CHKB

Summary

CHKB (choline kinase beta, HGNC:1938) is a protein-coding gene on chromosome 22q13.33, encoding Choline/ethanolamine kinase (Q9Y259). Has a key role in phospholipid metabolism, and catalyzes the first step of phosphatidylethanolamine and phosphatidylcholine biosynthesis.

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.

Source: NCBI Gene 1120 — RefSeq curated summary.

At a glance

• Gene–disease (curated): megaconial type congenital muscular dystrophy (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 275 total — 15 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 21
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_005198

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1938
Approved symbol	CHKB
Name	choline kinase beta
Location	22q13.33
Locus type	gene with protein product
Status	Approved
Aliases	CHETK
Ensembl gene	ENSG00000100288
Ensembl biotype	protein_coding
OMIM	612395
Entrez	1120

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 13 protein_coding, 8 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000406938, ENST00000463053, ENST00000464225, ENST00000465842, ENST00000468532, ENST00000471515, ENST00000476289, ENST00000479003, ENST00000481673, ENST00000484266, ENST00000489453, ENST00000492582, ENST00000885877, ENST00000885878, ENST00000885879, ENST00000885880, ENST00000939157, ENST00000939158, ENST00000939159, ENST00000939160, ENST00000939161, ENST00000949611, ENST00000949612, ENST00000949613

RefSeq mRNA: 1 — MANE Select: NM_005198 NM_005198

CCDS: CCDS14099

Canonical transcript exons

ENST00000406938 — 11 exons

Exon	Start	End
ENSE00002242446	50578963	50579255
ENSE00002530584	50582558	50582849
ENSE00003485132	50579426	50579507
ENSE00003489002	50581420	50581553
ENSE00003492050	50579727	50579830
ENSE00003520970	50580190	50580271
ENSE00003531622	50579974	50580082
ENSE00003550355	50580358	50580416
ENSE00003552485	50581749	50581862
ENSE00003567730	50580565	50580660
ENSE00003596028	50582249	50582357

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.7637 / max 163.6229, expressed in 1798 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194799	12.5570	1798
194798	0.2067	101

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pituitary gland	UBERON:0000007	98.68	gold quality
granulocyte	CL:0000094	98.64	gold quality
adenohypophysis	UBERON:0002196	98.57	gold quality
spleen	UBERON:0002106	98.50	gold quality
right lobe of thyroid gland	UBERON:0001119	98.34	gold quality
left lobe of thyroid gland	UBERON:0001120	98.18	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.16	gold quality
cerebellar hemisphere	UBERON:0002245	98.02	gold quality
cerebellar cortex	UBERON:0002129	98.01	gold quality
thyroid gland	UBERON:0002046	97.98	gold quality
right uterine tube	UBERON:0001302	97.96	gold quality
cerebellum	UBERON:0002037	97.94	gold quality
metanephros cortex	UBERON:0010533	97.76	gold quality
apex of heart	UBERON:0002098	97.72	gold quality
mucosa of stomach	UBERON:0001199	97.66	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.66	gold quality
right adrenal gland cortex	UBERON:0035827	97.46	gold quality
prostate gland	UBERON:0002367	97.45	gold quality
right adrenal gland	UBERON:0001233	97.34	gold quality
minor salivary gland	UBERON:0001830	97.32	gold quality
lymph node	UBERON:0000029	97.29	gold quality
cortex of kidney	UBERON:0001225	97.29	gold quality
fundus of stomach	UBERON:0001160	97.24	gold quality
small intestine	UBERON:0002108	97.22	gold quality
saliva-secreting gland	UBERON:0001044	97.16	gold quality
lower esophagus mucosa	UBERON:0035834	97.03	gold quality
left adrenal gland cortex	UBERON:0035825	97.02	gold quality
left adrenal gland	UBERON:0001234	96.91	gold quality
primary visual cortex	UBERON:0002436	96.84	gold quality
transverse colon	UBERON:0001157	96.83	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.34
E-MTAB-6386	no	207.48
E-MTAB-6058	no	121.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting CHKB, 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-4283	100.00	66.42	2097
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-1470	98.11	63.53	399
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-4690-3P	97.02	64.72	981
HSA-MIR-5685	97.02	64.34	1004
HSA-MIR-3194-5P	96.80	64.90	1027
HSA-MIR-6828-3P	96.06	67.61	1155

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 20)

• A single nucleotide polymorphism located between CPT1B and CHKB, was associated with narcolepsy in Japanese (rs5770917[C], odds ratio (OR) = 1.79, combined P = 4.4 x 10(-7)) and other ancestry groups (OR = 1.40, P = 0.02). (PMID:18820697)
• Japanese CNS hypersomnias (essential hypersomnia: EHS) other than narcolepsy with cataplexy was significantly associated with SNP rs5770917 (located between CPT1B and CHKB) and HLA-DRB1*1501-DQB1*0602 haplotype (PMID:19404393)
• ChoKalpha and ChoKbeta isoforms have different physiological roles and implications in human carcinogenesis (PMID:19915674)
• kinetic studies revealed that HC-3 is a much more potent inhibitor for ChoKalpha isoforms (alpha1 and alpha2) compared with ChoKbeta. (PMID:20299452)
• homozygous or compound heterozygous mutations in the gene encoding choline kinase beta were identified in individulas with congenital muscular dystrophy. (PMID:21665002)
• The study extends on the observation of a strong multiethnic association of polymorphisms in the TCRA and P2RY11 with narcolepsy, but does not confirm the association of CPT1B/CHKB (rs5770917) in the Chinese population. (PMID:22177342)
• CHKB activity was reduced in all three patients, significant reduction in choline:N-acetyl aspartate and choline:creatine ratios in keeping with a general decrease in the amount of choline and phosphocholine-based substrate (PMID:23692895)
• CHKB encodes choline kinase beta, an enzyme that catalyzes the first de-novo biosynthetic step of phosphatidylcholine, the most abundant phospholipid in the eukaryotic membrane [review] (PMID:23945283)
• Its mutations cause congenital muscular dystrophy.[Review] (PMID:24291895)
• study identified a novel haplotype consisting of the indel variation, which had not been detected in previous studies in Japanese and Korean populations, and observed four single-nucleotide polymorphisms in CHKB/CPT1B (PMID:24571861)
• A novel silent variant in the choline kinase beta causing muscular dystrophy. (PMID:25740612)
• A new form of congenital muscular dystrophy with multisystem involvement and characteristic mitochondrial structural changes, due to choline kinase beta gene defects has been characterized. (PMID:26067811)
• The whole exome sequencing revealed a novel homozygous missense mutation in the Choline Kinase-Beta (CHKB) gene in exon 9. (PMID:27123443)
• findings suggest that CKbeta, in concert with CKalpha, and depending on its phosphorylation status, might play a critical role as a druggable target in carcinogenesis (PMID:27149373)
• Alteration of mitochondrial membrane inner potential in three Italian patients with megaconial congenital muscular dystrophy carrying new mutations in CHKB gene. (PMID:30986505)
• Megaconial congenital muscular dystrophy: Same novel homozygous mutation in CHKB gene in two unrelated Chinese patients. (PMID:31926838)
• Megaconial congenital muscular dystrophy secondary to novel CHKB mutations resemble atypical Rett syndrome. (PMID:33712684)
• Large heterozygous deletion and uniparental disomy masquerading as homozygosity in CHKB gene. (PMID:36896673)
• Megaconial congenital muscular dystrophy due to CHKB gene variants, the first report of thirteen Iranian patients. (PMID:37393748)
• Frameshift mutations of immunomodulatory BTN2A1, BTN2A2, and BTNL3 genes in colon cancers. (PMID:37634314)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	chkb	ENSDARG00000063167
mus_musculus	Chkb	ENSMUSG00000022617
rattus_norvegicus	Chkb	ENSRNOG00000011404
drosophila_melanogaster	CG2201	FBGN0032955
caenorhabditis_elegans		WBGENE00000509
caenorhabditis_elegans		WBGENE00000510
caenorhabditis_elegans		WBGENE00000511
caenorhabditis_elegans		WBGENE00000512
caenorhabditis_elegans		WBGENE00000513
caenorhabditis_elegans		WBGENE00000514

Paralogs (3): CHKA (ENSG00000110721), ETNK1 (ENSG00000139163), ETNK2 (ENSG00000143845)

Protein

Protein identifiers

Choline/ethanolamine kinase — Q9Y259 (reviewed: Q9Y259)

Alternative names: Choline kinase beta, Choline kinase-like protein, Ethanolamine kinase, Ethanolamine kinase beta, choline/ethanolamine kinase beta

All UniProt accessions (1): Q9Y259

UniProt curated annotations — full annotation on UniProt →

Function. Has a key role in phospholipid metabolism, and catalyzes the first step of phosphatidylethanolamine and phosphatidylcholine biosynthesis.

Subunit / interactions. Homodimer, and heterodimer with CHKA.

Disease relevance. Muscular dystrophy, congenital, megaconial type (MDCMC) [MIM:602541] An autosomal recessive, congenital muscular dystrophy characterized by early-onset muscle wasting, intellectual disability, and dilated cardiomyopathy in half of affected individuals. Some patients may die from cardiomyopathy in the first or second decade of life. Muscle biopsy shows peculiar enlarged mitochondria that are prevalent toward the periphery of the fibers but are sparse in the center. The disease is caused by variants affecting the gene represented in this entry.

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

Miscellaneous. This protein is produced by a bicistronic gene which also produces the CPT1B protein from a non-overlapping reading frame.

Similarity. Belongs to the choline/ethanolamine kinase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y259-1	1	yes
Q9Y259-2	2

RefSeq proteins (1): NP_005189* (*=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), 2 shown:

• choline + ATP = phosphocholine + ADP + H(+) (RHEA:12837)
• ethanolamine + ATP = phosphoethanolamine + ADP + H(+) (RHEA:13069)

UniProt features (54 total): helix 17, strand 13, sequence variant 11, binding site 6, splice variant 2, turn 2, initiator methionine 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3FEG	X-RAY DIFFRACTION	1.3
3LQ3	X-RAY DIFFRACTION	1.42
2IG7	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y259-F1	86.54	0.69

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): 75–81; 77–79; 104; 146–152; 244; 264

Post-translational modifications (1): 2

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: 169 (showing top): GGGACCA_MIR133A_MIR133B, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, PAX4_01, GOBP_PHOSPHATIDYLCHOLINE_BIOSYNTHETIC_PROCESS, HSIAO_HOUSEKEEPING_GENES, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, CACCAGC_MIR138, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_GLYCEROLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS

GO Biological Process (6): phosphatidylethanolamine biosynthetic process (GO:0006646), CDP-choline pathway (GO:0006657), muscle organ development (GO:0007517), lipid metabolic process (GO:0006629), phosphatidylcholine biosynthetic process (GO:0006656), phospholipid biosynthetic process (GO:0008654)

GO Molecular Function (6): choline kinase activity (GO:0004103), ethanolamine kinase activity (GO:0004305), ATP binding (GO:0005524), nucleotide binding (GO:0000166), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (2): cytoplasm (GO:0005737), 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
phosphatidylethanolamine metabolic process	1
choline kinase activity	1
diacylglycerol cholinephosphotransferase activity	1
phosphatidylcholine biosynthetic process	1
animal organ development	1
muscle structure development	1
primary metabolic process	1
phosphatidylcholine metabolic process	1
phospholipid metabolic process	1
lipid biosynthetic process	1
organophosphate biosynthetic process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1148 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHKB	CPT1B	Q92523	946
CHKB	TAC4	Q86UU9	927
CHKB	CPT1C	Q8TCG5	901
CHKB	TAC3	Q9UHF0	782
CHKB	TACR2	P21452	761
CHKB	PCYT2	Q99447	742
CHKB	TACR3	P29371	732
CHKB	TACR1	P25103	708
CHKB	PCYT1B	Q9Y5K3	700
CHKB	CPT1A	P50416	682
CHKB	PCYT1A	P49585	669
CHKB	CHPT1	Q8WUD6	653
CHKB	SELENOI	Q9C0D9	653
CHKB	CEPT1	Q9Y6K0	625
CHKB	PISD	Q9UG56	619

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ALB	SH3BP5	psi-mi:“MI:0914”(association)	0.350
HDLBP	SIRT5	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): CHKB (Affinity Capture-MS), CHKB (Affinity Capture-MS), CHKB (Affinity Capture-RNA), CHKB (Affinity Capture-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, A7SK27, D3ZRW8, O54783, O55229, O81024, P54352, Q869T9, Q8L518, Q9D4V0, Q9HBU6, Q9M9H6, Q9NVF9, Q9SZ92, Q9Y259, O54804, P35790, P46558, P46559, P46560, Q01134, Q22942, Q554D8

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
PRKACA	“up-regulates activity”	CHKB	phosphorylation
PKA	“up-regulates activity”	CHKB	phosphorylation
CHKB	“up-regulates quantity”	“choline phosphate(1-)”	“chemical modification”
CHKB	“down-regulates quantity”	choline	“chemical modification”
CHKB	“up-regulates quantity”	O-phosphonatoethanaminium(1-)	“chemical modification”
CHKB	“down-regulates quantity”	ethanolaminium(1+)	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	7
Uncertain significance	118
Likely benign	98
Benign	21

Top pathogenic / likely-pathogenic (22)

Variant ID	HGVS	Classification
1072448	NM_005198.5(CHKB):c.216C>G (p.Tyr72Ter)	Pathogenic
1075204	NM_005198.5(CHKB):c.1003G>T (p.Glu335Ter)	Pathogenic
1333660	NM_005198.5(CHKB):c.463del (p.Thr155fs)	Pathogenic
1456700	NM_005198.5(CHKB):c.808_809insC (p.Tyr270fs)	Pathogenic
2425317	NC_000022.10:g.(?51017610)(51021210_?)del	Pathogenic
2765810	NM_005198.5(CHKB):c.536del (p.Met179fs)	Pathogenic
2849953	NM_005198.5(CHKB):c.187C>T (p.Arg63Ter)	Pathogenic
30952	NM_005198.5(CHKB):c.810T>A (p.Tyr270Ter)	Pathogenic
30955	NM_005198.5(CHKB):c.922C>T (p.Gln308Ter)	Pathogenic
30956	NM_005198.5(CHKB):c.677+1G>A	Pathogenic
342172	NM_005198.5(CHKB):c.722A>G (p.Asn241Ser)	Pathogenic
3492304	NM_005198.5(CHKB):c.683dup (p.Leu228fs)	Pathogenic
4073557	NM_005198.5(CHKB):c.592_593del (p.Gln198fs)	Pathogenic
4799581	NM_005198.5(CHKB):c.689_690del (p.Glu230fs)	Pathogenic
632393	NM_005198.5(CHKB):c.565_568del (p.Phe189fs)	Pathogenic
1328477	NM_005198.5(CHKB):c.419del (p.Pro140fs)	Likely pathogenic
1691030	NM_005198.5(CHKB):c.467_468del (p.Gln156fs)	Likely pathogenic
1878551	NM_005198.5(CHKB):c.150C>A (p.Tyr50Ter)	Likely pathogenic
2429458	NM_005198.5(CHKB):c.844dup (p.Cys282fs)	Likely pathogenic
4292857	NM_005198.5(CHKB):c.1068G>A (p.Trp356Ter)	Likely pathogenic
430310	NM_005198.5(CHKB):c.736+2T>C	Likely pathogenic
4735782	NM_005198.5(CHKB):c.678-2A>G	Likely pathogenic

SpliceAI

2042 predictions. Top by Δscore:

Variant	Effect	Δscore
22:50579421:CTTA:C	donor_loss	1.0000
22:50579422:TTA:T	donor_loss	1.0000
22:50579423:TA:T	donor_loss	1.0000
22:50579424:A:AT	donor_loss	1.0000
22:50579503:CATAC:C	acceptor_gain	1.0000
22:50579507:CCTGG:C	acceptor_loss	1.0000
22:50579508:CT:C	acceptor_loss	1.0000
22:50579509:T:C	acceptor_loss	1.0000
22:50579720:T:TA	donor_gain	1.0000
22:50580080:CCC:C	acceptor_gain	1.0000
22:50580081:CC:C	acceptor_gain	1.0000
22:50580081:CCC:C	acceptor_gain	1.0000
22:50580082:CC:C	acceptor_gain	1.0000
22:50580582:AT:A	donor_gain	1.0000
22:50580656:GGTAC:G	acceptor_gain	1.0000
22:50580657:GTAC:G	acceptor_gain	1.0000
22:50580658:TAC:T	acceptor_gain	1.0000
22:50580661:CTGA:C	acceptor_loss	1.0000
22:50581418:A:AC	donor_gain	1.0000
22:50581419:C:CC	donor_gain	1.0000
22:50581419:CCG:C	donor_gain	1.0000
22:50581747:A:AC	donor_gain	1.0000
22:50581748:C:CC	donor_gain	1.0000
22:50581757:A:AC	donor_gain	1.0000
22:50581758:C:CC	donor_gain	1.0000
22:50582619:C:CA	donor_gain	1.0000
22:50579034:A:AC	donor_gain	0.9900
22:50579035:C:CC	donor_gain	0.9900
22:50579251:TAGTC:T	acceptor_gain	0.9900
22:50579253:GTC:G	acceptor_gain	0.9900

AlphaMissense

2561 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:50580216:G:C	D264E	1.000
22:50580216:G:T	D264E	1.000
22:50580217:T:A	D264V	1.000
22:50580369:T:A	D242V	1.000
22:50580369:T:G	D242A	1.000
22:50579435:A:C	F368L	0.999
22:50579435:A:T	F368L	0.999
22:50579437:A:G	F368L	0.999
22:50579473:A:G	W356R	0.999
22:50579473:A:T	W356R	0.999
22:50579482:A:G	W353R	0.999
22:50579482:A:T	W353R	0.999
22:50580195:G:C	N271K	0.999
22:50580195:G:T	N271K	0.999
22:50580204:G:C	S268R	0.999
22:50580204:G:T	S268R	0.999
22:50580206:T:G	S268R	0.999
22:50580209:A:G	Y267H	0.999
22:50580211:T:A	E266V	0.999
22:50580217:T:C	D264G	0.999
22:50580217:T:G	D264A	0.999
22:50580218:C:G	D264H	0.999
22:50580267:G:C	N247K	0.999
22:50580267:G:T	N247K	0.999
22:50580368:G:C	D242E	0.999
22:50580368:G:T	D242E	0.999
22:50580369:T:C	D242G	0.999
22:50580370:C:G	D242H	0.999
22:50580371:A:C	N241K	0.999
22:50580371:A:T	N241K	0.999

dbSNP variants (sampled 300 via entrez): RS1000710213 (22:50580170 A>G,T), RS1000782866 (22:50584481 A>G), RS1000897451 (22:50584283 T>G), RS1001500229 (22:50581039 C>T), RS1002005288 (22:50584102 C>T), RS1003166428 (22:50582387 C>A,G,T), RS1003449650 (22:50583136 G>A,C,T), RS1003521884 (22:50582180 A>C), RS1003911282 (22:50583218 C>T), RS1004350925 (22:50579114 G>A,C,T), RS1004895024 (22:50580750 C>T), RS1005012533 (22:50584240 C>G,T), RS1005127016 (22:50583968 G>A,T), RS1007072858 (22:50581519 G>A), RS1007074909 (22:50583660 G>T)

Disease associations

OMIM: gene MIM:612395 | disease phenotypes: MIM:602541

GenCC curated gene-disease

Disease	Classification	Inheritance
megaconial type congenital muscular dystrophy	Strong	Autosomal recessive

Mondo (2): megaconial type congenital muscular dystrophy (MONDO:0011246), muscular dystrophy (MONDO:0020121)

Orphanet (2): Megaconial congenital muscular dystrophy (Orphanet:280671), Muscular dystrophy (Orphanet:98473)

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001270	Motor delay
HP:0001290	Generalized hypotonia
HP:0001324	Muscle weakness
HP:0001644	Dilated cardiomyopathy
HP:0002465	Poor speech
HP:0002515	Waddling gait
HP:0003198	Myopathy
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003391	Gowers sign
HP:0003560	Muscular dystrophy
HP:0003593	Infantile onset
HP:0003677	Slowly progressive
HP:0008064	Ichthyosis
HP:0010628	Facial palsy
HP:0033686	Mitochondrial hypertrophy
HP:0100297	Increased endomysial connective tissue

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006585_2490	Blood protein levels	1.000000e-07
GCST011739_14	Cutaneous leishmaniasis	3.000000e-06

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D009136	Muscular Dystrophies	C05.651.534.500; C10.668.491.175.500; C16.320.577
C566527	Muscular Dystrophy, Congenital, Megaconial Type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3112385 (SINGLE PROTEIN)

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

ChEMBL bioactivities

12 potent at pChembl≥5 of 17 total, top 12 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.47	IC50	3355	nM	CHEMBL5087533
5.42	IC50	3767	nM	CHEMBL5076272
5.42	IC50	3809	nM	CHEMBL5079663
5.30	IC50	5031	nM	CHEMBL5075042
5.29	IC50	5094	nM	CHEMBL5077194
5.26	IC50	5429	nM	CHEMBL5093251
5.25	IC50	5693	nM	CHEMBL5088776
5.23	IC50	5906	nM	CHEMBL5094399
5.22	IC50	5984	nM	CHEMBL5084844
5.18	IC50	6563	nM	CHEMBL5090932
5.17	IC50	6709	nM	CHEMBL5091519
5.13	IC50	7377	nM	CHEMBL5090132

PubChem BioAssay actives

12 with measured affinity, of 50 total; 12 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
4-(6-amino-2-chloropurin-9-yl)-N-(1,3-benzothiazol-6-yl)cyclohexane-1-carboxamide	1807423: Inhibition of ChoKbeta (unknown origin) by HTS assay	ic50	3.3550	uM
4-(6-amino-2-chloropurin-9-yl)-N-(3-methoxyphenyl)cyclohexane-1-carboxamide	1807423: Inhibition of ChoKbeta (unknown origin) by HTS assay	ic50	3.7670	uM
4-(6-amino-2-chloropurin-9-yl)-N-[6-(2-amino-2-oxoethyl)-1,3-benzothiazol-2-yl]cyclohexane-1-carboxamide	1807423: Inhibition of ChoKbeta (unknown origin) by HTS assay	ic50	3.8090	uM
4-(6-amino-2-chloropurin-9-yl)-N-(6-methoxy-1,3-benzothiazol-2-yl)cyclohexane-1-carboxamide	1807423: Inhibition of ChoKbeta (unknown origin) by HTS assay	ic50	5.0310	uM
4-(6-amino-2-chloropurin-9-yl)-N-(6-hydroxy-1,3-benzothiazol-2-yl)cyclohexane-1-carboxamide	1807423: Inhibition of ChoKbeta (unknown origin) by HTS assay	ic50	5.0940	uM
4-(6-amino-2-chloropurin-9-yl)-N-[5-(2-amino-2-oxoethyl)-1,3-thiazol-2-yl]cyclohexane-1-carboxamide	1807423: Inhibition of ChoKbeta (unknown origin) by HTS assay	ic50	5.4290	uM
4-(6-amino-2-chloropurin-9-yl)-N-(4-hydroxy-1,3-benzothiazol-2-yl)cyclohexane-1-carboxamide	1807423: Inhibition of ChoKbeta (unknown origin) by HTS assay	ic50	5.6930	uM
4-(6-amino-2-chloropurin-9-yl)-N-(3,4-dimethoxyphenyl)cyclohexane-1-carboxamide	1807423: Inhibition of ChoKbeta (unknown origin) by HTS assay	ic50	5.9060	uM
4-(6-amino-2-chloropurin-9-yl)-N-(1,3-benzothiazol-2-yl)cyclohexane-1-carboxamide	1807423: Inhibition of ChoKbeta (unknown origin) by HTS assay	ic50	5.9840	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	1807423: Inhibition of ChoKbeta (unknown origin) by HTS assay	ic50	6.5630	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	1807423: Inhibition of ChoKbeta (unknown origin) by HTS assay	ic50	6.7090	uM
4-(6-amino-2-chloropurin-9-yl)-N-(4-methoxy-1,3-benzothiazol-2-yl)cyclohexane-1-carboxamide	1807423: Inhibition of ChoKbeta (unknown origin) by HTS assay	ic50	7.3770	uM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases methylation	2
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
methylmercuric chloride	affects expression	1
sodium arsenite	decreases expression, increases abundance	1
butyraldehyde	decreases expression	1
K 7174	increases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
Arsenic	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Carbamazepine	affects expression	1
Catechin	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Diclofenac	affects expression	1
Indomethacin	affects cotreatment, decreases expression	1
Mercuric Chloride	increases expression	1
Smoke	decreases expression	1
Tretinoin	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1
Acrylamide	decreases expression	1
Particulate Matter	increases expression	1

ChEMBL screening assays

11 unique, capped per target: 11 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3119749	Binding	Binding affinity to human CK-beta by tryptophan fluorescence spectroscopic analysis	Discovery of a new binding site on human choline kinase α1: design, synthesis, crystallographic studies, and biological evaluation of asymmetrical bispyridinium derivatives. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01882400	PHASE4	COMPLETED	Assessment of Response to Treatment of Osteoporosis With Oral Bisphosphonates in Patients With Muscular Dystrophy
NCT01254019	PHASE3	COMPLETED	A Clinical Study to Assess the Efficacy and Safety of GSK2402968 in Subjects With Duchenne Muscular Dystrophy
NCT01480245	PHASE3	TERMINATED	Open Label Study of GSK2402968 in Subjects With Duchenne Muscular Dystrophy
NCT01803412	PHASE3	TERMINATED	A Study of the Safety, Tolerability & Efficacy of Long-term Administration of Drisapersen in US & Canadian Subjects
NCT01826487	PHASE3	COMPLETED	Phase 3 Study of Ataluren in Participants With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD)
NCT01890798	PHASE3	WITHDRAWN	Drisapersen Duchenne Muscular Dystrophy (DMD) Treatment Protocol
NCT02090959	PHASE3	TERMINATED	An Extension Study of Ataluren (PTC124) in Participants With Nonsense Mutation Dystrophinopathy
NCT02432885	PHASE3	COMPLETED	Myocardial Fibrosis Progression in Duchenne and Becker Muscular Dystrophy - ACE Inhibitor Therapy Trial
NCT03179631	PHASE3	COMPLETED	Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy
NCT05126758	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Deramiocel (CAP-1002) in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy
NCT07587242	PHASE3	NOT_YET_RECRUITING	A Phase 3 Study to Evaluate the Safety and Efficacy of AOC 1044 (Also Referred to as Delpacibart Zotadirsen) in Participants With DMD With Gene Mutations Amenable to Exon 44 Skipping
NCT07608432	PHASE3	RECRUITING	Efficacy, Safety, and Tolerability of Zeleciment Rostudirsen (DYNE-251) Administered Intravenously Every 4 Weeks in Ambulatory Participants With Duchenne Muscular Dystrophy (FORZETTO)
NCT01153932	PHASE2	COMPLETED	Phase II Doubleblind Exploratory Study of GSK2402968 in Ambulant Subjects With Duchenne Muscular Dystrophy
NCT01462292	PHASE2	COMPLETED	A Clinical Study to Assess Two Doses of GSK2402968 in Subjects With Duchenne Muscular Dystrophy (DMD)
NCT01910649	PHASE2	TERMINATED	A Phase I/II, Open Label, Escalating Dose, Pilot Study to Assess Effect, Safety, Tolerability and PK of Multiple SC Doses of Drisapersen in Patients With Duchenne Muscular Dystrophy and to Assess the Potential for IV Dosing as an Alternative Route of Administration
NCT03406780	PHASE2	COMPLETED	A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy
NCT05479981	PHASE2	COMPLETED	Extension of AOC 1001-CS1 (MARINA) Study in Adult Myotonic Dystrophy Type 1 (DM1) Patients
NCT06290713	PHASE2	RECRUITING	Vasodilator and Exercise Study for DMD (VASO-REx)
NCT06547216	PHASE2	ACTIVE_NOT_RECRUITING	Phase 2 Open-label Extension Study of AOC 1020 in Participants With Facioscapulohumeral Muscular Dystrophy (FSHD)
NCT07287189	PHASE2	RECRUITING	Phase 2 Study of SAT-3247 in Pediatric Ambulatory Patients
NCT00494195	PHASE1	COMPLETED	Gene Transfer Therapy for Treating Children and Adults With Limb Girdle Muscular Dystrophy Type 2D (LGMD2D)
NCT00674843	PHASE1	UNKNOWN	The Efficacy of Using Far Infrared Radiation to Manage Muscular Dystrophies
NCT00873782	PHASE1	COMPLETED	Safety Study of Transvenous Limb Perfusion in Human Muscular Dystrophy
NCT01128855	PHASE1	COMPLETED	A Double-blind, Escalating Dose, Randomized, Placebo-controlled Study Assessing PK, Safety, Tolerability in Non-ambulant DMD Subjects
NCT02241928	PHASE1	WITHDRAWN	Stem Cell Therapy in Muscular Dystrophy
NCT03627494	PHASE1	COMPLETED	First Time in Human (FTIH) Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single and Repeat Doses of GSK3439171A in Healthy Subjects and to Assess Food Effect
NCT05492734	PHASE1	COMPLETED	A Study to Assess the Feasibility of Non-invasive Dried Blood Sampling
NCT05730842	PHASE1	COMPLETED	Absorption, Metabolism, Excretion and Absolute Bioavailability of EDG-5506 in Healthy Volunteers
NCT01834040	PHASE1/PHASE2	UNKNOWN	Study Safety and Efficacy of BMMNC for the Patient With Duchenne Muscular Dystrophy
NCT01834066	PHASE1/PHASE2	UNKNOWN	Study Safety and Efficacy of Bone Marrow Derived Autologous Cells for the Treatment of Muscular Dystrophy.
NCT02515669	PHASE1/PHASE2	TERMINATED	Study of an Investigational Drug, RO7239361 (BMS-986089), in Ambulatory Boys With DMD
NCT05230459	PHASE1/PHASE2	RECRUITING	A Study to Evaluate the Safety of AB-1003 (Previously LION-101) in Subjects With Genetic Confirmation of LGMD2I/R9 (Part1)
NCT05747924	PHASE1/PHASE2	COMPLETED	Phase 1/2 Study of AOC 1020 in Participants With Facioscapulohumeral Muscular Dystrophy (FSHD)
NCT02653833	EARLY_PHASE1	TERMINATED	The Study of Skeletal Muscle Blood Flow in Becker Muscular Dystrophy
NCT00001164	Not specified	COMPLETED	Studies of Patients With Skin Disease, Patients With Neurological Degenerations, and Normal Volunteers
NCT00004568	Not specified	RECRUITING	Study of Inherited Neurological Disorders
NCT00027391	Not specified	COMPLETED	Study of Albuterol and Oxandrolone in Patients With Facioscapulohumeral Dystrophy (FSHD)
NCT00082108	Not specified	RECRUITING	Myotonic Dystrophy and Facioscapulohumeral Muscular Dystrophy Registry
NCT00138931	Not specified	RECRUITING	Genetics of Cardiovascular and Neuromuscular Disease
NCT00313677	Not specified	RECRUITING	Clinical Trial Readiness for the Dystroglycanopathies