NT5C

Summary

NT5C (5’, 3’-nucleotidase, cytosolic, HGNC:17144) is a protein-coding gene on chromosome 17q25, encoding 5’(3’)-deoxyribonucleotidase, cytosolic type (Q8TCD5). Dephosphorylates the 5’ and 2’(3’)-phosphates of deoxyribonucleotides, with a preference for dUMP (Ref.12).

This gene encodes a nucleotidase that catalyzes the dephosphorylation of the 5’ deoxyribonucleotides (dNTP) and 2’(3’)-dNTP and ribonucleotides, but not 5’ ribonucleotides. Of the different forms of nucleotidases characterized, this enzyme is unique in its preference for 5’-dNTP. It may be one of the enzymes involved in regulating the size of dNTP pools in cells. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 30833 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 25 total
• GTEx eGene: eQTL in 33 tissues, sQTL in 11 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.19 (unconstrained)
• MANE Select transcript: NM_014595

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17144
Approved symbol	NT5C
Name	5’, 3’-nucleotidase, cytosolic
Location	17q25
Locus type	gene with protein product
Status	Approved
Aliases	DNT1, DNT-1, PN-I, cdN, dNT-1
Ensembl gene	ENSG00000125458
Ensembl biotype	protein_coding
OMIM	191720
Entrez	30833

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 15 protein_coding, 5 retained_intron, 5 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000245552

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 8, TSL 3: 5

ENST00000245552, ENST00000577523, ENST00000578095, ENST00000578337, ENST00000578407, ENST00000579023, ENST00000579082, ENST00000580423, ENST00000580758, ENST00000582160, ENST00000582170, ENST00000582744, ENST00000583655, ENST00000584352, ENST00000876511, ENST00000876512, ENST00000876513, ENST00000954192, ENST00001007611, ENST00001018397, ENST00001018399, ENST00001018400, ENST00001018402, ENST00001018403, ENST00001088574, ENST00001143739

RefSeq mRNA: 2 — MANE Select: NM_014595 NM_001252377, NM_014595

CCDS: CCDS11715

Canonical transcript exons

ENST00000245552 — 5 exons

Exon	Start	End
ENSE00000744348	75131045	75131105
ENSE00001174732	75131534	75131742
ENSE00003519493	75130228	75130642
ENSE00003541934	75131181	75131281
ENSE00003675341	75130753	75130867

Expression profiles

Bgee: expression breadth ubiquitous, 225 present calls, max score 97.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.7968 / max 208.4856, expressed in 1806 samples.

Highest expression (Bgee): mucosa of transverse colon, transverse colon, small intestine Peyer’s patch, uterine tube, granulocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

NT5C is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 33 tissues and its splicing (sQTL) in 11 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 44 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	3.5e-21	-0.23	17:75131588:T:C
Esophagus Muscularis	eqtl	5.7e-20	-0.23	17:75131588:T:C
Nerve Tibial	eqtl	2.1e-18	+0.20	17:75126986:C:T
Artery Tibial	eqtl	5.5e-18	+0.20	17:75131122:G:C
Testis	eqtl	9.2e-16	-0.25	17:75131588:T:C
Esophagus Gastroesophageal Junction	eqtl	3.0e-14	+0.26	17:75176431:T:C
Spleen	eqtl	7.3e-14	+0.26	17:75131122:G:C
Adipose Subcutaneous	eqtl	1.2e-11	+0.20	17:75131122:G:C
Whole Blood	eqtl	4.4e-11	+0.75	17:75131751:C:T
Adipose Visceral Omentum	eqtl	1.9e-10	+0.20	17:75131122:G:C
Lung	eqtl	2.1e-10	+0.17	17:75175355:C:T
Esophagus Mucosa	eqtl	2.2e-09	+0.63	17:75131751:C:T
Skin Sun Exposed Lower leg	eqtl	2.6e-09	+0.81	17:75131751:C:T
Skin Not Sun Exposed Suprapubic	eqtl	1.2e-08	+0.74	17:75200359:C:T
Breast Mammary Tissue	eqtl	1.5e-08	-0.18	17:75187691:A:G
Pituitary	eqtl	1.5e-08	+0.25	17:75146065:G:T
Prostate	eqtl	1.5e-07	+0.24	17:75126986:C:T
Colon Sigmoid	eqtl	4.9e-07	+0.18	17:75131122:G:C
Cells Cultured fibroblasts	eqtl	7.7e-07	+0.16	17:75176617:AAAC:A
Muscle Skeletal	eqtl	7.7e-07	+0.17	17:75126986:C:T

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
168036	24.4431	1804
168035	2.5667	1419
168033	0.8643	571
168034	0.4812	272
168037	0.4415	233

Top tissues by expression

showing 100 of 259 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	97.03	gold quality
transverse colon	UBERON:0001157	95.79	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.58	gold quality
right uterine tube	UBERON:0001302	95.32	gold quality
granulocyte	CL:0000094	95.29	gold quality
mucosa of stomach	UBERON:0001199	95.12	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.05	gold quality
lower esophagus mucosa	UBERON:0035834	95.04	gold quality
left ovary	UBERON:0002119	94.64	gold quality
right lobe of thyroid gland	UBERON:0001119	94.52	gold quality
right ovary	UBERON:0002118	94.52	gold quality
ectocervix	UBERON:0012249	94.52	gold quality
body of stomach	UBERON:0001161	94.50	gold quality
left lobe of thyroid gland	UBERON:0001120	94.46	gold quality
metanephros cortex	UBERON:0010533	94.36	gold quality
endocervix	UBERON:0000458	94.23	gold quality
tibial nerve	UBERON:0001323	94.13	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.88	gold quality
body of uterus	UBERON:0009853	93.84	gold quality
right lung	UBERON:0002167	93.71	gold quality
lower esophagus	UBERON:0013473	93.67	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.67	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.60	gold quality
esophagus mucosa	UBERON:0002469	93.51	gold quality
ventricular zone	UBERON:0003053	93.41	gold quality
small intestine	UBERON:0002108	93.30	gold quality
esophagus	UBERON:0001043	93.29	gold quality
left uterine tube	UBERON:0001303	93.29	gold quality
right coronary artery	UBERON:0001625	93.05	gold quality
left coronary artery	UBERON:0001626	93.05	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.02	gold quality
spleen	UBERON:0002106	93.00	gold quality
skin of leg	UBERON:0001511	92.69	gold quality
thyroid gland	UBERON:0002046	92.65	gold quality
tibial artery	UBERON:0007610	92.62	gold quality
left adrenal gland cortex	UBERON:0035825	92.62	gold quality
popliteal artery	UBERON:0002250	92.60	gold quality
cerebellar hemisphere	UBERON:0002245	92.59	gold quality
right atrium auricular region	UBERON:0006631	92.58	gold quality
cerebellar cortex	UBERON:0002129	92.53	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.36	gold quality
apex of heart	UBERON:0002098	92.28	gold quality
upper lobe of left lung	UBERON:0008952	92.24	gold quality
left adrenal gland	UBERON:0001234	92.20	gold quality
aorta	UBERON:0000947	92.16	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.15	gold quality
body of pancreas	UBERON:0001150	92.13	gold quality
skin of abdomen	UBERON:0001416	92.09	gold quality
right adrenal gland	UBERON:0001233	91.99	gold quality
ascending aorta	UBERON:0001496	91.89	gold quality
thoracic aorta	UBERON:0001515	91.88	gold quality
colon	UBERON:0001155	91.86	gold quality
coronary artery	UBERON:0001621	91.86	gold quality
stomach	UBERON:0000945	91.75	gold quality
minor salivary gland	UBERON:0001830	91.75	gold quality
gastrocnemius	UBERON:0001388	91.69	gold quality
intestine	UBERON:0000160	91.59	gold quality
omental fat pad	UBERON:0010414	91.55	gold quality
right adrenal gland cortex	UBERON:0035827	91.55	gold quality
peritoneum	UBERON:0002358	91.50	gold quality
large intestine	UBERON:0000059	91.40	gold quality
muscle of leg	UBERON:0001383	91.22	gold quality
calcaneal tendon	UBERON:0003701	91.22	gold quality
adenohypophysis	UBERON:0002196	91.05	gold quality
adrenal cortex	UBERON:0001235	91.00	gold quality
descending thoracic aorta	UBERON:0002345	90.91	gold quality
right lobe of liver	UBERON:0001114	90.67	gold quality
adipose tissue of abdominal region	UBERON:0007808	90.67	gold quality
cerebellum	UBERON:0002037	90.63	gold quality
ganglionic eminence	UBERON:0004023	90.63	gold quality
cardiac atrium	UBERON:0002081	90.62	gold quality
vagina	UBERON:0000996	89.98	gold quality
spinal cord	UBERON:0002240	89.95	gold quality
mouth mucosa	UBERON:0003729	89.93	gold quality
ovary	UBERON:0000992	89.90	gold quality
saliva-secreting gland	UBERON:0001044	89.89	gold quality
adrenal gland	UBERON:0002369	89.76	gold quality
subcutaneous adipose tissue	UBERON:0002190	89.69	gold quality
upper lobe of lung	UBERON:0008948	89.51	gold quality
heart left ventricle	UBERON:0002084	89.49	gold quality
rectum	UBERON:0001052	89.36	gold quality
heart	UBERON:0000948	89.05	gold quality
cardiac ventricle	UBERON:0002082	89.03	gold quality
pituitary gland	UBERON:0000007	88.98	gold quality
zone of skin	UBERON:0000014	88.91	gold quality
lymph node	UBERON:0000029	88.88	gold quality
fundus of stomach	UBERON:0001160	88.87	gold quality
tendon	UBERON:0000043	88.84	gold quality
monocyte	CL:0000576	88.58	gold quality
prostate gland	UBERON:0002367	88.51	gold quality
stromal cell of endometrium	CL:0002255	88.29	gold quality
leukocyte	CL:0000738	87.96	gold quality
amygdala	UBERON:0001876	87.94	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.91	gold quality
mononuclear cell	CL:0000842	87.85	gold quality
pancreas	UBERON:0001264	87.41	gold quality
right frontal lobe	UBERON:0002810	87.36	gold quality
anterior cingulate cortex	UBERON:0009835	87.14	gold quality
cingulate cortex	UBERON:0003027	87.08	gold quality
adipose tissue	UBERON:0001013	87.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-114	yes	58.99
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Frontal cortex	tissue	51.3
Vagina	tissue	35.0	not detected
Caudate putamen	tissue	30.5
Small intestine	tissue	26.8	medium
Skeletal muscle	tissue	24.9	not detected
Colon	tissue	23.2	medium
Duodenum	tissue	23.0	medium
Stomach 1	tissue	22.4	medium
Ovary	tissue	20.3	medium
Pituitary gland	tissue	19.0
Spleen	tissue	18.7	low
Lymph node	tissue	17.2	low
Appendix	tissue	16.9	medium
Pancreas	tissue	15.8	medium
Bone marrow	tissue	15.3	low
Tongue	tissue	15.0
Thymus	tissue	14.9
Seminal vesicle	tissue	14.4	low
Salivary gland	tissue	14.4	low
Tonsil	tissue	14.2	medium
Adrenal gland	tissue	14.1	low
Fallopian tube	tissue	13.7	medium
Kidney	tissue	13.2	medium
Heart muscle	tissue	13.0	not detected
Prostate	tissue	12.5	low
Adipose tissue	tissue	12.4	not detected
Rectum	tissue	12.3	medium
Urinary bladder	tissue	12.1	medium
Choroid plexus	tissue	11.8
Nucleus accumbens	tissue	11.5
Lung	tissue	11.5	medium
Thyroid gland	tissue	11.4	medium
Skin 1	tissue	11.1	not detected
Breast	tissue	10.9	low
Parathyroid gland	tissue	10.9	medium
Endometrium 1	tissue	10.9	medium
Locus coeruleus	tissue	10.8
Esophagus	tissue	10.5	low
Hippocampus	tissue	10.5	medium
Placenta	tissue	9.6	medium
Liver	tissue	9.4	medium
Cervix	tissue	9.3	low
Postcentral gyrus	tissue	9.2
Retina	tissue	8.1
Gallbladder	tissue	7.8	medium
Smooth muscle	tissue	7.1	low
Cerebellum	tissue	5.2	medium
Testis	tissue	5.1	medium
Epididymis	tissue	4.9	medium
Corpus callosum	tissue	4.5
Spinal cord	tissue	4.1
Substantia nigra	tissue	4.0
Olfactory bulb	tissue	3.9
Basal ganglia	tissue	3.7	low
Putamen	tissue	3.7
Cerebral cortex	tissue	3.6	medium
Amygdala	tissue	3.6
Midbrain	tissue	3.6
Superior colliculi	tissue	3.6
Insular cortex	tissue	3.6

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Blood vessel (34.5), Dorsal funiculus (white matter) (19.1), Area postrema (16.9), Nucleus ambiguus (16.8), Anterior funiculus (white matter) (16.6).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting NT5C by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

3 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-3194-5P	96.80	64.90	1027
HSA-MIR-4281	92.91	63.60	271

Functional genomics

gnomAD constraint: pLI 0.000631, LOEUF 1.19, missense Z -1.8 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000245552 — one region, missense o/e 1.18.

Literature-anchored findings (GeneRIF, showing 2)

• Data show that PN-I shows a higher affinity for oxynucleosides rather than deoxynucleosides, while the opposite is true for PN-II. (PMID:12418222)
• Mutation analysis in the P5N-I gene led to the identification of 3 novel mutations (PMID:12714505)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nt5c	ENSMUSG00000020736
rattus_norvegicus	Nt5c	ENSRNOG00000003650

Paralogs (1): NT5M (ENSG00000205309)

Additional cross-species homologs

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

Organism	UniProt	Identity	Method
Bordetella parapertussis 12822	Q7WC96	98.4%	Diamond
Bordetella bronchiseptica RB50	Q7WQA0	98.4%	Diamond
Bordetella pertussis Tohama I	Q7W066	97.8%	Diamond
Acanthamoeba polyphaga mimivirus	Q5UQH3	34.8%	Diamond

Genomic neighbors (locus context)

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

Symbol	Type	Entrez
TRR-TCG3-1	tRNA	100189371
ATP5PD	protein-coding	10476
KCTD2	protein-coding	23510
ARMC7	protein-coding	79637
SLC16A5	protein-coding	9121
JPT1	protein-coding	51155
SUMO2	protein-coding	6613
NUP85	protein-coding	79902
GGA3	protein-coding	23163
MRPS7	protein-coding	51081

Protein

Protein identifiers

5’(3’)-deoxyribonucleotidase, cytosolic type — Q8TCD5 (reviewed: Q8TCD5)

Alternative names: Cytosolic 5’,3’-pyrimidine nucleotidase, Deoxy-5’-nucleotidase 1

All UniProt accessions (7): J3KRC4, Q8TCD5, J3KSF0, J3KSX6, J3KSY6, J3QQX8, V9HWF3

UniProt curated annotations — full annotation on UniProt →

Function. Dephosphorylates the 5’ and 2’(3’)-phosphates of deoxyribonucleotides, with a preference for dUMP (Ref.12). Also dephosphsphorylates dTMP, exhibits intermediate activity towards dGMP, and low activity towards dCMP and dAMP.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Tissue specificity. Detected in skeletal muscle, heart and pancreas.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the 5’(3’)-deoxyribonucleotidase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TCD5-1	1	yes
Q8TCD5-2	2

RefSeq proteins (2): NP_001239306, NP_055410* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010708	5’(3’)-deoxyribonucleotidase	Family
IPR023214	HAD_sf	Homologous_superfamily
IPR036412	HAD-like_sf	Homologous_superfamily

Pfam: PF06941

Catalyzed reactions (Rhea)

• dTMP + H2O = thymidine + phosphate (RHEA:11080)
• IMP + H2O = inosine + phosphate (RHEA:27718)
• 3’-UMP + H2O = uridine + phosphate (RHEA:27890)
• dUMP + H2O = 2’-deoxyuridine + phosphate (RHEA:29355)
• UMP + H2O = uridine + phosphate (RHEA:29359)
• dCMP + H2O = 2’-deoxycytidine + phosphate (RHEA:29363)
• dAMP + H2O = 2’-deoxyadenosine + phosphate (RHEA:29371)
• dGMP + H2O = 2’-deoxyguanosine + phosphate (RHEA:29379)
• thymidine 3’-phosphate + H2O = thymidine + phosphate (RHEA:37247)
• uridine 2’-phosphate + H2O = uridine + phosphate (RHEA:37355)

UniProt features (38 total): helix 11, binding site 10, strand 6, splice variant 3, turn 3, active site 2, chain 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

4 structures by resolution:

PDB	Title	Method	Resolution (Å)
4L57	High resolutin structure of human cytosolic 5’(3’)-deoxyribonucleotidase	X-RAY DIFFRACTION	1.08
2I7D	Structure of Human cytosolic deoxyribonucleotidase in complex with deoxyuridine, AlF4 and …	X-RAY DIFFRACTION	1.2
6G2N	Crystal structure of human cytosolic 5’(3’)-deoxyribonucleotidase in complex with the …	X-RAY DIFFRACTION	1.4
4YIH	Crystal structure of human cytosolic 5’(3’)-deoxyribonucleotidase in complex with the …	X-RAY DIFFRACTION	1.82

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TCD5-F1	96.19	0.96

Human Protein Atlas

Protein class: Metabolic proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol

Antibody reliability (HPA): IH approved · IF supported

Functional residue map

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

Catalytic / active sites (2)

Position	Role
10	nucleophile
12	proton donor

Ligand- & substrate-binding residues (10)

Position	Role
134	dGMP
134	dUMP
145	Mg(2+)
10	Mg(2+)
12	Mg(2+)
46	dGMP
46	dUMP
65	dUMP
100	dGMP
100	dUMP

Post-translational modifications (1)

Type	Positions
Phosphoserine	182

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-74259	Purine catabolism	curated
R-HSA-73621	Pyrimidine catabolism	curated
R-HSA-1430728	Metabolism	—
R-HSA-15869	Metabolism of nucleotides	—
R-HSA-8956319	Nucleotide catabolism	—

MSigDB gene sets: 148 (showing top): REACTOME_PYRIMIDINE_CATABOLISM, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_PYRIMIDINE_CONTAINING_COMPOUND_CATABOLIC_PROCESS, GOBP_PYRIMIDINE_NUCLEOTIDE_METABOLIC_PROCESS, GOBP_PYRIMIDINE_NUCLEOTIDE_CATABOLIC_PROCESS, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_PYRIMIDINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_CATABOLIC_PROCESS, KEGG_PURINE_METABOLISM, GOBP_NUCLEOSIDE_PHOSPHATE_CATABOLIC_PROCESS, GOBP_DEPHOSPHORYLATION

GO Biological Process (14): IMP catabolic process (GO:0006204), dCMP catabolic process (GO:0006249), pyrimidine deoxyribonucleotide catabolic process (GO:0009223), dephosphorylation (GO:0016311), GMP catabolic process (GO:0046038), TMP catabolic process (GO:0046045), UMP catabolic process (GO:0046050), dGMP catabolic process (GO:0046055), dAMP catabolic process (GO:0046059), dTMP catabolic process (GO:0046074), dUMP catabolic process (GO:0046079), nucleobase-containing compound metabolic process (GO:0006139), nucleotide metabolic process (GO:0009117), deoxyribonucleotide catabolic process (GO:0009264)

GO Molecular Function (9): nucleotidase activity (GO:0008252), 5’-nucleotidase activity (GO:0008253), 3’-nucleotidase activity (GO:0008254), pyrimidine nucleotide binding (GO:0019103), identical protein binding (GO:0042802), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), hydrolase activity (GO:0016787), phosphatase activity (GO:0016791)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Nucleotide catabolism	2
Metabolism	1
Metabolism of nucleotides	1

GO top-level categories

39 GO namespaces:

Category	Terms
pyrimidine deoxyribonucleoside monophosphate catabolic process	3
pyrimidine deoxyribonucleotide catabolic process	3
purine ribonucleotide catabolic process	2
purine ribonucleoside monophosphate catabolic process	2
pyrimidine ribonucleoside monophosphate catabolic process	2
pyrimidine ribonucleotide catabolic process	2
purine deoxyribonucleotide catabolic process	2
purine deoxyribonucleoside monophosphate catabolic process	2
nucleotidase activity	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
cytoplasm	2
IMP metabolic process	1
dCMP metabolic process	1
pyrimidine nucleotide catabolic process	1
pyrimidine deoxyribonucleotide metabolic process	1
deoxyribose phosphate catabolic process	1
phosphate-containing compound metabolic process	1
GMP metabolic process	1
TMP metabolic process	1
UMP metabolic process	1
dGMP metabolic process	1
dAMP metabolic process	1
dTMP metabolic process	1
dUMP metabolic process	1
primary metabolic process	1
nucleoside phosphate metabolic process	1
catabolic process	1
deoxyribonucleotide metabolic process	1
phosphatase activity	1
nucleotide binding	1
protein binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
phosphoric ester hydrolase activity	1
intracellular anatomical structure	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 10 of 28 annotations. The rest are phylogenetic / computational / electronic (IEA).

10 experimentally-supported GO terms:

GO term	NS	Evidence
dephosphorylation	BP	direct assay
pyrimidine deoxyribonucleotide catabolic process	BP	direct assay
cytoplasm	CC	direct assay
cytosol	CC	direct assay
extracellular exosome	CC	high-throughput assay
mitochondrion	CC	high-throughput
nucleus	CC	direct assay
identical protein binding	MF	physical interaction
nucleotidase activity	MF	direct assay
pyrimidine nucleotide binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 738 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NT5C	NT5C3A	Q9H0P0	946
NT5C	TK1	P04183	730
NT5C	GALK1	P51570	682
NT5C	NT5C2	P49902	674
NT5C	PRPS1L1	P21108	664
NT5C	NT5C1A	Q9BXI3	662
NT5C	PRPS2	P11908	636
NT5C	PRPS1	P09329	606
NT5C	TYMP	P19971	604
NT5C	NT5C1B	Q96P26	532
NT5C	SLC4A1	P02730	502
NT5C	CRYBA1	P05813	498
NT5C	DCK	P27707	455
NT5C	DCTD	P32321	409
NT5C	ZGPAT	Q8N5A5	402

IntAct

Human interaction partners of NT5C in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

Partner	Interaction type	MIscore	Records
RAP1GDS1	association	0.530	2
RAB23	physical association	0.400	1
TNS2	physical association	0.370	1
APAF1	association	0.350	1
DISC1	physical association	0.000	1

BioGRID (57 interactions; top human partners by supporting records): ARPC1B (Affinity Capture-MS; 3 records), C1orf86 (Affinity Capture-MS; 2 records), FLNC (Affinity Capture-MS; 2 records), RAP1GDS1 (Affinity Capture-MS; 2 records), SIRPD (Affinity Capture-MS; 2 records), ZNF581 (Affinity Capture-MS; 2 records), AAAS (Affinity Capture-MS), ACTR8 (Affinity Capture-MS), AMBRA1 (Proximity Label-MS), ANKS1A (Affinity Capture-MS), APAF1 (Affinity Capture-MS), APEX1 (Affinity Capture-RNA), ARAP3 (Affinity Capture-MS), ARHGEF1 (Affinity Capture-MS), ASCC3 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for NT5C: 25 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	1
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 35 predictions of 329):

Position(s)	Effect	Δscore	Sites
17:75130868–75130870	acceptor_loss	1.0000	7
17:75131174	donor_gain	1.0000
17:75131532–75131533	donor_loss	1.0000	4
17:75130872	acceptor_gain	0.9900
17:75131179–75131180	donor_loss	0.9900	5
17:75131282–75131283	acceptor_loss	0.9900	6
17:75131532–75131533	donor_loss	0.9900	2
17:75131179	donor_loss	0.9800
17:75131106–75131107	acceptor_loss	0.9700	6
17:75130864–75130865	acceptor_gain	0.9600	2

AlphaMissense

501 missense substitutions predicted likely pathogenic (of 1,303 scored), across 122 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
D12	8	0.969	0.984
D145	8	0.961	0.986
D10	8	0.955	0.977
D144	8	0.949	0.977
N168	8	0.892	0.982
D133	8	0.884	0.941
F70	8	0.881	0.983
F71	8	0.881	0.977
F18	8	0.871	0.977
M11	8	0.824	0.937
H160	8	0.691	0.894
F163	7	0.970	0.993
W158	7	0.962	0.985
W183	7	0.961	0.986
W115	7	0.945	0.981
C98	7	0.939	0.993
K134	7	0.935	0.990
F26	7	0.932	0.979
K112	7	0.920	0.981
W187	7	0.916	0.966

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

2 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	5.31e-05
Ovary Serous Cystadenocarcinoma (validation)	favorable	0.000508

Disease associations

OMIM: gene MIM:191720 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST006585_931	Blood protein levels	3e-77

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3751653 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Adenosine turnover

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases expression, decreases expression	3
Benzo(a)pyrene	increases expression, increases methylation, decreases expression	3
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	increases expression	1
tetrabromobisphenol A	increases expression	1
perfluorooctanoic acid	decreases expression	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
monomethylarsonous acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	decreases expression	1
Calcium Chloride	increases expression	1
Catechin	decreases expression, affects cotreatment	1
Cisplatin	decreases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3755232	Binding	Inhibition of N-terminal hexaHis-tagged human cytosolic 5’(3’)-deoxynucleotidase using dUMP as substrate	Structure-based design of a bisphosphonate 5(3)-deoxyribonucleotidase inhibitor — *Medchemcomm*

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3CW	Abcam HEK293T NT5C KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for NT5C across ~30M SureChEMBL compounds — explore on Sugi Predict.