PHKA1

phosphorylase kinase regulatory subunit alpha 1, the group of Phosphorylase kinase subunits

Basic information

Region (hg38): X:72578813-72714319

Previous symbols: [ "PHKA" ]

Links

ENSG00000067177 ∙ NCBI:5255 ∙ OMIM:311870 ∙ HGNC:8925 ∙ Uniprot:P46020 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glycogen storage disease IXd (Strong), mode of inheritance: XL
• glycogen storage disease IXd (Strong), mode of inheritance: XL
• glycogen storage disease IXd (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycogen storage disease, type IXd	XL	Pharmacogenomic; Musculoskeletal; Renal	Individuals should avoid circumstances such as vigorous exercise as well as certain medications (eg, succinylcholine, statins) due to risk of rhabdomyolysis	Biochemical; Musculoskeletal; Renal	2252364; 7874115; 9731190; 12825073; 21634085

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PHKA1 gene.

• Glycogen storage disease IXd (314 variants)
• not provided (132 variants)
• not specified (35 variants)
• Inborn genetic diseases (28 variants)
• Glycogen phosphorylase kinase deficiency (8 variants)
• PHKA1-related condition (3 variants)
• Spinocerebellar ataxia, X-linked (1 variants)
• Peripheral neuropathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PHKA1 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				54	11	65
missense			178	8	2	188
nonsense	7	1				8
start loss						0
frameshift	3	2				5
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)		5	1			6
splice region			12	10	2	24
non coding			19	63	36	118
Total	10	9	199	125	49

Highest pathogenic variant AF is 0.0000269

Variants in PHKA1

This is a list of pathogenic ClinVar variants found in the PHKA1 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-72578892-T-C		Glycogen storage disease IXd	Uncertain significance (Jan 13, 2018)
X-72578946-A-T		Glycogen storage disease IXd	Uncertain significance (Jan 12, 2018)
X-72579137-C-A		Glycogen storage disease IXd	Uncertain significance (Jan 13, 2018)
X-72579205-T-C		Glycogen storage disease IXd	Uncertain significance (Jan 12, 2018)
X-72579627-T-C		Glycogen storage disease IXd	Benign (Jan 13, 2018)
X-72579699-A-G		Glycogen storage disease IXd	Uncertain significance (Jan 13, 2018)
X-72579727-T-C		Glycogen storage disease IXd	Conflicting classifications of pathogenicity (Dec 01, 2022)
X-72579737-TAC-T		Glycogen phosphorylase kinase deficiency	Uncertain significance (Jun 14, 2016)
X-72579737-T-TAC		Glycogen phosphorylase kinase deficiency	Benign (Jun 14, 2016)
X-72579737-T-TACAC		Glycogen phosphorylase kinase deficiency	Uncertain significance (Jun 14, 2016)
X-72579851-G-A		Glycogen storage disease IXd	Uncertain significance (Jan 12, 2018)
X-72580115-T-C		Glycogen storage disease IXd	Uncertain significance (Jan 12, 2018)
X-72580198-G-A		Glycogen storage disease IXd	Benign (Jan 13, 2018)
X-72580230-G-A		Glycogen storage disease IXd	Uncertain significance (Jan 13, 2018)
X-72580328-T-G		Glycogen storage disease IXd	Uncertain significance (Jan 12, 2018)
X-72580371-CAG-C		Glycogen phosphorylase kinase deficiency	Benign (Jun 14, 2016)
X-72580449-G-A		Glycogen storage disease IXd	Uncertain significance (Jan 12, 2018)
X-72580499-G-A		Glycogen storage disease IXd	Uncertain significance (Jan 13, 2018)
X-72580502-G-T		Glycogen storage disease IXd	Benign (Jan 12, 2018)
X-72580535-A-G		Glycogen storage disease IXd	Uncertain significance (Jan 13, 2018)
X-72580771-T-A		Glycogen storage disease IXd	Benign (Jan 13, 2018)
X-72581005-T-C		Glycogen storage disease IXd	Benign (Jan 13, 2018)
X-72581017-G-A		Glycogen storage disease IXd	Likely benign (Mar 17, 2022)
X-72581043-C-T		Glycogen storage disease IXd	Uncertain significance (Aug 17, 2023)
X-72581044-G-A		Glycogen storage disease IXd	Likely benign (Aug 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PHKA1	protein_coding	protein_coding	ENST00000373542	32	135504

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.09e-7	1.00	125714	13	20	125747	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.88	363	479	0.758	0.0000368	7976
Missense in Polyphen		94	151.89	0.61887		2513
Synonymous	-0.546	177	168	1.05	0.0000123	2386
Loss of Function	4.33	22	57.4	0.383	0.00000484	858

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000189	0.000160
Ashkenazi Jewish	0.000134	0.0000992
East Asian	0.000361	0.000272
Finnish	0.000125	0.0000924
European (Non-Finnish)	0.000197	0.000141
Middle Eastern	0.000361	0.000272
South Asian	0.000318	0.000196
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 9D (GSD9D) [MIM:300559]: A metabolic disorder characterized by slowly progressive, predominantly distal muscle weakness and atrophy. Clinical features include exercise intolerance with early fatigability, pain, cramps and occasionally myoglobinuria. {ECO:0000269|PubMed:12825073}. 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: 0.190

Intolerance Scores

• loftool: 0.0318
• rvis_EVS: -0.8
• rvis_percentile_EVS: 12.46

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.759
• ghis: 0.528

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.184

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Phka1
• Phenotype: homeostasis/metabolism phenotype; muscle phenotype

Gene ontology

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