CHKB

protein-coding

choline kinase beta

Gene summary

Choline kinase (CK) and ethanolamine kinase (EK) catalyze the phosphorylation of choline/ethanolamine to phosphocholine/phosphoethanolamine. This is the first enzyme in the biosynthesis of phosphatidylcholine/phosphatidylethanolamine in all animal cells. The highly purified CKs from mammalian sources and their recombinant gene products have been shown to have EK activity also, indicating that both activities reside on the same protein. The choline kinase-like protein encoded by CHKL belongs to the choline/ethanolamine kinase family; however, its exact function is not known. Read-through transcripts are expressed from this locus that include exons from the downstream CPT1B locus. [provided by RefSeq, Jun 2009]

Previous symbols:

CHKL

MANE transcript

NM_005198.5

Inheritance

ClinVar variants

P:46U:162B:103

Top phenotype

Muscular dystrophy, congenital, megaconial type

gnomAD constraint

pLI —, LoF o/e 0.59

Max pathogenic AF

—

Genomic locus

chr22:50,578,959-50,601,455

External References & Databases

Ensembl (ENSG00000100288)

Transcript & Mutation Effects

hg38 • Region Span ~22.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

megaconial type congenital muscular dystrophySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011246

Submitter: Orphanet

megaconial type congenital muscular dystrophySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011246

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Muscular dystrophy, congenital, megaconial typeAR

Manifestation: Cardiovascular; Dermatologic; Musculoskeletal; Neurologic

Intervention: Cardiovascular

Rationale: The condition can include cardiac sequelae (eg, cardiomyopathy and arrhythmias), and surveillance (eg, with echocardiogram and electrocardiogram) can allow potentially beneficial medical interventions

Refs: 9427222; 21665002; 22782513; 24997086

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CHKB variants in ClinVar

10 Conditions Cataloged

Megaconial type congenital muscular dystrophyTotal: 373

Inborn genetic diseasesTotal: 55

not providedTotal: 53

not specifiedTotal: 33

CHKB-related disorderTotal: 16

SeizureTotal: 1

Muscular dystrophyTotal: 1

CHKB-Related Congenital Muscular Dystrophy (CHKB-CMD)Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005198.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	89 clinvar	2 clinvar	94
missense	1 clinvar	2 clinvar	155 clinvar	10 clinvar	2 clinvar	170
nonsense	11 clinvar	4 clinvar	1 clinvar			16
start loss			1 clinvar			1
frameshift	13 clinvar	5 clinvar				18
splice donor/acceptor (+/-2bp)	4 clinvar	6 clinvar	2 clinvar			12
Total	29	17	162	99	4	311

Highest pathogenic variant AF is 0.000086175045

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005198.5	RefSeq	NP_005189.2	11	MANE Select
ENST00000406938.3	Ensembl	ENSP00000384400.3	11	MANE Select
ENST00000885877.1	Ensembl	ENSP00000555936.1	11	Standard
ENST00000885877.2	Ensembl	ENSP00000555936.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

phosphatidylethanolamine biosynthetic process
phosphatidylcholine biosynthetic process
CDP-choline pathway
phosphorylation

Molecular Function

choline kinase activity
ethanolamine kinase activity
ATP binding

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000406938
Coding exons: 11
Length: 22507
Individuals with no LoFs: 125709
Homozygous LoFs: 0
Heterozygous LoFs: 39
Defined: 125748
p: 0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.533	236	214	1.10	0.0000120	2526
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00014	0.00012	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00055	0.00054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.000098	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.121

Intolerance Scores

LoFtool: 0.847
RVIS EVS: -0.31
RVIS percentile EVS: 31.93

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.292

Gene Damage Prediction

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