CMPK2

Summary

CMPK2 (cytidine/uridine monophosphate kinase 2, HGNC:27015) is a protein-coding gene on chromosome 2p25.2, encoding UMP-CMP kinase 2, mitochondrial (Q5EBM0). Mitochondrial nucleotide monophosphate kinase needed for salvage dNTP synthesis that mediates immunomodulatory and antiviral activities through IFN-dependent and IFN-independent pathways.

This gene encodes one of the enzymes in the nucleotide synthesis salvage pathway that may participate in terminal differentiation of monocytic cells. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 129607 — RefSeq curated summary.

At a glance

• Gene–disease (curated): basal ganglia calcification, idiopathic, 10, autosomal recessive (Limited, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 122 total — 3 pathogenic, 2 likely-pathogenic
• GTEx eGene: eQTL in 7 tissues, sQTL in 5 (q < 0.05)
• Phenotypes (HPO): 48
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.71 (unconstrained)
• MANE Select transcript: NM_207315
• Notable: 122 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27015
Approved symbol	CMPK2
Name	cytidine/uridine monophosphate kinase 2
Location	2p25.2
Locus type	gene with protein product
Status	Approved
Aliases	TYKi, UMP-CMPK2, NDK
Ensembl gene	ENSG00000134326
Ensembl biotype	protein_coding
OMIM	611787
Entrez	129607

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 4 protein_coding_CDS_not_defined

MANE Select: ENST00000256722

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 1, TSL 4: 2, TSL 5: 1

ENST00000256722, ENST00000404168, ENST00000458098, ENST00000465619, ENST00000470479, ENST00000478738, ENST00000491738, ENST00001001512, ENST00001038696, ENST00001144526

RefSeq mRNA: 3 — MANE Select: NM_207315 NM_001256477, NM_001256478, NM_207315

CCDS: CCDS42648, CCDS58695, CCDS58696

Canonical transcript exons

ENST00000256722 — 5 exons

Exon	Start	End
ENSE00001862268	6848316	6849973
ENSE00001935604	6865022	6865907
ENSE00003497098	6851450	6851683
ENSE00003521409	6863464	6863578
ENSE00003629631	6861184	6861385

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 96.63.

FANTOM5 (CAGE): breadth broad, TPM avg 8.4259 / max 742.3218, expressed in 802 samples.

Highest expression (Bgee): palpebral conjunctiva, epithelial cell of pancreas, trabecular bone tissue, decidua, amniotic fluid.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CMPK2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 7 tissues and its splicing (sQTL) in 5 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

12 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Lung	sqtl	1.3e-09	-0.72	2:6849889:C:T
Testis	sqtl	2.8e-08	+1.13	2:6842130:T:C
Adipose Visceral Omentum	sqtl	3.0e-03	-0.74	2:6845966:T:G
Adipose Subcutaneous	sqtl	1.7e-02	-0.44	2:6849889:C:T
Brain Putamen basal ganglia	eqtl	1.9e-02	+0.67	2:6881760:G:A
Brain Hypothalamus	eqtl	2.5e-02	+0.98	2:7850176:C:T
Adipose Visceral Omentum	eqtl	2.9e-02	-0.56	2:7048635:G:A
Cells Cultured fibroblasts	eqtl	2.9e-02	+0.18	2:7015620:G:T
Brain Spinal cord cervical c-1	eqtl	3.0e-02	+0.75	2:7863886:G:T
Heart Atrial Appendage	sqtl	3.5e-02	-0.57	2:6849889:C:T
Pituitary	eqtl	4.8e-02	+0.25	2:6749782:T:C
Brain Cerebellum	eqtl	4.9e-02	+1.28	2:6578897:A:G

FANTOM5 promoters

7 alternative TSS:

Promoter ID	TPM avg	Samples expressed
26740	6.1189	650
26739	1.4680	242
26741	0.3306	132
26743	0.1914	78
26742	0.1374	51
26738	0.0936	32
26744	0.0859	41

Top tissues by expression

showing 100 of 255 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	96.63	gold quality
epithelial cell of pancreas	CL:0000083	96.48	gold quality
trabecular bone tissue	UBERON:0002483	95.76	gold quality
decidua	UBERON:0002450	95.52	gold quality
amniotic fluid	UBERON:0000173	93.40	gold quality
jejunal mucosa	UBERON:0000399	93.09	gold quality
bronchial epithelial cell	CL:0002328	92.19	gold quality
ileal mucosa	UBERON:0000331	92.11	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.87	gold quality
endothelial cell	CL:0000115	91.79	gold quality
visceral pleura	UBERON:0002401	91.75	gold quality
bronchus	UBERON:0002185	91.05	gold quality
pigmented layer of retina	UBERON:0001782	89.42	gold quality
bone marrow	UBERON:0002371	89.09	gold quality
middle temporal gyrus	UBERON:0002771	88.77	gold quality
monocyte	CL:0000576	88.76	gold quality
leukocyte	CL:0000738	88.50	gold quality
germinal epithelium of ovary	UBERON:0001304	88.27	gold quality
parietal pleura	UBERON:0002400	88.10	gold quality
epithelium of nasopharynx	UBERON:0001951	87.91	gold quality
heart right ventricle	UBERON:0002080	87.05	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.62	gold quality
tendon of biceps brachii	UBERON:0008188	85.47	gold quality
duodenum	UBERON:0002114	85.43	gold quality
colonic mucosa	UBERON:0000317	84.18	gold quality
caput epididymis	UBERON:0004358	83.83	gold quality
nasal cavity mucosa	UBERON:0001826	83.66	gold quality
lower lobe of lung	UBERON:0008949	83.60	gold quality
mucosa of sigmoid colon	UBERON:0004993	83.28	gold quality
primary visual cortex	UBERON:0002436	83.20	gold quality
placenta	UBERON:0001987	82.74	gold quality
medial globus pallidus	UBERON:0002477	82.66	gold quality
nasal cavity epithelium	UBERON:0005384	82.60	gold quality
parotid gland	UBERON:0001831	82.59	gold quality
apex of heart	UBERON:0002098	82.19	gold quality
jejunum	UBERON:0002115	81.45	gold quality
entorhinal cortex	UBERON:0002728	81.40	gold quality
seminal vesicle	UBERON:0000998	81.20	gold quality
mucosa of paranasal sinus	UBERON:0005030	80.92	gold quality
bone marrow cell	CL:0002092	80.77	gold quality
blood	UBERON:0000178	80.65	gold quality
granulocyte	CL:0000094	80.40	gold quality
left ventricle myocardium	UBERON:0006566	79.91	gold quality
globus pallidus	UBERON:0001875	79.66	gold quality
myocardium	UBERON:0002349	79.55	gold quality
right lung	UBERON:0002167	79.33	gold quality
Brodmann (1909) area 46	UBERON:0006483	79.11	gold quality
occipital lobe	UBERON:0002021	78.92	gold quality
esophagus squamous epithelium	UBERON:0006920	78.89	gold quality
pancreatic ductal cell	CL:0002079	78.76	gold quality
lung	UBERON:0002048	78.73	gold quality
oviduct epithelium	UBERON:0004804	78.34	gold quality
superior frontal gyrus	UBERON:0002661	78.27	gold quality
postcentral gyrus	UBERON:0002581	77.78	gold quality
vermiform appendix	UBERON:0001154	77.72	gold quality
tendon	UBERON:0000043	77.71	gold quality
nucleus accumbens	UBERON:0001882	77.70	gold quality
upper lobe of lung	UBERON:0008948	77.30	gold quality
caudate nucleus	UBERON:0001873	77.28	gold quality
gall bladder	UBERON:0002110	77.01	gold quality
islet of Langerhans	UBERON:0000006	76.99	gold quality
thymus	UBERON:0002370	76.96	gold quality
smooth muscle tissue	UBERON:0001135	76.94	gold quality
putamen	UBERON:0001874	76.90	gold quality
upper lobe of left lung	UBERON:0008952	76.87	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	76.80	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.63	gold quality
penis	UBERON:0000989	76.41	gold quality
lymph node	UBERON:0000029	76.38	gold quality
ganglionic eminence	UBERON:0004023	76.17	gold quality
sural nerve	UBERON:0015488	76.12	gold quality
prefrontal cortex	UBERON:0000451	76.09	gold quality
cardiac muscle of right atrium	UBERON:0003379	76.03	silver quality
thoracic mammary gland	UBERON:0005200	75.93	gold quality
rectum	UBERON:0001052	75.60	gold quality
mammary gland	UBERON:0001911	75.59	gold quality
superficial temporal artery	UBERON:0001614	75.44	gold quality
parietal lobe	UBERON:0001872	75.35	gold quality
caecum	UBERON:0001153	75.29	gold quality
layer of synovial tissue	UBERON:0007616	75.28	gold quality
calcaneal tendon	UBERON:0003701	75.18	gold quality
adipose tissue	UBERON:0001013	75.07	gold quality
urinary bladder	UBERON:0001255	75.06	gold quality
pancreas	UBERON:0001264	75.05	gold quality
cardiac ventricle	UBERON:0002082	75.03	gold quality
tibia	UBERON:0000979	74.95	gold quality
temporal lobe	UBERON:0001871	74.92	gold quality
right uterine tube	UBERON:0001302	74.85	gold quality
heart left ventricle	UBERON:0002084	74.82	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	74.81	silver quality
fallopian tube	UBERON:0003889	74.79	gold quality
cauda epididymis	UBERON:0004360	74.70	gold quality
cerebral cortex	UBERON:0000956	74.64	gold quality
adult organism	UBERON:0007023	74.56	gold quality
forebrain	UBERON:0001890	74.47	gold quality
frontal cortex	UBERON:0001870	74.42	gold quality
Ammon’s horn	UBERON:0001954	74.40	gold quality
neocortex	UBERON:0001950	74.31	gold quality
spleen	UBERON:0002106	74.18	gold quality
mucosa of transverse colon	UBERON:0004991	74.09	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.81
E-GEOD-75367	no	507.06
E-MTAB-7052	no	132.98

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Caudate putamen	tissue	19.0
Frontal cortex	tissue	17.6
Thalamus	tissue	8.9
Superior colliculi	tissue	8.7
Nucleus accumbens	tissue	8.3
Pons	tissue	8.0
Salivary gland	tissue	8.0	low
Cerebral cortex	tissue	7.7	low
Occipital cortex	tissue	7.7
Somatosensory cortex	tissue	7.6
Hypothalamus	tissue	7.5
Putamen	tissue	7.3
Septum	tissue	7.3
Locus coeruleus	tissue	7.2
Prefrontal cortex	tissue	6.9
Midbrain	tissue	6.9
Choroid plexus	tissue	6.7
Basal ganglia	tissue	6.5	medium
Spinal cord	tissue	6.5
Substantia nigra	tissue	6.4
Motor cortex	tissue	6.3
Ventral forebrain	tissue	6.2
Retrosplenial and cingulate cortex	tissue	6.2
Bone marrow	tissue	6.1	low
Hippocampal formation	tissue	6.1
Entorhinal cortex	tissue	6.1
Medulla oblongata	tissue	5.9
Temporal cortex	tissue	5.8
Retrosplenial cortex	tissue	5.7
Postcentral gyrus	tissue	5.6
Insular cortex	tissue	5.3
Hippocampus	tissue	5.2	not detected
Periaqueductal gray	tissue	5.1
Cerebellum	tissue	5.0	low
Olfactory bulb	tissue	5.0
Amygdala	tissue	4.9
Spleen	tissue	3.3	low
Stomach 1	tissue	2.7	medium
Small intestine	tissue	2.1	medium
Corpus callosum	tissue	2.1
Lung	tissue	2.0	medium
Thymus	tissue	1.8
Adipose tissue	tissue	1.7	not detected
Tongue	tissue	1.5
Placenta	tissue	1.5	medium
Duodenum	tissue	1.5	medium
Appendix	tissue	1.4	medium
Lymph node	tissue	1.2	low
Testis	tissue	1.2	medium
Colon	tissue	1.2	medium
Heart muscle	tissue	0.8	low
Parathyroid gland	tissue	0.8	medium
Smooth muscle	tissue	0.8	medium
Liver	tissue	0.8	low
Pituitary gland	tissue	0.7
Seminal vesicle	tissue	0.7	medium
Skeletal muscle	tissue	0.7	medium
Gallbladder	tissue	0.7	medium
Tonsil	tissue	0.7	low
Rectum	tissue	0.6	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Cervical spinal cord, dorsal horn (25.9), Nucleus ambiguus (15.2), Nucleus gracilis (13.0), Nucleus tractus solitarii (12.4), Parvicellular reticular nuclei, medullary (10.9).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CMPK2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 113 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
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-3120-5P	100.00	65.56	965
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502

Functional genomics

gnomAD constraint: pLI 7.16e-13, LOEUF 1.71, missense Z -2.62 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000256722 — one region, missense o/e 1.09.

Literature-anchored findings (GeneRIF, showing 6)

• a human mitochondrial UMP-CMP kinase (UMP-CMPK, cytidylate kinase; EC 2.7.4.14), designated as UMP-CMP kinase 2 (UMP-CMPK2), is identified. (PMID:17999954)
• Upregulated in monocyte/macrophage differentiating cells, suggesting coordinated regulation with the terminal differentiation program. (PMID:18498354)
• Mitochondrial protein CMPK2 regulates IFN alpha-enhanced foam cell formation, potentially contributing to premature atherosclerosis in SLE. (PMID:33874983)
• The mitochondrial gene-CMPK2 functions as a rheostat for macrophage homeostasis. (PMID:36451821)
• CMPK2 restricts Zika virus replication by inhibiting viral translation. (PMID:37075076)
• Microglial CMPK2 promotes neuroinflammation and brain injury after ischemic stroke. (PMID:38701781)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cmpk2	ENSDARG00000031359
mus_musculus	Cmpk2	ENSMUSG00000020638
rattus_norvegicus	Cmpk2	ENSRNOG00000007690
caenorhabditis_elegans		WBGENE00011272

Paralogs (1): DTYMK (ENSG00000168393)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:99830) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 12 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased locomotor activity	1
increased mean corpuscular volume	1
increased circulating cholesterol level	1
increased total body fat amount	1
decreased bone mineral content	1
abnormal mitochondrial ATP synthesis coupled electron transport	1
abnormal mitochondrial crista morphology	1
disorganized mitochondrial cristae	1
decreased cellular ATP level	1
decreased neuron mitochondrial DNA content	1
increased phosphate level	1
calcified brain	1

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
GRASLND	ncRNA	386597
RSAD2	protein-coding	91543
RNF144A	protein-coding	9781
LINC00487	ncRNA	400941
MIR7515	ncRNA	102466235
LINC03156	ncRNA	102800314
NRIR	ncRNA	104326052

Protein

Protein identifiers

UMP-CMP kinase 2, mitochondrial — Q5EBM0 (reviewed: Q5EBM0)

Alternative names: Nucleoside-diphosphate kinase

All UniProt accessions (1): Q5EBM0

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial nucleotide monophosphate kinase needed for salvage dNTP synthesis that mediates immunomodulatory and antiviral activities through IFN-dependent and IFN-independent pathways. Restricts the replication of multiple viruses including flaviviruses or coronaviruses. Together with viperin/RSAD2 and ddhCTP, suppresses the replication of several coronaviruses through inhibition of the viral RNA-dependent RNA polymerase activities. Concerning flaviviruses, restricts RNA translation when localized to the mitochondria independently of its kinase activity. Is able to phosphorylate dUMP, dCMP, CMP, UMP and monophosphates of the pyrimidine nucleoside analogs ddC, dFdC, araC, BVDU and FdUrd with ATP as phosphate donor. Efficacy is highest for dUMP followed by dCMP while CMP and UMP are poor substrates. Controls therefore mitochondrial DNA synthesis by supplying required deoxyribonucleotides. CMPK2-dependent mitochondrial DNA synthesis is necessary for the production of oxidized mitochondrial DNA fragments after exposure to NLRP3 activators. In turn, cytosolic oxidized mtDNA associates with the NLRP3 inflammasome complex and is required for its activation.

Subcellular location. Mitochondrion.

Tissue specificity. High levels are observed in myeloid, lymphoid and mesenchymal tissues.

Disease relevance. Basal ganglia calcification, idiopathic, 10, autosomal recessive (IBGC10) [MIM:621018] A form of basal ganglia calcification, a genetically heterogeneous condition characterized by symmetric calcification in the basal ganglia and other brain regions. Affected individuals can either be asymptomatic or show a wide spectrum of neuropsychiatric symptoms, including parkinsonism, dystonia, tremor, ataxia, dementia, psychosis, seizures, and chronic headache. Serum levels of calcium, phosphate, alkaline phosphatase and parathyroid hormone are normal. The neuropathological hallmark of the disease is vascular and pericapillary calcification, mainly of calcium phosphate, in the affected brain areas. IBGC10 is a progressive form characterized by motor dysfunction, speech impairment, and impaired cognition. The disease may be caused by variants affecting the gene represented in this entry.

Induction. By interferon-alpha. IRF1 is crucial for the transcriptional activation of CMPK2.

Similarity. Belongs to the thymidylate kinase family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q5EBM0-1	1	yes
Q5EBM0-2	2
Q5EBM0-3	3
Q5EBM0-4	4

RefSeq proteins (3): NP_001243406, NP_001243407, NP_997198* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR014505	UMP-CMP_kinase_2	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR039430	Thymidylate_kin-like_dom	Domain

Pfam: PF02223

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)
• dCMP + ATP = dCDP + ADP (RHEA:25094)
• a 2’-deoxyribonucleoside 5’-diphosphate + ATP = a 2’-deoxyribonucleoside 5’-triphosphate + ADP (RHEA:44640)

UniProt features (11 total): splice variant 4, sequence variant 2, transit peptide 1, chain 1, sequence conflict 1, coiled-coil region 1, binding site 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5EBM0-F1	87.26	0.66

Human Protein Atlas

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

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria; nucleoplasm

Antibody reliability (HPA): IH supported · 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 (1)

Position	Role
259–266	ATP

Function

Pathways and Gene Ontology

Reactome pathways

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

MSigDB gene sets: 427 (showing top): chr2p25, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_PYRIMIDINE_NUCLEOSIDE_TRIPHOSPHATE_BIOSYNTHETIC_PROCESS, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (5): dUDP biosynthetic process (GO:0006227), dTDP biosynthetic process (GO:0006233), dTTP biosynthetic process (GO:0006235), pyrimidine nucleotide biosynthetic process (GO:0006221), nucleoside monophosphate phosphorylation (GO:0046940)

GO Molecular Function (12): nucleoside diphosphate kinase activity (GO:0004550), dTMP kinase activity (GO:0004798), ATP binding (GO:0005524), UMP kinase activity (GO:0033862), CMP kinase activity (GO:0036430), dCMP kinase activity (GO:0036431), dUMP kinase activity (GO:0120136), nucleotide binding (GO:0000166), kinase activity (GO:0016301), transferase activity (GO:0016740), deoxynucleoside phosphate kinase activity, ATP as phosphate donor (GO:0047507), nucleoside monophosphate kinase activity (GO:0050145)

GO Cellular Component (2): cytoplasm (GO:0005737), mitochondrion (GO:0005739)

GO top-level categories

27 GO namespaces:

Category	Terms
pyrimidine deoxyribonucleotide biosynthetic process	3
phosphotransferase activity, phosphate group as acceptor	3
nucleobase-containing compound kinase activity	3
deoxynucleoside phosphate kinase activity, ATP as phosphate donor	3
pyrimidine deoxyribonucleoside diphosphate biosynthetic process	2
nucleotide biosynthetic process	2
nucleoside monophosphate kinase activity	2
deoxyribonucleoside diphosphate biosynthetic process	1
dUDP metabolic process	1
dTDP metabolic process	1
deoxyribonucleoside triphosphate biosynthetic process	1
pyrimidine deoxyribonucleoside triphosphate biosynthetic process	1
dTTP metabolic process	1
pyrimidine nucleotide metabolic process	1
pyrimidine-containing compound biosynthetic process	1
nucleoside monophosphate metabolic process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 19 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
mitochondrion	CC	direct assay
UMP kinase activity	MF	direct assay
nucleoside diphosphate kinase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,120 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CMPK2	CMPK1	P30085	907
CMPK2	DTYMK	P23919	897
CMPK2	RSAD2	Q8WXG1	765
CMPK2	NME4	O00746	681
CMPK2	EPSTI1	Q96J88	629
CMPK2	AK4	P27144	622
CMPK2	USP18	Q9UMW8	617
CMPK2	NT5M	Q9NPB1	612
CMPK2	IFIT3	O14879	599
CMPK2	AK3	Q9UIJ7	590
CMPK2	DGUOK	P78532	584
CMPK2	MX1	P20591	575
CMPK2	IFIT1	P09914	573
CMPK2	IFI44	Q8TCB0	564
CMPK2	HERC6	Q8IVU3	556

IntAct

BioGRID (3 interactions; top human partners by supporting records): PARP3 (Proximity Label-MS), SUCLG2 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for CMPK2: 122 ClinVar records (5 pathogenic / likely pathogenic); 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	2
Uncertain significance	98
Likely benign	11
Benign	0

Top pathogenic / likely-pathogenic (5)

Showing all 5 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
4850568	NM_207315.4(CMPK2):c.181del (p.Arg61fs)	Likely pathogenic	criteria provided, single submitter	1
3381199	NM_207315.4(CMPK2):c.2T>C (p.Met1Thr)	Pathogenic	no assertion criteria provided	1
3381200	NM_207315.4(CMPK2):c.1A>C (p.Met1Leu)	Pathogenic	no assertion criteria provided	1
3381201	NM_207315.4(CMPK2):c.1241A>G (p.Tyr414Cys)	Pathogenic	no assertion criteria provided	1
2664507	GRCh37/hg19 2p25.2-25.1(chr2:5689487-7379378)x3	Likely pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CMPK2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 25 predictions of 562):

Position(s)	Effect	Δscore	Sites
2:6861182–6861183	donor_loss	1.0000	5
2:6861386–6861387	acceptor_loss	1.0000	3
2:6863462–6863463	donor_loss	1.0000	5
2:6865020–6865021	donor_loss	1.0000	2
2:6861386–6861387	acceptor_loss	0.9900	3
2:6861395	acceptor_gain	0.9900
2:6863561	acceptor_gain	0.9900
2:6864344	donor_gain	0.9900
2:6865020–6865021	donor_loss	0.9900	3
2:6849751	acceptor_gain	0.9800

AlphaMissense

706 missense substitutions predicted likely pathogenic (of 2,871 scored), across 198 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D261	8	0.984	0.990
D330	8	0.971	0.986
F295	8	0.943	0.987
S335	8	0.923	0.996
F406	8	0.917	0.985
N311	8	0.906	0.991
D296	8	0.870	0.940
F45	8	0.828	0.972
D365	8	0.814	0.921
M417	8	0.807	0.946
K265	7	0.974	0.997
W362	7	0.973	0.996
W333	7	0.961	0.993
R331	7	0.960	0.996
F306	7	0.949	0.991
E258	7	0.948	0.979
R385	7	0.921	0.989
F164	7	0.919	0.975
F213	7	0.919	0.961
E397	7	0.916	0.952

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Stomach Adenocarcinoma)

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Rectum Adenocarcinoma (validation)	favorable	0.000201

Disease associations

OMIM: gene MIM:611787 | disease phenotypes: MIM:621018

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
basal ganglia calcification, idiopathic, 10, autosomal recessive	Limited	Autosomal recessive

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (7 panels, 7 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

7 panels:

Panel	Rating
Hypotonic infant	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Mitochondrial disorders	green
Paediatric disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green
White matter disorders and cerebral calcification - childhood onset	green

Mondo (1): basal ganglia calcification, idiopathic, 10, autosomal recessive (MONDO:0975875)

HPO phenotypes

48 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000012	Urinary urgency
HP:0000298	Mask-like facies
HP:0000709	Psychosis
HP:0000726	Dementia
HP:0000739	Anxiety
HP:0000751	Personality changes
HP:0000802	Impotence
HP:0000822	Hypertension
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001260	Dysarthria
HP:0001266	Choreoathetosis
HP:0001332	Dystonia
HP:0001337	Tremor
HP:0001350	Slurred speech
HP:0002015	Dysphagia
HP:0002063	Rigidity
HP:0002067	Bradykinesia
HP:0002135	Basal ganglia calcification
HP:0002312	Clumsiness
HP:0002315	Headache
HP:0002317	Unsteady gait
HP:0002321	Vertigo
HP:0002344	Progressive neurologic deterioration
HP:0002354	Memory impairment
HP:0002401	Stroke-like episode
HP:0003165	Elevated circulating parathyroid hormone level
HP:0003388	Easy fatigability
HP:0003394	Muscle spasm
HP:0003493	Antinuclear antibody positivity
HP:0003596	Middle age onset
HP:0004305	Involuntary movements
HP:0004363	Abnormal circulating calcium concentration
HP:0007146	Bilateral basal ganglia lesions
HP:0007229	Intracerebral periventricular calcifications
HP:0007256	Abnormal pyramidal sign
HP:0007352	Cerebellar calcifications
HP:0011450	Unusual CNS infection
HP:0011462	Young adult onset
HP:0012229	CSF pleocytosis
HP:0025041	Thalamic calcification
HP:0031627	Globus pallidus calcification
HP:0031987	Diminished ability to concentrate
HP:0032180	Abnormal circulating metabolite concentration
HP:0100529	Abnormal circulating phosphate ion concentration
HP:0100543	Cognitive impairment
HP:0100660	Dyskinesia

GWAS associations

2 associations:

Study	Trait	p-value
GCST007324_119	Adventurousness	7e-10
GCST007325_131	General risk tolerance (MTAG)	2e-9

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0008579	risk-taking behaviour

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, affects methylation, decreases expression, increases expression	4
Valproic Acid	decreases expression, increases expression	4
Estradiol	affects cotreatment, decreases expression, increases expression	3
bisphenol A	decreases expression, increases expression	2
Acetaminophen	decreases expression	2
Lipopolysaccharides	decreases reaction, increases expression, affects binding, increases reaction, affects cotreatment	2
TL8-506	affects cotreatment, increases expression	1
alpha phellandrene	increases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	increases methylation	1
cyclotene	increases expression	1
ferrous chloride	decreases expression	1
nickel sulfate	decreases expression	1
hydroquinone	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression, decreases reaction	1
epigallocatechin gallate	decreases expression	1
ethyl maltol	increases expression	1
2-chloro-5-nitrobenzanilide	decreases reaction, increases expression	1
belinostat	decreases expression	1
bisphenol S	increases expression	1
(+)-JQ1 compound	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Ethanol	increases expression	1
Arsenic	affects methylation	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Cannabidiol	affects binding, increases reaction, decreases expression, decreases reaction, increases expression	1
Carbamazepine	affects expression	1
Chenodeoxycholic Acid	affects cotreatment, increases expression	1
Cisplatin	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1EX	Abcam A-549 CMPK2 KO 2	Cancer cell line	Male
CVCL_B2MF	Abcam A-549 CMPK2 KO 1	Cancer cell line	Male

Clinical trials (associated diseases)

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