NUDT4B

Summary

NUDT4B (nudix hydrolase 4B, HGNC:18012) is a protein-coding gene on chromosome 1q21.2, encoding Diphosphoinositol polyphosphate phosphohydrolase NUDT4B (A0A024RBG1). Cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 (diphosphoinositol pentakisphosphate), PP-InsP4 and [PP]2-InsP4 (bisdiphosphoinositol tetrakisphosphate), suggesting that it may play a role in signal transduction.

Predicted to enable pyrophosphatase activity. Predicted to be involved in diphosphoinositol polyphosphate metabolic process and nucleotide catabolic process. Located in cytosol.

Source: NCBI Gene 440672 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001355407

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18012
Approved symbol	NUDT4B
Name	nudix hydrolase 4B
Location	1q21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000177144
Ensembl biotype	protein_coding
Entrez	440672

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000322209

RefSeq mRNA: 1 — MANE Select: NM_001355407 NM_001355407

CCDS: CCDS86013

Canonical transcript exons

ENST00000322209 — 1 exons

Exon	Start	End
ENSE00001263412	148748774	148752415

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 86.91.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gall bladder	UBERON:0002110	86.91	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.37	gold quality
bone marrow	UBERON:0002371	82.55	gold quality
bone marrow cell	CL:0002092	80.04	gold quality
monocyte	CL:0000576	79.00	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.14	gold quality
leukocyte	CL:0000738	78.06	gold quality
islet of Langerhans	UBERON:0000006	77.04	gold quality
rectum	UBERON:0001052	76.77	gold quality
placenta	UBERON:0001987	75.70	gold quality
duodenum	UBERON:0002114	75.15	gold quality
skeletal muscle tissue	UBERON:0001134	75.07	gold quality
blood	UBERON:0000178	74.82	gold quality
smooth muscle tissue	UBERON:0001135	73.98	gold quality
stromal cell of endometrium	CL:0002255	73.66	gold quality
muscle tissue	UBERON:0002385	72.59	gold quality
vermiform appendix	UBERON:0001154	71.98	gold quality
gastrocnemius	UBERON:0001388	71.89	gold quality
descending thoracic aorta	UBERON:0002345	71.37	gold quality
lymph node	UBERON:0000029	71.10	gold quality
right coronary artery	UBERON:0001625	71.06	gold quality
muscle of leg	UBERON:0001383	70.90	gold quality
right adrenal gland cortex	UBERON:0035827	70.72	gold quality
prefrontal cortex	UBERON:0000451	70.54	gold quality
right adrenal gland	UBERON:0001233	70.27	gold quality
popliteal artery	UBERON:0002250	69.89	gold quality
tibial artery	UBERON:0007610	69.82	gold quality
left testis	UBERON:0004533	68.87	gold quality
testis	UBERON:0000473	68.83	gold quality
thoracic aorta	UBERON:0001515	68.77	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9221	yes	18.86
E-HCAD-9	yes	5.29
E-ANND-3	no	0.86

Regulation

Is transcription factor: no

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nudt4b	ENSDARG00000045878
danio_rerio	nudt4a	ENSDARG00000057767
mus_musculus	Nudt4	ENSMUSG00000020029
rattus_norvegicus	Nudt4	ENSRNOG00000009094
drosophila_melanogaster	Aps	FBGN0036111

Paralogs (4): NUDT10 (ENSG00000122824), NUDT4 (ENSG00000173598), NUDT11 (ENSG00000196368), NUDT3 (ENSG00000272325)

Protein

Protein identifiers

Diphosphoinositol polyphosphate phosphohydrolase NUDT4B — A0A024RBG1 (reviewed: A0A024RBG1)

Alternative names: Nucleoside diphosphate-linked moiety X motif 4B, Nudix hydrolase 4B

All UniProt accessions (1): A0A024RBG1

UniProt curated annotations — full annotation on UniProt →

Function. Cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 (diphosphoinositol pentakisphosphate), PP-InsP4 and [PP]2-InsP4 (bisdiphosphoinositol tetrakisphosphate), suggesting that it may play a role in signal transduction. Also able to catalyze the hydrolysis of dinucleoside oligophosphate Ap6A, but not Ap5A. The major reaction products are ADP and p4a from Ap6A. Also able to hydrolyze 5-phosphoribose 1-diphosphate. Does not play a role in U8 snoRNA decapping activity. Binds U8 snoRNA.

Subcellular location. Cytoplasm.

Cofactor. Binds 3 Mg(2+) or Mn(2+) ions per subunit.

Similarity. Belongs to the Nudix hydrolase family. DIPP subfamily.

RefSeq proteins (1): NP_001342336* (*=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
IPR047198	DDP-like_NUDIX	Domain

Pfam: PF00293

UniProt features (14 total): binding site 10, chain 1, domain 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0A024RBG1-F1	85.03	0.73

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): 69 (proton acceptor)

Ligand- & substrate-binding residues (10): 70; 90–92; 116; 134; 10; 18–20; 39–41; 50; 66; 66

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 25 (showing top): GOBP_INOSITOL_PHOSPHATE_METABOLIC_PROCESS, GOBP_POLYOL_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_CATABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_CATABOLIC_PROCESS, GOBP_PURINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_PURINE_CONTAINING_COMPOUND_CATABOLIC_PROCESS, GOBP_ALCOHOL_METABOLIC_PROCESS, chr1q21, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ACID_ANHYDRIDES, SRC_UP.V1_UP, GOBP_DIADENOSINE_POLYPHOSPHATE_METABOLIC_PROCESS

GO Biological Process (4): diphosphoinositol polyphosphate metabolic process (GO:0071543), diadenosine pentaphosphate catabolic process (GO:1901907), diadenosine hexaphosphate catabolic process (GO:1901909), adenosine 5’-(hexahydrogen pentaphosphate) catabolic process (GO:1901911)

GO Molecular Function (9): endopolyphosphatase activity (GO:0000298), RNA binding (GO:0003723), diphosphoinositol-polyphosphate diphosphatase activity (GO:0008486), bis(5’-adenosyl)-hexaphosphatase activity (GO:0034431), bis(5’-adenosyl)-pentaphosphatase activity (GO:0034432), metal ion binding (GO:0046872), protein binding (GO:0005515), pyrophosphatase activity (GO:0016462), hydrolase activity (GO:0016787)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
pyrophosphatase activity	4
diadenosine polyphosphate catabolic process	2
cellular anatomical structure	2
inositol phosphate metabolic process	1
purine ribonucleotide catabolic process	1
nucleic acid binding	1
cation binding	1
binding	1
hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

868 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUDT4B	NUDT22	Q9BRQ3	580
NUDT4B	NUDT17	P0C025	580
NUDT4B	NUDT5	Q9UKK9	577
NUDT4B	NUDT14	O95848	570
NUDT4B	NUDT2	P50583	543
NUDT4B	NUDT1	P36639	521
NUDT4B	NUDT18	Q6ZVK8	519
NUDT4B	NUDT12	Q9BQG2	518
NUDT4B	NUDT7	P0C024	501
NUDT4B	PLEKHA5	Q9HAU0	494
NUDT4B	ACTR10	Q9NZ32	488
NUDT4B	NUDT15	Q9NV35	478
NUDT4B	MPHOSPH8	Q99549	476
NUDT4B	NUDT9	Q9BW91	458
NUDT4B	NUDT6	P53370	452

IntAct

4 interactions, top by confidence:

A	B	Type	Score
NUDT10	NUDT4B	psi-mi:“MI:0914”(association)	0.500
NUDT10	NUDT4B	psi-mi:“MI:0915”(physical association)	0.500
ANKLE2	NUDT4B	psi-mi:“MI:0914”(association)	0.350

BioGRID (19): NUDT4 (Two-hybrid), NUDT4 (Affinity Capture-MS), NUDT4 (Affinity Capture-MS), NUDT4 (Affinity Capture-MS), NUDT4 (Affinity Capture-MS), NUDT4 (Positive Genetic), NUDT4 (Affinity Capture-MS), NUDT4 (Affinity Capture-MS), NUDT4 (Affinity Capture-MS), NUDT4 (Proximity Label-MS), NUDT4 (Affinity Capture-MS), NUDT4 (Proximity Label-MS), NUDT4 (Proximity Label-MS), NUDT4 (Proximity Label-MS), NUDT4 (Affinity Capture-MS)

ESM2 similar proteins: A0A024RBG1, A2VE79, A3KMI0, A7E320, B0R160, B6CHA3, F4JLK2, F6UA42, O22951, O45830, O59761, O95989, P0C027, P0C028, P32271, Q08C92, Q09790, Q566C7, Q58CW0, Q5RAF0, Q5RDX4, Q5U243, Q6NPD7, Q6P5D3, Q7TMI3, Q7TPK1, Q7YTB0, Q8BJM7, Q8CIG3, Q8L7W2, Q8NB78, Q8NFP7, Q8R2U6, Q8VDF2, Q8VHT6, Q91WU5, Q96G61, Q96PU4, Q96T88, Q99321

Diamond homologs: A0A024RBG1, A2VE79, O95989, P0C027, P0C028, P53370, P70563, P96590, Q09790, Q52K88, Q566C7, Q58CW0, Q5RAF0, Q8CH40, Q8NFP7, Q8R2U6, Q8VY81, Q93ZY7, Q96G61, Q99321, Q99MY2, Q9JI46, Q9LE73, Q9LHK1, Q9LQU5, Q9NZJ9, Q9ZU95, Q9RVK2, P32091, P59659, F1P963, O45830, P36639, P41354, P46351, P53368, P53369, P95781, P9WIX8, P9WIX9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1174 scored. Top likely-pathogenic:

dbSNP variants (sampled 272 via entrez): RS112714472 (1:148749091 A>T), RS112945491 (1:148748672 G>C), RS11484529 (1:148747971 C>T), RS11487273 (1:148751758 T>G), RS1158870262 (1:148752042 ATTT>A,AT,ATT,ATTTT,ATTTTT,ATTTTTT,ATTTTTTT), RS1161280150 (1:148752375 C>A), RS1168332961 (1:148751725 T>C), RS1176259313 (1:148751959 T>G), RS1178385750 (1:148751899 C>T), RS1183259236 (1:148751927 G>A), RS1189963906 (1:148752393 ATG>A), RS1193422303 (1:148751776 G>A), RS1199482602 (1:148752519 C>T), RS1201268047 (1:148751975 G>A), RS1203133189 (1:148751807 G>A)

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

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
jinfukang	decreases expression	1
Smoke	decreases expression	1
Valproic Acid	decreases methylation	1

Clinical trials (associated diseases)

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