NTPCR

Summary

NTPCR (nucleoside-triphosphatase, cancer-related, HGNC:28204) is a protein-coding gene on chromosome 1q42.2, encoding Cancer-related nucleoside-triphosphatase (Q9BSD7). Has nucleotide phosphatase activity towards ATP, GTP, CTP, TTP and UTP.

The protein encoded by this gene is a non-specific nucleoside triphosphatase that is slow-acting in vitro. This gene is overexpressed in many tumor tissues, and while it is not essential for the cell, overexpression is cytotoxic. However, the cytotoxicity is not related to its triphosphatase activity.

Source: NCBI Gene 84284 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 39 total
• Druggable target: yes
• MANE Select transcript: NM_032324

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28204
Approved symbol	NTPCR
Name	nucleoside-triphosphatase, cancer-related
Location	1q42.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC13186, HCR-NTPase, THEP1
Ensembl gene	ENSG00000135778
Ensembl biotype	protein_coding
Entrez	84284

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 6 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000366627, ENST00000366628, ENST00000479125, ENST00000487953, ENST00000490098, ENST00000490807, ENST00000494689, ENST00000496662, ENST00000926799, ENST00000926800, ENST00000926801, ENST00000926802

RefSeq mRNA: 3 — MANE Select: NM_032324 NM_001329452, NM_001329453, NM_032324

CCDS: CCDS1597

Canonical transcript exons

ENST00000366628 — 5 exons

Exon	Start	End
ENSE00001442206	232950611	232950744
ENSE00001850951	232978163	232983882
ENSE00003625491	232956347	232956443
ENSE00003644210	232969909	232970118
ENSE00003656995	232955557	232955719

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 97.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.4553 / max 251.8593, expressed in 1805 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9073	19.7549	1805
9072	0.7003	438

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	97.60	gold quality
kidney epithelium	UBERON:0004819	95.64	gold quality
islet of Langerhans	UBERON:0000006	95.38	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.84	gold quality
prefrontal cortex	UBERON:0000451	94.59	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.44	gold quality
right adrenal gland	UBERON:0001233	94.24	gold quality
right adrenal gland cortex	UBERON:0035827	94.21	gold quality
left ventricle myocardium	UBERON:0006566	94.15	gold quality
spinal cord	UBERON:0002240	94.05	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.90	gold quality
mucosa of transverse colon	UBERON:0004991	93.89	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.85	gold quality
anterior cingulate cortex	UBERON:0009835	93.78	gold quality
left adrenal gland cortex	UBERON:0035825	93.70	gold quality
epithelial cell of pancreas	CL:0000083	93.59	gold quality
right atrium auricular region	UBERON:0006631	93.55	gold quality
hypothalamus	UBERON:0001898	93.53	gold quality
left adrenal gland	UBERON:0001234	93.49	gold quality
rectum	UBERON:0001052	93.47	gold quality
cardiac atrium	UBERON:0002081	93.45	gold quality
nucleus accumbens	UBERON:0001882	93.35	gold quality
putamen	UBERON:0001874	93.33	gold quality
substantia nigra	UBERON:0002038	93.28	gold quality
adrenal cortex	UBERON:0001235	93.18	gold quality
muscle of leg	UBERON:0001383	93.03	gold quality
myocardium	UBERON:0002349	93.02	gold quality
heart left ventricle	UBERON:0002084	92.94	gold quality
cardiac ventricle	UBERON:0002082	92.80	gold quality
gastrocnemius	UBERON:0001388	92.72	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	14.41
E-GEOD-83139	yes	8.53
E-MTAB-9388	no	10.14
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

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

miRNA	Max score	Avg score	miRNA target_count
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-449B-3P	99.20	67.24	1047
HSA-MIR-6792-5P	98.39	68.16	1330
HSA-MIR-484	98.16	66.92	1074
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-517-5P	97.13	68.43	781
HSA-MIR-5586-5P	96.29	68.02	685
HSA-MIR-6125	95.17	67.26	91

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ntpcr	ENSDARG00000021853
mus_musculus	Ntpcr	ENSMUSG00000031851
rattus_norvegicus	Ntpcr	ENSRNOG00000019922
drosophila_melanogaster	CG10581	FBGN0037046

Protein

Protein identifiers

Cancer-related nucleoside-triphosphatase — Q9BSD7 (reviewed: Q9BSD7)

Alternative names: Nucleoside triphosphate phosphohydrolase

All UniProt accessions (3): Q9BSD7, Q5TDE9, Q5TDF0

UniProt curated annotations — full annotation on UniProt →

Function. Has nucleotide phosphatase activity towards ATP, GTP, CTP, TTP and UTP. Hydrolyzes nucleoside diphosphates with lower efficiency.

Subunit / interactions. Monomer.

Similarity. Belongs to the THEP1 NTPase family.

RefSeq proteins (3): NP_001316381, NP_001316382, NP_115700* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003593	AAA+_ATPase	Domain
IPR004948	Nuc-triphosphatase_THEP1	Family
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF03266

Catalyzed reactions (Rhea), 5 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)
• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)
• a ribonucleoside 5’-triphosphate + H2O = a ribonucleoside 5’-diphosphate + phosphate + H(+) (RHEA:23680)
• CTP + H2O = CDP + phosphate + H(+) (RHEA:29387)
• 5-methyl-UTP + H2O = 5-methyl-UDP + phosphate + H(+) (RHEA:65580)

UniProt features (28 total): strand 11, helix 6, turn 2, binding site 2, modified residue 2, mutagenesis site 2, initiator methionine 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2I3B	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BSD7-F1	78.30	0.00

Functional residue map

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

Ligand- & substrate-binding residues (2): 9–16; 109–116

Post-translational modifications (2): 2, 165

Mutagenesis-validated functional residues (2):

Position	Phenotype
114	reduced activity, especially towards atp, gtp and ttp.
116	reduced activity, especially towards atp, gtp and ttp.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 114 (showing top): CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, MORF_ATRX, AREB6_01, DODD_NASOPHARYNGEAL_CARCINOMA_UP, ACEVEDO_LIVER_CANCER_UP, GOMF_GTPASE_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ACID_ANHYDRIDES, MORF_PAX7, MORF_TNFRSF25, MORF_RFC5, VECCHI_GASTRIC_CANCER_EARLY_UP, GOMF_ATP_HYDROLYSIS_ACTIVITY, GOMF_ADENYL_NUCLEOTIDE_BINDING, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_12, EIF4E_UP

GO Biological Process (0):

GO Molecular Function (8): RNA binding (GO:0003723), GTPase activity (GO:0003924), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), ribonucleoside triphosphate phosphatase activity (GO:0017111), CTPase activity (GO:0043273), nucleotide binding (GO:0000166), hydrolase activity (GO:0016787)

GO Cellular Component (2): mitochondrion (GO:0005739), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ribonucleoside triphosphate phosphatase activity	3
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ATP-dependent activity	1
pyrophosphatase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1016 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NTPCR	NUDT1	P36639	592
NTPCR	ENTPD2	Q9Y5L3	535
NTPCR	OGG1	P78554	529
NTPCR	ATIC	P31939	489
NTPCR	GUCY1B1	Q02153	451
NTPCR	B3GNT4	Q9C0J1	444
NTPCR	AK2	P54819	435
NTPCR	AK8	Q96MA6	434
NTPCR	ENTPD5	O75356	434
NTPCR	SH2D3A	Q9BRG2	432
NTPCR	RNGTT	O60942	430
NTPCR	PRSS57	Q6UWY2	419
NTPCR	SH2D3C	Q8N5H7	418
NTPCR	COX5A	P20674	410
NTPCR	OSGEP	Q9NPF4	406

IntAct

103 interactions, top by confidence:

A	B	Type	Score
IKBKG	IKBKB	psi-mi:“MI:0914”(association)	0.980
WDR19	TULP3	psi-mi:“MI:0914”(association)	0.860
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
EGFR	NDUFA4	psi-mi:“MI:0914”(association)	0.530
SLCO4C1	CLGN	psi-mi:“MI:0914”(association)	0.530
CDK18	UBL4A	psi-mi:“MI:0914”(association)	0.530
IFT140	ACSL3	psi-mi:“MI:0914”(association)	0.510
TPTE	NOP56	psi-mi:“MI:2364”(proximity)	0.420
AIFM1	HAX1	psi-mi:“MI:0914”(association)	0.420
TUBA1A	TUBAL3	psi-mi:“MI:0914”(association)	0.420
TGOLN2	PGRMC1	psi-mi:“MI:0914”(association)	0.420
ALK	PIK3R2	psi-mi:“MI:0914”(association)	0.420
FLT4	ILVBL	psi-mi:“MI:0914”(association)	0.420
AATK	NDUFA4	psi-mi:“MI:0914”(association)	0.420
MET	NDUFA4	psi-mi:“MI:2364”(proximity)	0.420
STAMBP	NTPCR	psi-mi:“MI:0915”(physical association)	0.370
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
NUP58	ABCC5	psi-mi:“MI:0914”(association)	0.350
SSX2IP	IPO7	psi-mi:“MI:0914”(association)	0.350
WDR35	TTC21B	psi-mi:“MI:0914”(association)	0.350
MAPK6		psi-mi:“MI:0914”(association)	0.350
RIPK4	VWA8	psi-mi:“MI:0914”(association)	0.350
NS1	SAC3D1	psi-mi:“MI:0914”(association)	0.350
PPEF1	ILVBL	psi-mi:“MI:0914”(association)	0.350

BioGRID (176): NTPCR (Affinity Capture-MS), NTPCR (Co-fractionation), NTPCR (Affinity Capture-MS), NTPCR (Affinity Capture-MS), NTPCR (Affinity Capture-MS), NTPCR (Affinity Capture-MS), WDR19 (Affinity Capture-MS), WDR35 (Affinity Capture-MS), NTPCR (Affinity Capture-MS), NTPCR (Affinity Capture-MS), NTPCR (Affinity Capture-MS), NTPCR (Affinity Capture-MS), NTPCR (Affinity Capture-MS), NTPCR (Affinity Capture-MS), NTPCR (Affinity Capture-MS)

ESM2 similar proteins: A4IH68, A5GFY8, B8A5W4, O34932, O74414, O95396, P23919, P34558, Q03941, Q0P4C4, Q13057, Q16774, Q17CA7, Q1JPA0, Q1LZ78, Q2JUC0, Q32PY9, Q3A3D2, Q3SZ73, Q3ZBS0, Q5KWC4, Q5R9W5, Q5T6J7, Q6AY55, Q7Q732, Q7ZV79, Q7ZW24, Q80UN9, Q8AWD2, Q8BHC4, Q8IQF1, Q8MIR4, Q8N5I4, Q8R0J8, Q8TB37, Q8TC12, Q8WVC6, Q91348, Q91WL8, Q94DR2

Diamond homologs: A1RRZ4, A1RYX5, A2BL86, A3DNY5, A3MX10, A4WLK1, A4YEP4, A5IL32, A8ABE2, A8MB70, B1LAB2, B1Y9N2, B2A6V4, O27140, O29444, O58522, O67322, Q1LZ78, Q467J7, Q58954, Q5JF42, Q8TH18, Q8TKK3, Q8TX49, Q8ZTE6, Q96YL7, Q97WP0, Q9BSD7, Q9CQA9, Q9UZ81, Q9WXP3, Q9YDY8, B1L726, Q4JCN8, O51461, Q0SMZ9, Q97AR1, Q9HJH0, Q6L2J8, P49540

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 130 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
EPH-ephrin mediated repulsion of cells	6	14.8×	4e-04
Constitutive Signaling by Aberrant PI3K in Cancer	10	14.3×	6e-07
Hedgehog ‘off’ state	6	12.0×	9e-04
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	11	12.0×	6e-07
Intraflagellar transport	5	11.3×	3e-03
EPH-Ephrin signaling	6	11.2×	1e-03
PIP3 activates AKT signaling	11	8.2×	2e-05
RAF/MAP kinase cascade	10	6.9×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine phosphorylation	8	28.8×	3e-07
ephrin receptor signaling pathway	6	17.6×	2e-04
protein localization to cilium	5	17.1×	1e-03
cell surface receptor protein tyrosine kinase signaling pathway	10	14.8×	8e-07
protein autophosphorylation	10	12.4×	3e-06
neuron apoptotic process	6	9.5×	4e-03
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	12	8.0×	1e-05
positive regulation of MAPK cascade	11	7.6×	5e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1358 predictions. Top by Δscore:

Variant	Effect	Δscore
1:232955716:T:G	donor_gain	1.0000
1:232956439:GGAAT:G	donor_gain	1.0000
1:232956440:GAAT:G	donor_gain	1.0000
1:232956440:GAATG:G	donor_gain	1.0000
1:232956441:A:T	donor_gain	1.0000
1:232956442:AT:A	donor_gain	1.0000
1:232956442:ATGT:A	donor_loss	1.0000
1:232956443:TGTG:T	donor_loss	1.0000
1:232956444:G:GG	donor_gain	1.0000
1:232956446:G:GT	donor_loss	1.0000
1:232956446:GA:G	donor_gain	1.0000
1:232956448:G:GG	donor_gain	1.0000
1:232978157:CCACA:C	acceptor_loss	1.0000
1:232978158:CACAG:C	acceptor_loss	1.0000
1:232978160:CA:C	acceptor_loss	1.0000
1:232978161:AGGTC:A	acceptor_loss	1.0000
1:232978162:G:GC	acceptor_loss	1.0000
1:232978225:G:GT	donor_gain	1.0000
1:232978305:GGCT:G	donor_gain	1.0000
1:232978306:GCTG:G	donor_gain	1.0000
1:232955653:G:T	donor_gain	0.9900
1:232955712:A:T	donor_gain	0.9900
1:232955715:GTTGG:G	donor_gain	0.9900
1:232956342:TTCA:T	acceptor_loss	0.9900
1:232956343:TCAG:T	acceptor_loss	0.9900
1:232956344:CAGG:C	acceptor_loss	0.9900
1:232956345:A:G	acceptor_loss	0.9900
1:232956441:AAT:A	donor_gain	0.9900
1:232970061:A:T	donor_gain	0.9900
1:232970101:G:GT	donor_gain	0.9900

AlphaMissense

1218 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:232955670:T:C	F50L	0.999
1:232955672:C:A	F50L	0.999
1:232955672:C:G	F50L	0.999
1:232955566:A:T	K15I	0.996
1:232969955:A:T	E114V	0.996
1:232970039:G:A	G142D	0.995
1:232955668:G:A	G49E	0.994
1:232955671:T:C	F50S	0.994
1:232970038:G:C	G142R	0.994
1:232955565:A:C	K15Q	0.993
1:232955569:C:T	T16I	0.993
1:232955626:G:A	G35E	0.993
1:232969952:A:T	D113V	0.993
1:232969967:T:C	M118T	0.993
1:232955563:G:A	G14E	0.992
1:232955628:T:C	F36L	0.992
1:232955630:T:A	F36L	0.992
1:232955630:T:G	F36L	0.992
1:232969955:A:C	E114A	0.992
1:232955567:A:C	K15N	0.991
1:232955567:A:T	K15N	0.991
1:232956390:T:C	Y81H	0.991
1:232956397:T:A	V83D	0.991
1:232969952:A:C	D113A	0.991
1:232969961:G:A	G116E	0.991
1:232969978:A:C	S122R	0.991
1:232969980:T:A	S122R	0.991
1:232969980:T:G	S122R	0.991
1:232969953:T:A	D113E	0.990
1:232969953:T:G	D113E	0.990

dbSNP variants (sampled 300 via entrez): RS1000065437 (1:232967791 G>A), RS1000134563 (1:232960596 C>A), RS1000142043 (1:232965995 G>A), RS1000215964 (1:232968150 T>TACC), RS1000219224 (1:232960861 T>C,G), RS1000317118 (1:232982784 G>A), RS1000382346 (1:232961715 C>T), RS1000440281 (1:232955138 T>G), RS1000556673 (1:232962425 T>C), RS1000677617 (1:232956175 T>G), RS1000721850 (1:232949804 C>A), RS1000742130 (1:232954517 A>G), RS1000770040 (1:232950121 C>T), RS1000837665 (1:232962019 T>G), RS1000913669 (1:232979778 G>A,T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295936 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.24	Kd	57.43	nM	CHEMBL5653589
7.22	ED50	60.81	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 6 total; 1 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148893: Binding affinity to human NTPCR incubated for 45 mins by Kinobead based pull down assay	kd	0.0574	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects expression, decreases methylation, increases expression	3
bisphenol A	affects cotreatment, affects methylation, increases expression	2
Acetaminophen	decreases expression	2
Benzo(a)pyrene	increases expression	2
Cisplatin	affects cotreatment, increases expression	2
Valproic Acid	increases expression	2
Cyclosporine	affects expression, decreases expression	2
Cadmium Chloride	increases expression	2
bisphenol F	increases expression	1
chloroacetaldehyde	increases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression	1
adefovir dipivoxil	increases expression	1
corosolic acid	increases expression	1
bisphenol B	increases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	decreases expression	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects methylation, decreases methylation, affects cotreatment	1
Cidofovir	increases expression	1
Atrazine	increases expression	1
Clodronic Acid	increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	affects binding, increases reaction	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118694	Binding	Binding affinity to NTPCR in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3CX	Abcam HEK293T NTPCR KO	Transformed cell line	Female

Clinical trials (associated diseases)

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