NUDT8

Summary

NUDT8 (nudix hydrolase 8, HGNC:8055) is a protein-coding gene on chromosome 11q13.2, encoding Mitochondrial coenzyme A diphosphatase NUDT8 (Q8WV74). Acyl-CoA diphosphatase that mediates the hydrolysis of a wide range of CoA and CoA esters yielding 3’,5’-ADP and the corresponding 4’-phosphopantetheine derivative as products.

Predicted to enable magnesium ion binding activity and manganese ion binding activity. Predicted to be involved in nucleoside phosphate catabolic process. Located in mitochondrion.

Source: NCBI Gene 254552 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 21 total
• MANE Select transcript: NM_001243750

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8055
Approved symbol	NUDT8
Name	nudix hydrolase 8
Location	11q13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ41567
Ensembl gene	ENSG00000167799
Ensembl biotype	protein_coding
Entrez	254552

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 retained_intron

ENST00000301490, ENST00000376693, ENST00000534054, ENST00000877639, ENST00000877640, ENST00000943309, ENST00000943310

RefSeq mRNA: 2 — MANE Select: NM_001243750 NM_001243750, NM_181843

CCDS: CCDS58151, CCDS8174

Canonical transcript exons

ENST00000376693 — 4 exons

Exon	Start	End
ENSE00001185394	67628919	67629051
ENSE00001185399	67629718	67629937
ENSE00001471375	67627938	67628251
ENSE00001471377	67628323	67628400

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 95.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.0595 / max 97.9508, expressed in 1609 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120954	8.0595	1609

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	95.74	gold quality
right atrium auricular region	UBERON:0006631	93.36	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.11	gold quality
heart left ventricle	UBERON:0002084	92.76	gold quality
lower esophagus mucosa	UBERON:0035834	92.67	gold quality
quadriceps femoris	UBERON:0001377	92.48	gold quality
thymus	UBERON:0002370	92.34	silver quality
esophagus mucosa	UBERON:0002469	91.70	gold quality
mucosa of transverse colon	UBERON:0004991	90.00	gold quality
right lobe of liver	UBERON:0001114	89.92	gold quality
gastrocnemius	UBERON:0001388	89.78	gold quality
heart	UBERON:0000948	89.71	gold quality
muscle of leg	UBERON:0001383	88.71	gold quality
skin of leg	UBERON:0001511	87.15	gold quality
adult mammalian kidney	UBERON:0000082	86.86	gold quality
liver	UBERON:0002107	86.66	gold quality
zone of skin	UBERON:0000014	86.33	gold quality
skeletal muscle tissue	UBERON:0001134	86.00	gold quality
right lobe of thyroid gland	UBERON:0001119	85.84	gold quality
skin of abdomen	UBERON:0001416	85.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.18	gold quality
left lobe of thyroid gland	UBERON:0001120	84.83	gold quality
cortex of kidney	UBERON:0001225	84.64	gold quality
saliva-secreting gland	UBERON:0001044	84.46	gold quality
minor salivary gland	UBERON:0001830	84.23	gold quality
thyroid gland	UBERON:0002046	83.85	gold quality
duodenum	UBERON:0002114	83.27	gold quality
metanephros cortex	UBERON:0010533	82.86	gold quality
muscle tissue	UBERON:0002385	81.95	gold quality
esophagus	UBERON:0001043	81.23	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting NUDT8, 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-1184	99.99	68.19	1458
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-3665	97.73	65.08	975
HSA-MIR-379-5P	97.52	67.81	485
HSA-MIR-6779-3P	97.51	65.82	789
HSA-MIR-1910-5P	97.42	66.36	844
HSA-MIR-4640-5P	97.42	66.33	1543
HSA-MIR-4726-5P	97.24	65.67	1299
HSA-MIR-3529-5P	97.12	67.06	440
HSA-MIR-6759-3P	96.94	68.31	823
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280
HSA-MIR-7976	95.75	65.67	1186
HSA-MIR-483-5P	93.53	65.81	111
HSA-MIR-4707-5P	90.95	65.69	110

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Mitochondrial coenzyme A diphosphatase NUDT8 — Q8WV74 (reviewed: Q8WV74)

Alternative names: Nucleoside diphosphate-linked moiety X motif 8

All UniProt accessions (1): Q8WV74

UniProt curated annotations — full annotation on UniProt →

Function. Acyl-CoA diphosphatase that mediates the hydrolysis of a wide range of CoA and CoA esters yielding 3’,5’-ADP and the corresponding 4’-phosphopantetheine derivative as products. Hydrolyzes short- and medium-chain acyl-CoAs, exhibiting the highest activity toward free CoA, hexanoyl-CoA, and octanoyl-CoA and the lowest activity against acetyl-CoA. Exhibits decapping activity towards dpCoA-capped RNAs in vitro.

Subunit / interactions. Monomer.

Subcellular location. Mitochondrion.

Similarity. Belongs to the Nudix hydrolase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WV74-1	1	yes
Q8WV74-2	2

RefSeq proteins (2): NP_001230679, NP_862826 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000086	NUDIX_hydrolase_dom	Domain
IPR015797	NUDIX_hydrolase-like_dom_sf	Homologous_superfamily
IPR045121	CoAse	Family

Pfam: PF00293

Catalyzed reactions (Rhea), 10 shown:

• butanoyl-CoA + H2O = S-butanoyl-4’-phosphopantetheine + adenosine 3’,5’-bisphosphate + 2 H(+) (RHEA:49976)
• hexanoyl-CoA + H2O = hexanoyl-4’-phosphopantetheine + adenosine 3’,5’-bisphosphate + 2 H(+) (RHEA:49980)
• octanoyl-CoA + H2O = S-octanoyl-4’-phosphopantetheine + adenosine 3’,5’-bisphosphate + 2 H(+) (RHEA:50016)
• an acyl-CoA + H2O = an acyl-4’-phosphopantetheine + adenosine 3’,5’-bisphosphate + 2 H(+) (RHEA:50044)
• CoA + H2O = (R)-4’-phosphopantetheine + adenosine 3’,5’-bisphosphate + 2 H(+) (RHEA:64988)
• acetyl-CoA + H2O = S-acetyl-4’-phosphopantetheine + adenosine 3’,5’-bisphosphate + 2 H(+) (RHEA:64992)
• propanoyl-CoA + H2O = propanoyl-4’-phosphopantetheine + adenosine 3’,5’-bisphosphate + 2 H(+) (RHEA:67464)
• malonyl-CoA + H2O = malonyl-4’-phosphopantetheine + adenosine 3’,5’-bisphosphate + 2 H(+) (RHEA:67468)
• succinyl-CoA + H2O = succinyl-4’-phosphopantetheine + adenosine 3’,5’-bisphosphate + 2 H(+) (RHEA:67472)
• a 5’-end CoA-ribonucleoside in mRNA + H2O = a 5’-end phospho-adenosine-phospho-ribonucleoside in mRNA + (R)-4’-phosphopantetheine + 2 H(+) (RHEA:67592)

UniProt features (8 total): binding site 2, splice variant 2, chain 1, domain 1, short sequence motif 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WV74-F1	84.86	0.68

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): 85; 89

Post-translational modifications (1): 70

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-199220	Vitamin B5 (pantothenate) metabolism

MSigDB gene sets: 68 (showing top): RNGTGGGC_UNKNOWN, GOBP_FATTY_ACID_CATABOLIC_PROCESS, GOBP_COENZYME_A_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ACETYL_COA_METABOLIC_PROCESS, chr11q13, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_FATTY_ACYL_COA_METABOLIC_PROCESS, GOBP_SULFUR_COMPOUND_CATABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_CATABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS

GO Biological Process (7): coenzyme A catabolic process (GO:0015938), medium-chain fatty-acyl-CoA catabolic process (GO:0036114), butyryl-CoA catabolic process (GO:0044580), acetyl-CoA catabolic process (GO:0046356), succinyl-CoA catabolic process (GO:1901289), propionyl-CoA catabolic process (GO:1902859), malonyl-CoA catabolic process (GO:2001294)

GO Molecular Function (5): magnesium ion binding (GO:0000287), coenzyme A diphosphatase activity (GO:0010945), manganese ion binding (GO:0030145), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (1): mitochondrion (GO:0005739)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of water-soluble vitamins and cofactors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
sulfur compound catabolic process	4
purine-containing compound catabolic process	4
nucleoside phosphate catabolic process	4
fatty-acyl-CoA catabolic process	3
coenzyme A metabolic process	1
medium-chain fatty-acyl-CoA metabolic process	1
fatty acid catabolic process	1
acetyl-CoA metabolic process	1
succinyl-CoA metabolic process	1
propionyl-CoA metabolic process	1
malonyl-CoA metabolic process	1
metal ion binding	1
pyrophosphatase activity	1
transition metal ion binding	1
catalytic activity	1
cation binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

950 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUDT8	NUDT19	A8MXV4	658
NUDT8	NUDT15	Q9NV35	583
NUDT8	NUDT13	Q86X67	579
NUDT8	NUDT12	Q9BQG2	574
NUDT8	NUDT5	Q9UKK9	561
NUDT8	NUDT2	P50583	519
NUDT8	NUDT22	Q9BRQ3	494
NUDT8	NUDT18	Q6ZVK8	476
NUDT8	FAM174B	Q3ZCQ3	467
NUDT8	SLC25A42	Q86VD7	463
NUDT8	NUDT17	P0C025	447
NUDT8	NUDT14	O95848	419
NUDT8	ZBED5	Q49AG3	419
NUDT8	C6orf136	Q5SQH8	412
NUDT8	COASY	Q13057	404

IntAct

31 interactions, top by confidence:

A	B	Type	Score
ODAPH	TCAF2	psi-mi:“MI:0914”(association)	0.530
NPPA	A2ML1	psi-mi:“MI:0914”(association)	0.530
CDRT15	CDRT15L2	psi-mi:“MI:0914”(association)	0.530
SPINK2	STRN	psi-mi:“MI:0914”(association)	0.530
PMPCA	CLUH	psi-mi:“MI:0914”(association)	0.530
NPPA	VGF	psi-mi:“MI:0914”(association)	0.530
PMPCA	PMPCB	psi-mi:“MI:0914”(association)	0.530
SPATA20	PMPCB	psi-mi:“MI:0914”(association)	0.350
NIT1	NDUFS6	psi-mi:“MI:0914”(association)	0.350
SPATA20	NDUFAB1	psi-mi:“MI:0914”(association)	0.350
NIT1	PMPCB	psi-mi:“MI:0914”(association)	0.350
COQ8A	ESYT2	psi-mi:“MI:0914”(association)	0.350
UQCRFS1	VWA8	psi-mi:“MI:0914”(association)	0.350
MRPL51		psi-mi:“MI:0914”(association)	0.350
MMAB	DPYSL4	psi-mi:“MI:0914”(association)	0.350
KRTAP13-2	HTRA2	psi-mi:“MI:0914”(association)	0.350
LINC02872	NMT2	psi-mi:“MI:0914”(association)	0.350
CCDC69	PMPCB	psi-mi:“MI:0914”(association)	0.350
MEI1	PMPCB	psi-mi:“MI:0914”(association)	0.350
DNAJC8	PMPCB	psi-mi:“MI:0914”(association)	0.350
KRT75	PMPCB	psi-mi:“MI:0914”(association)	0.350
SOST	PPP1R12A	psi-mi:“MI:0914”(association)	0.350
KRT86	PMPCB	psi-mi:“MI:0914”(association)	0.350
FECH	GTPBP10	psi-mi:“MI:0914”(association)	0.350
	VWA8	psi-mi:“MI:2364”(proximity)	0.270
HSPD1	VWA8	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (29): NUDT8 (Affinity Capture-MS), NUDT8 (Affinity Capture-MS), NUDT8 (Affinity Capture-MS), NUDT8 (Affinity Capture-MS), NUDT8 (Affinity Capture-MS), NUDT8 (Affinity Capture-MS), NUDT8 (Affinity Capture-MS), NUDT8 (Affinity Capture-MS), NUDT8 (Affinity Capture-MS), NUDT8 (Proximity Label-MS), NUDT8 (Proximity Label-MS), NUDT8 (Proximity Label-MS), NUDT8 (Affinity Capture-MS), NUDT8 (Affinity Capture-MS), NUDT8 (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: A1ABY1, A1JMC0, A4TKD0, A4WBH1, A6TAY4, A7FJ95, A7MKE8, A7ZMT6, A8A110, A8AFP5, A9MVU1, A9R5X2, B1J0S5, B1JP41, B1LD60, B1XH80, B2K0H0, B2U449, B4SUL8, B4TKF7, B4TXZ6, B5BHD1, B5F3R6, B5FTK8, B5R2U5, B5XQ60, B5YQV4, B6IBP0, B7L6U1, B7LPN4, B7M287, B7MBL9, B7MVU2, B7NBF9, B7NSW2, B7USI8, C0Q309, C4ZZG9, O22951, P0A2K9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

557 predictions. Top by Δscore:

Variant	Effect	Δscore
11:67628916:TA:T	donor_loss	1.0000
11:67628917:A:AC	donor_gain	1.0000
11:67628918:C:CT	donor_gain	1.0000
11:67628918:CCG:C	donor_gain	1.0000
11:67628918:CCGG:C	donor_gain	1.0000
11:67628918:CCGGA:C	donor_gain	1.0000
11:67629050:AA:A	acceptor_gain	1.0000
11:67629052:C:CC	acceptor_gain	1.0000
11:67628324:T:TA	donor_gain	0.9900
11:67628396:TTTTG:T	acceptor_gain	0.9900
11:67628398:T:C	acceptor_gain	0.9900
11:67628398:TTG:T	acceptor_gain	0.9900
11:67628399:TG:T	acceptor_gain	0.9900
11:67628401:C:CC	acceptor_gain	0.9900
11:67628917:AC:A	donor_gain	0.9900
11:67628918:CC:C	donor_gain	0.9900
11:67629047:GGAAA:G	acceptor_gain	0.9900
11:67629048:GAAA:G	acceptor_gain	0.9900
11:67629049:AAA:A	acceptor_gain	0.9900
11:67629712:CTGTA:C	donor_loss	0.9900
11:67629713:TGTAC:T	donor_loss	0.9900
11:67629714:GTA:G	donor_loss	0.9900
11:67629715:TA:T	donor_loss	0.9900
11:67629716:A:AT	donor_loss	0.9900
11:67629717:CCTG:C	donor_loss	0.9900
11:67628315:CAGCT:C	donor_loss	0.9800
11:67628316:AGCTC:A	donor_loss	0.9800
11:67628317:GCTC:G	donor_loss	0.9800
11:67628318:CTCAC:C	donor_loss	0.9800
11:67628319:TCA:T	donor_loss	0.9800

AlphaMissense

1458 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:67628112:G:A	T182I	0.991
11:67628144:G:C	F171L	0.990
11:67628144:G:T	F171L	0.990
11:67628146:A:G	F171L	0.990
11:67629051:A:C	S65R	0.988
11:67629051:A:T	S65R	0.988
11:67629719:T:G	S65R	0.988
11:67628145:A:G	F171S	0.987
11:67628991:T:A	E85D	0.986
11:67628991:T:G	E85D	0.986
11:67628109:G:T	A183D	0.985
11:67629001:G:T	A82D	0.985
11:67629049:A:G	F66S	0.984
11:67629767:A:C	Y49D	0.983
11:67628237:A:C	F140L	0.982
11:67628237:A:T	F140L	0.982
11:67628239:A:G	F140L	0.982
11:67629048:G:C	F66L	0.982
11:67629048:G:T	F66L	0.982
11:67629050:A:G	F66L	0.982
11:67628992:T:A	E85V	0.980
11:67628238:A:G	F140S	0.979
11:67628145:A:C	F171C	0.978
11:67628995:C:G	R84P	0.978
11:67628183:G:C	F158L	0.976
11:67628183:G:T	F158L	0.976
11:67628185:A:G	F158L	0.976
11:67628124:A:T	V178D	0.975
11:67628120:C:A	W179C	0.972
11:67628120:C:G	W179C	0.972

dbSNP variants (sampled 300 via entrez): RS1000701724 (11:67629484 G>A,T), RS1001334269 (11:67630083 G>A), RS1001556307 (11:67631001 A>G,T), RS1001868996 (11:67629855 T>A,C), RS1003138806 (11:67631170 G>A), RS1003420872 (11:67631355 C>T), RS1004454966 (11:67629131 A>G), RS1004898759 (11:67627923 C>A,T), RS1005254857 (11:67627614 G>C), RS1005413921 (11:67630625 G>T), RS1006157121 (11:67630499 C>A), RS1006338173 (11:67630150 G>A,C), RS1007041048 (11:67630693 C>A,T), RS1007304515 (11:67629768 C>T), RS1009993254 (11:67629495 G>A,C)

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: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects splicing, decreases expression, increases expression	4
Cisplatin	increases expression, affects cotreatment	2
GSK-J4	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
zinc chromate	decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
K 7174	decreases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	decreases expression	1
Tunicamycin	decreases expression	1
Urethane	decreases expression	1
Thapsigargin	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2FA	HAP1 NUDT8 (-) 1	Cancer cell line	Male
CVCL_E2FB	HAP1 NUDT8 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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