CKM

Summary

CKM (creatine kinase, M-type, HGNC:1994) is a protein-coding gene on chromosome 19q13.32, encoding Creatine kinase M-type (P06732). Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate).

The protein encoded by this gene is a cytoplasmic enzyme involved in energy homeostasis and is an important serum marker for myocardial infarction. The encoded protein reversibly catalyzes the transfer of phosphate between ATP and various phosphogens such as creatine phosphate. It acts as a homodimer in striated muscle as well as in other tissues, and as a heterodimer with a similar brain isozyme in heart. The encoded protein is a member of the ATP:guanido phosphotransferase protein family.

Source: NCBI Gene 1158 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 76 total
• Druggable target: yes
• MANE Select transcript: NM_001824

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1994
Approved symbol	CKM
Name	creatine kinase, M-type
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000104879
Ensembl biotype	protein_coding
OMIM	123310
Entrez	1158

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 18 protein_coding

ENST00000221476, ENST00000859489, ENST00000859490, ENST00000859491, ENST00000859492, ENST00000859493, ENST00000969553, ENST00000969554, ENST00000969555, ENST00000969556, ENST00000969557, ENST00000969558, ENST00000969559, ENST00000969560, ENST00000969561, ENST00000969562, ENST00000969563, ENST00000969564

RefSeq mRNA: 1 — MANE Select: NM_001824 NM_001824

CCDS: CCDS12659

Canonical transcript exons

ENST00000221476 — 8 exons

Exon	Start	End
ENSE00000712858	45307461	45307650
ENSE00000712860	45308409	45308532
ENSE00000712863	45311749	45311920
ENSE00000712865	45315465	45315597
ENSE00001158571	45306413	45306928
ENSE00001335081	45322821	45322875
ENSE00002314738	45319521	45319731
ENSE00002434331	45317825	45317979

Expression profiles

Bgee: expression breadth ubiquitous, 192 present calls, max score 100.00.

FANTOM5 (CAGE): breadth broad, TPM avg 144.6250 / max 36919.9299, expressed in 262 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181491	140.1864	248
181489	0.9609	42
181486	0.8487	48
181488	0.4947	49
181461	0.4378	39
181483	0.3539	33
181459	0.3335	33
181458	0.2207	36
181460	0.1436	26
181485	0.1417	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
diaphragm	UBERON:0001103	100.00	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	100.00	gold quality
biceps brachii	UBERON:0001507	99.99	gold quality
triceps brachii	UBERON:0001509	99.99	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.99	gold quality
gastrocnemius	UBERON:0001388	99.98	gold quality
deltoid	UBERON:0001476	99.97	gold quality
gluteal muscle	UBERON:0002000	99.96	gold quality
heart right ventricle	UBERON:0002080	99.96	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.96	gold quality
left ventricle myocardium	UBERON:0006566	99.95	gold quality
body of tongue	UBERON:0011876	99.94	gold quality
tibialis anterior	UBERON:0001385	99.93	gold quality
apex of heart	UBERON:0002098	99.92	gold quality
cardiac atrium	UBERON:0002081	99.89	gold quality
right atrium auricular region	UBERON:0006631	99.89	gold quality
myocardium	UBERON:0002349	99.88	gold quality
skeletal muscle tissue	UBERON:0001134	99.87	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.87	gold quality
cardiac ventricle	UBERON:0002082	99.56	gold quality
heart left ventricle	UBERON:0002084	99.55	gold quality
vena cava	UBERON:0004087	98.96	gold quality
vastus lateralis	UBERON:0001379	98.23	gold quality
muscle organ	UBERON:0001630	98.16	gold quality
skeletal muscle organ	UBERON:0014892	98.16	gold quality
muscle of leg	UBERON:0001383	97.96	gold quality
quadriceps femoris	UBERON:0001377	97.59	gold quality
heart	UBERON:0000948	96.84	gold quality
muscle tissue	UBERON:0002385	96.64	gold quality
pharyngeal mucosa	UBERON:0000355	95.15	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ASCL1, ASCL2, E2F1, ELF4, FOXC1, HES1, ID1, ID3, JUN, JUNB, KLF3, MAZ, MEF2A, MEF2C, MSC, MYF5, MYF6, MYOD1, MYOG, NFATC1, NFIX, NFKB1, NR3C2, NR4A1, NVL, PAX1, PAX7, PRRX1, RCOR2, SP1, SRF, TCF21, TCF3, TP53, TWIST2, WT1, YY1

miRNA regulators (miRDB)

31 targeting CKM, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-548S	98.50	67.17	1213
HSA-MIR-92A-1-5P	98.28	64.51	631
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-6819-5P	97.96	66.59	1071
HSA-MIR-3921	97.81	67.45	1431
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-6737-5P	97.75	66.54	1044
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-4314	97.50	67.30	1369
HSA-MIR-3187-3P	97.38	65.80	904
HSA-MIR-4653-5P	97.22	67.72	1429
HSA-MIR-505-5P	97.01	65.54	778
HSA-MIR-3192-5P	96.98	65.76	1926
HSA-MIR-514A-5P	96.94	65.49	801
HSA-MIR-4701-5P	96.45	68.41	1121
HSA-MIR-588	96.45	68.36	1127
HSA-MIR-4435	95.90	65.47	1201
HSA-MIR-6874-5P	95.73	64.94	545

Literature-anchored findings (GeneRIF, showing 40)

• A short version of the muscle creatine kinase promoter(MCK1350) allows for sustained dystrophin expression in skeletal muscle of newborn mdx mice. (PMID:11922612)
• Results identify muscle-type creatine kinase as a binding partner of a central portion of myomesin and the closely related M-protein. (PMID:12972258)
• The roles of Ile-69 and Val-325 are discussed in the delivery of both substrate specificity and catalysis of human muscle creatine kinase isozyme. (PMID:15504039)
• In top-level professional cyclists capable of completing a classic 3-wk tour race, the frequency distribution of the D allele and the DD genotype seems to be higher than in other endurance athletes such as elite runners. (PMID:16037885)
• Creatinine kinase-MB levels are elevated after adverse outcomes following percutaneous coronary interventions (PMID:16087811)
• Elevated levels of creatinine kinase-MB after percutaneous coronary intervention are not a predictor of adverse outcomes (PMID:16092153)
• first monomeric intermediate captured during refolding of muscle-type creatine kinase; authors propose that aggregation is caused by interaction between such monomeric intermediates. (PMID:16373479)
• CK-MM autoantibodies can modulate the rate of CK clearance from the circulation in myositis (PMID:16810680)
• The results show conclusively that, Cys283 is not responsible for the pKa of 5.4 observed in the WT V/K(creatine) pH profile. (PMID:16981706)
• generation of O-CK is a negative regulation of R-CK and O-CK might play essential roles in the molecular turnover of MM-CK (PMID:17303563)
• CK-MM AA genotype and percent body fat may be part of the constellation of mechanisms that explain susceptibility to exertional rhabdomyolysis. (PMID:17478608)
• Indicate a positive association of the ACE ID genotype with creatine kinase response to strenuous exercise. Genotype may determine risk for developing muscle damage. (PMID:17885020)
• Muscle type CK elevation in hypertrabeculation/noncompaction suggests neuromuscular disorder and prompts neurological investigations. (PMID:18055044)
• Cardiac involvement of major thalassemia and evaluation of total serum CK-mB isoenzyme in these patients is reported. (PMID:18810980)
• We suggest that the occurrence of familial hyperCKemia may have triggered the early onset of symptoms in our patient. (PMID:18833644)
• CK-MB values > or =5 times the reference after elective cardiac surgery are associated with reduced long-term event-free survival (PMID:19039220)
• Plasma CPK was increased at 10 km of the marathon race and up to threefold at the end of the race. This was further increased on day 1, only returning to pre-race level on day 6. Plasma CPK was increased 35-fold at the end of the 200-km race (PMID:19125286)
• Report the effects of prior calcium channel blocker therapy on creatine kinase-MB (myocardial form) levels after percutaneous coronary interventions. (PMID:19337554)
• The Dimension Vista cTnI, CK-MB, MYO, NTproBNP, and hsCRP methods demonstrate acceptable performance characteristics for use as an aid in the diagnosis and risk assessment of patients presenting with suspected acute coronary syndromes. (PMID:19523464)
• Elevated CK-MB values after elective angioplasty predicts reduced long-term event-free survival. (PMID:19670037)
• The researchers found no association between the CK response after exercise and the presence of the CK-MM NcoI polymorphism. (PMID:20157874)
• Common variants of MSTN and CKM genes don’t play a role in attaining high level endurance performance in Caucasians. (PMID:20536908)
• two residues close to the dimer interface of MMCK were crucial for species-specific thermal stability (PMID:20558199)
• A single troponin I value at 3 days from symptom onset is a better predictor of infarct size compared to peak values and CK-MB. (PMID:20588136)
• Elevated creatine kinase-MB is associated with elevated white blood cell count and atherosclerotic plaque in patients with elective stent implantation. (PMID:20591515)
• percutaneous coronary intervention induces temporal changes of P-selectin, Mg, and CK-MB, which may be involved in restenosis and ischemia-reperfusion injury, but not PAI-1 (PMID:20669347)
• Muscle-type creatine kinase physically interacts with the slow skeletal muscle-type MyBPC1 (myosin-binding protein C1). (PMID:21426302)
• Cardiac troponin T and creatine kinase have roles in infarct size and left ventricular function after acute myocardial infarction (PMID:21448949)
• The overall efficacy of IMA [ischemia modified albumin]in differentiating AMI[Acute Myocardial Infarction] from Non-AMI cases appears to be comparable to that of CK-MB and cTnI (PMID:21456469)
• Results indicate that these polymorphisms can indirectly influence performance, contribute to higher susceptibility to exercise-induced inflammation or protection against it, and perhaps affect future risks of CVD in athletes. (PMID:21516340)
• Creatine kinase MM TaqI and methylenetetrahydrofolate reductase C677T and A1298C gene polymorphisms influence exercise-induced C-reactive protein levels. (PMID:21706313)
• strong down-regulation of MCK activity contributes to F-actin instability and induces post-translational modification of alphaB-crystallin and desmin (PMID:21768101)
• This study explored the relationship of cardiac function examined by echocardiography and serum creatine kinase (CK) and CK-MB levels with myocardial ischemia-reperfusion injury in a cohort of Chinese acute myocardial infarction patients. (PMID:21873942)
• The results suggested that the intra- and inter-subunit domain interactions modified the behavior of kinetic refolding. (PMID:21931810)
• High levels of blood creatine-kinase MB are associated with embolism source during acute phase of ischemic stroke. (PMID:22592287)
• The current enzymatic definition of procedural myocardial infarct (MI) (CK-myocardial band more than 3 times the upper limit of normal) used in clinical trials is less strongly associated with death than that of spontaneous MI. (PMID:23122801)
• The crystal structure of CK indicates that the E79 and K138 interaction plays key roles in sustaining the recognition between N-terminal and C-terminal domains of muscle creatine kinase. (PMID:23274523)
• 3D mapping of the CK reaction rates and metabolic fluxes can be achieved in the skeletal muscle in vivo at relatively high spatial resolution and with acquisition times well tolerated by patients. (PMID:23436474)
• Estimation of CK and its CK isoenzyme fractions can aid in quick and accurate diagnosis of tubal ectopic pregnancy. (PMID:23876027)
• Cardiac enzyme elevations post-cardiac bypass or post-percutaneous coronary intervention are associated with an adverse long-term mortality; the causes of which are multifactorial. (PMID:23993326)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	ckma	ENSDARG00000035327
danio_rerio	ckmb	ENSDARG00000040565
mus_musculus	Ckm	ENSMUSG00000030399
rattus_norvegicus	Ckm	ENSRNOG00000016837
drosophila_melanogaster	Argk1	FBGN0000116
drosophila_melanogaster	Argk2	FBGN0035957
drosophila_melanogaster	CG4546	FBGN0038373
drosophila_melanogaster	CG30274	FBGN0050274
caenorhabditis_elegans		WBGENE00009706
caenorhabditis_elegans	ZC434.8	WBGENE00013894
caenorhabditis_elegans	F32B5.1	WBGENE00017975
caenorhabditis_elegans		WBGENE00018519
caenorhabditis_elegans	W10C8.5	WBGENE00021128

Paralogs (4): CKMT2 (ENSG00000131730), CKB (ENSG00000166165), CKMT1A (ENSG00000223572), CKMT1B (ENSG00000237289)

Protein

Protein identifiers

Creatine kinase M-type — P06732 (reviewed: P06732)

Alternative names: Creatine kinase M chain, Creatine phosphokinase M-type, M-CK

All UniProt accessions (1): P06732

UniProt curated annotations — full annotation on UniProt →

Function. Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, brain and spermatozoa.

Subunit / interactions. Dimer of identical or non-identical chains, which can be either B (brain type) or M (muscle type). With MM being the major form in skeletal muscle and myocardium, MB existing in myocardium, and BB existing in many tissues, especially brain.

Subcellular location. Cytoplasm.

Similarity. Belongs to the ATP:guanido phosphotransferase family.

RefSeq proteins (1): NP_001815* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000749	ATP-guanido_PTrfase	Family
IPR014746	Gln_synth/guanido_kin_cat_dom	Homologous_superfamily
IPR022413	ATP-guanido_PTrfase_N	Domain
IPR022414	ATP-guanido_PTrfase_cat	Domain
IPR022415	ATP-guanido_PTrfase_AS	Active_site
IPR036802	ATP-guanido_PTrfase_N_sf	Homologous_superfamily

Pfam: PF00217, PF02807

Enzyme classification (BRENDA):

• EC 2.7.3.2 — creatine kinase (BRENDA: 45 organisms, 67 substrates, 117 inhibitors, 317 Km, 122 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
ATP	0.042–20	133
CREATINE	0.35–167	102
PHOSPHOCREATINE	0.51–8.97	23
ADP	0.015–1.2	22
CREATINE PHOSPHATE	0.23–50	11
ALPHA-(RP)-BORANO SUBSTITUTED ADP	1	1
ALPHA-(SP)-BORANO SUBSTITUTED ADP	0.008	1
GLYCOCYAMINE	6.7	1
CYCLOCREATINE	—	0
N-ETHYLGLYCOCYAMINE	—	0

Catalyzed reactions (Rhea), 1 shown:

• creatine + ATP = N-phosphocreatine + ADP + H(+) (RHEA:17157)

UniProt features (58 total): helix 13, strand 9, modified residue 8, turn 8, sequence conflict 7, binding site 6, sequence variant 4, domain 2, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7BF2	X-RAY DIFFRACTION	1.43
1I0E	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P06732-F1	94.92	0.87

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): 128–132; 191; 236; 292; 320–325; 335

Post-translational modifications (8): 166, 178, 180, 199, 313, 322, 372, 164

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-71288	Creatine metabolism
R-HSA-1430728	Metabolism
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 107 (showing top): RNGTGGGC_UNKNOWN, ROVERSI_GLIOMA_COPY_NUMBER_UP, HUMMERICH_BENIGN_SKIN_TUMOR_DN, HUMMERICH_MALIGNANT_SKIN_TUMOR_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, MEF2_02, CAGCTG_AP4_Q5, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, SRF_Q5_01, MARTINEZ_RB1_TARGETS_UP, SRF_C, MYOD_01, TGCTGAY_UNKNOWN, MYOD_Q6, MODULE_440

GO Biological Process (1): phosphocreatine biosynthetic process (GO:0046314)

GO Molecular Function (8): creatine kinase activity (GO:0004111), ATP binding (GO:0005524), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), transferase activity, transferring phosphorus-containing groups (GO:0016772)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
phosphocreatine metabolic process	1
phosphagen biosynthetic process	1
kinase activity	1
phosphotransferase activity, nitrogenous group as acceptor	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
transferase activity	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1284 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CKM	ENO3	P13929	714
CKM	LDHAL6A	Q6ZMR3	685
CKM	LDHAL6B	Q9BYZ2	684
CKM	APOC2	P02655	668
CKM	LDHC	P07864	641
CKM	MYOG	P15173	640
CKM	PRKCG	P05129	625
CKM	GOT1L1	Q8NHS2	589
CKM	MYOD1	P15172	581
CKM	DAG1	Q14118	555
CKM	ERCC2	P18074	554
CKM	MYH6	P13533	533
CKM	MYF5	P13349	532
CKM	MYL1	P05976	514
CKM	PAX7	P23759	510

IntAct

67 interactions, top by confidence:

A	B	Type	Score
CKM	ASB9	psi-mi:“MI:0915”(physical association)	0.870
ASB9	CKM	psi-mi:“MI:0915”(physical association)	0.870
ASB9	CKM	psi-mi:“MI:0914”(association)	0.870
CKB	CKM	psi-mi:“MI:0915”(physical association)	0.690
CKB	CKM	psi-mi:“MI:0914”(association)	0.690
CKM	CKMT1A	psi-mi:“MI:0915”(physical association)	0.560
CKM	HTT	psi-mi:“MI:0915”(physical association)	0.560
PSMB9	PSMD11	psi-mi:“MI:0914”(association)	0.530
CKMT2	NME2P1	psi-mi:“MI:0914”(association)	0.530
ASB9	ARIH2	psi-mi:“MI:0914”(association)	0.530
ZNF24	CKM	psi-mi:“MI:0914”(association)	0.530
CKM	PALM2AKAP2	psi-mi:“MI:0914”(association)	0.530
	CKM	psi-mi:“MI:0915”(physical association)	0.400
CKM	HARS2	psi-mi:“MI:0915”(physical association)	0.400
CC2D1B	CKM	psi-mi:“MI:0915”(physical association)	0.400
TMEM98	CKM	psi-mi:“MI:0915”(physical association)	0.400
NOS1AP	CKM	psi-mi:“MI:0915”(physical association)	0.370
DUX4L9	CKM	psi-mi:“MI:0915”(physical association)	0.370
HSPB2	CKM	psi-mi:“MI:0915”(physical association)	0.370
ECE1	CKM	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (87): CKM (Two-hybrid), CKM (Two-hybrid), ASB9 (Two-hybrid), CKM (Affinity Capture-MS), CKM (Affinity Capture-MS), CKM (Affinity Capture-MS), ATP6V1C2 (Affinity Capture-MS), PALM2 (Affinity Capture-MS), CKM (Affinity Capture-MS), ABCB7 (Co-fractionation), CKM (Co-fractionation), CKM (Two-hybrid), CKM (Two-hybrid), ASB9 (Two-hybrid), CKM (Affinity Capture-MS)

ESM2 similar proteins: A0A286R7K5, A0A976YI25, B0FRF9, B1PVZ9, C7E3T4, C9EIP1, H6VGI2, H6VGI3, O61367, O77814, O96507, P00563, P00564, P00565, P00566, P04414, P05123, P05124, P06732, P07310, P07335, P09605, P11009, P12532, P14208, P17540, P24722, P25809, P30275, P48610, P51541, P51545, P70079, P91798, Q004B5, Q04447, Q29577, Q29594, Q3ZBP1, Q5EA61

Diamond homologs: A0A286R7K5, A0A976YI25, A4J0X5, A5D5K7, A8F953, B0FRF9, B1PVZ9, C1KYG4, C7E3T4, C9EIP1, G1ESZ9, H6VGI2, H6VGI3, O15989, O15990, O15991, O15992, O61367, O77814, O96507, P00563, P00564, P00565, P00566, P00567, P04414, P05122, P05123, P05124, P06732, P07310, P07335, P09605, P11009, P12277, P12532, P14208, P16641, P17540, P18294

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
creatine	“up-regulates activity”	CKM	“chemical activation”
CKM	“up-regulates quantity”	N-phosphocreatine	“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	0
Uncertain significance	65
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

593 predictions. Top by Δscore:

Variant	Effect	Δscore
19:45306924:GCCAC:G	acceptor_gain	1.0000
19:45306925:CCAC:C	acceptor_gain	1.0000
19:45306925:CCACC:C	acceptor_gain	1.0000
19:45306926:CAC:C	acceptor_gain	1.0000
19:45306926:CACC:C	acceptor_gain	1.0000
19:45306927:AC:A	acceptor_gain	1.0000
19:45306927:ACC:A	acceptor_loss	1.0000
19:45306928:CC:C	acceptor_gain	1.0000
19:45306929:C:CC	acceptor_gain	1.0000
19:45306930:T:A	acceptor_loss	1.0000
19:45306938:C:CT	acceptor_gain	1.0000
19:45307456:CGTA:C	donor_loss	1.0000
19:45307457:GTAC:G	donor_loss	1.0000
19:45307458:TACC:T	donor_loss	1.0000
19:45307460:C:G	donor_loss	1.0000
19:45307646:TCAAT:T	acceptor_gain	1.0000
19:45307647:CAAT:C	acceptor_gain	1.0000
19:45307647:CAATC:C	acceptor_gain	1.0000
19:45307648:AAT:A	acceptor_gain	1.0000
19:45307649:AT:A	acceptor_gain	1.0000
19:45307650:TCTGA:T	acceptor_loss	1.0000
19:45307651:C:A	acceptor_loss	1.0000
19:45307651:C:CC	acceptor_gain	1.0000
19:45307652:T:G	acceptor_loss	1.0000
19:45307656:G:C	acceptor_gain	1.0000
19:45307656:G:GC	acceptor_gain	1.0000
19:45307659:C:CT	acceptor_gain	1.0000
19:45307660:A:T	acceptor_gain	1.0000
19:45308406:CAC:C	donor_loss	1.0000
19:45308408:CCTT:C	donor_gain	1.0000

AlphaMissense

2539 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:45306882:G:C	N338K	1.000
19:45306882:G:T	N338K	1.000
19:45307469:C:A	R320M	1.000
19:45307559:C:T	G290E	1.000
19:45307560:C:A	G290W	1.000
19:45307565:C:A	G288V	1.000
19:45307565:C:T	G288D	1.000
19:45307566:C:G	G288R	1.000
19:45307570:G:C	N286K	1.000
19:45307570:G:T	N286K	1.000
19:45307574:G:A	S285F	1.000
19:45307580:C:T	C283Y	1.000
19:45307581:A:G	C283R	1.000
19:45308488:T:A	D233V	1.000
19:45308488:T:G	D233A	1.000
19:45308489:C:G	D233H	1.000
19:45308491:T:A	E232V	1.000
19:45308493:C:A	E231D	1.000
19:45308493:C:G	E231D	1.000
19:45308494:T:A	E231V	1.000
19:45308502:C:A	W228C	1.000
19:45308502:C:G	W228C	1.000
19:45308504:A:G	W228R	1.000
19:45308504:A:T	W228R	1.000
19:45308509:A:G	L226P	1.000
19:45311756:C:G	G216R	1.000
19:45311759:G:T	R215S	1.000
19:45311769:C:A	W211C	1.000
19:45311769:C:G	W211C	1.000
19:45311771:A:G	W211R	1.000

dbSNP variants (sampled 300 via entrez): RS1000102560 (19:45320135 G>A), RS1000229767 (19:45311880 G>A,C,T), RS1000561040 (19:45320012 A>C,T), RS1000604221 (19:45323978 T>A,C), RS1000910743 (19:45316337 A>AT), RS1001142354 (19:45309227 C>A), RS1001217434 (19:45311408 T>G), RS1001534538 (19:45314075 G>C), RS1001606611 (19:45313773 G>A), RS1001722165 (19:45324369 A>AC), RS1001808855 (19:45311213 C>G,T), RS1001988544 (19:45324177 C>T), RS1002066267 (19:45323593 G>A,T), RS1002076419 (19:45323268 G>A,C,T), RS1002678152 (19:45314069 G>A)

Disease associations

OMIM: gene MIM:123310 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002603_1	Creatine kinase levels in statin users	4.000000e-16
GCST005316_237	Intelligence (MTAG)	2.000000e-08
GCST005950_15	Body mass index x sex x age interaction (4df test)	2.000000e-10
GCST005951_56	Body mass index	1.000000e-06
GCST005952_8	Body mass index (age>50)	9.000000e-12
GCST005954_4	Body mass index x age interaction	2.000000e-07
GCST007320_93	Alzheimer’s disease or family history of Alzheimer’s disease	4.000000e-08
GCST007827_3	Alzheimer’s disease or HDL levels (pleiotropy)	1.000000e-97

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004534	creatine kinase measurement
EFO:0004337	intelligence
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0009268	family history of Alzheimer’s disease
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2656 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, affects binding, increases reaction, increases expression	4
Doxorubicin	decreases expression	4
graphene oxide	increases expression	2
bisphenol A	increases abundance, increases expression, affects cotreatment, affects expression	2
Daunorubicin	decreases expression	2
Mitoxantrone	decreases expression	2
Tobacco Smoke Pollution	increases expression, affects expression	2
Cadmium Chloride	decreases expression, affects cotreatment	2
ginger extract	affects cotreatment, affects expression, increases abundance	1
notexin	increases secretion	1
lead acetate	affects cotreatment, decreases expression	1
fluoroacetic acid	increases secretion	1
chromous chloride	affects cotreatment, decreases expression	1
chromic oxide	affects cotreatment, decreases expression	1
2,7-dihydroxynaphthalene	decreases expression	1
abrine	increases expression	1
incobotulinumtoxinA	decreases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	increases expression	1
Albuterol	increases secretion	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Carbimazole	increases expression	1
Carmustine	decreases expression	1
Cocaine	affects binding, increases secretion	1
Etoposide	decreases expression	1
Oils, Volatile	affects cotreatment, affects expression, increases abundance	1
Oxygen	increases expression, decreases reaction	1
Phenytoin	increases expression	1
Silicon Dioxide	increases expression	1
Triclosan	decreases expression	1

ChEMBL screening assays

20 unique, capped per target: 19 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1054176	Binding	Activity of human creatine kinase isoform MM assessed as formation of RO2433 triphosphate at 200 uM	The mechanism of action of beta-D-2’-deoxy-2’-fluoro-2’-C-methylcytidine involves a second metabolic pathway leading to beta-D-2’-deoxy-2’-fluoro-2’-C-methyluridine 5’-triphosphate, a potent inhibitor of the hepatitis C virus RNA-dependent RNA polymerase. — Antimicrob Agents Chemother
CHEMBL822428	Functional	Concentration required to antagonise the creatine kinase release induced by Bothrops jararacussu venom	Synthesis and preliminary pharmacological evaluation of coumestans with different patterns of oxygenation. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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