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
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 87.4% of screened cell lines
• MANE Select transcript: NM_016308

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: 11 — 9 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000371870, ENST00000371871, ENST00000371873, ENST00000450808, ENST00000471289, ENST00000699074, ENST00000699075, ENST00000873428, ENST00000873429, ENST00000954781, ENST00000954782

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.

FANTOM5 promoters (2 alternative TSS)

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

Top tissues by expression

288 total, 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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

127 targeting CMPK1, 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-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

DepMap (CRISPR cell-line fitness): dependent in 87.4% of screened cell lines.

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)

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, P30085, E9PJD2, 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), 5 shown:

• 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 (35 total): binding site 9, helix 8, 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.

PDB	Method	Resolution (Å)
1TEV	X-RAY DIFFRACTION	2.1
7E9V	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

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

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): 151; 179; 13–18; 39; 61–63; 93–96; 100; 134; 140

Post-translational modifications (6): 33, 43, 55, 106, 180, 73

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-499943	Interconversion of nucleotide di- and triphosphates
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 (15): 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), obsolete (d)CMP kinase activity (GO:0004127), protein binding (GO:0005515), obsolete UMP/dUMP kinase activity (GO:0009041), 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 (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of nucleotides	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
pyrimidine ribonucleotide biosynthetic process	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
nucleoside monophosphate kinase activity	2
transferase activity, transferring phosphorus-containing groups	2
nuclear lumen	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
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
intracellular membraneless organelle	1
intracellular anatomical structure	1
cytoplasm	1
extracellular vesicle	1

Protein interactions and networks

STRING

3263 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CMPK1	DTYMK	P23919	923
CMPK1	CMPK2	Q5EBM0	918
CMPK1	ENTPD5	O75356	832
CMPK1	UCK2	Q9BZX2	799
CMPK1	NT5M	Q9NPB1	761
CMPK1	NME4	O00746	757
CMPK1	ENTPD3	O75355	717
CMPK1	DGUOK	P78532	713
CMPK1	PGD	P52209	704
CMPK1	DCK	P27707	699
CMPK1	FUCA1	P04066	689
CMPK1	ENO1	P06733	689
CMPK1	PGM1	P36871	662
CMPK1	TK2	O00142	643
CMPK1	UMPS	P11172	631

IntAct

34 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CMPK1	TTC19	psi-mi:“MI:0915”(physical association)	0.560
MOK	H1-3	psi-mi:“MI:0914”(association)	0.530
	TK2	psi-mi:“MI:0915”(physical association)	0.400
YWHAZ	CMPK1	psi-mi:“MI:0915”(physical association)	0.400
CMPK1		psi-mi:“MI:0915”(physical association)	0.370
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
KSR1	DDX39A	psi-mi:“MI:0914”(association)	0.350
KSR1	FAM168B	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
SH3GL3	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
ABI1	MYO1C	psi-mi:“MI:0914”(association)	0.350
CAV1	PPM1G	psi-mi:“MI:0914”(association)	0.350
CAV1	ACOT7	psi-mi:“MI:0914”(association)	0.350
PRKD1		psi-mi:“MI:0914”(association)	0.350
CDKN2A	NHERF1	psi-mi:“MI:0914”(association)	0.350
STX17	A2ML1	psi-mi:“MI:0914”(association)	0.350
CDK15	A2ML1	psi-mi:“MI:0914”(association)	0.350
CMPK1	GOT1	psi-mi:“MI:0914”(association)	0.350
RWDD2B	CMPK1	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
MRPL49	UBA6	psi-mi:“MI:0914”(association)	0.350
SMPD2	A2ML1	psi-mi:“MI:0914”(association)	0.350
TTC9C		psi-mi:“MI:0914”(association)	0.350
GPKOW	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
DDX6	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
EIF6	CMPK1	psi-mi:“MI:0915”(physical association)	0.000
CMPK1	TNIK	psi-mi:“MI:0915”(physical association)	0.000
MCC	CMPK1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (135): CMPK1 (Affinity Capture-RNA), CMPK1 (Affinity Capture-RNA), TTC19 (Affinity Capture-MS), CMPK1 (Co-fractionation), CMPK1 (Co-fractionation), ECE2 (Co-fractionation), NIT2 (Co-fractionation), TATDN1 (Co-fractionation), TTC19 (Affinity Capture-MS), CMPK1 (Affinity Capture-RNA), CMPK1 (Proximity Label-MS), CMPK1 (Affinity Capture-MS), CMPK1 (Affinity Capture-MS), CMPK1 (Affinity Capture-MS), SUCLG2 (Co-fractionation)

ESM2 similar proteins: A4W7F8, A8GAV3, B2JDV1, B2T6M4, B2UB85, B4F1Q2, B7MDZ6, B7MQI9, B7NIF6, B7UKF4, C3KEC6, C6DB87, G4V9S0, O04905, O17622, O59771, P00569, P12115, P15700, P20425, P25824, P30085, P43412, Q0TKG7, Q129C6, Q13UR8, Q1LR08, Q20140, Q20230, Q28H12, Q29561, Q2KIW9, Q32J54, Q3Z4S5, Q48F36, Q4KM73, Q4ZWV2, Q5ZKE7, Q6K7H2, Q7N0P5

Diamond homologs: A1KGL4, A1UBR9, A2BTB8, A2BYR7, A2C4Y0, A3PF28, A3PVF5, A4IFD0, A5FMV7, A5GIS6, A5GVX9, A5U0B9, A6GZB9, A6LD69, A8G742, A9BCM8, B0RP52, B0SA26, B0SSF7, B1VEX6, B2FT48, B2KEK1, B2RIY8, B4SI37, B5XCA1, B5YHP1, B6YRA7, C0R000, C1AL67, G4V9S0, O04905, O17622, O24464, O59771, O59845, P00568, P00569, P00570, P00571, P05081

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1207 predictions. Top by Δscore:

Variant	Effect	Δscore
1:47334114:GAGGT:G	donor_loss	1.0000
1:47334115:AGGTG:A	donor_loss	1.0000
1:47334116:GGTGA:G	donor_loss	1.0000
1:47334117:G:C	donor_loss	1.0000
1:47334118:T:G	donor_loss	1.0000
1:47368537:G:GG	donor_gain	1.0000
1:47368573:A:T	donor_gain	1.0000
1:47368612:GAGG:G	donor_gain	1.0000
1:47372951:TTA:T	acceptor_loss	1.0000
1:47372953:A:AG	acceptor_gain	1.0000
1:47372953:AG:A	acceptor_gain	1.0000
1:47372954:G:GC	acceptor_gain	1.0000
1:47372954:GG:G	acceptor_gain	1.0000
1:47372954:GGA:G	acceptor_gain	1.0000
1:47372954:GGAA:G	acceptor_gain	1.0000
1:47372954:GGAAA:G	acceptor_gain	1.0000
1:47373040:G:GT	donor_gain	1.0000
1:47373062:G:GT	donor_gain	1.0000
1:47373062:G:T	donor_gain	1.0000
1:47373063:A:T	donor_gain	1.0000
1:47373066:G:GT	donor_gain	1.0000
1:47373067:C:T	donor_gain	1.0000
1:47373069:G:GT	donor_gain	1.0000
1:47373100:A:AG	donor_gain	1.0000
1:47375192:TGCA:T	acceptor_loss	1.0000
1:47375193:GCAG:G	acceptor_loss	1.0000
1:47375194:CA:C	acceptor_loss	1.0000
1:47375195:A:AC	acceptor_loss	1.0000
1:47375195:A:AG	acceptor_gain	1.0000
1:47375196:G:GG	acceptor_gain	1.0000

AlphaMissense

1516 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000154247 (1:47364548 A>C), RS1000187052 (1:47364270 A>G), RS1000209082 (1:47335751 C>G,T), RS1000246051 (1:47345662 T>G), RS1000336238 (1:47339479 A>G), RS1000394987 (1:47377500 T>C), RS1000413272 (1:47334436 C>T), RS1000460217 (1:47378094 A>G), RS1000477428 (1:47341767 T>A), RS1000549014 (1:47341153 G>A), RS1000583244 (1:47344265 A>G), RS1000809742 (1:47337364 A>G), RS1000829836 (1:47353477 T>C), RS1000875217 (1:47339132 G>A), RS1000893879 (1:47356939 G>A,T)

Disease associations

OMIM: gene MIM:191710 | disease phenotypes: MIM:610256, MIM:107250

GenCC curated gene-disease

Mondo (2): congenital primary aphakia (MONDO:0012456), anterior segment dysgenesis (MONDO:0019503)

Orphanet (2): Congenital primary aphakia (Orphanet:83461), Anterior segment developmental anomaly (Orphanet:88632)

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002502_1	Corneal curvature	3.000000e-12
GCST010696_1	Cortical thickness (min-P)	7.000000e-09
GCST010697_11	Cortical surface area (min-P)	3.000000e-10
GCST010698_70	Subcortical volume (min-P)	1.000000e-14
GCST010699_77	Brain morphology (min-P)	4.000000e-17
GCST010700_17	Cortical thickness (MOSTest)	4.000000e-12
GCST010701_126	Cortical surface area (MOSTest)	1.000000e-10
GCST010702_41	Subcortical volume (MOSTest)	2.000000e-10
GCST010703_86	Brain morphology (MOSTest)	2.000000e-103

EFO canonical traits (3, from GWAS)

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

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537786	Aphakia, congenital primary (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5681 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 6,092 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL2105728	CRENOLANIB	3	2,167
CHEMBL223360	LINIFANIB	3	3,925

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

PharmGKB clinical annotations

5 annotations.

Variant	Type	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

7 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1044457	CMPK1	3	2.50	1	gemcitabine
rs3925058	CMPK1		0.00	0
rs4492666	CMPK1	3	2.50	1	cisplatin;gemcitabine
rs7543016	CMPK1	3	1.75	1	gemcitabine
rs11211524	CMPK1	3	0.75	1	gemcitabine
rs12090346	CMPK1		0.00	0
rs35687416	CMPK1	3	3.25	1	gemcitabine

Binding affinities (BindingDB)

4 measured of 4 human assays (4 total across all organisms); most potent 4 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
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 153 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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, decreases 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	affects cotreatment, affects localization, decreases expression	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
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	increases expression, affects cotreatment	1
Furaldehyde	affects cotreatment, affects localization, increases expression	1
Ivermectin	decreases expression	1
Lead	increases expression	1
Smoke	decreases 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

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06447402	PHASE3	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