PHKA2

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

Basic information

Region (hg38): X:18892298-18984114

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 (350 variants)
• not_provided (165 variants)
• Inborn_genetic_diseases (109 variants)
• not_specified (78 variants)
• PHKA2-related_disorder (35 variants)
• Glycogen_storage_disease_IXa2 (8 variants)
• Glycogen_phosphorylase_kinase_deficiency (5 variants)
• Glycogen_storage_disease_IXd (1 variants)
• Intellectual_disability (1 variants)
• See_cases (1 variants)
• Increased_hepatic_glycogen_content (1 variants)
• Genetic_developmental_and_epileptic_encephalopathy (1 variants)
• Aland_island_eye_disease (1 variants)
• Abnormality_of_neuronal_migration (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. These statistics are base on transcript: NM_000000292.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	68	11	82
missense	10	28	205	52	4	299
nonsense	26	5				31
start loss	1	1				2
frameshift	21	7	1			29
splice donor/acceptor (+/-2bp)	7	21				28
Total	65	62	209	120	15

Highest pathogenic variant AF is 0.0000579114

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