PHKA1

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

Basic information

Region (hg38): X:72578814-72714319

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 (476 variants)
not_provided (140 variants)
Inborn_genetic_diseases (92 variants)
not_specified (41 variants)
PHKA1-related_disorder (20 variants)
Glycogen_phosphorylase_kinase_deficiency (5 variants)
Spinocerebellar_ataxia,_X-linked (1 variants)
Peripheral_neuropathy (1 variants)
Ornithine_carbamoyltransferase_deficiency (1 variants)
Intellectual_disability (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. These statistics are base on transcript: NM_000002637.4. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	101 clinvar	9 clinvar	113
missense	2 clinvar		290 clinvar	25 clinvar	2 clinvar	319
nonsense	12 clinvar	6 clinvar	1 clinvar			19
start loss						0
frameshift	8 clinvar	2 clinvar	2 clinvar			12
splice donor/acceptor (+/-2bp)	1 clinvar	11 clinvar	2 clinvar			14
Total	23	19	298	126	11

Highest pathogenic variant AF is 0.000014948974

Loading clinvar variants...

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

pHI
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