PHKB

phosphorylase kinase regulatory subunit beta, the group of Phosphorylase kinase subunits

Basic information

Region (hg38): 16:47461123-47701523

Links

ENSG00000102893 ∙ NCBI:5257 ∙ OMIM:172490 ∙ HGNC:8927 ∙ Uniprot:Q93100 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glycogen storage disease IXb (Supportive), mode of inheritance: AR
• glycogen storage disease IXb (Definitive), mode of inheritance: AR
• glycogen storage disease IXb (Strong), mode of inheritance: AR
• glycogen storage disease IXb (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycogen storage disease IXb	AR	Biochemical; Gastrointestinal; Musculoskeletal	Dietary measures to prevent sequelae (eg, frequent feedings high in complex carbohydrates/protein), as well as specific measures if hypoglycemia/ketosis is present (eg, Polycose, fruit juice, IV glucose) can be beneficial; Surveillance liver ultrasonography is indicated in childhood; Certain diets and medications should be avoided (eg, copious simple sugars, sulfonylureas, alcohol, succinylcholine, statins), as well as vigorous exercise	Biochemical; Gastrointestinal; Musculoskeletal	6938920; 6422139; 9215682; 17689125; 21646031; 21634085; 25266922; 33317799

ClinVar

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

• Glycogen storage disease IXb (41 variants)
• Glycogen phosphorylase kinase deficiency (2 variants)
• not provided (2 variants)
• PHKB-related disorder (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PHKB 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			2	229	3	234
missense			241	23	2	266
nonsense	15	9		2		26
start loss			1			1
frameshift	25	3	2			30
inframe indel				1		1
splice donor/acceptor (+/-2bp)	3	25	1			29
splice region			14	56	3	73
non coding		2	33	215	23	273
Total	43	39	280	470	28

Highest pathogenic variant AF is 0.000105

Variants in PHKB

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

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

Position	Type	Phenotype	Significance	ClinVar
16-47461306-A-G		not specified	Likely benign (Sep 08, 2016)
16-47461343-G-C		not specified • PHKB-related disorder	Likely benign (Sep 05, 2017)
16-47461351-A-G		Glycogen storage disease IXb • not specified	Uncertain significance (Dec 07, 2023)
16-47461355-CG-C		Glycogen storage disease IXb	Uncertain significance (Oct 17, 2022)
16-47461356-G-C		Glycogen storage disease IXb	Likely benign (Dec 31, 2022)
16-47461356-G-T		Glycogen storage disease IXb	Likely benign (Dec 06, 2021)
16-47461358-G-C		Glycogen storage disease IXb	Uncertain significance (Jul 05, 2022)
16-47461362-G-C		Glycogen storage disease IXb	Likely benign (Sep 10, 2023)
16-47461364-C-T		Glycogen storage disease IXb	Uncertain significance (Nov 22, 2021)
16-47461366-G-A		Glycogen storage disease IXb	Uncertain significance (Jun 08, 2022)
16-47461368-A-T		Glycogen storage disease IXb	Likely benign (Aug 28, 2023)
16-47461371-C-T		Glycogen storage disease IXb	Likely benign (Nov 17, 2023)
16-47461374-G-A			Likely benign (Oct 17, 2017)
16-47461375-G-A		Glycogen storage disease IXb • Inborn genetic diseases	Uncertain significance (Apr 25, 2023)
16-47461376-C-T		Inborn genetic diseases	Uncertain significance (Jul 14, 2021)
16-47461377-A-C		Glycogen storage disease IXb	Likely benign (Dec 29, 2023)
16-47461377-A-G		Glycogen storage disease IXb	Likely benign (Jan 11, 2024)
16-47461380-A-C		Glycogen storage disease IXb	Conflicting classifications of pathogenicity (Dec 31, 2023)
16-47461381-G-A		Glycogen storage disease IXb	Uncertain significance (Sep 09, 2021)
16-47461388-G-A		Glycogen storage disease IXb	Likely benign (Mar 13, 2023)
16-47461389-G-A		Glycogen storage disease IXb • not specified • PHKB-related disorder	Benign/Likely benign (Jul 01, 2024)
16-47461392-G-A		Glycogen storage disease IXb	Likely benign (Apr 26, 2023)
16-47461395-C-T		Glycogen storage disease IXb	Likely benign (Dec 30, 2023)
16-47461412-G-C		Glycogen storage disease IXb • Inborn genetic diseases	Uncertain significance (Sep 13, 2023)
16-47461416-C-T		Glycogen storage disease IXb	Likely benign (Apr 05, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PHKB	protein_coding	protein_coding	ENST00000323584	31	240401

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.58e-21	0.962	125026	2	720	125748	0.00287

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.299	568	588	0.965	0.0000320	7165
Missense in Polyphen		184	214.81	0.85658		2673
Synonymous	0.739	199	213	0.936	0.0000119	2053
Loss of Function	2.66	44	67.6	0.651	0.00000341	811

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00139	0.00138
Ashkenazi Jewish	0.00111	0.00109
East Asian	0.000653	0.000653
Finnish	0.0141	0.0140
European (Non-Finnish)	0.00299	0.00288
Middle Eastern	0.000653	0.000653
South Asian	0.000760	0.000752
Other	0.00266	0.00261

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I. The beta chain acts as a regulatory unit and modulates the activity of the holoenzyme in response to phosphorylation.
• Disease: DISEASE: Glycogen storage disease 9B (GSD9B) [MIM:261750]: A metabolic disorder characterized by hepatomegaly, only slightly elevated transaminases and plasma lipids, clinical improvement with increasing age, and remarkably no clinical muscle involvement. Biochemical observations suggest that this mild phenotype is caused by an incomplete holoenzyme that lacks the beta subunit, but that may possess residual activity. {ECO:0000269|PubMed:9402963}. 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: 0.216

Intolerance Scores

• loftool: 0.0562
• rvis_EVS: 0.37
• rvis_percentile_EVS: 74.74

Haploinsufficiency Scores

• pHI: 0.346
• hipred: Y
• hipred_score: 0.706
• ghis: 0.560

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.926

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Phkb

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;protein binding;calmodulin binding