CHKB

choline kinase beta

Basic information

Region (hg38): 22:50578958-50601455

Previous symbols: [ "CHKL" ]

Links

ENSG00000100288 ∙ NCBI:1120 ∙ OMIM:612395 ∙ HGNC:1938 ∙ Uniprot:Q9Y259 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• megaconial type congenital muscular dystrophy (Strong), mode of inheritance: AR
• megaconial type congenital muscular dystrophy (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Muscular dystrophy, congenital, megaconial type	AR	Cardiovascular	The condition can include cardiac sequelae (eg, cardiomyopathy and arrhythmias), and surveillance (eg, with echocardiogram and electrocardiogram) can allow potentially beneficial medical interventions	Cardiovascular; Dermatologic; Musculoskeletal; Neurologic	9427222; 21665002; 22782513; 24997086

ClinVar

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

• Megaconial type congenital muscular dystrophy (303 variants)
• not provided (48 variants)
• not specified (24 variants)
• Inborn genetic diseases (14 variants)
• Congenital Muscular Dystrophy, CHKB-related (2 variants)
• Severe global developmental delay;Seizure (1 variants)
• CHKB-related condition (1 variants)
• Muscular dystrophy (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHKB 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			3	60	1	64
missense			134	3	1	138
nonsense	6	2				8
start loss			1			1
frameshift	8	2				10
inframe indel			4			4
splice donor/acceptor (+/-2bp)	2	2	1			5
splice region			7	16	2	25
non coding			6	40	18	64
Total	16	6	149	103	20

Highest pathogenic variant AF is 0.00000658

Variants in CHKB

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

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

Position	Type	Phenotype	Significance	ClinVar
22-50578965-G-C		Megaconial type congenital muscular dystrophy	Benign (Jun 28, 2018)
22-50578973-A-C		Megaconial type congenital muscular dystrophy	Uncertain significance (Jan 12, 2018)
22-50579047-A-G		Megaconial type congenital muscular dystrophy	Benign (Jun 28, 2018)
22-50579055-G-A		Megaconial type congenital muscular dystrophy	Uncertain significance (Jan 13, 2018)
22-50579085-C-G		Megaconial type congenital muscular dystrophy	Benign/Likely benign (Jun 28, 2018)
22-50579190-G-C		Megaconial type congenital muscular dystrophy	Likely benign (Oct 15, 2023)
22-50579196-G-A		Megaconial type congenital muscular dystrophy	Likely benign (Jul 07, 2023)
22-50579200-C-T		Megaconial type congenital muscular dystrophy	Uncertain significance (Apr 25, 2022)
22-50579209-T-G		Megaconial type congenital muscular dystrophy	Uncertain significance (Jan 06, 2020)
22-50579212-C-T		Megaconial type congenital muscular dystrophy	Uncertain significance (Apr 21, 2022)
22-50579222-G-C		Inborn genetic diseases	Uncertain significance (Jul 25, 2023)
22-50579232-C-T		Megaconial type congenital muscular dystrophy	Likely benign (Jan 11, 2020)
22-50579236-A-T		Inborn genetic diseases	Uncertain significance (Dec 06, 2023)
22-50579240-G-A		Megaconial type congenital muscular dystrophy	Conflicting classifications of pathogenicity (Aug 29, 2019)
22-50579240-G-C		Megaconial type congenital muscular dystrophy	Uncertain significance (Sep 05, 2021)
22-50579248-G-A		Megaconial type congenital muscular dystrophy	Uncertain significance (Dec 04, 2019)
22-50579255-C-G		Megaconial type congenital muscular dystrophy	Uncertain significance (Nov 15, 2022)
22-50579258-A-C		Megaconial type congenital muscular dystrophy	Uncertain significance (Jan 12, 2018)
22-50579261-G-A		Megaconial type congenital muscular dystrophy	Conflicting classifications of pathogenicity (Jan 28, 2021)
22-50579269-C-T		Megaconial type congenital muscular dystrophy	Uncertain significance (Jan 12, 2018)
22-50579272-A-AC		Megaconial type congenital muscular dystrophy	Benign (Sep 08, 2023)
22-50579284-G-A			Benign (Jun 28, 2018)
22-50579345-C-T			Likely benign (Jun 16, 2018)
22-50579365-A-G			Benign (Jun 28, 2018)
22-50579422-T-A		Megaconial type congenital muscular dystrophy	Uncertain significance (Sep 07, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHKB	protein_coding	protein_coding	ENST00000406938	11	22507

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.78e-7	0.946	125709	0	39	125748	0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.533	236	214	1.10	0.0000120	2526
Missense in Polyphen		77	75.957	1.0137		922
Synonymous	0.488	84	89.9	0.934	0.00000506	760
Loss of Function	1.88	14	23.9	0.586	0.00000113	266

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000374	0.000355
Ashkenazi Jewish	0.00	0.00
East Asian	0.000546	0.000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000135	0.000132
Middle Eastern	0.000546	0.000544
South Asian	0.0000981	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Has a key role in phospholipid biosynthesis. Catalyzes the first step in phosphatidylethanolamine biosynthesis. Phosphorylates ethanolamine, and can also act on choline (in vitro). Has higher activity with ethanolamine. May not significantly contribute to in vivo phosphatidylcholine biosynthesis. {ECO:0000269|PubMed:19915674}.
• Pathway: Glycerophospholipid metabolism - Homo sapiens (human);Choline metabolism in cancer - Homo sapiens (human);Fatty Acid Beta Oxidation;Kennedy pathway from Sphingolipids;One carbon metabolism and related pathways;Signal Transduction;mitochondrial L-carnitine shuttle;Metabolism of lipids;Import of palmitoyl-CoA into the mitochondrial matrix;phosphatidylcholine biosynthesis;Metabolism;Fatty acid metabolism;Synthesis of PC;Synthesis of PE;phosphatidylethanolamine biosynthesis II;Signaling by Retinoic Acid;Signaling by Nuclear Receptors;Glycerophospholipid biosynthesis;Phospholipid metabolism;FOXA2 and FOXA3 transcription factor networks (Consensus)

Recessive Scores

• pRec: 0.121

Intolerance Scores

• loftool: 0.847
• rvis_EVS: -0.31
• rvis_percentile_EVS: 31.93

Haploinsufficiency Scores

• pHI: 0.113
• hipred: N
• hipred_score: 0.210
• ghis: 0.563

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.292

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Chkb
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; limbs/digits/tail phenotype; muscle phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: phosphatidylethanolamine biosynthetic process;phosphatidylcholine biosynthetic process;CDP-choline pathway;phosphorylation
• Cellular component: cytosol
• Molecular function: choline kinase activity;ethanolamine kinase activity;ATP binding