CHKA

Summary

CHKA (choline kinase alpha, HGNC:1937) is a protein-coding gene on chromosome 11q13.2, encoding Choline kinase alpha (P35790). Plays a key role in phospholipid biosynthesis by catalyzing the phosphorylation of free choline to phosphocholine, the first step in phosphatidylcholine biosynthesis. It is a selective cancer dependency (DepMap: 18.2% of cell lines).

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.

Source: NCBI Gene 1119 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 76 total — 5 likely-pathogenic
• Phenotypes (HPO): 28
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 18.2% of screened cell lines
• MANE Select transcript: NM_001277

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1937
Approved symbol	CHKA
Name	choline kinase alpha
Location	11q13.2
Locus type	gene with protein product
Status	Approved
Aliases	CKI
Ensembl gene	ENSG00000110721
Ensembl biotype	protein_coding
OMIM	118491
Entrez	1119

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 8 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000265689, ENST00000356135, ENST00000525155, ENST00000528235, ENST00000530730, ENST00000531341, ENST00000533728, ENST00000533910, ENST00000868449, ENST00000868450, ENST00000868451, ENST00000868452, ENST00000931669

RefSeq mRNA: 6 — MANE Select: NM_001277 NM_001277, NM_001376219, NM_001376220, NM_001376221, NM_001376222, NM_212469

CCDS: CCDS8178, CCDS8179

Canonical transcript exons

ENST00000265689 — 12 exons

Exon	Start	End
ENSE00000736981	68064525	68064631
ENSE00000736982	68065786	68065894
ENSE00000736983	68066429	68066516
ENSE00001117236	68061953	68062034
ENSE00001166765	68052859	68054047
ENSE00002184538	68120828	68121388
ENSE00003459920	68070189	68070293
ENSE00003469335	68070724	68070857
ENSE00003473965	68074717	68074830
ENSE00003515000	68097019	68097130
ENSE00003540701	68068879	68068937
ENSE00003614432	68081404	68081457

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 97.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.7350 / max 227.2495, expressed in 1798 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120987	19.4126	1786
120986	2.7240	1137
120988	0.4355	207
120985	0.1630	46

Top tissues by expression

293 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	97.45	gold quality
right testis	UBERON:0004534	97.40	gold quality
right lobe of thyroid gland	UBERON:0001119	97.06	gold quality
left lobe of thyroid gland	UBERON:0001120	97.04	gold quality
body of pancreas	UBERON:0001150	96.59	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.57	gold quality
right frontal lobe	UBERON:0002810	96.56	gold quality
mucosa of transverse colon	UBERON:0004991	96.42	gold quality
thyroid gland	UBERON:0002046	96.41	gold quality
mucosa of stomach	UBERON:0001199	96.24	gold quality
body of stomach	UBERON:0001161	96.10	gold quality
right adrenal gland cortex	UBERON:0035827	95.87	gold quality
testis	UBERON:0000473	95.81	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.75	gold quality
nucleus accumbens	UBERON:0001882	95.66	gold quality
right adrenal gland	UBERON:0001233	95.55	gold quality
cingulate cortex	UBERON:0003027	95.49	gold quality
anterior cingulate cortex	UBERON:0009835	95.46	gold quality
caudate nucleus	UBERON:0001873	95.29	gold quality
spinal cord	UBERON:0002240	95.25	gold quality
amygdala	UBERON:0001876	95.22	gold quality
tibial nerve	UBERON:0001323	95.04	gold quality
right lobe of liver	UBERON:0001114	94.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.85	gold quality
ventricular zone	UBERON:0003053	94.76	gold quality
left adrenal gland cortex	UBERON:0035825	94.75	gold quality
putamen	UBERON:0001874	94.71	gold quality
transverse colon	UBERON:0001157	94.66	gold quality
left adrenal gland	UBERON:0001234	94.52	gold quality
minor salivary gland	UBERON:0001830	94.50	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7249	no	252.69
E-CURD-10	no	170.00
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, E2F1, HIF1A, HINFP, JUN, MYC, PDX1, TP53

miRNA regulators (miRDB)

78 targeting CHKA, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-199A-3P	99.75	70.48	929

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 18.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• activity regulated by Ras proteins through Ral-GDS and PI-3-kinase; has role in malignant transformation (PMID:11840339)
• ChoK overexpression was found in 17% of the samples. ChoK may be related to the development of human breast cancer, suggesting that this finding may suggest a novel antitumoral strategy. (PMID:12082619)
• upregulation of choline kinase is a frequent feature in human tumor-derived cell lines and in lung, prostate, and colorectal cancers (PMID:12176020)
• ChoK may have a role in carcinogenesis (PMID:16820874)
• Analyses showed genotype effects of CHKA genes on spina bifida risk, but did not show evidence of gene-nutrient. (PMID:17184542)
• These data suggest that HIF-1 activation of HREs within the putative chk-a promoter region can increase Chk-A expression within hypoxic environments, consequently increasing cellular PC and tCho levels within these environments. (PMID:18172309)
• The molecular basis to understand the connection between phospholipids metabolism and cell cycle regulation through choline kinase is reported. (PMID:18296102)
• The rates of choline kinase reaction in cell lysates of MDA-MB-231 breast, PC-3 prostate and HeLa cervical cancer cells and in solutions of purified human ChoK, was measured. (PMID:19156696)
• ChoKalpha plays a role in the aggressiveness of bladder tumors and constitutes a new approach for bladder cancer treatment. (PMID:19448670)
• Data show that RNA silencing of choline kinase in HeLa cells completely abrogates the high concentration of phosphocholine, which in turn decreases phosphatidylcholine, phosphatidic acid and signaling through the MAPK and PI3K/AKT pathways. (PMID:19855431)
• ChoKalpha and ChoKbeta isoforms have different physiological roles and implications in human carcinogenesis (PMID:19915674)
• From our data, we proposed that Choline kinase plays a key role in regulating Akt(ser473) phosphorylation, thereby promoting cell survival and proliferation (PMID:20042122)
• kinetic studies revealed that HC-3 is a much more potent inhibitor for ChoKalpha isoforms (alpha1 and alpha2) compared with ChoKbeta. (PMID:20299452)
• these results strongly implicate a new c-Src-dependent link between CHKA and EGFR, which contributes to the regulation of cell proliferation and tumorigenesis. (PMID:21822308)
• Data show choline kinase alpha (CHKalpha) expressed in both cytoplasm and nucleus in malignant lesions. (PMID:22038995)
• ASAH1 inhibition synergistically sensitizes lung cancer cells resistant to the antiproliferative effect of choline kinase alpha inhibitors. (PMID:22515519)
• CHKA SNPs (rs3794186 and rs11481) are not associated with HCC development; however, rs3794186 may correlate with serum AFP levels in HCC. (PMID:22972156)
• HK2 and CKA expression may have biologic and prognostic significance in hepatocellular carcinoma, with tumor HK2 expression being a potential independent predictor of survival. (PMID:23071593)
• A combination of initial velocity and product inhibition studies, together with the kinetic and structural characterisation of a novel ChoKalpha inhibitor is used to support a mechanism of action for human ChoKalpha. (PMID:23416529)
• High choline kinase A expression is associated with colorectal cancer. (PMID:23762272)
• Chk-alpha expression and the effect of its downregulation in human umbilical vein endothelial cells, is reported. (PMID:23775813)
• In EOC that CHKA downregulation significantly decreased the aggressive EOC cell. (PMID:24281000)
• pharmacological inhibition of ChoKalpha induces cancer cell death through a mechanism that involves the activation of exaggerated and persistent ER stress supported by CHOP overproduction. (PMID:24287694)
• Downregulation of Chk-alpha with siRNA increased PLD1 expression, and downregulation of PLD1 increased Chk-alpha expression. (PMID:24556997)
• Our data suggest that choline kinase and its product phosphocholine are required for the normal growth and mineralization of MG-63 cells. (PMID:24583375)
• choline kinase alpha is inhibited by a near-infrared fluorescent carbocyanine (PMID:25028471)
• The significance of CHKA overexpression on a TMA. (PMID:25267063)
• there is a role for the ChoKalpha protein in promoting cancer cell survival that is independent of its catalytic activity. (PMID:25522435)
• Chokalpha possessed oncogenic activity and could be a potential therapeutic target in T-cell lymphoma , as well as other hematological malignancies with interrupted Ras signaling pathways (PMID:25768400)
• Identify choline kinase alpha as a key regulator of glutathione-dependent antioxidant cell defense in ovarian carcinoma. (PMID:25796169)
• Increased expression of CHKA is seen in malignant lesions of prostate cancer (PMID:26041862)
• Downregulation of choline kinase-alpha enhances autophagy in tamoxifen-resistant breast cancer cells. (PMID:26496360)
• These data also support the approach of antitumor strategies that destabilize Chk-alpha protein or downregulate PtdCho in breast cancer treatment. (PMID:26503172)
• CHKA can act as an AR chaperone, providing, to our knowledge, the first evidence for kinases as molecular chaperones, making CHKA both a marker of tumor progression and a potential therapeutic target for PCa. (PMID:26657335)
• Study shows increased CHKA expression in pancreatic ductal adenocarcinoma tumors and may be a predictive marker of response to chemotherapy. (PMID:26769123)
• These findings demonstrate that hCKalpha forms a complex with hepatitis C virus NS5A and that hCKalpha activity enhances the targeting of the complex to the endoplasmic reticulum, where hCKalpha protein, not activity, mediates NS5A binding to NS5B, thereby promoting functional membranous viral replication complex assembly and viral RNA replication. (PMID:27489281)
• Results indicate that choline kinase alpha (CHKA) contributes to tumor progression and metastasis and may serve as a prognostic biomarker and potential therapeutic target in colorectal carcinoma (CRC). (PMID:27556502)
• We found levels of CHKA to be increased in human HCCs compared to nontumor tissues, and increased expression to be associated with tumor aggressiveness. Overexpression of CHKA in HCC cell lines increased their invasiveness, resistance to EGFR inhibitors, and ability to form metastatic tumors in mice by promoting interaction of EGFR with mechanistic target of rapamycin complex 2. (PMID:28065789)
• There is no correlation between single CHKA rs7928739 polymorphism and the incidence of intrauterine fetal death. (PMID:28509322)
• hCKalpha functions as an indispensable regulator that bridges PI4KIIIalpha and hepatitis C virus NS5A and potentiates NS5A-stimulated PI4KIIIalpha activity, which then facilitates the targeting of the ternary complex to the endoplasmic reticulum for viral replication. (PMID:28566381)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	chka	ENSDARG00000041078
mus_musculus	Chka	ENSMUSG00000024843
rattus_norvegicus	Chka	ENSRNOG00000016791
drosophila_melanogaster	CG2201	FBGN0032955
caenorhabditis_elegans		WBGENE00000509
caenorhabditis_elegans		WBGENE00000510
caenorhabditis_elegans		WBGENE00000511
caenorhabditis_elegans		WBGENE00000512
caenorhabditis_elegans		WBGENE00000513
caenorhabditis_elegans		WBGENE00000514

Paralogs (3): CHKB (ENSG00000100288), ETNK1 (ENSG00000139163), ETNK2 (ENSG00000143845)

Protein

Protein identifiers

Choline kinase alpha — P35790 (reviewed: P35790)

Alternative names: CHETK-alpha, Ethanolamine kinase

All UniProt accessions (3): P35790, E9PM06, H0YD02

UniProt curated annotations — full annotation on UniProt →

Function. Plays a key role in phospholipid biosynthesis by catalyzing the phosphorylation of free choline to phosphocholine, the first step in phosphatidylcholine biosynthesis. Also phosphorylates ethanolamine, thereby contributing to phosphatidylethanolamine biosynthesis. Has higher activity with choline. May contribute to tumor cell growth. This isoform plays a key role in lipolysis of lipid droplets following glucose deprivation. In response to glucose deprivation, phosphorylated by AMPK, promoting localization to lipid droplets. Phosphorylation is followed by acetylation by KAT5, leading to dissociation of the homodimer into a monomer. Monomeric CHKA isoform 1 is converted into a tyrosine-protein kinase, which phosphorylates lipid droplet structural proteins PLIN2 and PLIN3, leading to lipolysis of lipid droplets.

Subunit / interactions. Homodimer. Heterodimer with CHKB. Monomer; acetylation by KAT5 promotes dissociation of the homodimer and monomerization. (Microbial infection) Interacts with PI4KA/PI4KIIIalpha; CHKA bridges PI4KA/PI4KIIIalpha and hepatitis C virus (HCV) non-structural protein 5A (NS5A) and potentiates NS5A-stimulated PI4KA activity, which then facilitates the targeting of the ternary complex to the ER for viral replication.

Subcellular location. Cytoplasm. Cytosol Lipid droplet.

Post-translational modifications. Phosphorylated at Ser-279 by AMPK in response to glucose deprivation, leading to localization to lipid droplets. Acetylated by KAT5 at Lys-247 following phosphorylation by AMPK, leading to monomerization and conversion into a tyrosine-protein kinase.

Disease relevance. Neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures (NEDMIMS) [MIM:620023] An autosomal recessive neurodevelopmental disorder characterized by severe global developmental delay, impaired intellectual development, microcephaly, early-onset seizures, and movement abnormalities. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Homodimerization or heterodimerization is required for the choline and ethanolamine kinase activities.

Pathway. Phospholipid metabolism; phosphatidylcholine biosynthesis; phosphocholine from choline: step 1/1. Phospholipid metabolism; phosphatidylethanolamine biosynthesis; phosphatidylethanolamine from ethanolamine: step 1/3.

Similarity. Belongs to the choline/ethanolamine kinase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P35790-1	1, CHKalpha2, alpha-2	yes
P35790-2	2, CHKalpha1, alpha-1

RefSeq proteins (6): NP_001268, NP_001363148, NP_001363149, NP_001363150, NP_001363151, NP_997634 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011009	Kinase-like_dom_sf	Homologous_superfamily

Pfam: PF01633

Enzyme classification (BRENDA):

• EC 2.7.1.32 — choline kinase (BRENDA: 36 organisms, 80 substrates, 326 inhibitors, 145 Km, 49 kcat entries)

Substrate kinetics (BRENDA)

10 substrates with measured Km, best-characterized 10. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CHOLINE	0.002–13	64
ATP	0.0206–45	50
ETHANOLAMINE	0.787–75	11
N-MONOMETHYLETHANOLAMINE	0.118–3.7	4
N,N-DIMETHYLETHANOLAMINE	0.022–0.085	3
BETA-METHYLCHOLINE	0.444	2
N,N-DIETHYLETHANOLAMINE	0.025	2
N,N-DIISOPROPYLETHANOLAMINE	0.4	2
N,N-DIMETHYLAMINOPROPANOL	0.208	2
DIMETHYLETHANOLAMINE	0.94	1

Catalyzed reactions (Rhea), 3 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)
• choline + ATP = phosphocholine + ADP + H(+) (RHEA:12837)
• ethanolamine + ATP = phosphoethanolamine + ADP + H(+) (RHEA:13069)

UniProt features (60 total): helix 17, strand 14, mutagenesis site 8, binding site 6, sequence variant 5, sequence conflict 3, modified residue 2, compositionally biased region 2, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

26 structures.

PDB	Method	Resolution (Å)
5FTG	X-RAY DIFFRACTION	1.45
5FUT	X-RAY DIFFRACTION	1.6
3G15	X-RAY DIFFRACTION	1.7
4CGA	X-RAY DIFFRACTION	1.74
4CG8	X-RAY DIFFRACTION	1.75
7A06	X-RAY DIFFRACTION	1.8
4CG9	X-RAY DIFFRACTION	1.83
2I7Q	X-RAY DIFFRACTION	1.9
3ZM9	X-RAY DIFFRACTION	1.9
7NB3	X-RAY DIFFRACTION	2
2CKO	X-RAY DIFFRACTION	2.15
7A04	X-RAY DIFFRACTION	2.15
4BR3	X-RAY DIFFRACTION	2.2
5AFV	X-RAY DIFFRACTION	2.25
7NB1	X-RAY DIFFRACTION	2.3
3F2R	X-RAY DIFFRACTION	2.35
5EQP	X-RAY DIFFRACTION	2.35
5W6O	X-RAY DIFFRACTION	2.35
2CKQ	X-RAY DIFFRACTION	2.4
4DA5	X-RAY DIFFRACTION	2.4
5EQE	X-RAY DIFFRACTION	2.4
7NB2	X-RAY DIFFRACTION	2.4
8BI6	X-RAY DIFFRACTION	2.4
5EQY	X-RAY DIFFRACTION	2.5
8BI5	X-RAY DIFFRACTION	2.5
2CKP	X-RAY DIFFRACTION	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35790-F1	83.95	0.72

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (6): 117–123; 119–121; 146; 207–213; 308; 330

Post-translational modifications (2): 247, 279

Mutagenesis-validated functional residues (8):

Position	Phenotype
175	does not affect interaction with plin2 and plin3.
177–179	does not affect interaction with plin2 and plin3.
182–184	does not affect interaction with plin2 and plin3.
186–187	abolished interaction with plin2 and plin3.
247	mimics acetylation; promoting monomerization, leading to decreased choline kinase activity. increased lipolysis of lipid
247	abolished acetylation by kat5, leading to prevent conversion into a tyrosine-protein kinase.
279	abolished phosphorylation by ampk, preventing localization to lipid droplets and subsequent acetylation by kat5.
279	mimics phosphorylation; promoting localization to lipid droplets.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1483191	Synthesis of PC
R-HSA-1483213	Synthesis of PE

MSigDB gene sets: 284 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, ELVIDGE_HYPOXIA_DN, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_BIOSYNTHETIC_PROCESS, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, chr11q13, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, SP1_Q2_01, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS

GO Biological Process (8): lipid metabolic process (GO:0006629), phosphatidylethanolamine biosynthetic process (GO:0006646), phosphatidylcholine biosynthetic process (GO:0006656), CDP-choline pathway (GO:0006657), lipid transport (GO:0006869), cellular response to glucose starvation (GO:0042149), lipid droplet disassembly (GO:1905691), phospholipid biosynthetic process (GO:0008654)

GO Molecular Function (11): choline kinase activity (GO:0004103), cholinesterase activity (GO:0004104), ethanolamine kinase activity (GO:0004305), protein tyrosine kinase activity (GO:0004713), ATP binding (GO:0005524), protein homodimerization activity (GO:0042803), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), identical protein binding (GO:0042802)

GO Cellular Component (3): cytoplasm (GO:0005737), lipid droplet (GO:0005811), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glycerophospholipid biosynthetic process	2
kinase activity	2
phosphotransferase activity, alcohol group as acceptor	2
cellular anatomical structure	2
primary metabolic process	1
phosphatidylethanolamine metabolic process	1
phosphatidylcholine metabolic process	1
choline kinase activity	1
diacylglycerol cholinephosphotransferase activity	1
phosphatidylcholine biosynthetic process	1
transport	1
lipid localization	1
cellular response to starvation	1
lipid droplet organization	1
organelle disassembly	1
phospholipid metabolic process	1
lipid biosynthetic process	1
organophosphate biosynthetic process	1
carboxylic ester hydrolase activity	1
protein kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
identical protein binding	1
protein dimerization activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
protein binding	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
cytoplasm	1

Protein interactions and networks

STRING

1476 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHKA	AXIN1	O15169	989
CHKA	GSK3B	P49841	981
CHKA	PCYT1B	Q9Y5K3	953
CHKA	PCYT1A	P49585	942
CHKA	CCNL2	Q96S94	799
CHKA	CDK2	P24941	791
CHKA	CSNK1D	P48730	784
CHKA	CDK4	P11802	759
CHKA	CEPT1	Q9Y6K0	744
CHKA	CHPT1	Q8WUD6	729
CHKA	PCYT2	Q99447	716
CHKA	CDK6	Q00534	707
CHKA	CSNK1E	P49674	706
CHKA	CCNA2	P20248	693
CHKA	SELENOI	Q9C0D9	673

IntAct

3 interactions, top by confidence:

A	B	Type	Score
IDE	NEFL	psi-mi:“MI:0914”(association)	0.350
FCHSD2	CHKA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (27): CHKA (Negative Genetic), CHKA (Affinity Capture-MS), CHKA (Affinity Capture-MS), ENO1 (Affinity Capture-MS), TUBA1B (Affinity Capture-MS), TUBA1C (Affinity Capture-MS), TRIM25 (Affinity Capture-MS), CHKA (Affinity Capture-Western), ENO1 (Reconstituted Complex), CHKA (Affinity Capture-Western), TRIM25 (Reconstituted Complex), CHKA (Biochemical Activity), ENO1 (Affinity Capture-Western), TRIM25 (Affinity Capture-Western), CHKA (Proximity Label-MS)

ESM2 similar proteins: A2AIG8, A6NFX1, O15315, O35083, O35719, O35790, O43502, O54783, O54804, O55229, O73884, P16442, P20417, P35790, P35821, P47802, Q01134, Q08DW9, Q27HK4, Q2TBS1, Q3T9M1, Q3U129, Q4R3I0, Q4R766, Q4R7M4, Q5E9H2, Q5E9T4, Q5SUV1, Q5SX19, Q5VYX0, Q6GV29, Q86XW9, Q8BVM4, Q8CIW5, Q8N2K0, Q8NBA8, Q8QGV6, Q8R2J9, Q8TCT0, Q924H5

Diamond homologs: A7MCT6, D3ZRW8, O54783, O54804, O55229, O81024, P35790, P46558, P46559, P46560, P54352, Q01134, Q22942, Q869T9, Q8L518, Q9D4V0, Q9HBU6, Q9M9H6, Q9NVF9, Q9SZ92, Q9Y259, A7SK27, Q554D8

SIGNOR signaling

20 interactions.

A	Effect	B	Mechanism
SRC	“up-regulates activity”	CHKA	phosphorylation
CHKA	“up-regulates activity”	EGFR	binding
AMPK	“up-regulates activity”	CHKA	phosphorylation
KAT5	“up-regulates activity”	CHKA	acetylation
CHKA	“down-regulates quantity by destabilization”	PLIN2	phosphorylation
CHKA	“down-regulates quantity by destabilization”	PLIN3	phosphorylation
CHKA	“down-regulates activity”	VANGL2	phosphorylation
CHKA	“down-regulates quantity by destabilization”	KDR	phosphorylation
CHKA	“down-regulates activity”	CTNNB1	phosphorylation
CHKA	“up-regulates activity”	TUT1	phosphorylation
CHKA	“down-regulates quantity by destabilization”	DEPTOR	phosphorylation
CHKA	“down-regulates quantity by destabilization”	MDM2	phosphorylation
CHKA	“down-regulates activity”	SRC	phosphorylation
ATR	“up-regulates activity”	CHKA	phosphorylation
CHKA	“down-regulates activity”	LPIN1	phosphorylation
CHKA	“down-regulates quantity by destabilization”	NCOA3	phosphorylation
CHKA	“up-regulates quantity”	“choline phosphate(1-)”	“chemical modification”
CHKA	“down-regulates quantity”	choline	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

76 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	5
Uncertain significance	49
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1325845	NM_001277.3(CHKA):c.421C>T (p.Arg141Trp)	Likely pathogenic
1325846	NM_001277.3(CHKA):c.580C>T (p.Pro194Ser)	Likely pathogenic
1325847	NM_001277.3(CHKA):c.14dup (p.Cys6fs)	Likely pathogenic
1325848	NM_001277.3(CHKA):c.1021T>C (p.Phe341Leu)	Likely pathogenic
3911508	NM_001277.3(CHKA):c.1030G>T (p.Gly344Ter)	Likely pathogenic

SpliceAI

2509 predictions. Top by Δscore:

Variant	Effect	Δscore
11:68064633:T:C	acceptor_gain	1.0000
11:68065781:CCTA:C	donor_loss	1.0000
11:68065782:CTA:C	donor_loss	1.0000
11:68065783:TACCT:T	donor_loss	1.0000
11:68065784:A:AT	donor_loss	1.0000
11:68065785:C:CT	donor_loss	1.0000
11:68065891:TCCC:T	acceptor_gain	1.0000
11:68065892:CCC:C	acceptor_gain	1.0000
11:68065892:CCCC:C	acceptor_gain	1.0000
11:68065893:CC:C	acceptor_gain	1.0000
11:68065893:CCC:C	acceptor_gain	1.0000
11:68065893:CCCTG:C	acceptor_loss	1.0000
11:68065894:CC:C	acceptor_gain	1.0000
11:68065894:CCT:C	acceptor_loss	1.0000
11:68065895:C:CA	acceptor_loss	1.0000
11:68065895:C:CC	acceptor_gain	1.0000
11:68065896:T:G	acceptor_loss	1.0000
11:68066423:CAGTA:C	donor_loss	1.0000
11:68066424:AGTAC:A	donor_loss	1.0000
11:68066425:GTAC:G	donor_loss	1.0000
11:68066426:TA:T	donor_loss	1.0000
11:68066427:A:C	donor_loss	1.0000
11:68066428:CCTGT:C	donor_loss	1.0000
11:68066514:TACCT:T	acceptor_loss	1.0000
11:68066518:T:G	acceptor_loss	1.0000
11:68068934:TGAT:T	acceptor_gain	1.0000
11:68068938:C:CC	acceptor_gain	1.0000
11:68070184:CTCA:C	donor_loss	1.0000
11:68070185:TCA:T	donor_loss	1.0000
11:68070186:CA:C	donor_loss	1.0000

AlphaMissense

3014 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:68061962:A:C	F435L	1.000
11:68061962:A:T	F435L	1.000
11:68061964:A:G	F435L	1.000
11:68066455:A:C	D330E	1.000
11:68066455:A:T	D330E	1.000
11:68066456:T:A	D330V	1.000
11:68066456:T:G	D330A	1.000
11:68066512:A:C	N311K	1.000
11:68066512:A:T	N311K	1.000
11:68068890:T:A	D306V	1.000
11:68068890:T:G	D306A	1.000
11:68074795:A:C	F184L	1.000
11:68074795:A:T	F184L	1.000
11:68074797:A:G	F184L	1.000
11:68097115:G:C	N122K	1.000
11:68097115:G:T	N122K	1.000
11:68120871:A:G	W103R	1.000
11:68120871:A:T	W103R	1.000
11:68062000:A:G	W423R	0.999
11:68062000:A:T	W423R	0.999
11:68062009:A:G	W420R	0.999
11:68062009:A:T	W420R	0.999
11:68066443:G:C	S334R	0.999
11:68066443:G:T	S334R	0.999
11:68066445:T:G	S334R	0.999
11:68066450:T:A	E332V	0.999
11:68066451:C:T	E332K	0.999
11:68066456:T:C	D330G	0.999
11:68066457:C:G	D330H	0.999
11:68068889:G:C	D306E	0.999

dbSNP variants (sampled 300 via entrez): RS1000010515 (11:68117333 G>A), RS1000048065 (11:68068778 C>G), RS1000072308 (11:68063444 G>A,C), RS1000100528 (11:68114236 G>A), RS1000114152 (11:68103068 T>C,G), RS1000208726 (11:68111674 T>A,G), RS1000257993 (11:68088662 C>A), RS1000304080 (11:68123385 C>T), RS1000320227 (11:68075186 A>C), RS1000328280 (11:68076725 CAT>C), RS1000337509 (11:68120318 G>A), RS1000386086 (11:68082692 T>C), RS1000403968 (11:68107732 G>A), RS1000437562 (11:68099846 T>C), RS1000464375 (11:68092931 G>C)

Disease associations

OMIM: gene MIM:118491 | disease phenotypes: MIM:620023

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures	Strong	Autosomal recessive

Mondo (2): microcephaly (MONDO:0001149), neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures (MONDO:0859282)

Orphanet (0):

HPO phenotypes

28 total (28 of 28 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000639	Nystagmus
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000752	Hyperactivity
HP:0000787	Nephrolithiasis
HP:0001266	Choreoathetosis
HP:0001276	Hypertonia
HP:0001344	Absent speech
HP:0001347	Hyperreflexia
HP:0002063	Rigidity
HP:0002194	Delayed gross motor development
HP:0002360	Sleep disturbance
HP:0002540	Inability to walk
HP:0002650	Scoliosis
HP:0003429	CNS hypomyelination
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0011344	Severe global developmental delay
HP:0011463	Childhood onset
HP:0011968	Feeding difficulties
HP:0033725	Thin corpus callosum
HP:0100660	Dyskinesia
HP:0100704	Cerebral visual impairment
HP:0100716	Self-injurious behavior
HP:0200134	Epileptic encephalopathy

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012232_20	Lipoprotein (a) levels	6.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006925	lipoprotein A measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3117 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 7 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL192986	RSM-932A	1	7

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

186 potent at pChembl≥5 of 246 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.00	Kd	10	nM	CHEMBL3763540
7.85	IC50	14	nM	CHEMBL5091519
7.85	IC50	14	nM	CHEMBL5094847
7.70	IC50	20	nM	CHEMBL3765554
7.70	IC50	20	nM	CHEMBL5079663
7.70	IC50	20	nM	CHEMBL5078600
7.68	Kd	21	nM	CHEMBL3764278
7.68	IC50	21	nM	CHEMBL5090932
7.66	IC50	22	nM	CHEMBL5077194
7.64	IC50	23	nM	CHEMBL5075042
7.57	IC50	27	nM	CHEMBL5089356
7.55	IC50	28	nM	CHEMBL5084844
7.55	IC50	28	nM	CHEMBL5085262
7.54	IC50	29	nM	CHEMBL5090132
7.51	IC50	31	nM	CHEMBL5081222
7.51	IC50	31	nM	CHEMBL5075110
7.51	IC50	31	nM	CHEMBL5093152
7.48	IC50	33	nM	CHEMBL5088776
7.47	IC50	34	nM	CHEMBL5091201
7.40	IC50	40	nM	CHEMBL5086885
7.37	IC50	43	nM	CHEMBL5078057
7.31	IC50	49	nM	CHEMBL5085127
7.31	IC50	49	nM	CHEMBL5088850
7.21	IC50	61	nM	CHEMBL5089748
7.18	IC50	66	nM	CHEMBL3763540
7.07	IC50	85	nM	CHEMBL3763931
7.06	Kd	88	nM	CHEMBL3763792
7.06	IC50	88	nM	CHEMBL5093251
7.01	IC50	97	nM	CHEMBL5077317
7.00	Kd	99	nM	CHEMBL3763931
6.98	IC50	104	nM	CHEMBL5089440
6.96	Kd	110	nM	CHEMBL3112879
6.96	IC50	111	nM	CHEMBL5075746
6.90	IC50	126	nM	CHEMBL5085340
6.86	IC50	138	nM	CHEMBL5087533
6.84	IC50	146	nM	CHEMBL5094938
6.82	IC50	151	nM	CHEMBL5086986
6.78	IC50	165	nM	CHEMBL3763982
6.73	Kd	185	nM	CHEMBL4747352
6.71	Kd	195	nM	CHEMBL3765239
6.68	Kd	211	nM	CHEMBL3763982
6.64	IC50	227	nM	CHEMBL5076272
6.63	IC50	233	nM	CHEMBL3764278
6.63	IC50	236	nM	CHEMBL5092659
6.61	IC50	248	nM	CHEMBL5091650
6.60	IC50	251	nM	CHEMBL3765239
6.60	IC50	249	nM	CHEMBL5094399
6.59	IC50	255	nM	CHEMBL3763453
6.59	Kd	259	nM	CHEMBL3763453
6.57	IC50	268	nM	CHEMBL3763792

PubChem BioAssay actives

186 with measured affinity, of 352 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-[(4-methyl-1,4-diazepan-1-yl)methyl]-2-[4-[(4-methyl-1,4-diazepan-1-yl)methyl]phenyl]benzonitrile	1276666: Binding affinity to human N-terminal truncated ChoKalpha1 (75 to 457 residues) by surface plasmon resonance assay	kd	0.0100	uM
4-(6-amino-2-chloropurin-9-yl)-N-(4,4,6,6-tetramethyl-5,7-dihydro-[1,3]thiazolo[5,4-c]pyridin-2-yl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.0140	uM
4-(6-amino-2-chloropurin-9-yl)-N-(5-cyclopropyl-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridin-2-yl)cyclohexane-1-carboxamide;hydrochloride	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.0140	uM
(1S)-1-(1-azabicyclo[2.2.2]octan-3-yl)-3-[2-(oxan-4-yloxy)phenyl]-1-phenylpropan-1-ol	1276682: Inhibition of recombinant human ChoKalpha using choline as substrate by ultraviolet spectroscopic assay	ic50	0.0200	uM
4-(6-amino-2-chloropurin-9-yl)-N-(6,7-dihydro-4H-pyrano[4,3-d][1,3]thiazol-2-yl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.0200	uM
4-(6-amino-2-chloropurin-9-yl)-N-[6-(2-amino-2-oxoethyl)-1,3-benzothiazol-2-yl]cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.0200	uM
1-[[2,3-difluoro-4-[4-[(4-methyl-1,4-diazepan-1-yl)methyl]phenyl]phenyl]methyl]-4-methyl-1,4-diazepane	1276666: Binding affinity to human N-terminal truncated ChoKalpha1 (75 to 457 residues) by surface plasmon resonance assay	kd	0.0210	uM
4-(6-amino-2-chloropurin-9-yl)-N-(5-methyl-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridin-2-yl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.0210	uM
4-(6-amino-2-chloropurin-9-yl)-N-(6-hydroxy-1,3-benzothiazol-2-yl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.0220	uM
4-(6-amino-2-chloropurin-9-yl)-N-(6-methoxy-1,3-benzothiazol-2-yl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.0230	uM
4-(6-amino-2-chloropurin-9-yl)-N-(4,5,6,7-tetrahydro-[1,3]thiazolo[5,4-c]pyridin-2-yl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.0270	uM
4-(6-amino-2-chloropurin-9-yl)-N-(1,3-benzothiazol-2-yl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.0280	uM
4-(6-amino-2-chloropurin-9-yl)-N-(6-fluoro-1,3-benzothiazol-2-yl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.0280	uM
4-(6-amino-2-chloropurin-9-yl)-N-(4-methoxy-1,3-benzothiazol-2-yl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.0290	uM
2-[[4-(6-amino-2-chloropurin-9-yl)cyclohexanecarbonyl]amino]-1,3-benzothiazole-6-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.0310	uM
4-(6-amino-2-fluoropurin-9-yl)-N-(4,4,6,6-tetramethyl-5,7-dihydro-[1,3]thiazolo[5,4-c]pyridin-2-yl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.0310	uM
4-(6-amino-2-fluoropurin-9-yl)-N-(5-methyl-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridin-2-yl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.0310	uM
4-(6-amino-2-chloropurin-9-yl)-N-(4-hydroxy-1,3-benzothiazol-2-yl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.0330	uM
4-(6-amino-2-fluoropurin-9-yl)-N-(4-methyl-1,3-thiazol-2-yl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.0340	uM
4-(6-amino-2-chloropurin-9-yl)-N-(5-methyl-1,3-thiazol-2-yl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.0400	uM
4-(6-amino-2-chloropurin-9-yl)-N-(5-propan-2-yl-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridin-2-yl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.0430	uM
4-(6-amino-2-chloropurin-9-yl)-N-(4-methyl-1,3-thiazol-2-yl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.0490	uM
4-(6-amino-2-chloropurin-9-yl)-N-(5,5-dioxo-6,7-dihydro-4H-thiopyrano[4,3-d][1,3]thiazol-2-yl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.0490	uM
4-(6-amino-2-chloropurin-9-yl)-N-[4-(2-amino-2-oxoethyl)-1,3-thiazol-2-yl]cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.0610	uM
2-[2-fluoro-4-[(4-methyl-1,4-diazepan-1-yl)methyl]phenyl]-5-[(4-methyl-1,4-diazepan-1-yl)methyl]benzonitrile	1276672: Inhibition of human N-terminal truncated ChoKalpha1 (75 to 457 residues) using choline chloride as substrate measured over 10 to 30 mins by coupled ATP regeneration assay	ic50	0.0850	uM
1-[[2-chloro-4-[4-[(4-methyl-1,4-diazepan-1-yl)methyl]phenyl]phenyl]methyl]-4-methyl-1,4-diazepane	1276666: Binding affinity to human N-terminal truncated ChoKalpha1 (75 to 457 residues) by surface plasmon resonance assay	kd	0.0880	uM
4-(6-amino-2-chloropurin-9-yl)-N-[5-(2-amino-2-oxoethyl)-1,3-thiazol-2-yl]cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.0880	uM
4-(6-amino-2-chloropurin-9-yl)-N-(4,6-difluoro-1,3-benzothiazol-2-yl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.0970	uM
4-(6-amino-2-chloropurin-9-yl)-N-[4-(trifluoromethyl)-1,3-thiazol-2-yl]cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.1040	uM
1-[[4-[4-[4-[[4-(4-chloro-N-methylanilino)pyridin-1-ium-1-yl]methyl]phenyl]butyl]phenyl]methyl]-N,N-dimethylpyridin-1-ium-4-amine dibromide	1068560: Binding affinity to human CK-alpha1 by tryptophan fluorescence spectroscopic analysis	kd	0.1100	uM
4-(6-amino-2-chloropurin-9-yl)-N-(1,5-dimethylpyrazol-3-yl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.1110	uM
4-(6-amino-2-chloropurin-9-yl)-N-(5-methyl-1,3,4-thiadiazol-2-yl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.1260	uM
4-(6-amino-2-chloropurin-9-yl)-N-(1,3-benzothiazol-6-yl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.1380	uM
4-(6-amino-2-chloropurin-9-yl)-N-(4-phenyl-1,3-thiazol-2-yl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.1460	uM
4-(6-amino-2-chloropurin-9-yl)-N-pyridin-2-ylcyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.1510	uM
1-[[3-fluoro-4-[4-[(4-methyl-1,4-diazepan-1-yl)methyl]phenyl]phenyl]methyl]-4-methyl-1,4-diazepane	1276672: Inhibition of human N-terminal truncated ChoKalpha1 (75 to 457 residues) using choline chloride as substrate measured over 10 to 30 mins by coupled ATP regeneration assay	ic50	0.1650	uM
7-chloro-N-methyl-N-phenyl-1-[(4-phenylphenyl)methyl]quinolin-1-ium-4-amine bromide	1706113: Binding affinity to human CKalpha1 assessed as dissociation constant by spectroflurometry	kd	0.1850	uM
(4-methyl-1,4-diazepan-1-yl)-[4-[4-[(4-methyl-1,4-diazepan-1-yl)methyl]phenyl]phenyl]methanone	1276666: Binding affinity to human N-terminal truncated ChoKalpha1 (75 to 457 residues) by surface plasmon resonance assay	kd	0.1950	uM
4-(6-amino-2-chloropurin-9-yl)-N-(3-methoxyphenyl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.2270	uM
4-(6-aminopurin-9-yl)-N-[3-(trifluoromethylsulfonyl)phenyl]cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.2360	uM
4-(6-amino-2-chloropurin-9-yl)-N-[4-(trifluoromethylsulfonyl)phenyl]cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.2480	uM
4-(6-amino-2-chloropurin-9-yl)-N-(3,4-dimethoxyphenyl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.2490	uM
1-[[2,6-difluoro-4-[4-[(4-methyl-1,4-diazepan-1-yl)methyl]phenyl]phenyl]methyl]-4-methyl-1,4-diazepane	1276672: Inhibition of human N-terminal truncated ChoKalpha1 (75 to 457 residues) using choline chloride as substrate measured over 10 to 30 mins by coupled ATP regeneration assay	ic50	0.2550	uM
4-(6-amino-2-chloropurin-9-yl)-N-(1H-imidazol-2-yl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.2880	uM
4-(6-aminopurin-9-yl)-N-(3-methylsulfonylphenyl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.2890	uM
4-(6-aminopurin-9-yl)-N-[4-(trifluoromethylsulfonyl)phenyl]cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.2900	uM
12,20-diaza-1,8-diazoniapentacyclo[19.2.2.23,6.28,11.114,18]triaconta-1(23),3(30),4,6(29),8(28),9,11(27),14,16,18(26),21,24-dodecaene dibromide	52128: Ex vivo inhibitory activity against human choline kinase was determined	ic50	0.3000	uM
2-[4-[2-[4-[4-[4-[1-[2-(dimethylamino)-2-oxoethyl]pyridin-1-ium-4-yl]-5-(trifluoromethyl)-1,3-oxazol-2-yl]phenyl]phenyl]-5-(trifluoromethyl)-1,3-oxazol-4-yl]pyridin-1-ium-1-yl]-N,N-dimethylacetamide dichloride	626587: Inhibition of recombinant human Choline kinase alpha using [methyl-14C]choline chloride as substrate after 30 mins by autoradiography	ic50	0.3000	uM
4-(6-aminopurin-9-yl)-N-(4-methylsulfonylphenyl)cyclohexane-1-carboxamide	1807422: Inhibition of ChoKalpha (unknown origin) by HTS assay	ic50	0.3070	uM
4-(azepan-1-yl)-1-[[4-[[4-[[4-(azepan-1-yl)thieno[2,3-d]pyrimidin-1-ium-1-yl]methyl]phenyl]disulfanyl]phenyl]methyl]thieno[2,3-d]pyrimidin-1-ium dibromide	2002210: Inhibition of human Choline kinase alpha 1 incubated for 10 mins by liquid-scintillation counter analysis	ic50	0.3200	uM

CTD chemical–gene interactions

54 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	3
Tretinoin	decreases expression, increases expression	3
mercuric bromide	increases expression, affects cotreatment	2
Methyl Methanesulfonate	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Valproic Acid	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
Vitamin K 3	affects expression	2
methylmercuric chloride	decreases response to substance, decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases expression, affects binding, increases activity	1
bisphenol A	increases expression	1
deoxynivalenol	increases expression	1
trichostatin A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
ochratoxin A	decreases expression	1
nickel sulfate	increases expression	1
methyl carbamate	increases expression	1
beta-methylcholine	affects expression	1
tamibarotene	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
deguelin	increases expression	1
fenpyroximate	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
thifluzamide	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1

ChEMBL screening assays

45 unique, capped per target: 45 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1772322	Binding	Inhibition of ChoK in HT29 cells using [methyl-14C]choline chloride as substrate after 14 hrs by radiography	Homodimeric bis-quaternary heterocyclic ammonium salts as potent acetyl- and butyrylcholinesterase inhibitors: a systematic investigation of the influence of linker and cationic heads over affinity and selectivity. — J Med Chem

Clinical trials (associated diseases)

17 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT00001639	Not specified	COMPLETED	Evaluation of Patients With Unresolved Chromosome Abnormalities
NCT01151462	Not specified	WITHDRAWN	Postnatal HCMV Infection in Very Preterm Infants. Implications, Morbidity, Growth and Neurodevelopmental Outcomes.
NCT01565005	Not specified	COMPLETED	Microcephaly Genetic Deficiency in Neural Progenitors
NCT02510170	Not specified	COMPLETED	Fetal and Maternal Head Circumference During Pregnancy in Israeli Population
NCT02741882	Not specified	COMPLETED	Zika and Microcephaly: Case-control Study
NCT02943304	Not specified	COMPLETED	Neurodevelopment Outcome of Newborns Exposed to Zika Virus (ZIKV) in Utero
NCT03255369	Not specified	UNKNOWN	Vertical Exposure to Zika Virus and Its Consequences for Child Neurodevelopment (ZIKVIRUSIFF)
NCT03325946	Not specified	RECRUITING	The FBRI VTC Neuromotor Research Clinic
NCT03330600	Not specified	COMPLETED	Efficacy of Aquatic Physiotherapy in Children With Microcephaly by Zika Virus Congenital Syndrome
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT03651687	Not specified	COMPLETED	Guangzhou Surveillance and Clinical Study in Microcephaly (GSCSM)
NCT03922594	Not specified	TERMINATED	Surveillance of Zika-related Microcephaly in Sub-Saharan Africa and Asia
NCT04816175	Not specified	COMPLETED	Intensive Therapy for Children With Microcephaly, Hyperkinetic Movements, or Global Developmental Delay
NCT05322980	Not specified	COMPLETED	Summary of Infants Weighing 500 Grams or Less
NCT06019182	Not specified	RECRUITING	MEHMO Natural History and Biomarkers
NCT06566066	Not specified	RECRUITING	Register for Patients With Thyroid Hormone Resistance.