.89
  • stem cell CL0000034
    CSI 1.74
    rCSI 1.67%
    PRS 70.3
  • myeloid leukocyte CL0000766
    CSI 1.74
    rCSI 1.6%
    PRS 78.95
  • intestinal tuft cell CL0019032
    CSI 1.72
    rCSI 2.63%
    PRS 81.36
  • ciliated cell CL0000064
    CSI 1.69
    rCSI 2.74%
    PRS 72.62
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.61
    rCSI 2%
    PRS 57
  • hematopoietic stem cell CL0000037
    CSI 1.58
    rCSI 1.05%
    PRS 80.26
  • colon epithelial cell CL0011108
    CSI 1.57
    rCSI 1.64%
    PRS 74.66
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 1.56
    rCSI 1.2%
    PRS 80.04
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.55
    rCSI 2.5%
    PRS 60.79
  • transit amplifying cell CL0009010
    CSI 1.52
    rCSI 2.33%
    PRS 86.27
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.51
    rCSI 2.67%
    PRS 58.31
  • pulmonary ionocyte CL0017000
    CSI 1.42
    rCSI 1.73%
    PRS 83.97
  • luminal cell of prostate epithelium CL0002340
    CSI 1.41
    rCSI 7.58%
    PRS 85.43
  • luminal epithelial cell of mammary gland CL0002326
    CSI 1.4
    rCSI 2.55%
    PRS 88.12
  • ependymal cell CL0000065
    CSI 1.36
    rCSI 2.75%
    PRS 55.61
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.21
    rCSI 2.71%
    PRS 59.85
  • CD8-positive, CD28-negative, alpha-beta regulatory T cell CL0000920
    CSI 1.1
    rCSI 2.2%
    PRS 89.58
  • CD4-positive, alpha-beta cytotoxic T cell CL0000934
    CSI 1.08
    rCSI 1.48%
    PRS 92.66
  • colonocyte CL1000347
    CSI 1.06
    rCSI 1.52%
    PRS 78.56
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 1.04
    rCSI 5.2%
    PRS 88.91
  • placental villous trophoblast CL2000060
    CSI 1.04
    rCSI 1.6%
    PRS 76.44
  • colon goblet cell CL0009039
    CSI 0.98
    rCSI 2.33%
    PRS 83.39
  • dopaminergic neuron CL0000700
    CSI 0.68
    rCSI 3.85%
    PRS 63.11
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.47
    rCSI 1.68%
    PRS 57.06

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [PHKG2](/details-gene/5261) encodes the gamma 2 catalytic subunit of phosphorylase kinase (PhK), an enzyme central to energy metabolism. PhK is a key regulator of glycogenolysis, the process of breaking down glycogen into glucose-1-phosphate, thereby providing a rapid source of glucose for cellular processes. The [PHKG2](/details-gene/5261) isoform is predominantly expressed in the liver and testis, and its function is critical for maintaining glucose homeostasis. Mutations in this gene are clinically associated with autosomal recessive liver glycogen storage disease type IXc ([172471](https://omim.org/entry/172471)), characterized by hepatomegaly and impaired glycogen metabolism ([Link](https://doi.org/10.1038/ng1196-337), [Link](https://doi.org/10.1093/hmg/7.1.149)). Expression data suggest its role extends beyond the liver, showing significant activity in various immune cells and progenitors, pointing to a broader function in fueling high-energy cellular activities. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [PHKG2](/details-gene/5261) highlights its importance in cells with high metabolic demands, particularly within the immune and hematopoietic systems. Its most significant expression is observed in [lung macrophage](/details-cell/CL1001603) (CSI: 6.98), suggesting a critical role for rapid energy mobilization via glycogenolysis to fuel functions like phagocytosis and inflammatory responses. The gene also demonstrates high significance in hematopoietic progenitors, including [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) (CSI: 5.84) and [common myeloid progenitor](/details-cell/CL0000049) (CSI: 3.32), which is consistent with the high energy requirements of cellular differentiation and proliferation. Furthermore, [PHKG2](/details-gene/5261) is prominently expressed across multiple professional antigen-presenting cells and lymphocytes. This includes [dendritic cell, human](/details-cell/CL0001056) (CSI: 3.94), [plasmacytoid dendritic cell, human](/details-cell/CL0001058) (CSI: 2.85), [effector CD8-positive, alpha-beta T cell](/details-cell/CL0001050) (CSI: 3.39), and developing lymphocytes like [double negative thymocyte](/details-cell/CL0002489) (CSI: 3.59) and [precursor B cell](/details-cell/CL0000817) (CSI: 3.14). This pattern suggests that [PHKG2](/details-gene/5261)-mediated energy supply is fundamental for immune cell activation, maturation, and effector functions. Its presence in various epithelial cell types, such as [multi-ciliated epithelial cell](/details-cell/CL0005012) and [duct epithelial cell](/details-cell/CL0000068), indicates a broader role in maintaining metabolic function in tissues beyond its classic association with the liver. ## Pathways and Molecular Function The functions of [PHKG2](/details-gene/5261) are primarily centered on energy metabolism and protein phosphorylation. As the catalytic subunit, it directly performs [Phosphorylase kinase activity](/details-go/GO:0004689) within the larger [Phosphorylase kinase complex](/details-go/GO:0005964). This activity is a crucial step in the [Glycogen catabolic process](/details-go/GO:0005980), as annotated by the Gene Ontology. Reactome pathway analysis reinforces this, placing [PHKG2](/details-gene/5261) as a central component of [Glycogen breakdown (glycogenolysis)](https://reactome.org/content/detail/R-HSA-70221) and the broader [Metabolism of carbohydrates](https://reactome.org/content/detail/R-HSA-71387) pathway. Its involvement in these pathways is consistent with its high expression in metabolically active cells like macrophages and progenitors, which require immediate access to glucose from glycogen stores. Beyond its metabolic role, its annotated [Protein serine/threonine kinase activity](/details-go/GO:0004674) and ability to bind ATP ([ATP binding](/details-go/GO:0005524)) and calmodulin ([Calmodulin binding](/details-go/GO:0005516)) indicate its integration into complex signaling networks that regulate cellular energy status. ## Research Directions The established role of [PHKG2](/details-gene/5261) in liver glycogenosis provides a clear clinical anchor, but its significant expression in immune and progenitor cells suggests unexplored functions in immunology and hematopoiesis. Understanding how this 'liver-type' isoform contributes to the bioenergetics of non-hepatic cells is a key area for future investigation. **Proposed Hypotheses:** 1. **Hypothesis 1:** [PHKG2](/details-gene/5261)-mediated glycogenolysis is indispensable for the initial burst of metabolic activity required for macrophage and dendritic cell activation. Its disruption would impair key innate immune functions such as phagocytosis, antigen presentation, and pro-inflammatory cytokine production. 2. **Hypothesis 2:** During hematopoiesis, the high expression of [PHKG2](/details-gene/5261) in progenitor cells like [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) is necessary to fuel the energetic demands of lineage commitment and differentiation. Loss of [PHKG2](/details-gene/5261) function may lead to defects in the generation of mature myeloid and erythroid cells. **Experimental Approach to Test Hypothesis 1:** To test the role of [PHKG2](/details-gene/5261) in macrophage function, a cell-specific knockout mouse model could be generated by crossing a `Phkg2-floxed` mouse with a `Lyz2-Cre` mouse, specifically deleting the gene in myeloid cells. Bone marrow-derived macrophages (BMDMs) would be isolated from knockout and wild-type littermates. These BMDMs would then be challenged with lipopolysaccharide (LPS). Key functional readouts would include: (1) quantification of phagocytic capacity using fluorescently labeled beads or bacteria, (2) measurement of ATP and lactate levels to assess metabolic flux, and (3) analysis of cytokine secretion (e.g., TNF-alpha, IL-6) by ELISA and transcriptomic changes by RNA-sequencing. A significant reduction in these functions in the knockout cells would confirm the hypothesis. **Therapeutic Potential:** The therapeutic relevance of [PHKG2](/details-gene/5261) is primarily in the context of glycogen storage disease type IXc ([172471](https://omim.org/entry/172471)), a loss-of-function disorder. Therefore, therapeutic strategies would focus on **restoration of function** rather than inhibition. Potential avenues include gene therapy to deliver a functional copy of the [PHKG2](/details-gene/5261) gene to hepatocytes or the development of small-molecule activators that could enhance the activity of a partially functional mutant enzyme. Given its critical role in the bioenergetics of immune and hematopoietic cells, systemic inhibition of [PHKG2](/details-gene/5261) for other diseases would likely carry a high risk of on-target toxicities, including myelosuppression and immunodeficiency.

Genular Protein ID: 741191997

Symbol: PHKG2_HUMAN

Name: Phosphorylase b kinase gamma catalytic chain, liver/testis isoform

UniProtKB Accession Codes:

P15735 A8K0C7 B4DEB7 E9PEU3 P11800

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CPTAC 4 CTD 1 ChEBI 2 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugCentral 1 EC 1 EMBL 8 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 13 Gene3D 1 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PIR 1 PRINTS 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 1 RefSeq 2 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 2915644

Title: Messenger ribonucleic acid encoding an apparent isoform of phosphorylase kinase catalytic subunit is abundant in the adult testis.

PubMed ID: 2915644

DOI: 10.1210/mend-3-1-110

PubMed ID: 9384616

Title: Liver glycogenosis due to phosphorylase kinase deficiency: PHKG2 gene structure and mutations associated with cirrhosis.

PubMed ID: 9384616

DOI: 10.1093/hmg/7.1.149

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15616553

Title: The sequence and analysis of duplication-rich human chromosome 16.

PubMed ID: 15616553

DOI: 10.1038/nature03187

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 2948189

Title: Homology probing: identification of cDNA clones encoding members of the protein-serine kinase family.

PubMed ID: 2948189

DOI: 10.1073/pnas.84.2.388

PubMed ID: 9245685

Title: Autosomal recessive liver phosphorylase kinase deficiency caused by a novel splice-site mutation in the gene encoding the liver gamma subunit (PHKG2).

PubMed ID: 9245685

DOI: 10.1006/bbrc.1997.7006

PubMed ID: 10487978

Title: Phosphorylase kinase: the complexity of its regulation is reflected in the complexity of its structure.

PubMed ID: 10487978

DOI: 10.2741/brushia

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 8896567

Title: Mutations in the testis/liver isoform of the phosphorylase kinase gamma subunit (PHKG2) cause autosomal liver glycogenosis in the gsd rat and in humans.

PubMed ID: 8896567

DOI: 10.1038/ng1196-337

PubMed ID: 12930917

Title: Severe phenotype of phosphorylase kinase-deficient liver glycogenosis with mutations in the PHKG2 gene.

PubMed ID: 12930917

DOI: 10.1203/01.pdr.0000088069.09275.10

PubMed ID: 17344846

Title: Patterns of somatic mutation in human cancer genomes.

PubMed ID: 17344846

DOI: 10.1038/nature05610

PubMed ID: 35549678

Title: A very rare case report of glycogen storage disease type IXc with novel PHKG2 variants.

PubMed ID: 35549678

DOI: 10.1186/s12887-021-03055-7

Sequence Information:

  • Length: 406
  • Mass: 46442
  • Checksum: E991CFF2D3D70F60
  • Sequence:
    • MTLDVGPEDE LPDWAAAKEF YQKYDPKDVI GRGVSSVVRR CVHRATGHEF AVKIMEVTAE 
RLSPEQLEEV REATRRETHI LRQVAGHPHI ITLIDSYESS SFMFLVFDLM RKGELFDYLT 
EKVALSEKET RSIMRSLLEA VSFLHANNIV HRDLKPENIL LDDNMQIRLS DFGFSCHLEP 
GEKLRELCGT PGYLAPEILK CSMDETHPGY GKEVDLWACG VILFTLLAGS PPFWHRRQIL 
MLRMIMEGQY QFSSPEWDDR SSTVKDLISR LLQVDPEARL TAEQALQHPF FERCEGSQPW 
NLTPRQRFRV AVWTVLAAGR VALSTHRVRP LTKNALLRDP YALRSVRHLI DNCAFRLYGH 
WVKKGEQQNR AALFQHRPPG PFPIMGPEEE GDSAAITEDE AVLVLG