CHKA

protein-coding

choline kinase alpha

Gene summary

The major pathway for the biosynthesis of phosphatidylcholine occurs via the CDP-choline pathway. The protein encoded by this gene is the initial enzyme in the sequence and may play a regulatory role. The encoded protein also catalyzes the phosphorylation of ethanolamine. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Previous symbols:

MANE transcript

NM_001277.3

Inheritance

ClinVar variants

P:5U:57B:5

Top phenotype

Neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures

gnomAD constraint

pLI —, LoF o/e 0.24

Max pathogenic AF

—

Genomic locus

chr11:68,052,859-68,121,444

External References & Databases

Ensembl (ENSG00000110721)

Transcript & Mutation Effects

hg38 • Region Span ~68.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with microcephaly, movement abnormalities, and seizuresSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859282

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorder with microcephaly, movement abnormalities, and seizuresMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0859282

Submitter: G2P

neurodevelopmental disorder with microcephaly, movement abnormalities, and seizuresLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0859282

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with microcephaly, movement abnormalities, and seizuresAR

Manifestation: Neurologic; Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 35202461

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CHKA variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 50

Neurodevelopmental disorder with microcephaly, movement abnormalities, and seizuresTotal: 9

not providedTotal: 5

Severe intellectual disabilityTotal: 5

SeizureTotal: 5

MicrocephalyTotal: 5

CHKA-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001277.3. 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			1 clinvar	3 clinvar		4
missense		3 clinvar	51 clinvar	2 clinvar		56
nonsense		1 clinvar	1 clinvar			2
start loss			1 clinvar			1
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	5	57	5	0	67

Highest pathogenic variant AF is 0.0000034214797

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 53 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001277.3	RefSeq	NP_001268.2	12	MANE Select
ENST00000265689.9	Ensembl	ENSP00000265689.4	12	MANE Select
NM_001376219.1	RefSeq	NP_001363148.1	13	Standard
NM_001376220.1	RefSeq	NP_001363149.1	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)
Phospholipid Biosynthesis
Kennedy pathway from Sphingolipids
One carbon metabolism and related pathways

Biological Process

ethanolamine metabolic process
lipid metabolic process
phosphatidylethanolamine biosynthetic process
phosphatidylcholine biosynthetic process
CDP-choline pathway

Molecular Function

choline kinase activity
cholinesterase activity
ethanolamine kinase activity
ATP binding
drug binding

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000265689
Coding exons: 12
Length: 68586
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 125748
p: 0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.00	163	203	0.802	0.0000103	2986
Missense (PolyPhen)		50	89.472	0.55883		1284
Synonymous	0.740	68	76.2	0.892	0.00000409	854
Loss of Function	3.49	6	24.7	0.243	0.00000130	305

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.00011	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Has a key role in phospholipid biosynthesis and may contribute to tumor cell growth. Catalyzes the first step in phosphatidylcholine biosynthesis. Contributes to phosphatidylethanolamine biosynthesis. Phosphorylates choline and ethanolamine. Has higher activity with choline. {ECO:0000269|PubMed:19915674}.;

Recessive Scores

pRec: 0.261

Intolerance Scores

LoFtool: 0.603
RVIS EVS: -0.43
RVIS percentile EVS: 25.37

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.919

Gene Damage Prediction

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