NT5C3B

Summary

NT5C3B (5’-nucleotidase, cytosolic IIIB, HGNC:28300) is a protein-coding gene on chromosome 17q21.2, encoding 7-methylguanosine phosphate-specific 5’-nucleotidase (Q969T7). Specifically hydrolyzes 7-methylguanosine monophosphate (m(7)GMP) to 7-methylguanosine and inorganic phosphate.

Predicted to enable 5’-nucleotidase activity. Predicted to be involved in nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay. Predicted to be located in cytosol. Predicted to be active in cytoplasm.

Source: NCBI Gene 115024 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 39 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_052935

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28300
Approved symbol	NT5C3B
Name	5’-nucleotidase, cytosolic IIIB
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC20781, cN-IIIB
Ensembl gene	ENSG00000141698
Ensembl biotype	protein_coding
OMIM	620041
Entrez	115024

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 11 protein_coding, 10 retained_intron, 2 nonsense_mediated_decay

ENST00000393910, ENST00000415460, ENST00000435506, ENST00000445655, ENST00000460893, ENST00000469698, ENST00000470690, ENST00000475053, ENST00000476921, ENST00000481693, ENST00000486304, ENST00000495317, ENST00000517701, ENST00000520442, ENST00000521789, ENST00000523903, ENST00000899638, ENST00000899639, ENST00000913258, ENST00000913259, ENST00000913260, ENST00000913261, ENST00000946251

RefSeq mRNA: 1 — MANE Select: NM_052935 NM_052935

CCDS: CCDS11410

Canonical transcript exons

ENST00000435506 — 9 exons

Exon	Start	End
ENSE00001625522	41836182	41836232
ENSE00002127801	41825057	41825657
ENSE00003522478	41828790	41828952
ENSE00003524371	41835070	41835116
ENSE00003541430	41835203	41835272
ENSE00003559673	41835859	41835957
ENSE00003614944	41830801	41830890
ENSE00003616516	41827426	41827626
ENSE00003631173	41832392	41832477

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 97.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.9410 / max 268.2509, expressed in 1802 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166051	36.7690	1801
208194	0.5953	360
166052	0.5767	327

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nucleus accumbens	UBERON:0001882	97.55	gold quality
putamen	UBERON:0001874	97.50	gold quality
right lobe of thyroid gland	UBERON:0001119	97.45	gold quality
caudate nucleus	UBERON:0001873	97.35	gold quality
left lobe of thyroid gland	UBERON:0001120	97.30	gold quality
cortical plate	UBERON:0005343	97.28	gold quality
left testis	UBERON:0004533	97.22	gold quality
right testis	UBERON:0004534	97.19	gold quality
thyroid gland	UBERON:0002046	97.14	gold quality
right frontal lobe	UBERON:0002810	97.11	gold quality
mucosa of stomach	UBERON:0001199	97.01	gold quality
right coronary artery	UBERON:0001625	96.83	gold quality
anterior cingulate cortex	UBERON:0009835	96.76	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.71	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.70	gold quality
prefrontal cortex	UBERON:0000451	96.69	gold quality
lower esophagus	UBERON:0013473	96.68	gold quality
amygdala	UBERON:0001876	96.63	gold quality
ganglionic eminence	UBERON:0004023	96.59	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.58	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.53	gold quality
popliteal artery	UBERON:0002250	96.40	gold quality
tibial artery	UBERON:0007610	96.40	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.40	gold quality
left coronary artery	UBERON:0001626	96.36	gold quality
coronary artery	UBERON:0001621	96.35	gold quality
adult organism	UBERON:0007023	96.28	gold quality
cerebellar cortex	UBERON:0002129	96.27	gold quality
cerebellar hemisphere	UBERON:0002245	96.27	gold quality
aorta	UBERON:0000947	96.26	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.69
E-GEOD-75367	no	479.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting NT5C3B, 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-335-3P	99.93	73.36	4958
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-371A-5P	99.08	66.51	1914
HSA-MIR-4733-3P	98.35	65.20	994
HSA-MIR-4299	98.28	66.96	850
HSA-MIR-4518	98.12	66.82	1030
HSA-MIR-1266-5P	97.71	66.92	1052
HSA-MIR-4308	97.56	67.13	1385
HSA-MIR-6787-5P	97.54	63.85	457
HSA-MIR-3907	96.76	65.04	662
HSA-MIR-597-3P	96.46	68.03	1035
HSA-MIR-10396B-5P	94.99	63.57	358
HSA-MIR-1908-5P	94.99	63.41	352
HSA-MIR-663A	94.99	63.54	378

Literature-anchored findings (GeneRIF, showing 1)

• NT5C3B is involved in airway wall thickening and thereby with airway obstruction. (PMID:25517131)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nt5c3b	ENSMUSG00000017176
rattus_norvegicus	Nt5c3b	ENSRNOG00000016475
drosophila_melanogaster	cN-IIIB	FBGN0034988
caenorhabditis_elegans		WBGENE00012423
caenorhabditis_elegans		WBGENE00017775

Paralogs (1): NT5C3A (ENSG00000122643)

Protein

Protein identifiers

7-methylguanosine phosphate-specific 5’-nucleotidase — Q969T7 (reviewed: Q969T7)

Alternative names: Cytosolic 5’-nucleotidase 3B, Cytosolic 5’-nucleotidase III-like protein, N(7)-methylguanylate 5’-phosphatase

All UniProt accessions (6): C9IZA4, C9J758, E5RH64, E5RJR6, Q969T7, U3KQB1

UniProt curated annotations — full annotation on UniProt →

Function. Specifically hydrolyzes 7-methylguanosine monophosphate (m(7)GMP) to 7-methylguanosine and inorganic phosphate. The specific activity for m(7)GMP may protect cells against undesired salvage of m(7)GMP and its incorporation into nucleic acids. Also has weak activity for CMP. UMP and purine nucleotides are poor substrates.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm.

Similarity. Belongs to the pyrimidine 5’-nucleotidase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q969T7-1	1	yes
Q969T7-2	2

RefSeq proteins (1): NP_443167* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006434	Pyrimidine_nucleotidase_eu	Family
IPR023214	HAD_sf	Homologous_superfamily
IPR036412	HAD-like_sf	Homologous_superfamily

Pfam: PF05822

Catalyzed reactions (Rhea), 3 shown:

• a ribonucleoside 5’-phosphate + H2O = a ribonucleoside + phosphate (RHEA:12484)
• CMP + H2O = cytidine + phosphate (RHEA:29367)
• N(7)-methyl-GMP + H2O = N(7)-methylguanosine + phosphate (RHEA:37107)

UniProt features (39 total): helix 15, strand 8, binding site 7, active site 2, sequence variant 2, turn 2, chain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7ZEE	X-RAY DIFFRACTION	1.36
7ZEH	X-RAY DIFFRACTION	1.5
7ZEG	X-RAY DIFFRACTION	1.56

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q969T7-F1	92.76	0.87

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 (2): 41 (nucleophile); 43 (proton donor)

Ligand- & substrate-binding residues (7): 41; 43; 88; 88; 156–157; 205; 230

Post-translational modifications (1): 256

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-429958	mRNA decay by 3’ to 5’ exoribonuclease
R-HSA-429914	Deadenylation-dependent mRNA decay
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 102 (showing top): TGCGCANK_UNKNOWN, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, TGTGTGA_MIR377, GOBP_NUCLEAR_TRANSCRIBED_MRNA_CATABOLIC_PROCESS_DEADENYLATION_DEPENDENT_DECAY, BROWN_MYELOID_CELL_DEVELOPMENT_DN, HAND1E47_01, TAATGTG_MIR323

GO Biological Process (2): nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay (GO:0000288), nucleotide metabolic process (GO:0009117)

GO Molecular Function (5): nucleotide binding (GO:0000166), magnesium ion binding (GO:0000287), 5’-nucleotidase activity (GO:0008253), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

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

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Deadenylation-dependent mRNA decay	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
nuclear-transcribed mRNA catabolic process	1
mRNA destabilization	1
nucleoside phosphate metabolic process	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
metal ion binding	1
nucleotidase activity	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

460 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NT5C3B	NT5C1B	Q96P26	599
NT5C3B	NT5M	Q9NPB1	581
NT5C3B	DCPS	Q96C86	571
NT5C3B	NT5C1A	Q9BXI3	490
NT5C3B	NT5C	Q8TCD5	480
NT5C3B	NT5C2	P49902	437
NT5C3B	GPATCH8	Q9UKJ3	341
NT5C3B	CCDC43	Q96MW1	336
NT5C3B	FHIP2A	Q5W0V3	326
NT5C3B	RUNDC1	Q96C34	325
NT5C3B	TMEM101	Q96IK0	324
NT5C3B	SNUPN	O95149	318
NT5C3B	FHL3	Q13643	314
NT5C3B	KRTAP3-3	Q9BYR6	311
NT5C3B	NTAQ1	Q96HA8	304

IntAct

5 interactions, top by confidence:

A	B	Type	Score
NT5C3B	RBMY1B	psi-mi:“MI:0915”(physical association)	0.400
NT5C3B	MLH1	psi-mi:“MI:0915”(physical association)	0.370
MTPN	PLCG1	psi-mi:“MI:0914”(association)	0.350

BioGRID (12): NT5C3B (Affinity Capture-RNA), NT5C3B (Affinity Capture-RNA), NT5C3B (Affinity Capture-RNA), NT5C3B (Affinity Capture-MS), RBMY1B (Affinity Capture-MS), VAPA (Co-fractionation), NT5C3B (Proximity Label-MS), NT5C3B (Proximity Label-MS), NT5C3B (Proximity Label-MS), NT5C3B (Proximity Label-MS), NT5C3B (Cross-Linking-MS (XL-MS)), NT5C3B (Two-hybrid)

ESM2 similar proteins: A0A0K9RL25, A0A0U1WZ18, A0A1S4A695, B9N1F9, O15305, O35621, O80840, O88958, O97555, O97556, P21856, P31150, P46926, P50396, P50398, P50399, P60028, P78330, Q16HW7, Q1W374, Q1W375, Q1W376, Q1W377, Q259G4, Q2KHU0, Q3SZJ9, Q3UFY7, Q4R7R3, Q5E982, Q5R8T8, Q5RB83, Q5ZID6, Q5ZKF6, Q60HD6, Q61598, Q64422, Q6AYP7, Q6Q7J2, Q7SYN4, Q7XPW5

Diamond homologs: Q09315, Q2TAG6, Q3UFY7, Q5ZID6, Q5ZKF6, Q6AYP7, Q7SYN4, Q7ZWS2, Q969T7, Q9D020, Q9H0P0, Q9W197

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	27
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
58696	GRCh38/hg38 17q12-21.31(chr17:39199873-45629579)x3	Pathogenic

SpliceAI

1282 predictions. Top by Δscore:

Variant	Effect	Δscore
17:41827422:CCAC:C	donor_loss	1.0000
17:41827422:CCACC:C	donor_gain	1.0000
17:41827423:CAC:C	donor_loss	1.0000
17:41827425:C:CA	donor_loss	1.0000
17:41828789:CAT:C	donor_gain	1.0000
17:41828879:CAA:C	acceptor_gain	1.0000
17:41828880:A:T	acceptor_gain	1.0000
17:41828881:A:AC	acceptor_gain	1.0000
17:41828886:C:CT	acceptor_gain	1.0000
17:41828886:C:T	acceptor_gain	1.0000
17:41828888:C:CT	acceptor_gain	1.0000
17:41828889:A:T	acceptor_gain	1.0000
17:41832478:C:CC	acceptor_gain	1.0000
17:41832487:CCAAA:C	acceptor_gain	1.0000
17:41832488:C:T	acceptor_gain	1.0000
17:41832488:CAAA:C	acceptor_gain	1.0000
17:41832489:A:T	acceptor_gain	1.0000
17:41832491:A:AC	acceptor_gain	1.0000
17:41832491:A:C	acceptor_gain	1.0000
17:41835065:CCCA:C	donor_loss	1.0000
17:41835066:CCA:C	donor_loss	1.0000
17:41835067:CAC:C	donor_loss	1.0000
17:41835068:A:C	donor_loss	1.0000
17:41835069:CCT:C	donor_gain	1.0000
17:41835114:TAT:T	acceptor_gain	1.0000
17:41835116:TCTGG:T	acceptor_loss	1.0000
17:41835117:C:CC	acceptor_gain	1.0000
17:41835117:CT:C	acceptor_loss	1.0000
17:41835201:A:AC	donor_gain	1.0000
17:41835202:C:CC	donor_gain	1.0000

AlphaMissense

2007 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:41835261:A:C	D41E	0.995
17:41835261:A:T	D41E	0.995
17:41828952:C:A	R135S	0.994
17:41828952:C:G	R135S	0.994
17:41835262:T:A	D41V	0.994
17:41835243:G:C	S47R	0.993
17:41835243:G:T	S47R	0.993
17:41835245:T:G	S47R	0.993
17:41835258:A:C	F42L	0.993
17:41835258:A:T	F42L	0.993
17:41835260:A:G	F42L	0.993
17:41827579:C:A	K205N	0.992
17:41827579:C:G	K205N	0.992
17:41835256:T:A	D43V	0.992
17:41827439:A:G	F252S	0.990
17:41827438:G:C	F252L	0.989
17:41827438:G:T	F252L	0.989
17:41827440:A:G	F252L	0.989
17:41827492:G:C	D234E	0.989
17:41827492:G:T	D234E	0.989
17:41830801:C:G	R135T	0.989
17:41835263:C:G	D41H	0.989
17:41827442:C:T	G251D	0.988
17:41827493:T:G	D234A	0.988
17:41827514:A:G	L227P	0.988
17:41828811:G:C	N182K	0.988
17:41828811:G:T	N182K	0.988
17:41830825:A:T	V127D	0.988
17:41835237:A:C	F49L	0.988
17:41835237:A:T	F49L	0.988

dbSNP variants (sampled 300 via entrez): RS1000083147 (17:41826453 C>A,G), RS1000309808 (17:41829451 A>G), RS1000409948 (17:41829930 A>G), RS1000426034 (17:41836028 C>T), RS1001145255 (17:41828374 G>A,T), RS1001190445 (17:41824691 C>A,G), RS1001310953 (17:41830942 A>G), RS1001325759 (17:41831252 G>T), RS1001552401 (17:41837003 T>A,G), RS1001642942 (17:41824906 G>A), RS1003583189 (17:41826364 C>A,G,T), RS1003667163 (17:41832729 G>A,T), RS1003937714 (17:41825889 G>A), RS1004388276 (17:41832322 G>A,C), RS1004677606 (17:41830657 T>C)

Disease associations

OMIM: gene MIM:620041 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002794_16	Airway wall thickness	2.000000e-06
GCST002794_2	Airway wall thickness	3.000000e-06
GCST002794_9	Airway wall thickness	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006898	airway wall thickness measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295921 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
beta-lapachone	decreases expression, increases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
Sunitinib	decreases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Ozone	affects cotreatment, increases expression, increases abundance	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	affects expression	1
Vanadates	decreases expression	1
Sodium Selenite	decreases expression	1
Volatile Organic Compounds	affects cotreatment, increases expression	1

ChEMBL screening assays

12 unique, capped per target: 12 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4182506	Binding	Inhibition of recombinant His6/SUMO-tagged human cN3B (1 to 300 residues) expressed in Escherichia coli BL21(DE3) RIL assessed as reduction in dephosphorylation of m7GMP substrate after 45 mins by malachite green dye based assay	7-Methylguanosine monophosphate analogues with 5’-(1,2,3-triazoyl) moiety: Synthesis and evaluation as the inhibitors of cNIIIB nucleotidase. — Bioorg Med Chem

Clinical trials (associated diseases)

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