CMPK1

Summary

CMPK1 (cytidine/uridine monophosphate kinase 1, HGNC:18170) is a protein-coding gene on chromosome 1p33, encoding UMP-CMP kinase (P30085). Catalyzes the phosphorylation of pyrimidine nucleoside monophosphates at the expense of ATP. It is a selective cancer dependency (DepMap: 87.4% of cell lines).

This gene encodes one of the enzymes required for cellular nucleic acid biosynthesis. This enzyme catalyzes the transfer of a phosphate group from ATP to CMP, UMP, or dCMP, to form the corresponding diphosphate nucleotide. Alternate splicing results in both coding and non-coding transcript variants.

Source: NCBI Gene 51727 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 21 total
• GTEx eGene: eQTL in 27 tissues, sQTL in 26 (q < 0.05)
• ChEMBL bioactivity: 2 clinical-phase molecules tested; no curated mechanism-of-action drug
• Cancer dependency (DepMap): dependent in 87.4% of screened cell lines
• Constraint (gnomAD): pLI 0.18 (intermediate), LOEUF 0.90 (unconstrained)
• MANE Select transcript: NM_016308
• Interaction hub: 2,472 STRING partners (top 4% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18170
Approved symbol	CMPK1
Name	cytidine/uridine monophosphate kinase 1
Location	1p33
Locus type	gene with protein product
Status	Approved
Aliases	UMP-CMPK
Ensembl gene	ENSG00000162368
Ensembl biotype	protein_coding
OMIM	191710
Entrez	51727

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 15 protein_coding, 13 nonsense_mediated_decay, 1 retained_intron

MANE Select: ENST00000371873

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 4

ENST00000371873, ENST00000371870, ENST00000371871, ENST00000450808, ENST00000471289, ENST00000699074, ENST00000699075, ENST00000873428, ENST00000873429, ENST00000954781, ENST00000954782, ENST00000981265, ENST00000981266, ENST00000981267, ENST00000981268, ENST00000981269, ENST00000981270, ENST00001017178, ENST00001017179, ENST00001017180, ENST00001017183, ENST00001017185, ENST00001080117, ENST00001108907, ENST00001113389, ENST00001122429, ENST00001122430, ENST00001122431, ENST00001143760

RefSeq mRNA: 3 — MANE Select: NM_016308 NM_001136140, NM_001366135, NM_016308

CCDS: CCDS44135, CCDS549, CCDS90947

Canonical transcript exons

ENST00000371873 — 6 exons

Exon	Start	End
ENSE00001064474	47374909	47374985
ENSE00001064475	47372955	47373107
ENSE00001561138	47333790	47334116
ENSE00001831502	47376704	47378839
ENSE00003510178	47375197	47375293
ENSE00003537405	47368469	47368615

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 85.4047 / max 664.7939, expressed in 1827 samples.

Highest expression (Bgee): jejunal mucosa, palpebral conjunctiva, parotid gland, mucosa of sigmoid colon, duodenum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CMPK1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 27 tissues and its splicing (sQTL) in 26 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 53 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Aorta	eqtl	2.2e-24	+0.30	1:47294591:G:A
Artery Tibial	eqtl	1.5e-17	+0.19	1:47294591:G:A
Muscle Skeletal	sqtl	1.3e-12	+1.44	1:47284608:G:C
Cells Cultured fibroblasts	eqtl	4.6e-11	+0.11	1:47379923:C:T
Adipose Subcutaneous	sqtl	6.1e-11	+1.18	1:47324471:G:A
Nerve Tibial	eqtl	1.7e-10	+0.15	1:47286428:G:A
Thyroid	eqtl	3.1e-10	+0.12	1:47380039:T:A
Thyroid	sqtl	3.2e-09	+1.01	1:47284608:G:C
Esophagus Mucosa	sqtl	6.1e-09	+1.21	1:47284608:G:C
Esophagus Muscularis	sqtl	2.9e-08	+1.19	1:47284608:G:C
Skin Sun Exposed Lower leg	eqtl	6.0e-08	+0.12	1:47383368:A:G
Lung	sqtl	6.3e-08	+1.10	1:47303023:G:T
Pancreas	sqtl	7.3e-08	+1.46	1:47284608:G:C
Esophagus Mucosa	eqtl	8.5e-08	+0.10	1:47247647:G:A
Minor Salivary Gland	sqtl	2.2e-07	+1.70	1:47284608:G:C
Brain Frontal Cortex BA9	eqtl	3.2e-07	+0.20	1:47261763:T:A
Cells Cultured fibroblasts	sqtl	4.0e-07	+0.82	1:47284608:G:C
Adipose Visceral Omentum	eqtl	1.7e-06	-0.12	1:47356176:G:C
Adipose Visceral Omentum	sqtl	1.8e-06	+0.84	1:47291812:C:T
Breast Mammary Tissue	eqtl	2.8e-06	+0.10	1:47315824:T:C

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
2772	44.1313	1820
2773	41.2734	1820

Top tissues by expression

showing 100 of 288 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.36	gold quality
palpebral conjunctiva	UBERON:0001812	99.05	gold quality
parotid gland	UBERON:0001831	98.90	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.72	gold quality
duodenum	UBERON:0002114	98.69	gold quality
colonic mucosa	UBERON:0000317	98.62	gold quality
rectum	UBERON:0001052	98.61	gold quality
epithelium of nasopharynx	UBERON:0001951	98.46	gold quality
esophagus squamous epithelium	UBERON:0006920	98.33	gold quality
tibia	UBERON:0000979	98.31	gold quality
oral cavity	UBERON:0000167	98.30	gold quality
calcaneal tendon	UBERON:0003701	98.23	gold quality
nasal cavity mucosa	UBERON:0001826	98.17	gold quality
jejunum	UBERON:0002115	98.04	gold quality
upper arm skin	UBERON:0004263	97.95	gold quality
islet of Langerhans	UBERON:0000006	97.94	gold quality
gall bladder	UBERON:0002110	97.90	gold quality
penis	UBERON:0000989	97.88	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.82	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.82	gold quality
saliva-secreting gland	UBERON:0001044	97.81	gold quality
blood vessel layer	UBERON:0004797	97.74	gold quality
urethra	UBERON:0000057	97.56	gold quality
minor salivary gland	UBERON:0001830	97.56	gold quality
pleura	UBERON:0000977	97.54	gold quality
parietal pleura	UBERON:0002400	97.53	gold quality
mouth mucosa	UBERON:0003729	97.51	gold quality
pylorus	UBERON:0001166	97.50	gold quality
gingiva	UBERON:0001828	97.50	gold quality
epithelium of esophagus	UBERON:0001976	97.50	gold quality
visceral pleura	UBERON:0002401	97.49	gold quality
upper leg skin	UBERON:0004262	97.47	gold quality
skin of hip	UBERON:0001554	97.44	gold quality
popliteal artery	UBERON:0002250	97.43	gold quality
tibial artery	UBERON:0007610	97.43	gold quality
nasal cavity epithelium	UBERON:0005384	97.42	gold quality
saphenous vein	UBERON:0007318	97.41	gold quality
ileal mucosa	UBERON:0000331	97.40	gold quality
mammalian vulva	UBERON:0000997	97.40	gold quality
right coronary artery	UBERON:0001625	97.37	gold quality
pancreas	UBERON:0001264	97.30	gold quality
gingival epithelium	UBERON:0001949	97.30	gold quality
monocyte	CL:0000576	97.29	gold quality
bronchial epithelial cell	CL:0002328	97.29	gold quality
aorta	UBERON:0000947	97.29	gold quality
mononuclear cell	CL:0000842	97.25	gold quality
tonsil	UBERON:0002372	97.24	gold quality
leukocyte	CL:0000738	97.13	gold quality
synovial joint	UBERON:0002217	97.11	gold quality
body of pancreas	UBERON:0001150	97.10	gold quality
thoracic aorta	UBERON:0001515	97.10	gold quality
colonic epithelium	UBERON:0000397	97.09	gold quality
left coronary artery	UBERON:0001626	97.09	gold quality
ascending aorta	UBERON:0001496	97.08	gold quality
mammary duct	UBERON:0001765	97.06	gold quality
adipose tissue	UBERON:0001013	97.05	gold quality
liver	UBERON:0002107	97.00	gold quality
connective tissue	UBERON:0002384	96.98	gold quality
esophagus mucosa	UBERON:0002469	96.98	gold quality
trachea	UBERON:0003126	96.97	gold quality
subcutaneous adipose tissue	UBERON:0002190	96.95	gold quality
coronary artery	UBERON:0001621	96.94	gold quality
superior surface of tongue	UBERON:0007371	96.94	gold quality
epithelium of mammary gland	UBERON:0003244	96.88	gold quality
thoracic mammary gland	UBERON:0005200	96.88	gold quality
pharyngeal mucosa	UBERON:0000355	96.87	gold quality
descending thoracic aorta	UBERON:0002345	96.87	gold quality
mammary gland	UBERON:0001911	96.86	gold quality
caecum	UBERON:0001153	96.85	gold quality
right lobe of liver	UBERON:0001114	96.71	gold quality
esophagus	UBERON:0001043	96.69	gold quality
vermiform appendix	UBERON:0001154	96.69	gold quality
superficial temporal artery	UBERON:0001614	96.66	gold quality
decidua	UBERON:0002450	96.64	gold quality
bronchus	UBERON:0002185	96.63	gold quality
epithelium of bronchus	UBERON:0002031	96.62	gold quality
squamous epithelium	UBERON:0006914	96.60	gold quality
large intestine	UBERON:0000059	96.50	gold quality
substantia nigra pars compacta	UBERON:0001965	96.50	gold quality
layer of synovial tissue	UBERON:0007616	96.50	gold quality
right lung	UBERON:0002167	96.46	gold quality
lymph node	UBERON:0000029	96.44	gold quality
intestine	UBERON:0000160	96.42	gold quality
stromal cell of endometrium	CL:0002255	96.41	gold quality
colon	UBERON:0001155	96.40	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.39	gold quality
lower lobe of lung	UBERON:0008949	96.39	gold quality
endometrium	UBERON:0001295	96.35	gold quality
vagina	UBERON:0000996	96.33	gold quality
trigeminal ganglion	UBERON:0001675	96.33	gold quality
choroid plexus epithelium	UBERON:0003911	96.33	gold quality
smooth muscle tissue	UBERON:0001135	96.28	gold quality
lower esophagus	UBERON:0013473	96.28	gold quality
dorsal root ganglion	UBERON:0000044	96.27	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.27	gold quality
prostate gland	UBERON:0002367	96.25	gold quality
tendon	UBERON:0000043	96.23	gold quality
cortical plate	UBERON:0005343	96.22	gold quality
transverse colon	UBERON:0001157	96.17	gold quality
superior vestibular nucleus	UBERON:0007227	96.14	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	12.05
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	211.0	medium
Duodenum	tissue	155.7	high
Salivary gland	tissue	151.7	high
Small intestine	tissue	144.9	high
Rectum	tissue	136.8	high
Colon	tissue	128.3	high
Stomach 1	tissue	104.6	medium
Esophagus	tissue	104.6	medium
Breast	tissue	98.6	medium
Spinal cord	tissue	95.9
Prostate	tissue	92.6	medium
Midbrain	tissue	91.0
Pons	tissue	90.2
Thalamus	tissue	89.7
Thyroid gland	tissue	89.6	medium
Corpus callosum	tissue	88.6
Pancreas	tissue	87.1	medium
Medulla oblongata	tissue	86.0
Gallbladder	tissue	85.7	high
Tonsil	tissue	84.8	medium
Superior colliculi	tissue	84.7
Substantia nigra	tissue	83.1
Adipose tissue	tissue	82.7	not detected
Urinary bladder	tissue	77.1	medium
Kidney	tissue	75.6	medium
Putamen	tissue	73.2
Cervix	tissue	72.3	medium
Periaqueductal gray	tissue	71.4
Locus coeruleus	tissue	71.1
Hypothalamus	tissue	70.6
Cerebral cortex	tissue	69.8	medium
Somatosensory cortex	tissue	69.8
Lymph node	tissue	69.5	medium
Tongue	tissue	69.5
Occipital cortex	tissue	69.2
Motor cortex	tissue	68.7
Septum	tissue	64.9
Frontal cortex	tissue	64.7
Choroid plexus	tissue	64.5
Skin 1	tissue	64.1	medium
Hippocampal formation	tissue	62.3
Lung	tissue	62.0	high
Ventral forebrain	tissue	61.9
Prefrontal cortex	tissue	61.4
Heart muscle	tissue	61.3	high
Skeletal muscle	tissue	61.0	medium
Appendix	tissue	60.7	high
Vagina	tissue	60.3	high
Thymus	tissue	59.1
Retrosplenial cortex	tissue	58.6
Retrosplenial and cingulate cortex	tissue	58.2
Entorhinal cortex	tissue	57.9
Postcentral gyrus	tissue	57.3
Temporal cortex	tissue	56.4
Amygdala	tissue	55.8
Spleen	tissue	55.6	medium
Parathyroid gland	tissue	54.7	medium
Smooth muscle	tissue	52.5	medium
Insular cortex	tissue	52.4
Hippocampus	tissue	52.1	low

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (99.2), Ventral spinal cord (95.9), White matter (88.6), Dorsal spinal cord (84.3), Mammillary body (79.8).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CMPK1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 127 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-767-5P	99.95	70.85	993
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798

Functional genomics

gnomAD constraint: pLI 0.176, LOEUF 0.902, missense Z 0.926 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000371873 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
1:47,333,946–47,334,046	59 / 45.1	1.31	no
1:47,334,047–47,376,742	140 / 235.5	0.59	no
DepMap (CRISPR cell-line fitness): dependent in 87.4% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): AsPC-1 (-2.309), Detroit 562 (-2.086), SCC-9 (-1.962), VMRC-RCW (-1.895), BICR 31 (-1.774), SU-DHL-10 (-1.632), SNU-620 (-1.631), RERF-LC-Sq1 (-1.622), HSC-4 (-1.58), NCI-H716 (-1.579), MCF-7 (-1.578), JHH-4 (-1.568), Panc 05.04 (-1.553), KNS-60 (-1.507), MEL-HO (-1.502).

Literature-anchored findings (GeneRIF, showing 14)

• Characterization of human UMP/CMP kinase and its phosphorylation of D- and L-form deoxycytidine analogue monophosphates. (PMID:11912132)
• UMP/CMP kinase reveals the conformational changes that occur upon substrate binding (PMID:15163660)
• Models for the phosphorylation action and substrate specificity of human UMP/CMP kinase. (PMID:15550676)
• Several uracil vinylphosphonate derivatives had affinities for human UMP-CMP kinase similar to those of dUMP (PMID:17608725)
• thymidylate synthase/ribonucleotide reductase gene silencing and deoxycytidine kinase::uridine monophosphate kinase fusion gene gene overexpression markedly improved gemcitabine’s therapeutic activity (PMID:19568409)
• UMP/CMP kinase (EC 2.7.4.14) is not critical for the phosphorylation of CMP, dCMP and maintenance of natural nucleotide pools in cells (PMID:21559290)
• Single-nucleotide polymorphisms in CMPK1 gene is associated with treatment response in non-small cell lung cancer. (PMID:21642870)
• In particular, polymorphisms of the CMPK1 gene seem to provide important prognostic information (PMID:22838950)
• CMPK1 and RBP3 are associated with corneal curvature in Asian populations. (PMID:24963161)
• The role of CMP/UMP kinase (CMPK), an enzyme catalyzes cytidine diphosphate formation, in DNA repair, was investigated. (PMID:25659034)
• Nuclear CMPK1 expression is indicative of poor prognosis in the triple negative breast cancer patients. (PMID:27558661)
• TGF-b1 inhibited the expression of CMPK, which was blocked in the presence of a TGF-b type I receptor, SB431542, and was abolished by the inhibitor of miR-130b-3p, indicating that CMPK is regulated by the TGF-b signalling pathway through the upregulation of miR-130b-3p. (PMID:28414100)
• Study found that CMPK1 is a direct target of miR-3613 which bids to its 3’UTR. (PMID:31201869)
• Twenty-Four Percent of Wildland Firefighters Reach Critical Levels of Serum Creatine Kinase During 80-Hour Critical Training. (PMID:37258394)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cmpk1	ENSMUSG00000028719
rattus_norvegicus	Cmpk1	ENSRNOG00000007775
drosophila_melanogaster	Ak1	FBGN0022709

Paralogs (9): AK2 (ENSG00000004455), AK1 (ENSG00000106992), AK7 (ENSG00000140057), AK3 (ENSG00000147853), AK5 (ENSG00000154027), AK9 (ENSG00000155085), AK4 (ENSG00000162433), AK8 (ENSG00000165695), AK4P3 (ENSG00000233381)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1913838) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 5 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal retina vasculature morphology	1
polycystic kidney	1
increased circulating iron level	1
abnormal retina blood vessel morphology	1
preweaning lethality, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Sus scrofa	Q29561	98.5%	Diamond
Bos taurus	Q2KIW9	98.5%	Diamond
Oryctolagus cuniculus	P00569	96.9%	Diamond
Xenopus tropicalis	Q28H12	95.9%	Diamond
Xenopus laevis	Q7ZX23	95.9%	Diamond
Schistosoma mansoni	G4V9S0	94.4%	Diamond
Oryza sativa Japonica Group	Q6K7H2	92.9%	Diamond
Gallus gallus	Q5ZKE7	90.3%	Diamond
Arabidopsis thaliana	O04905	84.2%	Diamond
Caenorhabditis elegans	O17622	81.2%	Diamond
Cyprinus carpio	P12115	78.0%	Diamond
Danio rerio	Q7ZWE9	76.4%	Diamond
Prunus armeniaca	O24464	65.9%	Diamond
Mesocricetus auratus	P86195	61.0%	Diamond
Lentinula edodes	O59845	57.9%	Diamond
Saccharomyces cerevisiae S288C	P15700	57.9%	Diamond
Dictyostelium discoideum	P20425	57.4%	Diamond
Schizosaccharomyces pombe 972h-	O59771	53.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
FOXE3	protein-coding	2301
FOXD2	protein-coding	2306
STIL	protein-coding	6491
FOXD2-AS1	ncRNA	84793
LINC01389	ncRNA	102724077
LINC00853	ncRNA	100874253
PDZK1IP1	protein-coding	10158
CYP4A22-AS1	ncRNA	105378701
TAL1	protein-coding	6886

Protein

Protein identifiers

UMP-CMP kinase — P30085 (reviewed: P30085)

Alternative names: Deoxycytidylate kinase, Nucleoside-diphosphate kinase, Uridine monophosphate/cytidine monophosphate kinase

All UniProt accessions (5): A0A494BXC7, A0A8V8TMN5, E9PJD2, P30085, Q5T0D2

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the phosphorylation of pyrimidine nucleoside monophosphates at the expense of ATP. Plays an important role in de novo pyrimidine nucleotide biosynthesis. Has preference for UMP and CMP as phosphate acceptors. Also displays broad nucleoside diphosphate kinase activity.

Subunit / interactions. Monomer.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Ubiquitously expressed.

Cofactor. Binds 1 Mg(2+) ion per monomer.

Domain organisation. Consists of three domains, a large central CORE domain and two small peripheral domains, NMPbind and LID, which undergo movements during catalysis. The LID domain closes over the site of phosphoryl transfer upon ATP binding. Assembling and disassembling the active center during each catalytic cycle provides an effective means to prevent ATP hydrolysis.

Miscellaneous. May be produced from an in-frame upstream initiation codon. However, experimental evidence indicates that use of the downstream initiation codon is more likely (isoform 1 sequence).

Similarity. Belongs to the adenylate kinase family. UMP-CMP kinase subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P30085-1	1	yes
P30085-2	2
P30085-3	3

RefSeq proteins (3): NP_001129612, NP_001353064, NP_057392* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000850	Adenylat/UMP-CMP_kin	Family
IPR006266	UMP_CMP_kinase	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR033690	Adenylat_kinase_CS	Conserved_site

Pfam: PF00406

Enzyme classification (BRENDA)

• EC 2.7.4.14 — UMP/CMP kinase (BRENDA: 12 organisms, 125 substrates, 43 inhibitors, 132 Km, 30 kcat entries)

Substrate kinetics (BRENDA)

39 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CMP	0.0053–3.09	23
UMP	0.02–6.3	23
DCMP	0.017–2.77	17
ATP	0.029–0.68	12
DUMP	0.1–8.5	6
ARA-CMP	0.26–0.917	3
BETA-L-2’,3’-DIDEOXY-3’-THIACYTIDINE MONOPHOSPHA	0.15–2	3
DATP	0.074–0.61	3
BETA-D-2’,3’-DIDEOXY-CMP	0.272–1.037	2
CIDOFOVIR	1–2.3	2
CYTARABINE	0.315–0.327	2
D-CMP	0.02	2
D-DCMP	1	2
D-DUMP	1.3	2
D-UMP	0.05	2

Catalyzed reactions (Rhea)

• CMP + ATP = CDP + ADP (RHEA:11600)
• a ribonucleoside 5’-diphosphate + ATP = a ribonucleoside 5’-triphosphate + ADP (RHEA:18113)
• UMP + ATP = UDP + ADP (RHEA:24400)
• dCMP + ATP = dCDP + ADP (RHEA:25094)
• a 2’-deoxyribonucleoside 5’-diphosphate + ATP = a 2’-deoxyribonucleoside 5’-triphosphate + ADP (RHEA:44640)

UniProt features (36 total): binding site 9, helix 9, modified residue 5, strand 5, region of interest 2, splice variant 2, chain 1, cross-link 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
1TEV	Crystal structure of the human UMP/CMP kinase in open conformation	X-RAY DIFFRACTION	2.1
7E9V	The Crystal Structure of human UMP-CMP kinase from Biortus.	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30085-F1	97.06	0.98

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH approved · IF supported

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 (9)

Position	Role
151	a ribonucleoside 5’-phosphate
179	ATP
13–18	ATP
39	a ribonucleoside 5’-phosphate
61–63	a ribonucleoside 5’-phosphate
93–96	a ribonucleoside 5’-phosphate
100	CMP
134	ATP
140	a ribonucleoside 5’-phosphate

Post-translational modifications (6)

Type	Positions
Phosphoserine	33, 180
N6-acetyllysine	43, 55
N6-succinyllysine	106
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	73

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-499943	Interconversion of nucleotide di- and triphosphates	curated
R-HSA-1430728	Metabolism	—
R-HSA-15869	Metabolism of nucleotides	—

MSigDB gene sets: 265 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, HORIUCHI_WTAP_TARGETS_DN, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, TGCACTT_MIR519C_MIR519B_MIR519A, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PYRIMIDINE_NUCLEOBASE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GTGCCTT_MIR506, GOBP_PYRIMIDINE_NUCLEOTIDE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS

GO Biological Process (12): ‘de novo’ pyrimidine nucleobase biosynthetic process (GO:0006207), UDP biosynthetic process (GO:0006225), pyrimidine ribonucleotide biosynthetic process (GO:0009220), nucleobase-containing small molecule interconversion (GO:0015949), CDP biosynthetic process (GO:0046705), nucleobase-containing compound metabolic process (GO:0006139), pyrimidine nucleotide biosynthetic process (GO:0006221), UMP biosynthetic process (GO:0006222), nucleotide metabolic process (GO:0009117), nucleoside monophosphate metabolic process (GO:0009123), nucleoside monophosphate phosphorylation (GO:0046940), pyrimidine-containing compound biosynthetic process (GO:0072528)

GO Molecular Function (14): nucleoside diphosphate kinase activity (GO:0004550), uridine kinase activity (GO:0004849), ATP binding (GO:0005524), UMP kinase activity (GO:0033862), CMP kinase activity (GO:0036430), dCMP kinase activity (GO:0036431), nucleoside monophosphate kinase activity (GO:0050145), nucleotide binding (GO:0000166), AMP kinase activity (GO:0004017), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), phosphotransferase activity, phosphate group as acceptor (GO:0016776), nucleobase-containing compound kinase activity (GO:0019205)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Metabolism of nucleotides	1
Metabolism	1

GO top-level categories

40 GO namespaces:

Category	Terms
pyrimidine ribonucleotide biosynthetic process	3
nucleoside monophosphate kinase activity	3
cellular anatomical structure	3
pyrimidine ribonucleoside diphosphate biosynthetic process	2
nucleotide biosynthetic process	2
nucleoside phosphate metabolic process	2
phosphotransferase activity, phosphate group as acceptor	2
nucleobase-containing compound kinase activity	2
transferase activity, transferring phosphorus-containing groups	2
pyrimidine nucleobase biosynthetic process	1
UDP metabolic process	1
pyrimidine nucleotide biosynthetic process	1
pyrimidine ribonucleotide metabolic process	1
ribonucleotide biosynthetic process	1
nucleobase-containing small molecule metabolic process	1
CDP metabolic process	1
primary metabolic process	1
pyrimidine nucleotide metabolic process	1
pyrimidine-containing compound biosynthetic process	1
pyrimidine ribonucleoside monophosphate biosynthetic process	1
UMP metabolic process	1
nucleoside monophosphate metabolic process	1
biosynthetic process	1
pyrimidine-containing compound metabolic process	1
UMP biosynthetic process	1
nucleoside kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
deoxynucleoside phosphate kinase activity, ATP as phosphate donor	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
kinase activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 31 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
UDP biosynthetic process	BP	direct assay
extracellular exosome	CC	high-throughput assay
nucleoplasm	CC	direct assay
UMP kinase activity	MF	direct assay
nucleoside diphosphate kinase activity	MF	direct assay
nucleoside monophosphate kinase activity	MF	experiment

Protein interactions and networks

STRING

showing 15 of 2,472 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CMPK1	CMPK2	Q5EBM0	907
CMPK1	DTYMK	P23919	891
CMPK1	ENTPD5	O75356	816
CMPK1	UCK2	Q9BZX2	793
CMPK1	NT5M	Q9NPB1	742
CMPK1	NME4	O00746	731
CMPK1	ENTPD3	O75355	705
CMPK1	UCK1	Q9HA47	693
CMPK1	ENO1	P06733	688
CMPK1	PGD	P52209	678
CMPK1	DCK	P27707	673
CMPK1	DGUOK	P78532	669
CMPK1	PGM1	P36871	664
CMPK1	FUCA1	P04066	641
CMPK1	UMPS	P11172	619

IntAct

Human interaction partners of CMPK1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

10 partners by confidence:

Partner	Interaction type	MIscore	Records
TTC19	physical association	0.560	1
YWHAZ	physical association	0.400	1
GOT1	association	0.350	1
RWDD2B	association	0.350	1
ATG5	physical association	0.000	1
EIF1B	physical association	0.000	1
EIF6	physical association	0.000	1
MCC	physical association	0.000	1
PRKAB1	physical association	0.000	1
TNIK	physical association	0.000	1

BioGRID (138 interactions; top human partners by supporting records): TTC19 (Affinity Capture-MS; 3 records), AGR2 (Proximity Label-MS; 2 records), CDC42 (Reconstituted Complex; 2 records), CLIC1 (Co-fractionation; 2 records), SUCLG2 (Co-fractionation; 2 records), ABI1 (Affinity Capture-MS), ACE2 (Proximity Label-MS), ACO2 (Co-fractionation), ACOT13 (Co-fractionation), AGO2 (Affinity Capture-RNA), AK5 (Negative Genetic), ARL8B (Proximity Label-MS), ATP5A1 (Co-fractionation), BRD4 (Affinity Capture-MS), BSG (Proximity Label-MS)

Disease & clinical

Genetic variants

Variant evidence for CMPK1: 21 ClinVar records (0 pathogenic / likely pathogenic); 5 PharmGKB clinical annotations; 9 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 33 predictions of 681):

Position(s)	Effect	Δscore	Sites
1:47334117–47334118	donor_loss	1.0000	5
1:47368573	donor_gain	1.0000
1:47372953–47372954	acceptor_loss	1.0000	3
1:47372954	acceptor_gain	1.0000
1:47373062–47373063	donor_gain	1.0000	2
1:47373067	donor_gain	1.0000
1:47375195–47375196	acceptor_loss	1.0000	4
1:47375294–47375295	donor_loss	1.0000	4
1:47376702–47376703	acceptor_loss	1.0000	6
1:47368467–47368468	acceptor_loss	0.9900	6

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	5.04e-06
Colon Adenocarcinoma (TCGA)	favorable	0.0004

Disease associations

OMIM: gene MIM:191710 | disease phenotypes:

GWAS associations

9 associations:

Study	Trait	p-value
GCST010703_129	Brain morphology (MOSTest)	2e-103
GCST010699_107	Brain morphology (min-P)	4e-17
GCST010698_22	Subcortical volume (min-P)	1e-14
GCST002502_1	Corneal curvature	3e-12
GCST010700_17	Cortical thickness (MOSTest)	4e-12
GCST010701_70	Cortical surface area (MOSTest)	1e-10
GCST010702_23	Subcortical volume (MOSTest)	2e-10
GCST010697_22	Cortical surface area (min-P)	3e-10
GCST010696_15	Cortical thickness (min-P)	7e-9

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0004345	corneal topography
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5681 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 6,372 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

2 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL2105728	CRENOLANIB	3	2,278
CHEMBL223360	LINIFANIB	3	4,094

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

5 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs1044457	Efficacy	3	gemcitabine	Neoplasms
rs11211524	Efficacy	3	gemcitabine	Neoplasms
rs35687416	Efficacy	3	gemcitabine	Pancreatic Neoplasms
rs4492666	Efficacy	3	cisplatin;gemcitabine	Non-Small Cell Lung Carcinoma
rs7543016	Efficacy	3	gemcitabine	Pancreatic Neoplasms

PharmGKB variants

5 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1044457	CMPK1	3	2.50	1	gemcitabine
rs4492666	CMPK1	3	2.50	1	cisplatin;gemcitabine
rs7543016	CMPK1	3	1.75	1	gemcitabine
rs11211524	CMPK1	3	0.75	1	gemcitabine
rs35687416	CMPK1	3	3.25	1	gemcitabine

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

7 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs4492666	cisplatin, gemcitabine	Efficacy	Genotype CC is associated with decreased response to cisplatin and gemcitabine in people with Carcinoma, Non-Small-Cell Lung as compared to genotypes AA + AC.	PMID:21642870
rs11211524	cisplatin, gemcitabine	Efficacy	Genotype CC is associated with decreased response to cisplatin and gemcitabine in people with Carcinoma, Non-Small-Cell Lung as compared to genotypes AA + AC.	PMID:21642870
rs1044457	gemcitabine	Efficacy	Genotype TT is associated with decreased clinical benefit to gemcitabine in people with Non-Small Cell Lung Carcinoma as compared to genotypes CC + CT.	PMID:40657553
rs1044457	gemcitabine	Other, Metabolism/PK	Genotype CC is associated with decreased formation clearance of dFdCTP when treated with gemcitabine in people with Neoplasms as compared to genotype TT.	PMID:22838949
rs1044457	gemcitabine	Efficacy	Genotype CC is associated with increased response to gemcitabine in people with Pancreatic Neoplasms as compared to genotypes CT + TT.	PMID:22838950
rs35687416	gemcitabine	Efficacy	Genotype GG is associated with increased response to gemcitabine in people with Pancreatic Neoplasms as compared to genotypes GT + TT.	PMID:22838950
rs7543016	gemcitabine	Efficacy	Genotype CC is associated with increased response to gemcitabine in people with Pancreatic Neoplasms as compared to genotypes CG + GG.	PMID:22838950

Binding affinities (BindingDB)

5 measured of 5 human assays (5 total across all organisms); most potent 5 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[3-[[[2-[4-[4-[4-[[2-(2-adamantyl)acetyl]amino]butyl]piperazin-1-yl]anilino]-5-chloropyrimidin-4-yl]amino]methyl]phenyl]prop-2-enamide	IC50	372 nM	US-9862688: Hydrophobically tagged janus kinase inhibitors and uses thereof
N-[3-[[[2-[4-[4-[3-[[2-(2-adamantyl)acetyl]amino]propyl]piperazin-1-yl]anilino]-5-chloropyrimidin-4-yl]amino]methyl]phenyl]prop-2-enamide	IC50	542 nM	US-9862688: Hydrophobically tagged janus kinase inhibitors and uses thereof
CHEMBL5653589	KD	1440 nM
N-[3-[[[2-[4-[4-[3-[[2-(2-adamantyl)acetyl]amino]propyl]piperazin-1-yl]-2-methoxyanilino]-5-chloropyrimidin-4-yl]amino]methyl]phenyl]prop-2-enamide	IC50	1820 nM	US-9862688: Hydrophobically tagged janus kinase inhibitors and uses thereof
N-[3-[[[2-[4-[4-[2-[[2-(2-adamantyl)acetyl]amino]ethyl]piperazin-1-yl]-2-methoxyanilino]-5-chloropyrimidin-4-yl]amino]methyl]phenyl]prop-2-enamide	IC50	2990 nM	US-9862688: Hydrophobically tagged janus kinase inhibitors and uses thereof

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.52	Kd	3	nM	CRENOLANIB
8.22	Kd	6	nM	LINIFANIB

PubChem BioAssay actives

2 with measured affinity, of 154 total; 2 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
1-[2-[5-[(3-methyloxetan-3-yl)methoxy]benzimidazol-1-yl]quinolin-8-yl]piperidin-4-amine	1424959: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0030	uM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methylphenyl)urea	1424959: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0060	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	2
Valproic Acid	affects expression, decreases expression, decreases methylation	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression, increases expression	1
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects cotreatment, affects localization	1
sodium arsenite	affects binding, increases reaction	1
tetrabromobisphenol A	decreases expression	1
ochratoxin A	affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Cidofovir	increases phosphorylation	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Citrinin	affects cotreatment, increases expression	1
Furaldehyde	affects cotreatment, affects localization, increases expression	1
Ivermectin	decreases expression	1
Lead	increases expression	1

ChEMBL screening assays

12 unique, capped per target: 11 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1054166	Binding	Activity of cloned UMP-CMP kinase in human HuH7 cells assessed as formation of uridine diphosphate by spectrophotometry	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*
CHEMBL4013446	ADMET	Drug metabolism in human HuH7 cells assessed as UMP-CMP kinase-mediated ((2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methyl dihydrogen phosphate metabolite formation at 50 uM after 48 hr	Discovery of Novel Nucleotide Prodrugs with Improved Potency Against HCV Variants Carrying NS5B S282T Mutation. — *J Med Chem*

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_F4KB	HyCyte HCT 116 hCMPK1_p.G8R_c.22G>C cell line	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

2 trials:

NCT	Phase	Status	Title
NCT06447402	Phase 3	RECRUITING	A Trial to Compare Nebulized Amphotericin B and Nebulized Normal Saline as Maintenance in Patients With Chronic Pulmonary Aspergillosis
NCT05641103	Not specified	COMPLETED	PREDIGA 2: Spanish Acronym of Educational and Diagnostic Project for Gaucher and ASMD

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CMPK1 across ~30M SureChEMBL compounds — explore on Sugi Predict.