PHKA2

phosphorylase kinase regulatory subunit alpha 2, the group of Phosphorylase kinase subunits

Basic information

Region (hg38): X:18892297-18984114

Previous symbols: [ "PHK", "PYK" ]

Links

ENSG00000044446 ∙ NCBI:5256 ∙ OMIM:300798 ∙ HGNC:8926 ∙ Uniprot:P46019 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glycogen storage disease IXa1 (Strong), mode of inheritance: XL
• glycogen storage disease IXa1 (Definitive), mode of inheritance: XL
• glycogen storage disease IXa1 (Strong), mode of inheritance: XL
• glycogen storage disease due to liver phosphorylase kinase deficiency (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycogen storage disease, type IXa1	XL	Biochemical; Gastrointestinal	The condition can include manifestations such as hypoglycemia, ketosis, and growth retardation, and recommendations for care include laboratory-based monitoring (eg, including liver function tests, glucose, and ketones), radiological monitoring (abdominal imaging), and nutritional recommendations and avoidance of certain medications in order to help improve metabolic to control and prevent the primary complications; Specific care during pregnancy has been recommended	Biochemical; Gastrointestinal; Musculoskeletal; Neurologic	5306139; 4518931; 280544; 2303074; 7711737; 7847371; 8733134; 9600238; 9835437; 9870210; 10330341; 11286390; 12809646; 12862311; 16354226; 17581768; 17689125; 19856867; 21131218; 21646031; 21634085; 21844581; 21857251; 21911307; 24055370; 25266922; 30659246; 33317799

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PHKA2 gene.

• Glycogen storage disease IXa1 (262 variants)
• not provided (136 variants)
• not specified (68 variants)
• Inborn genetic diseases (40 variants)
• Glycogen storage disease IXa2 (6 variants)
• Glycogen phosphorylase kinase deficiency (4 variants)
• PHKA2-related condition (3 variants)
• Ocular albinism, type II (1 variants)
• Increased hepatic glycogen content (1 variants)
• See cases (1 variants)
• Glycogen storage disease IXd (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PHKA2 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				48	11	59
missense	4	14	134	29	4	185
nonsense	16	3				19
start loss	1	1				2
frameshift	12	5				17
inframe indel		3	2			5
splice donor/acceptor (+/-2bp)	5	17	1			23
splice region			7	11	1	19
non coding			3	47	24	74
Total	38	43	140	124	39

Highest pathogenic variant AF is 0.00000894

Variants in PHKA2

This is a list of pathogenic ClinVar variants found in the PHKA2 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-18893485-C-G		Glycogen storage disease IXa1	Uncertain significance (Jan 19, 2022)
X-18893488-T-C		not specified • Glycogen storage disease IXa1	Benign (Sep 26, 2023)
X-18893503-C-G		Glycogen storage disease IXa1	Likely benign (Apr 17, 2023)
X-18893528-T-G		Glycogen storage disease IXa1 • Inborn genetic diseases	Likely benign (Dec 26, 2023)
X-18893546-G-GTT		Glycogen storage disease IXa1	Conflicting classifications of pathogenicity (Mar 31, 2021)
X-18893546-G-GTTA		Glycogen storage disease IXa1	Likely pathogenic (Jun 28, 2019)
X-18893564-C-T		Glycogen storage disease IXa1	Likely pathogenic (Nov 08, 2022)
X-18893565-C-T		Glycogen storage disease IXa1	Uncertain significance (Nov 11, 2019)
X-18893573-C-T		Inborn genetic diseases	Uncertain significance (Oct 03, 2023)
X-18893578-C-G		Glycogen storage disease IXa1	Likely benign (Dec 12, 2023)
X-18893578-C-T		not specified • PHKA2-related disorder • Glycogen storage disease IXa1	Likely benign (Dec 19, 2023)
X-18893579-G-A		Glycogen storage disease IXa1	Pathogenic (Oct 05, 2022)
X-18893591-TAAA-T			Likely pathogenic (Feb 09, 2018)
X-18893592-A-G		not specified	Uncertain significance (Oct 11, 2021)
X-18893603-C-A		Glycogen storage disease IXa1 • Inborn genetic diseases	Uncertain significance (Nov 12, 2021)
X-18893626-C-T		Glycogen storage disease IXa1	Likely benign (Jul 03, 2021)
X-18893628-C-T		PHKA2-related disorder	Likely benign (Jan 17, 2022)
X-18893636-T-G		Glycogen storage disease IXa1	Uncertain significance (Nov 24, 2023)
X-18893649-T-C		not specified	Uncertain significance (Oct 12, 2023)
X-18894212-G-A		Glycogen storage disease IXa1	Pathogenic (Oct 15, 2020)
X-18894219-C-T			Likely benign (Apr 02, 2018)
X-18894225-A-C		Glycogen storage disease IXa1	Uncertain significance (Aug 23, 2022)
X-18894232-A-G		not specified • Glycogen storage disease IXa1 • PHKA2-related disorder • Inborn genetic diseases	Benign/Likely benign (Dec 30, 2023)
X-18894234-C-T		Glycogen storage disease IXa1	Likely benign (Oct 04, 2022)
X-18894249-C-A		Glycogen storage disease IXa1	Likely benign (Aug 07, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PHKA2	protein_coding	protein_coding	ENST00000379942	33	92299

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.384	0.616	125736	3	9	125748	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.82	404	521	0.775	0.0000446	8091
Missense in Polyphen		91	175.63	0.51815		2743
Synonymous	-2.04	257	219	1.18	0.0000207	2414
Loss of Function	5.01	11	48.8	0.225	0.00000354	802

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000760	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.000144	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000110	0.0000791
Middle Eastern	0.000144	0.000109
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I. The alpha chain may bind calmodulin.
• Disease: DISEASE: Glycogen storage disease 9A (GSD9A) [MIM:306000]: A metabolic disorder resulting in a mild liver glycogenosis with clinical symptoms that include hepatomegaly, growth retardation, muscle weakness, elevation of glutamate-pyruvate transaminase and glutamate-oxaloacetate transaminase, hypercholesterolemia, hypertriglyceridemia, and fasting hyperketosis. Two subtypes are known: type 1 or classic type with no phosphorylase kinase activity in liver or erythrocytes, and type 2 or variant type with no phosphorylase kinase activity in liver, but normal activity in erythrocytes. Unlike other glycogenosis diseases, glycogen storage disease type 9A is generally a benign condition. Patients improve with age and are often asymptomatic as adults. Accurate diagnosis is therefore also of prognostic interest. {ECO:0000269|PubMed:10330341, ECO:0000269|PubMed:17689125, ECO:0000269|PubMed:7549948, ECO:0000269|PubMed:7847371, ECO:0000269|PubMed:8733133, ECO:0000269|PubMed:8733134, ECO:0000269|PubMed:9600238}. 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);Type II diabetes mellitus;Glycogen Metabolism;Metabolism of carbohydrates;Metabolism;Glycogen breakdown (glycogenolysis);Glycogen metabolism (Consensus)

Recessive Scores

• pRec: 0.392

Intolerance Scores

• loftool: 0.0519
• rvis_EVS: -0.57
• rvis_percentile_EVS: 19.05

Haploinsufficiency Scores

• pHI: 0.119
• hipred: Y
• hipred_score: 0.589
• ghis: 0.486

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.625

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Phka2

Gene ontology

• Biological process: carbohydrate metabolic process;glycogen metabolic process;generation of precursor metabolites and energy;cellular protein modification process;protein phosphorylation
• Cellular component: cytosol;plasma membrane;phosphorylase kinase complex
• Molecular function: phosphorylase kinase activity;protein binding;calmodulin binding