PHKG2

phosphorylase kinase catalytic subunit gamma 2, the group of Phosphorylase kinase subunits

Basic information

Region (hg38): 16:30748292-30761176

Links

ENSG00000156873 ∙ NCBI:5261 ∙ OMIM:172471 ∙ HGNC:8931 ∙ Uniprot:P15735 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glycogen storage disease IXc (Strong), mode of inheritance: AR
• glycogen storage disease IXc (Strong), mode of inheritance: AR
• glycogen storage disease due to liver phosphorylase kinase deficiency (Supportive), mode of inheritance: AR
• glycogen storage disease IXc (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycogen storage disease IXc	AR	Biochemical; Gastrointestinal	In Liver PhK deficiency, dietary management can prevent and treat hypoglycemia during acute and stable periods; Specific hepatic surveillance is indicated in childhood; Other interventions have also been reported as beneficial	Biochemical; Gastrointestinal; Musculoskeletal; Neurologic	6952760; 6962066; 8896567; 9245685; 9384616; 10905889; 12930917; 17689125; 21646031; 21634085; 24102521; 25266922; 33317799

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PHKG2 gene.

• Glycogen storage disease IXc (161 variants)
• not provided (41 variants)
• Inborn genetic diseases (26 variants)
• not specified (21 variants)
• Glycogen phosphorylase kinase deficiency (14 variants)
• Glycogen storage disease type IXc (2 variants)
• Mauriac syndrome (1 variants)
• PHKG2-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PHKG2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	36		37
missense	1	3	57			61
nonsense	9	1	1			11
start loss						0
frameshift	9		1			10
inframe indel			2			2
splice donor/acceptor (+/-2bp)	5	1				6
splice region			5	6		11
non coding		1	21	30	16	68
Total	24	6	83	66	16

Highest pathogenic variant AF is 0.0000132

Variants in PHKG2

This is a list of pathogenic ClinVar variants found in the PHKG2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-30748347-C-T		Glycogen storage disease IXc	Uncertain significance (Jan 12, 2018)
16-30748391-G-A		Glycogen storage disease IXc	Uncertain significance (Apr 27, 2017)
16-30748395-T-C		Glycogen storage disease IXc	Benign (Jun 29, 2018)
16-30748403-G-A		Glycogen storage disease IXc	Uncertain significance (Jan 12, 2018)
16-30748433-G-C		Glycogen storage disease IXc	Uncertain significance (Jan 12, 2018)
16-30748439-C-T		Glycogen phosphorylase kinase deficiency	Uncertain significance (Jun 14, 2016)
16-30748481-G-A		not specified	Likely benign (Jan 25, 2017)
16-30748481-G-T		Glycogen storage disease IXc • not specified	Conflicting classifications of pathogenicity (Jan 13, 2018)
16-30748488-C-G		not specified	Likely benign (Nov 07, 2016)
16-30748818-A-G		Glycogen storage disease IXc	Uncertain significance (Apr 27, 2017)
16-30748826-G-T		Glycogen storage disease IXc	Likely benign (Sep 14, 2023)
16-30748827-C-T		Glycogen storage disease IXc	Likely benign (Dec 10, 2023)
16-30748829-G-A		Glycogen storage disease IXc	Likely benign (Nov 07, 2023)
16-30748833-G-A		Inborn genetic diseases	Uncertain significance (Nov 30, 2022)
16-30748838-G-T		Glycogen storage disease IXc	Likely benign (Nov 06, 2023)
16-30748841-G-A		Glycogen storage disease IXc	Conflicting classifications of pathogenicity (Jan 31, 2024)
16-30748841-G-C		Glycogen storage disease IXc	Likely benign (Dec 26, 2023)
16-30748842-G-T		Glycogen storage disease IXc	Pathogenic (Jul 16, 2023)
16-30748844-G-A		Glycogen storage disease IXc	Likely benign (Aug 10, 2023)
16-30748856-C-T		not specified	Likely benign (-)
16-30748868-C-T		Glycogen storage disease IXc	Likely benign (Jul 16, 2023)
16-30748871-C-T		Glycogen storage disease IXc	Likely benign (Apr 09, 2023)
16-30748871-CAA-C		Glycogen storage disease IXc	Pathogenic (Feb 15, 2023)
16-30748891-A-G		Glycogen storage disease IXc	Uncertain significance (Dec 17, 2018)
16-30748892-C-A		Glycogen storage disease IXc	Pathogenic (Jul 19, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PHKG2	protein_coding	protein_coding	ENST00000563588	9	12900

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00386	0.995	125702	1	45	125748	0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.449	228	248	0.920	0.0000171	2624
Missense in Polyphen		94	103.77	0.90587		1078
Synonymous	-1.13	111	96.8	1.15	0.00000597	824
Loss of Function	2.76	8	22.0	0.364	0.00000135	215

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000181	0.000181
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00101	0.000878
European (Non-Finnish)	0.000114	0.000114
Middle Eastern	0.000163	0.000163
South Asian	0.0000980	0.0000980
Other	0.000655	0.000652

dbNSFP

Source: dbNSFP

• Function: 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 (By similarity). {ECO:0000250, ECO:0000269|PubMed:10487978}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:12930917, ECO:0000269|PubMed:8896567, ECO:0000269|PubMed:9245685}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glucagon signaling pathway - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Glycogen Metabolism;Metabolism of carbohydrates;Metabolism;Glycogen breakdown (glycogenolysis);Glycogen metabolism (Consensus)

Recessive Scores

• pRec: 0.196

Intolerance Scores

• loftool: 0.709
• rvis_EVS: -0.71
• rvis_percentile_EVS: 14.5

Haploinsufficiency Scores

• pHI: 0.186
• hipred: Y
• hipred_score: 0.652
• ghis: 0.576

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.994

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Phkg2
• Phenotype: hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: glycogen metabolic process;glycogen biosynthetic process;generation of precursor metabolites and energy;protein phosphorylation;positive regulation of glycogen catabolic process
• Cellular component: cellular_component;cytosol;phosphorylase kinase complex
• Molecular function: protein serine/threonine kinase activity;calmodulin-dependent protein kinase activity;phosphorylase kinase activity;protein binding;calmodulin binding;ATP binding;enzyme binding;tau-protein kinase activity