CDA

Summary

CDA (cytidine deaminase, HGNC:1712) is a protein-coding gene on chromosome 1p36.12, encoding Cytidine deaminase (P32320). This enzyme scavenges exogenous and endogenous cytidine and 2’-deoxycytidine for UMP synthesis.

This gene encodes an enzyme involved in pyrimidine salvaging. The encoded protein forms a homotetramer that catalyzes the irreversible hydrolytic deamination of cytidine and deoxycytidine to uridine and deoxyuridine, respectively. It is one of several deaminases responsible for maintaining the cellular pyrimidine pool. Mutations in this gene are associated with decreased sensitivity to the cytosine nucleoside analogue cytosine arabinoside used in the treatment of certain childhood leukemias.

Source: NCBI Gene 978 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 14 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001785

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1712
Approved symbol	CDA
Name	cytidine deaminase
Location	1p36.12
Locus type	gene with protein product
Status	Approved
Aliases	CDD
Ensembl gene	ENSG00000158825
Ensembl biotype	protein_coding
OMIM	123920
Entrez	978

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000375071, ENST00000461985, ENST00000904800, ENST00000904801, ENST00000904802, ENST00000916579, ENST00000916580

RefSeq mRNA: 1 — MANE Select: NM_001785 NM_001785

CCDS: CCDS210

Canonical transcript exons

ENST00000375071 — 4 exons

Exon	Start	End
ENSE00001041265	20613842	20613899
ENSE00001465671	20589097	20589283
ENSE00001906111	20618452	20618903
ENSE00003665273	20604928	20605039

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 98.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.2215 / max 2282.4233, expressed in 1095 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1124	22.4902	1062
1123	6.5607	595
1122	0.0871	45
1125	0.0835	37

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	98.01	gold quality
granulocyte	CL:0000094	97.31	gold quality
monocyte	CL:0000576	97.05	gold quality
leukocyte	CL:0000738	96.67	gold quality
mononuclear cell	CL:0000842	96.53	gold quality
blood	UBERON:0000178	96.07	gold quality
bone marrow	UBERON:0002371	96.01	gold quality
right lobe of liver	UBERON:0001114	95.25	gold quality
esophagus mucosa	UBERON:0002469	94.58	gold quality
trabecular bone tissue	UBERON:0002483	94.47	gold quality
bone marrow cell	CL:0002092	94.38	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.34	gold quality
rectum	UBERON:0001052	88.38	gold quality
liver	UBERON:0002107	88.38	gold quality
skin of leg	UBERON:0001511	86.92	gold quality
gingiva	UBERON:0001828	86.83	gold quality
spleen	UBERON:0002106	86.14	gold quality
mucosa of transverse colon	UBERON:0004991	85.94	gold quality
esophagus	UBERON:0001043	85.48	gold quality
tongue squamous epithelium	UBERON:0006919	85.46	silver quality
skin of abdomen	UBERON:0001416	85.45	gold quality
vagina	UBERON:0000996	85.03	gold quality
ileal mucosa	UBERON:0000331	84.99	gold quality
metanephros cortex	UBERON:0010533	84.85	gold quality
transverse colon	UBERON:0001157	84.59	gold quality
oral cavity	UBERON:0000167	84.54	gold quality
zone of skin	UBERON:0000014	84.23	gold quality
gingival epithelium	UBERON:0001949	84.10	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.75	gold quality
ectocervix	UBERON:0012249	83.33	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	1172.23
E-GEOD-109979	yes	98.05
E-MTAB-8410	yes	26.59
E-MTAB-6678	yes	22.85
E-CURD-112	yes	21.29
E-MTAB-9067	yes	10.17
E-MTAB-10042	yes	7.70
E-ANND-3	yes	6.61

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA1

miRNA regulators (miRDB)

15 targeting CDA, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-640	98.44	66.93	644
HSA-MIR-3929	98.32	65.58	1026
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-510-5P	97.66	65.82	916
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-122-5P	97.23	64.92	1024
HSA-MIR-3189-3P	96.80	66.34	896
HSA-MIR-7160-3P	96.40	64.15	462

Literature-anchored findings (GeneRIF, showing 40)

• serum adenosine deaminase and cytidine deaminase levels were significantly higher in systemic lupus erythematosus patients (PMID:12113294)
• The level of CDD mRNA expression varies at the different stage of acute leukemia. The expression level of CDD seems not to be a prognostic factor. (PMID:12844405)
• Intersubunit interactions in human cytidine deaminase using wild and recombinant, amino acid-substituted enzymes (PMID:14565460)
• Understanding the catalytic mechanism by crystallization of the E. coli homolog (PMID:14565461)
• Presence of several GATA1 binding sites in the CDAsf promoter and the uniform detection of GATA1 mutations in DS megakaryocytic leukemia suggested the potential role of GATA1 in regulating CDA transcription. (PMID:14744791)
• analysis of isoenzymatic forms of human cytidine deaminase (PMID:15713780)
• Molecular model of cytidine deaminase. (PMID:16303324)
• Gene transfer increased the resistance of CDD-transduced cord blood and peripheral blood-derived progenitor cells for 20-100 nM cytarabine and 8-10 nM gemcitabine. Protection was observed for progenitors of erythroid as well as myeloid differentiation. (PMID:16304576)
• 6 SNPs ( -92A>G, -205C>G, -451C>T, -897C>A, -1075A>G and -1181G>A) in promoter of CDA may influence Ara-C chemosensitivity. (PMID:16446974)
• Described the identification and characterization of HSCD, which is the product of alternative splicing of the HCD gene (PMID:17464349)
• After gene trasfer of CDA, this enzyme plus 5-fluorocytosine with TRAIL may be useful for the therapy of tumors resistant to TRAIL. (PMID:17479107)
• in the human cytidine deaminase, the side chain of arginine 68 involved in the catalytic process in one subunit active site might come from another subunit (PMID:17640070)
• The role of CDA Lys(27)Lys polymorphism as a possible predictive marker of activity, toxicity, time to progression, and overall survival in advanced NSCLC patients treated with cisplatin and gemcitabine. (PMID:18347182)
• Results provide evidence for a new regulatory mechanism that restricts activation-induced cytidine deaminase activity and can therefore be relevant to prevent B cell malignant transformation. (PMID:18762567)
• In leukoblasts from 82 patients with acute myeloid leukemia, various extent and frequency of differential allelic expression in the CDA, DCK, NT5C2, NT5C3, and TP53 genes was observed. (PMID:18775979)
• The cytidine deaminase 208A genotype is shown to be more sensitive to cytosine arabinoside than the 208G genotype in childhood acute leukemia. (PMID:19035178)
• Homozygous cytidine deaminase, CDA*3, is a major cause of life-threatening toxicities in gemcitabine-treated Japanese cancer patients. (PMID:19293806)
• Single Nucleotide Polymorphism in cytidine deaminase is associated with Acute Myeloid Leukemia. (PMID:19458626)
• Curcumin downregulated Helicobacter pylori induced cytidine deaminase expression in gastric epithelial cells. (PMID:19889077)
• The aim of this study was also to assess the distribution of genotypic variants of CDA in a central Italy population. (PMID:19941076)
• Activation-induced cytidine deaminase expression suggests diffuse large B-cell lymphoma may arise from a putative interfollicular large B cell. (PMID:20196672)
• Compared with their parental cells, the expressions of CDA, RRM1, PTEN and ERCC1 increase in human gemcitabine-resistant non-small cell lung cancer cell lines. (PMID:20211060)
• These investigations reinforced the hypothesis that in human CDA the side chain of Y33 is involved in intersubunit interactions with four glutamate residues forming a double latch that connects each of the two pairs of monomers of the tetrameric CDA. (PMID:20637228)
• the deleted allele of rs3215400 in the promoter of cytidine deaminase shows an increased allele-specific expression and is significantly associated with an increased risk of capecitabine-induced hand-foot syndrome (PMID:21325291)
• Single nucleotide polymorphisms in cytidine deaminase is associated with the pharmacological advantage of prolonged dose rate gemcitabine. (PMID:21332653)
• Aberrant activation-induced cytidine deaminase expression is correlated with persistent inflammatory condition induced by H. pylori infection and may contribute to the development of gastric cancer through an inflammatory condition and intestinalization. (PMID:21538122)
• In conclusion, in this prospective randomized adjuvant study of patients with pancreatic cancer, the cytidine deaminase polymorphism is validated as a predictive marker of gemcitabine hematological toxicity, but not with treatment response or survival (PMID:21625252)
• cytidine deaminase enzymatic activity appears to be the strongest candidate biomarker of activity and efficacy of platinum-gemcitabine-based chemotherapy in advanced non-small-cell lung cancer patients (PMID:21652582)
• Data show that the CDA/DCK ratio was 3 fold higher in non-responders than responders (P<.05), suggesting that this could be a mechanism of primary resistance. (PMID:21858090)
• Cytidine deaminase (CDA) 435 T/T genotype was significantly associated with better response to treatment and the CDA 435 C/T genotype was associated with a significantly increased risk of nonhematological toxicity. (PMID:22052224)
• CDA RNA expression as well as Ara-C IC showed wide variation in AML samples and normal controls. (PMID:22304580)
• Chinese patients carrying A79C variant C allele of CDA were found to be at higher risk of developing severe neutropenia after gemcitabine-based chemotherapy. (PMID:22546611)
• Data indicate cytidine deaminase rapid expression upon doxycycline application in mouse haematopoietic system. (PMID:22592598)
• It is evident that the DCK and CDA polymorphisms might be the important markers for the AML patients’ therapy outcomes in a Chinese population. (PMID:22884143)
• Studied human CDA using site-directed mutagenesis: through these studies it was possible to understand the role exerted by specific amino acid residues in CDA active site and in the contacts between subunits. (PMID:23033855)
• Carriers of the CDA*2B haplotype displayed higher CDA activity. (PMID:23651026)
• Variation in the DPYD, TYMS, CDA and MTHFR genes are clinically significant predictors of fluoropyrimidine toxicity. (PMID:23736036)
• ultrarapid metabolizer patients are nearly five-times more likely to have progressive disease than patients with normal or low CDA activities. (PMID:23837479)
• Macrophages mediate gemcitabine resistance of pancreatic adenocarcinoma by upregulating cytidine deaminase. (PMID:23995783)
• The T70 variant has a lower catalytic efficiency toward the analyzed substrates when compared to the A70 variant, suggesting that patients carrying the 208G>A SNP may have a greater exposure to cytosine based pro drugs (PMID:24183806)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdab	ENSDARG00000038199
danio_rerio	cdaa	ENSDARG00000111188
mus_musculus	Cda	ENSMUSG00000028755
rattus_norvegicus	Cda	ENSRNOG00000015677
caenorhabditis_elegans		WBGENE00000391
caenorhabditis_elegans		WBGENE00000392

Protein

Protein identifiers

Cytidine deaminase — P32320 (reviewed: P32320)

Alternative names: Cytidine aminohydrolase

All UniProt accessions (1): P32320

UniProt curated annotations — full annotation on UniProt →

Function. This enzyme scavenges exogenous and endogenous cytidine and 2’-deoxycytidine for UMP synthesis.

Subunit / interactions. Homotetramer.

Tissue specificity. Highly expressed in granulocytes while expression is very low in fibroblasts, chondrocytes, monocytes, and T- as well as B-cell lines.

Similarity. Belongs to the cytidine and deoxycytidylate deaminase family.

RefSeq proteins (1): NP_001776* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002125	CMP_dCMP_dom	Domain
IPR006262	Cyt_deam_tetra	Family
IPR016192	APOBEC/CMP_deaminase_Zn-bd	Binding_site
IPR016193	Cytidine_deaminase-like	Homologous_superfamily
IPR050202	Cyt/Deoxycyt_deaminase	Family

Pfam: PF00383

Enzyme classification (BRENDA):

• EC 3.5.4.5 — cytidine deaminase (BRENDA: 42 organisms, 92 substrates, 125 inhibitors, 130 Km, 8 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
CYTIDINE	0.0036–6.6	43
DEOXYCYTIDINE	0.0075–8.53	16
2’-DEOXYCYTIDINE	0.023–1.059	11
CYTOSINE ARABINOSIDE	0.058–0.385	11
5-AZACYTIDINE	0.058–2.27	6
5-METHYLCYTIDINE	0.04–1.25	4
1-(2’-DEOXY-2’-FLUORO-BETA-D-ARABINOFURANOSYL)-5	0.31–3.9	3
5-IODODEOXYCYTIDINE	0.087–0.1	3
1-(2’-DEOXY-2’-FLUORO-BETA-D-ARABINOFURANOSYL)CY	0.33–0.66	2
1-BETA-D-ARABINOFURANOSYLCYTOSINE	0.27–0.51	2
2’,2’-DIFLUORODEOXYCYTIDINE	0.0092–0.0957	2
4-AMINO-1-[(2R,3R,4S,5R)-3,4-DIHYDROXY-5-(HYDROX	0.063–0.075	2
4-AMINO-1-[(2R,3R,4S,5R)-3,4-DIHYDROXY-5-(HYDROX	0.034–0.049	2
5,6-DIHYDROCYTIDINE	0.11–0.113	2
7-AMINO-4-[(2R,3R,4S,5R)-3,4-DIHYDROXY-5-(HYDROX	0.0031–0.0044	2

Catalyzed reactions (Rhea), 2 shown:

• 2’-deoxycytidine + H2O + H(+) = 2’-deoxyuridine + NH4(+) (RHEA:13433)
• cytidine + H2O + H(+) = uridine + NH4(+) (RHEA:16069)

UniProt features (21 total): helix 7, strand 5, binding site 4, chain 1, domain 1, turn 1, active site 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1MQ0	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P32320-F1	94.06	0.91

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 67 (proton donor)

Ligand- & substrate-binding residues (4): 54–60; 65; 99; 102

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-73614	Pyrimidine salvage
R-HSA-1430728	Metabolism
R-HSA-15869	Metabolism of nucleotides
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-8956321	Nucleotide salvage

MSigDB gene sets: 216 (showing top): FERRANDO_TAL1_NEIGHBORS, REACTOME_INNATE_IMMUNE_SYSTEM, JAEGER_METASTASIS_DN, GOCC_SECRETORY_GRANULE, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, MODULE_45, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, MODULE_16, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PYRIMIDINE_NUCLEOBASE_METABOLIC_PROCESS

GO Biological Process (10): CMP catabolic process (GO:0006248), dCMP catabolic process (GO:0006249), pyrimidine-containing compound salvage (GO:0008655), cytosine metabolic process (GO:0019858), UMP salvage (GO:0044206), cellular response to external biotic stimulus (GO:0071217), obsolete cytidine deamination (GO:0009972), nucleobase-containing small molecule metabolic process (GO:0055086), pyrimidine-containing compound metabolic process (GO:0072527), carbohydrate derivative metabolic process (GO:1901135)

GO Molecular Function (9): nucleoside binding (GO:0001882), cytidine deaminase activity (GO:0004126), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), catalytic activity (GO:0003824), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (6): extracellular region (GO:0005576), cytosol (GO:0005829), secretory granule lumen (GO:0034774), tertiary granule lumen (GO:1904724), ficolin-1-rich granule lumen (GO:1904813), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Innate Immune System	1
Nucleotide salvage	1
Metabolism	1
Immune System	1
Metabolism of nucleotides	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
metabolic process	2
intracellular organelle lumen	2
pyrimidine ribonucleoside monophosphate catabolic process	1
pyrimidine ribonucleotide catabolic process	1
CMP metabolic process	1
pyrimidine deoxyribonucleoside monophosphate catabolic process	1
pyrimidine deoxyribonucleotide catabolic process	1
dCMP metabolic process	1
metabolic compound salvage	1
pyrimidine-containing compound biosynthetic process	1
pyrimidine nucleobase metabolic process	1
UMP biosynthetic process	1
pyrimidine ribonucleotide salvage	1
response to external biotic stimulus	1
cellular response to biotic stimulus	1
cellular response to external stimulus	1
nucleobase-containing compound metabolic process	1
small molecule metabolic process	1
carbohydrate derivative binding	1
heterocyclic compound binding	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amidines	1
deaminase activity	1
transition metal ion binding	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
molecular_function	1
binding	1
catalytic activity	1
cation binding	1
cytoplasm	1
secretory granule	1
cytoplasmic vesicle lumen	1
tertiary granule	1
ficolin-1-rich granule	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1993 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDA	APOBEC1	P41238	967
CDA	APOBEC3G	Q9HC16	945
CDA	DCK	P27707	941
CDA	APOBEC3A	P31941	917
CDA	DCTD	P32321	910
CDA	APOBEC3B	Q9UH17	883
CDA	APOBEC3H	Q6NTF7	868
CDA	APOBEC3D	Q96AK3	866
CDA	APOBEC3C	Q9NRW3	865
CDA	APOBEC4	Q8WW27	848
CDA	APOBEC2	Q9Y235	840
CDA	APOBEC3F	Q8IUX4	835
CDA	AICDA	Q9GZX7	782
CDA	UNG	P13051	735
CDA	TYMP	P19971	718

IntAct

87 interactions, top by confidence:

A	B	Type	Score
LNX1	CDA	psi-mi:“MI:0915”(physical association)	0.810
CDA	LNX1	psi-mi:“MI:0915”(physical association)	0.810
CDA	NTAQ1	psi-mi:“MI:0915”(physical association)	0.780
NTAQ1	CDA	psi-mi:“MI:0915”(physical association)	0.780
CDA	SDCBP	psi-mi:“MI:0915”(physical association)	0.720
CDA	ZBTB24	psi-mi:“MI:0915”(physical association)	0.720
PLEKHB2	CDA	psi-mi:“MI:0915”(physical association)	0.720
CDA	FNDC11	psi-mi:“MI:0915”(physical association)	0.720
SDCBP	CDA	psi-mi:“MI:0915”(physical association)	0.720
CDA	PLEKHB2	psi-mi:“MI:0915”(physical association)	0.720
FNDC11	CDA	psi-mi:“MI:0915”(physical association)	0.720
ZBTB24	CDA	psi-mi:“MI:0915”(physical association)	0.720
CDA	CDA	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (69): PSMA1 (Two-hybrid), PTGER3 (Two-hybrid), SDCBP (Two-hybrid), ZBTB24 (Two-hybrid), PLEKHB2 (Two-hybrid), WDYHV1 (Two-hybrid), C20orf195 (Two-hybrid), LNX1 (Two-hybrid), CDA (Co-fractionation), CDA (Co-fractionation), CLIC4 (Co-fractionation), CPNE1 (Co-fractionation), CPNE3 (Co-fractionation), DPYSL2 (Co-fractionation), EVPL (Co-fractionation)

ESM2 similar proteins: A0A1F3, A6QPU5, O95671, P00338, P00339, P11172, P13439, P13491, P17256, P19356, P19858, P22907, P28492, P31754, P32320, P33571, P56389, P79913, Q01415, Q03426, Q0P4H0, Q0V9A9, Q3TY86, Q4R3Y4, Q4V7V8, Q501L1, Q571F8, Q5R1W9, Q5R514, Q5R5F0, Q5R824, Q5RDY4, Q5RFI8, Q5RIV4, Q5XIG6, Q68FH4, Q6P1M0, Q7TSV4, Q8GWU0, Q91VE0

Diamond homologs: A5F1V7, C3LLS7, O65896, P0CI02, P19079, P32320, P33967, P47718, P56389, P75051, P9WPH2, P9WPH3, Q06549, Q09190, Q2NUD2, Q54I82, Q7N6K3, Q9CP11, Q9KD53, Q9KSM5, Q9S3M0, Q9S789, Q9XEX4, A8GC32, B4ESY3, B5FEN2, B7VPF1, C6DDS7, P47298, Q5E4R6, Q6LRI0, A1AD04, A7ZNW5, A8A204, B1IYC6, B1LKP0, B1X7N2, B2TVV2, B2VIF3, B5YW75

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CDA	“down-regulates quantity”	water	“chemical modification”
CDA	“up-regulates quantity”	uridine	“chemical modification”
CDA	“down-regulates quantity”	cytidine	“chemical modification”
CDA	“down-regulates quantity”	2’-deoxycytidine	“chemical modification”
CDA	“up-regulates quantity”	2’-deoxyuridine	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

880 predictions. Top by Δscore:

Variant	Effect	Δscore
1:20618450:A:AG	acceptor_gain	1.0000
1:20618451:G:GA	acceptor_gain	1.0000
1:20589207:G:GT	donor_gain	0.9900
1:20589265:G:GT	donor_gain	0.9900
1:20589279:CAAAG:C	donor_loss	0.9900
1:20589280:AAAG:A	donor_loss	0.9900
1:20589281:AAGGT:A	donor_loss	0.9900
1:20589282:AGGTA:A	donor_loss	0.9900
1:20589283:GGTAA:G	donor_loss	0.9900
1:20589284:GTAAA:G	donor_loss	0.9900
1:20589285:T:A	donor_loss	0.9900
1:20604926:AG:A	acceptor_gain	0.9900
1:20604927:GG:G	acceptor_gain	0.9900
1:20613840:A:AG	acceptor_gain	0.9900
1:20613841:G:GG	acceptor_gain	0.9900
1:20616723:A:G	donor_gain	0.9900
1:20618450:AGTTT:A	acceptor_gain	0.9900
1:20618451:GTTT:G	acceptor_gain	0.9900
1:20618451:GTTTG:G	acceptor_gain	0.9900
1:20589269:G:T	donor_gain	0.9800
1:20604922:TCTCA:T	acceptor_loss	0.9800
1:20604923:CTCAG:C	acceptor_loss	0.9800
1:20604925:CA:C	acceptor_loss	0.9800
1:20604927:G:T	acceptor_loss	0.9800
1:20618446:TTCCA:T	acceptor_loss	0.9800
1:20618447:TCCA:T	acceptor_loss	0.9800
1:20618448:CCA:C	acceptor_loss	0.9800
1:20618449:CAGTT:C	acceptor_loss	0.9800
1:20618450:AG:A	acceptor_loss	0.9800
1:20618451:G:GT	acceptor_loss	0.9800

AlphaMissense

954 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:20618536:T:C	F137L	0.994
1:20618538:T:A	F137L	0.994
1:20618538:T:G	F137L	0.994
1:20589247:G:C	A40P	0.989
1:20613884:G:C	R103S	0.989
1:20613884:G:T	R103S	0.989
1:20604976:G:C	R68P	0.988
1:20604940:A:T	E56V	0.986
1:20604994:C:A	A74D	0.986
1:20613883:G:C	R103T	0.986
1:20604970:C:A	A66D	0.985
1:20604974:A:C	E67D	0.985
1:20604974:A:T	E67D	0.985
1:20618452:T:C	F109L	0.985
1:20618454:T:A	F109L	0.985
1:20618454:T:G	F109L	0.985
1:20604944:T:A	N57K	0.984
1:20604944:T:G	N57K	0.984
1:20604966:T:C	C65R	0.984
1:20604982:C:A	A70D	0.983
1:20604993:G:C	A74P	0.983
1:20589250:G:C	A41P	0.982
1:20605023:G:C	A84P	0.982
1:20604935:C:A	N54K	0.981
1:20604935:C:G	N54K	0.981
1:20604981:G:C	A70P	0.981
1:20613883:G:T	R103M	0.980
1:20589283:G:T	G52W	0.979
1:20605030:C:A	A86D	0.979
1:20613870:T:C	C99R	0.979

dbSNP variants (sampled 300 via entrez): RS1000001457 (1:20607890 G>A), RS1000166590 (1:20600787 A>C), RS1000177680 (1:20603175 A>G), RS1000266307 (1:20591113 G>A), RS1000406349 (1:20596412 C>A,T), RS1000466426 (1:20616912 A>G,T), RS1000467415 (1:20603307 T>C), RS1000623840 (1:20597184 C>T), RS1000667811 (1:20595530 G>A), RS1000842768 (1:20603569 T>C), RS1000936613 (1:20591303 T>G), RS1001047278 (1:20615032 T>C), RS1001048056 (1:20608912 T>C), RS1001067926 (1:20615872 C>T), RS1001440321 (1:20615579 T>C)

Disease associations

OMIM: gene MIM:123920 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST004602_4	Mean corpuscular volume	4.000000e-09
GCST005352_14	Paclitaxel disposition in epithelial ovarian cancer	6.000000e-07
GCST009733_126	Urinary metabolite levels in chronic kidney disease	2.000000e-17
GCST010241_9	Apolipoprotein A1 levels	3.000000e-19
GCST010916_1	Proportion of activated microglia (inferior temporal cortex)	6.000000e-06
GCST012020_27	Serum metabolite levels	9.000000e-15
GCST90002380_76	Basophil percentage of white cells	3.000000e-09
GCST90002388_285	Lymphocyte count	2.000000e-13
GCST90002389_79	Lymphocyte percentage of white cells	3.000000e-13
GCST90002390_587	Mean corpuscular hemoglobin	7.000000e-14
GCST90002392_150	Mean corpuscular volume	2.000000e-27
GCST90002396_113	Mean reticulocyte volume	5.000000e-53
GCST90002397_172	Mean spheric corpuscular volume	7.000000e-46
GCST90002399_27	Neutrophil percentage of white cells	2.000000e-09
GCST90002403_35	Red blood cell count	5.000000e-12
GCST90002405_590	Reticulocyte count	7.000000e-12
GCST90011900_28	Serum alkaline phosphatase levels	3.000000e-17

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0005116	urinary metabolite measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0007992	basophil percentage of leukocytes
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004305	erythrocyte count
EFO:0007986	reticulocyte count
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4502 (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: 338 (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
CHEMBL3237547	CEDAZURIDINE	4	310
CHEMBL2311128	TETRAHYDROURIDINE	2	28

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

PharmGKB clinical annotations

16 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1048977	Other	3	gemcitabine	Neoplasms
rs1048977	Toxicity	3	capecitabine	Hyperbilirubinemia;Neoplasms
rs2072671	Toxicity	3	cytarabine	Leukemia;Lymphoma
rs2072671	Toxicity	3	capecitabine	Neoplasms
rs2072671	Toxicity	3	gemcitabine	Mesothelioma;Non-Small Cell Lung Carcinoma;Pancreatic Neoplasms
rs2072671	Toxicity	3	gemcitabine;paclitaxel	Nausea;Pancreatic Neoplasms
rs3215400	Toxicity	3	cytarabine
rs3215400	Toxicity	3	capecitabine	Hand-foot syndrome;Neoplasms
rs4655226	Metabolism/PK	3	difluorodeoxyuridine	Neoplasms
rs471760	Toxicity	3	gemcitabine	Neutropenia;Pancreatic Neoplasms
rs532545	Efficacy	3	cytarabine	Leukemia;Myeloid;Acute;Neoplasms
rs532545	Toxicity	3	cytarabine	Leukemia;Myeloid
rs602950	Toxicity	3	cytarabine
rs602950	Toxicity	3	capecitabine	Neoplasms
rs60369023	Other	3	cytarabine
rs60369023	Toxicity	3	gemcitabine	Neoplasms;Neutropenia

PharmGKB variants

12 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs532545	CDA	3	6.50	2	cytarabine
rs602950	CDA	3	3.50	2	capecitabine;cytarabine
rs818194	CDA		0.00	0
rs1048977	CDA	3	2.75	2	gemcitabine;capecitabine
rs2072671	CDA	3	7.00	4	capecitabine;cytarabine;gemcitabine;paclitaxel;gemcitabine
rs3215400	CDA	3	4.00	2	cytarabine;capecitabine
rs4655226	CDA	3	1.00	1	difluorodeoxyuridine
rs60369023	CDA	3	1.50	2	gemcitabine;cytarabine
rs6690069	CDA		0.00	0
rs10916825	CDA		0.00	0
rs12404655	CDA		0.00	0
rs471760	CDA	3	2.25	1	gemcitabine

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Pyrimidine salvage

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
cedazuridine	Inhibition	6.4	pIC50

Binding affinities (BindingDB)

14 measured of 14 human assays (14 total across all organisms); most potent 14 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4,7-dihydro-1H-1,3-diazepin-2-one	IC50	101 nM	US-9040501: Compositions and methods for treating cancer
1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one	IC50	113 nM	US-9040501: Compositions and methods for treating cancer
3-[(2R,3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4,7-dihydro-1H-1,3-diazepin-2-one	IC50	140 nM	US-9040501: Compositions and methods for treating cancer
(4R)-1-[(3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one	IC50	200 nM	US-8618075: Certain compounds, compositions and methods
3-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4,7-dihydro-1H-1,3-diazepin-2-one	IC50	237 nM	US-9040501: Compositions and methods for treating cancer
(4R)-1-[(4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one	IC50	400 nM	US-8618075: Certain compounds, compositions and methods
1-[(4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one	IC50	400 nM	US-8618075: Certain compounds, compositions and methods
(4R)-1-[(3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one	IC50	400 nM	US-8618075: Certain compounds, compositions and methods
3-[(2S,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4,7-dihydro-1H-1,3-diazepin-2-one	IC50	1620 nM	US-9040501: Compositions and methods for treating cancer
1-[(3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one	IC50	2000 nM	US-8618075: Certain compounds, compositions and methods
1-[(3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one	IC50	2000 nM	US-8618075: Certain compounds, compositions and methods
(4S)-1-[(3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one	IC50	4000 nM	US-8618075: Certain compounds, compositions and methods
(4S)-1-[(4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one	IC50	5000 nM	US-8618075: Certain compounds, compositions and methods
(4S)-1-[(3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one	IC50	5000 nM	US-8618075: Certain compounds, compositions and methods

ChEMBL bioactivities

35 potent at pChembl≥5 of 42 total, top 31 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.60	Ki	25	nM	CHEMBL610997
7.40	Ki	40	nM	CHEMBL2311129
7.00	IC50	101	nM	CHEMBL3658871
7.00	Ki	100	nM	TETRAHYDROURIDINE
6.95	IC50	113	nM	TETRAHYDROURIDINE
6.85	IC50	140	nM	CHEMBL3658873
6.70	IC50	200	nM	CHEMBL3237548
6.70	IC50	200	nM	CHEMBL3665107
6.62	IC50	237	nM	CHEMBL3658870
6.47	IC50	340	nM	TETRAHYDROURIDINE
6.40	Ki	400	nM	CHEMBL2367576
6.40	Ki	400	nM	TETRAHYDROURIDINE
6.40	IC50	400	nM	CEDAZURIDINE
6.40	IC50	400	nM	CHEMBL3237549
6.40	IC50	400	nM	CHEMBL3665106
6.40	IC50	400	nM	CHEMBL3665108
6.40	IC50	400	nM	CHEMBL3665114
6.05	Ki	900	nM	CHEMBL2311129
5.79	IC50	1616	nM	CHEMBL3658872
5.70	Ki	2000	nM	ZEBULARINE
5.70	IC50	2000	nM	CHEMBL3665110
5.70	IC50	2000	nM	CHEMBL3665111
5.64	Ki	2300	nM	ZEBULARINE
5.55	Ki	2800	nM	CHEMBL608656
5.40	IC50	4000	nM	CHEMBL3237551
5.40	IC50	4000	nM	CHEMBL3665109
5.30	IC50	5000	nM	CHEMBL3237550
5.30	IC50	5000	nM	CHEMBL3237552
5.30	IC50	5000	nM	CHEMBL3665112
5.30	IC50	5000	nM	CHEMBL3665113
5.05	Ki	9000	nM	CHEMBL608479

PubChem BioAssay actives

22 with measured affinity, of 86 total; 14 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
Uridine	55389: Compound was tested for its binding affinity against cytidine deaminase.	ki	<0.0001	uM
3-[(3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4,7-dihydro-1H-1,3-diazepin-2-one	238723: Binding affinity for human cytidine deaminase	ki	0.0250	uM
1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-hydroxy-1,3-diazepan-2-one	55376: Binding affinity against cytidine deaminase of human liver	ki	0.0400	uM
1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one	55378: Cytidine Deaminase Inhibition in human liver	ki	0.1000	uM
(4R)-1-[(2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one	1128123: Inhibition of human recombinant cytidine deaminase assessed as cytidine to uridine formation	ic50	0.2000	uM
1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3-diazepan-2-one	238723: Binding affinity for human cytidine deaminase	ki	0.4000	uM
(4R)-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one	1128123: Inhibition of human recombinant cytidine deaminase assessed as cytidine to uridine formation	ic50	0.4000	uM
(4R)-1-[(2R,3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one	1128123: Inhibition of human recombinant cytidine deaminase assessed as cytidine to uridine formation	ic50	0.4000	uM
1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one	238723: Binding affinity for human cytidine deaminase	ki	2.0000	uM
4-[(3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]piperazin-2-one	55376: Binding affinity against cytidine deaminase of human liver	ki	2.8000	uM
(4S)-1-[(2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one	1128123: Inhibition of human recombinant cytidine deaminase assessed as cytidine to uridine formation	ic50	4.0000	uM
(4S)-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one	1128123: Inhibition of human recombinant cytidine deaminase assessed as cytidine to uridine formation	ic50	5.0000	uM
(4S)-1-[(2R,3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one	1128123: Inhibition of human recombinant cytidine deaminase assessed as cytidine to uridine formation	ic50	5.0000	uM
1-[(3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3-diazepane-2,5-dione	55378: Cytidine Deaminase Inhibition in human liver	ki	9.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment	4
sodium arsenite	increases expression, affects cotreatment, decreases expression, increases abundance	3
sulforaphane	decreases expression, increases expression	2
entinostat	increases expression, affects cotreatment	2
Gemcitabine	affects response to substance, affects cotreatment, decreases expression, increases response to substance	2
Benzo(a)pyrene	increases methylation, affects methylation, increases expression	2
Estradiol	affects expression, affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Silicon Dioxide	increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Cyclosporine	increases expression, affects expression	2
Aflatoxin B1	decreases methylation, increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
5-fluorocytidine	increases metabolic processing	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
brequinar	increases expression	1
celastrol	increases expression	1
di-n-butylphosphoric acid	affects expression	1
diazepinone riboside	affects binding, decreases activity	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
gardiquimod	decreases expression, decreases reaction	1
(+)-JQ1 compound	decreases expression	1
Oxaliplatin	affects cotreatment, affects response to substance	1
Decitabine	increases degradation	1
Crizotinib	decreases expression, increases response to substance	1

ChEMBL screening assays

32 unique, capped per target: 17 binding, 15 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1051085	Binding	Activity of cloned cytidine deaminase in human HuH7 cells by spectrophotometric analysis	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
CHEMBL3132551	ADMET	Drug degradation assessed as recombinant human cytidine deaminase-mediated dFdU formation at 100 uM measured at 30 mins by UV absorption spectroscopic analysis	Application of ProTide technology to gemcitabine: a successful approach to overcome the key cancer resistance mechanisms leads to a new agent (NUC-1031) in clinical development. — J Med Chem

Cellosaurus cell lines

7 cell lines: 7 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1VN	Abcam A-549 CDA KO	Cancer cell line	Male
CVCL_D2A8	Abcam HCT 116 CDA KO	Cancer cell line	Male
CVCL_E1TC	HAP1 CDA (-) 1	Cancer cell line	Male
CVCL_E1TD	HAP1 CDA (-) 2	Cancer cell line	Male
CVCL_E1TE	HAP1 CDA (-) 3	Cancer cell line	Male
CVCL_E1TF	HAP1 CDA (-) 4	Cancer cell line	Male
CVCL_E1TG	HAP1 CDA (-) 5	Cancer cell line	Male

Clinical trials (associated diseases)

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