NUDT18

Summary

NUDT18 (nudix hydrolase 18, HGNC:26194) is a protein-coding gene on chromosome 8p21.3, encoding 8-oxo-dGDP phosphatase NUDT18 (Q6ZVK8). Mediates the hydrolysis of oxidized nucleoside diphosphate derivatives.

The protein encoded by this gene is a member of the Nudix hydrolase family. Nudix hydrolases eliminate potentially toxic nucleotide metabolites from the cell and regulate the concentrations and availability of many different nucleotide substrates, cofactors, and signaling molecules. This protein contains a Nudix hydrolase domain and hydrolyzes oxidized forms of guanosine and deoxyguanosine diphosphates.

Source: NCBI Gene 79873 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 16 total
• MANE Select transcript: NM_024815

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26194
Approved symbol	NUDT18
Name	nudix hydrolase 18
Location	8p21.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22494, MTH3
Ensembl gene	ENSG00000275074
Ensembl biotype	protein_coding
OMIM	615791
Entrez	79873

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000611621, ENST00000613958

RefSeq mRNA: 1 — MANE Select: NM_024815 NM_024815

CCDS: CCDS75706

Canonical transcript exons

ENST00000611621 — 3 exons

Exon	Start	End
ENSE00003715883	22109139	22109419
ENSE00003732097	22108133	22108346
ENSE00003745384	22106878	22107895

Expression profiles

Bgee: expression breadth ubiquitous, 193 present calls, max score 92.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.7829 / max 74.3740, expressed in 1743 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92194	5.9889	1732
92193	0.7941	447

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.34	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.71	gold quality
body of pancreas	UBERON:0001150	81.80	gold quality
mucosa of transverse colon	UBERON:0004991	81.65	gold quality
granulocyte	CL:0000094	81.62	gold quality
monocyte	CL:0000576	80.50	gold quality
leukocyte	CL:0000738	80.28	gold quality
apex of heart	UBERON:0002098	80.23	gold quality
mononuclear cell	CL:0000842	80.22	gold quality
stromal cell of endometrium	CL:0002255	79.74	gold quality
prefrontal cortex	UBERON:0000451	79.52	gold quality
pancreas	UBERON:0001264	78.46	gold quality
body of stomach	UBERON:0001161	77.98	gold quality
blood	UBERON:0000178	77.92	gold quality
ascending aorta	UBERON:0001496	77.59	gold quality
right lobe of thyroid gland	UBERON:0001119	77.58	gold quality
thoracic aorta	UBERON:0001515	77.51	gold quality
periodontal ligament	UBERON:0008266	77.33	silver quality
descending thoracic aorta	UBERON:0002345	77.16	gold quality
spleen	UBERON:0002106	77.04	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	76.77	gold quality
parotid gland	UBERON:0001831	76.71	gold quality
right adrenal gland	UBERON:0001233	76.58	gold quality
adenohypophysis	UBERON:0002196	76.40	gold quality
right adrenal gland cortex	UBERON:0035827	76.21	gold quality
left lobe of thyroid gland	UBERON:0001120	76.18	gold quality
left coronary artery	UBERON:0001626	76.14	gold quality
minor salivary gland	UBERON:0001830	76.13	gold quality
right hemisphere of cerebellum	UBERON:0014890	76.07	gold quality
left adrenal gland	UBERON:0001234	75.87	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting NUDT18, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-510-5P	97.66	65.82	916
HSA-MIR-3144-5P	97.64	65.45	646
HSA-MIR-512-5P	97.47	66.48	591
HSA-MIR-4268	94.45	64.09	819

Literature-anchored findings (GeneRIF, showing 1)

• MTH3 is specifically active against 8-oxo-dGDP and hardly cleaves 8-oxo-dGTP. Other types of oxidized nucleoside diphosphates, 2-hydroxy-dADP and 8-hydroxy-dADP, were also hydrolyzed by MTH3. (PMID:22556419)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nudt18	ENSDARG00000041576
mus_musculus	Nudt18	ENSMUSG00000045211
rattus_norvegicus	Nudt18	ENSRNOG00000011831
drosophila_melanogaster	CG10898	FBGN0037911
caenorhabditis_elegans	ndx-1	WBGENE00003578

Paralogs (3): NUDT1 (ENSG00000106268), NUDT12 (ENSG00000112874), NUDT17 (ENSG00000186364)

Protein

Protein identifiers

8-oxo-dGDP phosphatase NUDT18 — Q6ZVK8 (reviewed: Q6ZVK8)

Alternative names: 2-hydroxy-dADP phosphatase, 7,8-dihydro-8-oxoguanine phosphatase, MutT homolog 3, Nucleoside diphosphate-linked moiety X motif 18

All UniProt accessions (2): Q6ZVK8, A0A087WW30

UniProt curated annotations — full annotation on UniProt →

Function. Mediates the hydrolysis of oxidized nucleoside diphosphate derivatives. Hydrolyzes 8-oxo-7,8-dihydroguanine (8-oxo-Gua)-containing deoxyribo- and ribonucleoside diphosphates to the monophosphates. Hydrolyzes 8-oxo-dGDP and 8-oxo-GDP with the same efficiencies. Also hydrolyzes 8-OH-dADP and 2-OH-dADP. Exhibited no or minimal hydrolysis activity against 8-oxo-dGTP, 8-oxo-GTP, dGTP, GTP, dGDP and GDP. Probably removes oxidized guanine nucleotides from both the DNA and RNA precursor pools. In vitro, it catalyzes the hydrolysis of isoprene pyrophosphates, including (2E)-geranyl diphosphate, isopentenyl diphosphate, (2E,6E)-farnesyl diphosphate and dimethylallyl diphosphate. It may therefore play a role in the control of cellular levels of these metabolites that are essential for multiple cellular processes, including isoprenoids synthesis and protein isoprenylation.

Similarity. Belongs to the Nudix hydrolase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZVK8-1	1	yes
Q6ZVK8-2	2

RefSeq proteins (1): NP_079091* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000086	NUDIX_hydrolase_dom	Domain
IPR015797	NUDIX_hydrolase-like_dom_sf	Homologous_superfamily
IPR020084	NUDIX_hydrolase_CS	Conserved_site
IPR020476	Nudix_hydrolase	Domain
IPR042970	NUDT18_NUDIX	Domain

Pfam: PF00293

Catalyzed reactions (Rhea), 10 shown:

• 8-oxo-dGDP + H2O = 8-oxo-dGMP + phosphate + H(+) (RHEA:32063)
• 8-oxo-dADP + H2O = 8-oxo-dAMP + phosphate + H(+) (RHEA:35219)
• 2-oxo-dADP + H2O = 2-oxo-dAMP + phosphate + H(+) (RHEA:35223)
• (2E)-geranyl diphosphate + H2O = (2E)-geranyl phosphate + phosphate + H(+) (RHEA:47944)
• (2E,6E)-farnesyl diphosphate + H2O = (2E,6E)-farnesyl phosphate + phosphate + H(+) (RHEA:48128)
• 8-oxo-GDP + H2O = 8-oxo-GMP + phosphate + H(+) (RHEA:62356)
• (2E,6E,10E)-geranylgeranyl diphosphate + H2O = (2E,6E,10E)-geranylgeranyl phosphate + phosphate + H(+) (RHEA:68008)
• isopentenyl diphosphate + H2O = isopentenyl phosphate + phosphate + H(+) (RHEA:70503)
• dimethylallyl diphosphate + H2O = dimethylallyl phosphate + phosphate + H(+) (RHEA:70507)
• (R)-5-diphosphomevalonate + H2O = (R)-5-phosphomevalonate + phosphate + H(+) (RHEA:82355)

UniProt features (20 total): strand 8, helix 4, splice variant 2, sequence conflict 2, chain 1, domain 1, short sequence motif 1, binding site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4HVY	X-RAY DIFFRACTION	1.46
3GG6	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZVK8-F1	94.96	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.

Ligand- & substrate-binding residues (1): 58

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2393930	Phosphate bond hydrolysis by NUDT proteins

MSigDB gene sets: 103 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, FREAC2_01, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, CAGCTG_AP4_Q5, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, chr8p21, GOBP_ORGANOPHOSPHATE_CATABOLIC_PROCESS, GOBP_GDP_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_CATABOLIC_PROCESS, FREAC4_01, GOBP_PURINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_PURINE_CONTAINING_COMPOUND_CATABOLIC_PROCESS

GO Biological Process (5): dADP catabolic process (GO:0046057), dGDP catabolic process (GO:0046067), GDP catabolic process (GO:0046712), nucleobase-containing small molecule metabolic process (GO:0055086), nucleotide metabolic process (GO:0009117)

GO Molecular Function (8): 8-oxo-dGDP phosphatase activity (GO:0044715), 8-oxo-GDP phosphatase activity (GO:0044716), 8-hydroxy-dADP phosphatase activity (GO:0044717), metal ion binding (GO:0046872), isoprenoid diphosphate phosphatase activity (GO:0106405), protein binding (GO:0005515), hydrolase activity (GO:0016787), nucleoside diphosphate phosphatase activity (GO:0017110)

GO Cellular Component (1): cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Purine catabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleoside diphosphate phosphatase activity	3
purine deoxyribonucleotide catabolic process	2
purine deoxyribonucleoside diphosphate catabolic process	2
deoxyribonucleoside diphosphate catabolic process	2
pyrophosphatase activity	2
dADP metabolic process	1
dGDP metabolic process	1
purine ribonucleotide catabolic process	1
purine ribonucleoside diphosphate catabolic process	1
GDP metabolic process	1
nucleobase-containing compound metabolic process	1
small molecule metabolic process	1
nucleoside phosphate metabolic process	1
cation binding	1
binding	1
catalytic activity	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

568 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUDT18	NUDT15	Q9NV35	844
NUDT18	NUDT5	Q9UKK9	811
NUDT18	NUDT1	P36639	765
NUDT18	NUDT14	O95848	743
NUDT18	NUDT17	P0C025	736
NUDT18	NUDT12	Q9BQG2	715
NUDT18	NUDT22	Q9BRQ3	703
NUDT18	NUDT9	Q9BW91	670
NUDT18	NUDT2	P50583	647
NUDT18	NUDT6	P53370	545
NUDT18	NUDT3	O95989	526
NUDT18	NUDT4B	A0A024RBG1	519
NUDT18	FKBP8	Q14318	495
NUDT18	NUDT7	P0C024	476
NUDT18	NUDT8	Q8WV74	476

IntAct

78 interactions, top by confidence:

A	B	Type	Score
NUDT18	APIP	psi-mi:“MI:0915”(physical association)	0.710
APIP	NUDT18	psi-mi:“MI:0915”(physical association)	0.710
NUDT18	RABAC1	psi-mi:“MI:0915”(physical association)	0.620
PAICS	NUDT18	psi-mi:“MI:0915”(physical association)	0.620
EVI5L	NUDT18	psi-mi:“MI:0915”(physical association)	0.620
DHPS	NUDT18	psi-mi:“MI:0915”(physical association)	0.620
NUDT18	DUT	psi-mi:“MI:0915”(physical association)	0.620
NT5C2	NUDT18	psi-mi:“MI:0915”(physical association)	0.620
NUDT18	HSD17B14	psi-mi:“MI:0915”(physical association)	0.620
RAB3IL1	NUDT18	psi-mi:“MI:0915”(physical association)	0.620
RABAC1	NUDT18	psi-mi:“MI:0915”(physical association)	0.620
NUDT18	EVI5L	psi-mi:“MI:0915”(physical association)	0.620
HSD17B14	NUDT18	psi-mi:“MI:0915”(physical association)	0.620
DUT	NUDT18	psi-mi:“MI:0915”(physical association)	0.620
NUDT18	tax	psi-mi:“MI:0915”(physical association)	0.560
tax	NUDT18	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (54): NUDT18 (Two-hybrid), NUDT18 (Two-hybrid), NUDT18 (Two-hybrid), TIFA (Two-hybrid), NUDT18 (Two-hybrid), NUDT18 (Two-hybrid), NUDT18 (Two-hybrid), NUDT18 (Two-hybrid), NUDT18 (Two-hybrid), NUDT18 (Two-hybrid), KCTD13 (Two-hybrid), NUDT18 (Two-hybrid), NUDT18 (Two-hybrid), NUDT18 (Two-hybrid), NUDT18 (Two-hybrid)

ESM2 similar proteins: A4FU01, A4FUG7, A6NE52, D2HS90, D4A929, O15287, O94761, O95382, P0C025, P29473, P29474, P51617, P70313, P97270, Q05932, Q14296, Q15477, Q1JPD6, Q2LGB3, Q3MHT4, Q3U5Q7, Q3V1L6, Q562E7, Q5M8V2, Q5ND34, Q5PQ04, Q5RA67, Q5RAJ5, Q5XIS1, Q62406, Q69ZM6, Q6ZS72, Q6ZVH7, Q6ZVK8, Q75NR7, Q76MJ5, Q7M733, Q80UU1, Q8BLY7, Q8BTN6

Diamond homologs: A4VLQ5, A5W1F2, B0KMR5, B1J6H6, B7VM66, O06972, P32091, P46351, P96590, Q1IBF8, Q3KC83, Q6ZVK8, Q75UV1, Q87KQ7, Q88FQ8, A1AIG7, A3M1S5, A4W5B9, A5F3M9, A6TGQ3, A7ZUL1, A8A796, A9N0K8, B0VEE3, B0VLB6, B1IUQ1, B1LNU8, B1XBZ9, B2I354, B2TWI3, B4T0Z8, B4TCT5, B4TQK6, B5BJR5, B5F1H9, B5FQL1, B5QYF1, B5RFI8, B5XYE2, B5Z092

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

457 predictions. Top by Δscore:

Variant	Effect	Δscore
8:22109134:CTCA:C	donor_loss	1.0000
8:22109135:TCA:T	donor_loss	1.0000
8:22109136:CA:C	donor_loss	1.0000
8:22107894:ACC:A	acceptor_loss	0.9900
8:22107896:CT:C	acceptor_loss	0.9900
8:22107905:A:C	acceptor_gain	0.9900
8:22108342:TCATC:T	acceptor_gain	0.9900
8:22108343:CATC:C	acceptor_gain	0.9900
8:22108343:CATCC:C	acceptor_gain	0.9900
8:22108344:ATCC:A	acceptor_loss	0.9900
8:22108347:CTGA:C	acceptor_loss	0.9900
8:22109138:CCTG:C	donor_gain	0.9900
8:22107892:CCAC:C	acceptor_gain	0.9800
8:22107893:CACC:C	acceptor_gain	0.9800
8:22108345:TC:T	acceptor_gain	0.9800
8:22108346:CC:C	acceptor_gain	0.9800
8:22108347:C:CC	acceptor_gain	0.9800
8:22109137:A:AC	donor_gain	0.9800
8:22109138:C:CC	donor_gain	0.9800
8:22107896:C:CC	acceptor_gain	0.9700
8:22107905:A:AC	acceptor_gain	0.9700
8:22108127:CCATA:C	donor_loss	0.9700
8:22107893:CAC:C	acceptor_gain	0.9600
8:22108228:T:TA	donor_gain	0.9600
8:22108452:CTCA:C	donor_gain	0.9600
8:22107907:G:C	acceptor_gain	0.9500
8:22108126:GCCAT:G	donor_loss	0.9500
8:22107891:TCCAC:T	acceptor_gain	0.9400
8:22107892:CCACC:C	acceptor_gain	0.9400
8:22107907:G:GC	acceptor_gain	0.9400

AlphaMissense

2053 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:22108240:C:G	R90P	0.990
8:22108298:A:G	W71R	0.990
8:22108298:A:T	W71R	0.990
8:22108156:A:G	F118S	0.987
8:22108288:G:T	P74H	0.986
8:22107383:A:G	W297R	0.985
8:22107383:A:T	W297R	0.985
8:22108250:C:G	A87P	0.984
8:22107882:C:A	K130N	0.983
8:22107882:C:G	K130N	0.983
8:22108223:C:G	A96P	0.983
8:22108236:C:A	E91D	0.982
8:22108236:C:G	E91D	0.982
8:22107857:A:G	S139P	0.981
8:22108159:C:G	R117P	0.977
8:22108224:C:A	E95D	0.977
8:22108224:C:G	E95D	0.977
8:22108295:A:G	Y72H	0.977
8:22107684:A:C	F196L	0.976
8:22107684:A:T	F196L	0.976
8:22107686:A:G	F196L	0.976
8:22108323:C:A	E62D	0.976
8:22108323:C:G	E62D	0.976
8:22108225:T:A	E95V	0.975
8:22108296:C:A	W71C	0.975
8:22108296:C:G	W71C	0.975
8:22108324:T:A	E62V	0.975
8:22107381:C:A	W297C	0.974
8:22107381:C:G	W297C	0.974
8:22108249:G:T	A87E	0.974

dbSNP variants (sampled 300 via entrez): RS1000129020 (8:22112310 C>T), RS1000145902 (8:22112103 G>A), RS1000424477 (8:22106909 C>T), RS1001306273 (8:22109012 G>A), RS1001358117 (8:22108763 G>A,C), RS1002485468 (8:22112207 C>T), RS1002545915 (8:22108383 C>A), RS1003033113 (8:22109815 C>G,T), RS1003490103 (8:22109735 G>A,C), RS1004376406 (8:22109031 G>A,C), RS1004428690 (8:22108724 C>G), RS1005382204 (8:22110084 G>A,C), RS1005487611 (8:22108799 T>C), RS1005602352 (8:22109030 G>A,T), RS1005840832 (8:22109827 A>C,G)

Disease associations

OMIM: gene MIM:615791 | 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: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cisplatin	affects expression, affects cotreatment, increases expression	2
Cadmium Chloride	increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
sodium arsenate	decreases expression, increases abundance	1
zinc chromate	decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
jinfukang	affects cotreatment, increases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Air Pollutants, Occupational	affects expression	1
Arsenic	decreases expression, increases abundance	1
Calcitriol	increases expression, affects cotreatment	1
Niclosamide	increases expression	1
Rotenone	decreases expression	1
Silicon Dioxide	decreases expression	1
Testosterone	affects cotreatment, increases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Vitamin E	increases expression	1
Okadaic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2EV	HAP1 NUDT18 (-) 1	Cancer cell line	Male
CVCL_E2EW	HAP1 NUDT18 (-) 2	Cancer cell line	Male
CVCL_E2EX	HAP1 NUDT18 (-) 3	Cancer cell line	Male
CVCL_E2EY	HAP1 NUDT18 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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