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NT5C

gene
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Also known as DNT1DNT-1PN-IcdN

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 and dTMP, intermediate activity towards dGMP, and low activity towards dCMP and dAMP.

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
  • Druggable target: yes
  • MANE Select transcript: NM_014595

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:17144
Approved symbolNT5C
Name5’, 3’-nucleotidase, cytosolic
Location17q25
Locus typegene with protein product
StatusApproved
AliasesDNT1, DNT-1, PN-I, cdN, dNT-1
Ensembl geneENSG00000125458
Ensembl biotypeprotein_coding
OMIM191720
Entrez30833

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 10 protein_coding, 5 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000245552, ENST00000577523, ENST00000578095, ENST00000578337, ENST00000578407, ENST00000579023, ENST00000579082, ENST00000580423, ENST00000580758, ENST00000582160, ENST00000582170, ENST00000582744, ENST00000583655, ENST00000584352, ENST00000876511, ENST00000876512, ENST00000876513, ENST00000954192

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

CCDS: CCDS11715

Canonical transcript exons

ENST00000245552 — 5 exons

ExonStartEnd
ENSE000007443487513104575131105
ENSE000011747327513153475131742
ENSE000035194937513022875130642
ENSE000035419347513118175131281
ENSE000036753417513075375130867

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.

FANTOM5 promoters (5 alternative TSS)

Promoter IDTPM avgSamples expressed
16803624.44311804
1680352.56671419
1680330.8643571
1680340.4812272
1680370.4415233

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
mucosa of transverse colonUBERON:000499197.03gold quality
transverse colonUBERON:000115795.79gold quality
small intestine Peyer’s patchUBERON:000345495.58gold quality
right uterine tubeUBERON:000130295.32gold quality
granulocyteCL:000009495.29gold quality
mucosa of stomachUBERON:000119995.12gold quality
olfactory segment of nasal mucosaUBERON:000538695.05gold quality
lower esophagus mucosaUBERON:003583495.04gold quality
left ovaryUBERON:000211994.64gold quality
right lobe of thyroid glandUBERON:000111994.52gold quality
right ovaryUBERON:000211894.52gold quality
ectocervixUBERON:001224994.52gold quality
body of stomachUBERON:000116194.50gold quality
left lobe of thyroid glandUBERON:000112094.46gold quality
metanephros cortexUBERON:001053394.36gold quality
endocervixUBERON:000045894.23gold quality
tibial nerveUBERON:000132394.13gold quality
muscle layer of sigmoid colonUBERON:003580593.88gold quality
body of uterusUBERON:000985393.84gold quality
right lungUBERON:000216793.71gold quality
lower esophagusUBERON:001347393.67gold quality
lower esophagus muscularis layerUBERON:003583393.67gold quality
esophagogastric junction muscularis propriaUBERON:003584193.60gold quality
esophagus mucosaUBERON:000246993.51gold quality
ventricular zoneUBERON:000305393.41gold quality
small intestineUBERON:000210893.30gold quality
esophagusUBERON:000104393.29gold quality
left uterine tubeUBERON:000130393.29gold quality
right coronary arteryUBERON:000162593.05gold quality
left coronary arteryUBERON:000162693.05gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-CURD-114yes58.99
E-ANND-3no0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

3 targeting NT5C, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-3156-3P99.7666.72939
HSA-MIR-3194-5P96.8064.901027
HSA-MIR-428192.9163.60271

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

OrganismSymbolGene ID
mus_musculusNt5cENSMUSG00000020736
rattus_norvegicusNt5cENSRNOG00000003650

Paralogs (1): NT5M (ENSG00000205309)

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): Q8TCD5, J3KRC4, 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 and dTMP, 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 IDNamesCanonical?
Q8TCD5-11yes
Q8TCD5-22

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

Domains & families (InterPro)

IDNameType
IPR0107085’(3’)-deoxyribonucleotidaseFamily
IPR023214HAD_sfHomologous_superfamily
IPR036412HAD-like_sfHomologous_superfamily

Pfam: PF06941

UniProt features (35 total): helix 10, binding site 8, strand 6, splice variant 3, turn 3, active site 2, chain 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

4 structures.

PDBMethodResolution (Å)
4L57X-RAY DIFFRACTION1.08
2I7DX-RAY DIFFRACTION1.2
6G2NX-RAY DIFFRACTION1.4
4YIHX-RAY DIFFRACTION1.82

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q8TCD5-F196.190.96

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): 10 (nucleophile); 12 (proton donor)

Ligand- & substrate-binding residues (8): 145; 10; 12; 18; 44; 65; 99; 134

Post-translational modifications (1): 182

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

IDPathway
R-HSA-73621Pyrimidine catabolism
R-HSA-74259Purine 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 (13): allantoin metabolic process (GO:0000255), IMP catabolic process (GO:0006204), dCMP catabolic process (GO:0006249), pyrimidine deoxyribonucleotide catabolic process (GO:0009223), dephosphorylation (GO:0016311), obsolete amide catabolic process (GO:0043605), UMP catabolic process (GO:0046050), dGMP catabolic process (GO:0046055), 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 (8): nucleotidase activity (GO:0008252), 5’-nucleotidase activity (GO:0008253), 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

Rollup of top-1 pathways:

CategoryPathways
Nucleotide catabolism2

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
pyrimidine deoxyribonucleoside monophosphate catabolic process3
pyrimidine deoxyribonucleotide catabolic process3
intracellular membrane-bounded organelle2
cellular anatomical structure2
cytoplasm2
metabolic process1
purine ribonucleotide catabolic process1
purine ribonucleoside monophosphate catabolic process1
IMP metabolic process1
dCMP metabolic process1
pyrimidine nucleotide catabolic process1
pyrimidine deoxyribonucleotide metabolic process1
deoxyribose phosphate catabolic process1
phosphate-containing compound metabolic process1
pyrimidine ribonucleoside monophosphate catabolic process1
pyrimidine ribonucleotide catabolic process1
UMP metabolic process1
purine deoxyribonucleotide catabolic process1
purine deoxyribonucleoside monophosphate catabolic process1
dGMP metabolic process1
dTMP metabolic process1
dUMP metabolic process1
primary metabolic process1
nucleoside phosphate metabolic process1
catabolic process1
deoxyribonucleotide metabolic process1
phosphatase activity1
nucleotidase activity1
nucleotide binding1
protein binding1
cation binding1
nucleoside phosphate binding1
heterocyclic compound binding1
catalytic activity1
phosphoric ester hydrolase activity1
intracellular anatomical structure1
extracellular vesicle1

Protein interactions and networks

STRING

722 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
NT5CNT5C3AQ9H0P0960
NT5CTK1P04183769
NT5CGALK1P51570689
NT5CNT5C1AQ9BXI3686
NT5CPRPS1L1P21108686
NT5CTYMPP19971655
NT5CNT5C2P49902654
NT5CPRPS1P09329604
NT5CNT5C1BQ96P26598
NT5CPRPS2P11908590
NT5CDCKP27707507
NT5CSLC4A1P02730505
NT5CCRYBA1P05813497
NT5CNT5C3BQ969T7480
NT5CKCTD2Q14681437

IntAct

30 interactions, top by confidence:

ABTypeScore
ARPC1BARPC2psi-mi:“MI:0914”(association)0.920
LYRM2NDUFAB1psi-mi:“MI:0914”(association)0.730
NT5CNT5Cpsi-mi:“MI:0915”(physical association)0.670
VBP1PFDN6psi-mi:“MI:0914”(association)0.640
NT5CRAP1GDS1psi-mi:“MI:0914”(association)0.530
ZNF581DMWDpsi-mi:“MI:0914”(association)0.530
SIRPDHIKESHIpsi-mi:“MI:0914”(association)0.530
HIKESHICLEC3Apsi-mi:“MI:0914”(association)0.530
RAB23NT5Cpsi-mi:“MI:0915”(physical association)0.400
TNS2NT5Cpsi-mi:“MI:0915”(physical association)0.370
FAAP20FANCGpsi-mi:“MI:0914”(association)0.350
NT5CAPAF1psi-mi:“MI:0914”(association)0.350
NEUROG1PPM1Bpsi-mi:“MI:0914”(association)0.350
GTF2H4TUSC2psi-mi:“MI:0914”(association)0.350
DDX28UBA6psi-mi:“MI:0914”(association)0.350
VENTXUBA6psi-mi:“MI:0914”(association)0.350
psi-mi:“MI:0914”(association)0.350
DISC1NT5Cpsi-mi:“MI:0915”(physical association)0.000
NT5CNT5Cpsi-mi:“MI:0915”(physical association)0.000

BioGRID (55): NT5C (Affinity Capture-MS), NT5C (Two-hybrid), NT5C (Affinity Capture-MS), FLNC (Affinity Capture-MS), NT5C (Affinity Capture-MS), NT5C (Affinity Capture-MS), NT5C (Affinity Capture-MS), RAP1GDS1 (Affinity Capture-MS), NT5C (Affinity Capture-RNA), NT5C (Two-hybrid), NT5C (Proximity Label-MS), NT5C (Affinity Capture-RNA), NT5C (Affinity Capture-MS), NT5C (Affinity Capture-MS), RAP1GDS1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5PJB7, A1A4Q9, A5YM72, A6NLP5, D3KCC4, I3L5V6, O43292, P10938, Q00973, Q05B52, Q09200, Q10468, Q14623, Q148G5, Q16586, Q2V8X7, Q3SZV0, Q561R2, Q5E9M9, Q5M868, Q5ZL13, Q66H45, Q69ZF3, Q6P3D0, Q6P7A1, Q6P9Z4, Q6SZW1, Q6TEC1, Q6ZPS2, Q7TMC8, Q864R5, Q86TX2, Q8IXI1, Q8N0W3, Q8N3Y3, Q8N6R0, Q8NF37, Q8NI29, Q8TCD5, Q8VBW8

Diamond homologs: Q5UPP9, Q5UQH3, Q7W066, Q7WC96, Q7WQA0, Q8TCD5, Q8VCE6, Q9JM14, Q9NPB1, P59935

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance18
Likely benign1
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

619 predictions. Top by Δscore:

VariantEffectΔscore
17:75130795:C:CTdonor_gain1.0000
17:75130863:CGGTA:Cacceptor_gain1.0000
17:75130864:GGTA:Gacceptor_gain1.0000
17:75130865:GTAC:Gacceptor_loss1.0000
17:75130866:TA:Tacceptor_gain1.0000
17:75130868:C:CCacceptor_gain1.0000
17:75130869:T:Cacceptor_loss1.0000
17:75130870:G:GCacceptor_gain1.0000
17:75131174:T:Adonor_gain1.0000
17:75131179:A:ACdonor_gain1.0000
17:75131179:ACT:Adonor_gain1.0000
17:75131180:C:CTdonor_gain1.0000
17:75131180:CT:Cdonor_gain1.0000
17:75131180:CTC:Cdonor_gain1.0000
17:75131182:C:CAdonor_gain1.0000
17:75131530:CTACC:Cdonor_loss1.0000
17:75131531:TA:Tdonor_loss1.0000
17:75131533:C:CTdonor_loss1.0000
17:75131533:CCG:Cdonor_gain1.0000
17:75131560:A:ACdonor_gain1.0000
17:75131561:C:CCdonor_gain1.0000
17:75131561:CTG:Cdonor_gain1.0000
17:75130764:T:TAdonor_gain0.9900
17:75130796:C:CTdonor_gain0.9900
17:75130865:GTA:Gacceptor_gain0.9900
17:75130872:G:Cacceptor_gain0.9900
17:75130872:G:GCacceptor_gain0.9900
17:75131071:T:TAdonor_gain0.9900
17:75131175:CCTTA:Cdonor_loss0.9900
17:75131177:TTA:Tdonor_loss0.9900

AlphaMissense

1303 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
17:75130605:G:CF163L0.993
17:75130605:G:TF163L0.993
17:75130607:A:GF163L0.993
17:75131087:G:CC98W0.993
17:75130776:A:TI143N0.990
17:75130802:C:AK134N0.990
17:75130802:C:GK134N0.990
17:75131088:C:TC98Y0.989
17:75131091:A:TI97N0.988
17:75130547:A:GW183R0.986
17:75130547:A:TW183R0.986
17:75130770:T:AD145V0.986
17:75130620:C:AW158C0.985
17:75130620:C:GW158C0.985
17:75130622:A:GW158R0.984
17:75130622:A:TW158R0.984
17:75131673:T:AD12V0.984
17:75131085:G:AT99I0.983
17:75131246:A:CF70L0.983
17:75131246:A:TF70L0.983
17:75131248:A:GF70L0.983
17:75130590:A:CN168K0.982
17:75130590:A:TN168K0.982
17:75130769:G:CD145E0.982
17:75130769:G:TD145E0.982
17:75131587:G:TR41S0.982
17:75131674:C:GD12H0.982
17:75130545:C:AW183C0.981
17:75130545:C:GW183C0.981
17:75130789:C:AG139W0.981

dbSNP variants (sampled 300 via entrez): RS1000475075 (17:75132815 A>C), RS1001373677 (17:75133522 C>T), RS1001827959 (17:75133267 A>G), RS1001886544 (17:75129900 G>A,C), RS1002996357 (17:75131424 C>G), RS1003598291 (17:75130149 AGAGGG>A), RS1003692659 (17:75132166 C>T), RS1003767656 (17:75131888 G>C), RS1003816159 (17:75131851 G>A,C), RS1004056975 (17:75130408 G>A), RS1007225120 (17:75132897 C>A,T), RS1007787173 (17:75130826 T>C), RS1008164022 (17:75133127 C>A), RS1009950199 (17:75131747 G>A,C,T), RS1010071238 (17:75131676 A>G,T)

Disease associations

OMIM: gene MIM:191720 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

StudyTraitp-value
GCST006585_1564Blood protein levels3.000000e-77

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3751653 (SINGLE PROTEIN)

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

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.

ChemicalActions (top 5)PubMed papers
sodium arsenitedecreases expression, affects cotreatment, increases expression3
Benzo(a)pyrenedecreases expression, increases expression, increases methylation3
aristolochic acid Idecreases expression1
FR900359increases phosphorylation1
bisphenol Adecreases expression1
decabromobiphenyl etherincreases expression1
tetrabromobisphenol Aincreases expression1
perfluorooctanoic aciddecreases expression1
coumarinincreases phosphorylation1
di-n-butylphosphoric acidaffects expression1
perfluorooctane sulfonic aciddecreases expression1
perfluoro-n-nonanoic aciddecreases expression1
2-palmitoylglycerolincreases expression1
monomethylarsonous aciddecreases expression1
perfluorohexanesulfonic aciddecreases expression1
ICG 001increases expression1
abrineincreases expression1
Grape Seed Proanthocyanidinsaffects cotreatment, decreases expression1
pentabrominated diphenyl ether 100increases expression1
hexabrominated diphenyl ether 153increases expression1
jinfukangincreases expression1
(+)-JQ1 compounddecreases expression1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acidincreases expression1
Arsenic Trioxidedecreases expression1
Acetaminophendecreases expression1
Calcium Chlorideincreases expression1
Catechinaffects cotreatment, decreases expression1
Cisplatindecreases expression1
Ivermectindecreases expression1
Leadaffects expression1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL3755232BindingInhibition of N-terminal hexaHis-tagged human cytosolic 5’(3’)-deoxynucleotidase using dUMP as substrateStructure-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):

CellosaurusNameCategorySex
CVCL_B3CWAbcam HEK293T NT5C KOTransformed cell lineFemale

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 79

This page pulls from 79 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot