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NT5C1A

gene
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Also known as CN-ICN-IACN1ACN1MGC119199MGC119201

Summary

NT5C1A (5’-nucleotidase, cytosolic IA, HGNC:17819) is a protein-coding gene on chromosome 1p34.2, encoding Cytosolic 5’-nucleotidase 1A (Q9BXI3). Catalyzes the hydrolysis of ribonucleotide and deoxyribonucleotide monophosphates, releasing inorganic phosphate and the corresponding nucleoside.

Cytosolic nucleotidases, such as NT5C1A, dephosphorylate nucleoside monophosphates (Hunsucker et al., 2001 [PubMed 11133996]).

Source: NCBI Gene 84618 — RefSeq curated summary.

At a glance

  • GWAS associations: 1
  • Clinical variants (ClinVar): 41 total
  • MANE Select transcript: NM_032526

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:17819
Approved symbolNT5C1A
Name5’-nucleotidase, cytosolic IA
Location1p34.2
Locus typegene with protein product
StatusApproved
AliasesCN-I, CN-IA, CN1A, CN1, MGC119199, MGC119201
Ensembl geneENSG00000116981
Ensembl biotypeprotein_coding
OMIM610525
Entrez84618

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000235628, ENST00000905835

RefSeq mRNA: 1 — MANE Select: NM_032526 NM_032526

CCDS: CCDS440

Canonical transcript exons

ENST00000235628 — 6 exons

ExonStartEnd
ENSE000007678653966331239663434
ENSE000007678663966552139665650
ENSE000007678673966606939666236
ENSE000008246403965122939659486
ENSE000008246413967190439672107
ENSE000011276733966107939661263

Expression profiles

Bgee: expression breadth ubiquitous, 111 present calls, max score 84.11.

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
gastrocnemiusUBERON:000138884.11gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047383.91silver quality
muscle of legUBERON:000138383.68gold quality
hindlimb stylopod muscleUBERON:000425283.60gold quality
pancreatic ductal cellCL:000207980.19silver quality
tibialis anteriorUBERON:000138575.62silver quality
apex of heartUBERON:000209873.98gold quality
cardiac muscle of right atriumUBERON:000337973.44gold quality
left ventricle myocardiumUBERON:000656673.15gold quality
skeletal muscle tissueUBERON:000113472.79gold quality
right atrium auricular regionUBERON:000663172.71gold quality
cardiac atriumUBERON:000208172.06gold quality
heart left ventricleUBERON:000208471.00gold quality
cardiac ventricleUBERON:000208270.42gold quality
muscle tissueUBERON:000238570.33gold quality
heartUBERON:000094868.62gold quality
epithelial cell of pancreasCL:000008368.38gold quality
cerebellar cortexUBERON:000212968.00gold quality
cerebellar hemisphereUBERON:000224567.99gold quality
right hemisphere of cerebellumUBERON:001489067.42gold quality
cerebellumUBERON:000203766.41gold quality
quadriceps femorisUBERON:000137765.79gold quality
prefrontal cortexUBERON:000045165.51gold quality
ileal mucosaUBERON:000033164.87silver quality
vastus lateralisUBERON:000137964.85gold quality
skeletal muscle tissue of biceps brachiiUBERON:000450264.84gold quality
deltoidUBERON:000147664.81gold quality
biceps brachiiUBERON:000150764.51gold quality
myocardiumUBERON:000234962.09gold quality
endothelial cellCL:000011561.34gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

ExperimentMarker?Max mean expression
E-GEOD-111727no1705.15
E-ANND-3no1.14

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 9)

  • overexpression of 5’-nucleotidase inhibits Natural Killer cell cytotoxicity to ameliorate rejection after xenotransplantation (PMID:15888028)
  • deoxycytidine kinase, deoxyguanosine kinase, and cytosolic 5’-nucleotidase I are regulated in a cell cycle-dependent manner in MOLT-4 cells (PMID:17065091)
  • There was no correlation between expression of cN-I and fiber type. (PMID:19352542)
  • NT5C1A suppression promotes AMP-activated protein kinase (AMPK) phosphorylation and metabolism in human and mouse skeletal muscle (PMID:21873433)
  • seropositivity to the NT5c1A antibody is associated with greater motor and functional disability in sporadic inclusion body myositis (PMID:25857661)
  • Anti-NT5C1A is a common target of circulating autoantibodies in autoimmune diseases. (PMID:25892010)
  • Individual missense changes in NT5C1A showed considerable variation in response to the different nucleoside analogs tested. (PMID:26906009)
  • NT5C1A is robustly expressed in tumor cells of resected PDAC patients. Moreover, NT5C1A mediates gemcitabine resistance by decreasing the amount of intracellular dFdCTP, leading to reduced tumor cell apoptosis and larger pancreatic tumors in mice. (PMID:30709769)
  • Anti-NT5c1A Autoantibodies as Biomarkers in Inclusion Body Myositis. (PMID:31024569)

Cross-species orthologs

4 orthologs

OrganismSymbolGene ID
danio_reriont5c1aaENSDARG00000035883
danio_reriont5c1abENSDARG00000070590
mus_musculusNt5c1aENSMUSG00000054958
rattus_norvegicusNt5c1aENSRNOG00000068555

Paralogs (1): NT5C1B (ENSG00000185013)

Protein

Protein identifiers

Cytosolic 5’-nucleotidase 1A — Q9BXI3 (reviewed: Q9BXI3)

Alternative names: 5’-deoxynucleotidase, Cytosolic 5’-nucleotidase IA

All UniProt accessions (1): Q9BXI3

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolysis of ribonucleotide and deoxyribonucleotide monophosphates, releasing inorganic phosphate and the corresponding nucleoside. AMP is the major substrate but can also hydrolyze dCMP and IMP.

Subcellular location. Cytoplasm.

Tissue specificity. Highly expressed in skeletal muscle. Detected at intermediate levels in heart, brain, kidney and pancreas.

Activity regulation. Activated by ADP.

Similarity. Belongs to the 5’-nucleotidase type 3 family.

RefSeq proteins (1): NP_115915* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR0103945-nucleotidaseFamily

Pfam: PF06189

Enzyme classification (BRENDA):

  • EC 3.1.3.5 — 5’-nucleotidase (BRENDA: 107 organisms, 375 substrates, 402 inhibitors, 307 Km, 66 kcat entries)

Substrate kinetics (BRENDA)

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

SubstrateKm (mM)Measurements
5’-AMP0.0003–2373
5’-IMP0.0071–1849
5’-GMP0.0064–7.229
5’-UMP0.014–5627
5’-CMP0.002–10019
INOSINE0.25–10.213
5’-DAMP0.012–359
AMP0.0091–1.498
5’-DGMP0.044–1427
4-NITROPHENYL PHOSPHATE0.224–21.786
5’-DCMP0.023–0.756
DCMP0.012–0.1936
5’-TMP0.008–0.735
5’-XMP0.065–2.95
5’-DTMP0.008–224

Catalyzed reactions (Rhea), 5 shown:

  • a ribonucleoside 5’-phosphate + H2O = a ribonucleoside + phosphate (RHEA:12484)
  • IMP + H2O = inosine + phosphate (RHEA:27718)
  • dCMP + H2O = 2’-deoxycytidine + phosphate (RHEA:29363)
  • AMP + H2O = adenosine + phosphate (RHEA:29375)
  • a 2’-deoxyribonucleoside 5’-phosphate + H2O = a 2’-deoxyribonucleoside + phosphate (RHEA:36167)

UniProt features (4 total): chain 1, region of interest 1, active site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9BXI3-F187.090.68

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): 211 (nucleophile)

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

IDPathway
R-HSA-73621Pyrimidine catabolism
R-HSA-74259Purine catabolism
R-HSA-1430728Metabolism
R-HSA-15869Metabolism of nucleotides
R-HSA-8956319Nucleotide catabolism

MSigDB gene sets: 72 (showing top): BENPORATH_ES_WITH_H3K27ME3, REACTOME_PYRIMIDINE_CATABOLISM, MAZ_Q6, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, chr1p34, GOBP_ORGANOPHOSPHATE_CATABOLIC_PROCESS, KEGG_PURINE_METABOLISM, GOBP_NUCLEOSIDE_PHOSPHATE_CATABOLIC_PROCESS, GOBP_NUCLEOSIDE_MONOPHOSPHATE_METABOLIC_PROCESS, GOBP_PURINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_PURINE_CONTAINING_COMPOUND_CATABOLIC_PROCESS

GO Biological Process (9): allantoin metabolic process (GO:0000255), AMP catabolic process (GO:0006196), IMP catabolic process (GO:0006204), nucleoside metabolic process (GO:0009116), dGMP catabolic process (GO:0046055), dAMP catabolic process (GO:0046059), adenosine metabolic process (GO:0046085), nucleotide metabolic process (GO:0009117), purine nucleoside monophosphate catabolic process (GO:0009128)

GO Molecular Function (6): nucleotide binding (GO:0000166), magnesium ion binding (GO:0000287), 5’-deoxynucleotidase activity (GO:0002953), 5’-nucleotidase activity (GO:0008253), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-3 pathways:

CategoryPathways
Nucleotide catabolism2
Metabolism1
Metabolism of nucleotides1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
purine ribonucleotide catabolic process2
purine ribonucleoside monophosphate catabolic process2
purine deoxyribonucleotide catabolic process2
purine deoxyribonucleoside monophosphate catabolic process2
cellular anatomical structure2
metabolic process1
AMP metabolic process1
IMP metabolic process1
nucleobase-containing small molecule metabolic process1
carbohydrate derivative metabolic process1
dGMP metabolic process1
dAMP metabolic process1
purine ribonucleoside metabolic process1
nucleoside phosphate metabolic process1
nucleoside monophosphate catabolic process1
purine nucleoside monophosphate metabolic process1
nucleoside phosphate binding1
heterocyclic compound binding1
metal ion binding1
5’-nucleotidase activity1
nucleotidase activity1
binding1
catalytic activity1
intracellular anatomical structure1
cytoplasm1

Protein interactions and networks

STRING

2037 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
NT5C1ACNIH2Q6PI25873
NT5C1ACNIH1O95406865
NT5C1ACNIH4Q9P003832
NT5C1ACNIH3Q8TBE1815
NT5C1ANT5C2P49902692
NT5C1ANT5CQ8TCD5686
NT5C1AMORC3Q14149670
NT5C1ATGFAP01135655
NT5C1ANT5MQ9NPB1654
NT5C1AGOLPH3Q9H4A6633
NT5C1ANT5C3AQ9H0P0588
NT5C1AAMPD1P23109578
NT5C1ATRIM33Q9UPN9544
NT5C1ADCKP27707501
NT5C1ANT5C3BQ969T7490

IntAct

18 interactions, top by confidence:

ABTypeScore
NT5C1ANTAQ1psi-mi:“MI:0915”(physical association)0.760
NTAQ1NT5C1Apsi-mi:“MI:0915”(physical association)0.760
CDC37NT5C1Apsi-mi:“MI:0915”(physical association)0.560
NPY2RRTL8Cpsi-mi:“MI:0914”(association)0.530
NT5C1AHNRNPUpsi-mi:“MI:0915”(physical association)0.400
ICAM1RTL8Cpsi-mi:“MI:0914”(association)0.350
ICAM1TUBB8Bpsi-mi:“MI:0914”(association)0.350
SLC22A4RTL8Cpsi-mi:“MI:0914”(association)0.350
HCRTR2FADS1psi-mi:“MI:0914”(association)0.350
NT5C1AA2ML1psi-mi:“MI:0914”(association)0.350
CDC37NT5C1Apsi-mi:“MI:0915”(physical association)0.000
NTAQ1NT5C1Apsi-mi:“MI:0915”(physical association)0.000

BioGRID (29): NT5C1A (Two-hybrid), NT5C1A (Affinity Capture-MS), NT5C1A (Affinity Capture-MS), NT5C1A (Two-hybrid), WDYHV1 (Two-hybrid), NT5C1A (Proximity Label-MS), NT5C1A (Affinity Capture-MS), NT5C1A (Affinity Capture-MS), NT5C1A (Affinity Capture-MS), NT5C1A (Affinity Capture-MS), IVL (Affinity Capture-MS), SDR9C7 (Affinity Capture-MS), ATP12A (Affinity Capture-MS), S100A9 (Affinity Capture-MS), CTSH (Affinity Capture-MS)

ESM2 similar proteins: A1Z3X3, A3KFX0, A4GWN3, E9Q4Z2, O00763, P13255, P50747, P82922, Q0J035, Q14749, Q1LZ96, Q28559, Q28C34, Q29513, Q29555, Q3TFD2, Q3UHE1, Q3UX43, Q5E9L7, Q5IH13, Q5IH14, Q5ZJT0, Q60HG1, Q64311, Q68EN5, Q6NWD4, Q6NYU2, Q6Q0N3, Q6ZN16, Q80YV4, Q86UY8, Q8BJQ9, Q8C092, Q8C5H8, Q8N6S4, Q8NFZ0, Q8TDX6, Q91W86, Q91XQ2, Q91YY4

Diamond homologs: A3KFX0, Q91YE9, Q96P26, Q9BXI3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance35
Likely benign0
Benign3

Top pathogenic / likely-pathogenic (0)

SpliceAI

736 predictions. Top by Δscore:

VariantEffectΔscore
1:39661261:TCC:Tacceptor_gain1.0000
1:39661262:CCC:Cacceptor_gain1.0000
1:39661264:CT:Cacceptor_loss1.0000
1:39663307:CTTA:Cdonor_loss1.0000
1:39663308:TTAC:Tdonor_loss1.0000
1:39663309:TA:Tdonor_loss1.0000
1:39663310:A:ACdonor_gain1.0000
1:39663310:A:Cdonor_loss1.0000
1:39663310:AC:Adonor_gain1.0000
1:39663310:ACC:Adonor_gain1.0000
1:39663310:ACCCT:Adonor_gain1.0000
1:39663311:C:CAdonor_loss1.0000
1:39663311:C:CCdonor_gain1.0000
1:39663311:CC:Cdonor_gain1.0000
1:39663311:CCC:Cdonor_gain1.0000
1:39663311:CCCT:Cdonor_gain1.0000
1:39663311:CCCTC:Cdonor_gain1.0000
1:39663430:CAGGT:Cacceptor_gain1.0000
1:39663431:AGGT:Aacceptor_gain1.0000
1:39663432:GGT:Gacceptor_gain1.0000
1:39663432:GGTC:Gacceptor_loss1.0000
1:39663433:GT:Gacceptor_gain1.0000
1:39663435:C:CCacceptor_gain1.0000
1:39663435:CTGGG:Cacceptor_loss1.0000
1:39663436:T:Aacceptor_loss1.0000
1:39665516:CTCA:Cdonor_loss1.0000
1:39665517:TCA:Tdonor_loss1.0000
1:39665518:CACC:Cdonor_loss1.0000
1:39665519:A:Tdonor_loss1.0000
1:39665520:C:CTdonor_loss1.0000

AlphaMissense

2408 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
1:39659242:T:AD329V0.999
1:39659242:T:GD329A0.999
1:39659245:T:AD328V0.999
1:39659286:C:AK314N0.999
1:39659286:C:GK314N0.999
1:39659401:C:GR276P0.999
1:39661121:G:CF233L0.999
1:39661121:G:TF233L0.999
1:39661123:A:GF233L0.999
1:39661169:G:CF217L0.999
1:39661169:G:TF217L0.999
1:39661171:A:GF217L0.999
1:39661173:A:TL216H0.999
1:39661180:C:GA214P0.999
1:39661182:T:AD213V0.999
1:39661182:T:CD213G0.999
1:39661188:T:AD211V0.999
1:39661194:G:TA209D0.999
1:39661200:C:GR207P0.999
1:39661254:G:TA189D0.999
1:39663353:A:GL172S0.999
1:39663359:A:GL170P0.999
1:39666208:G:TA55D0.999
1:39659241:G:CD329E0.998
1:39659241:G:TD329E0.998
1:39659242:T:CD329G0.998
1:39659248:A:GF327S0.998
1:39659250:G:CF326L0.998
1:39659250:G:TF326L0.998
1:39659252:A:GF326L0.998

dbSNP variants (sampled 300 via entrez): RS1000351455 (1:39651280 C>T), RS1000360319 (1:39669287 T>G), RS1000434240 (1:39655172 C>A), RS1000487978 (1:39655446 G>A), RS1000538364 (1:39662633 C>T), RS1000641732 (1:39669474 GC>G), RS1000666642 (1:39656406 T>G), RS1000770612 (1:39653778 C>A), RS1001089925 (1:39666930 C>G), RS1001363535 (1:39660674 A>C), RS1001442865 (1:39650901 C>T), RS1001561033 (1:39654835 G>A,T), RS1001674059 (1:39657001 TGCCCCAAG>T), RS1001804235 (1:39661588 G>C,T), RS1001950421 (1:39653622 C>G,T)

Disease associations

OMIM: gene MIM:610525 | 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
GCST000406_3Amyotrophic lateral sclerosis8.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

3 annotations.

VariantTypeLevelDrugsPhenotypes
rs201045130Other3cladribine;fluorouracil;gemcitabine
rs370457585Other3cladribine;fluorouracil;gemcitabine
rs374150125Other3cladribine;fluorouracil;gemcitabine

PharmGKB variants

3 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs201045130NT5C1A30.001cladribine;fluorouracil;gemcitabine
rs370457585NT5C1A30.001cladribine;fluorouracil;gemcitabine
rs374150125NT5C1A30.001cladribine;fluorouracil;gemcitabine

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Adenosine turnover

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

ChemicalActions (top 5)PubMed papers
Resveratroldecreases expression, affects cotreatment2
benzo(e)pyrenedecreases methylation1
S-(1,2-dichlorovinyl)cysteineincreases expression, affects cotreatment, decreases expression, affects response to substance1
CGP 52608affects binding, increases reaction1
Benzo(a)pyreneincreases methylation, affects methylation1
Copperaffects cotreatment, decreases expression1
Lipopolysaccharidesaffects cotreatment, decreases expression, affects response to substance, increases expression1
Methapyrilenedecreases methylation1
Plant Extractsaffects cotreatment, decreases expression1
Aflatoxin B1decreases methylation1
Copper Sulfateincreases expression1

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 76

This page pulls from 76 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot