NT5C1B

Summary

NT5C1B (5’-nucleotidase, cytosolic IB, HGNC:17818) is a protein-coding gene on chromosome 2p24.2, encoding Cytosolic 5’-nucleotidase 1B (Q96P26). Catalyzes the hydrolysis of nucleotide monophosphates, releasing inorganic phosphate and the corresponding nucleoside, AMP is the major substrate.

Cytosolic 5-prime nucleotidases, such as NT5C1B, catalyze production of adenosine, which regulates diverse physiologic processes (Sala-Newby and Newby, 2001 [PubMed 11690631]).

Source: NCBI Gene 93034 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 109 total
• MANE Select transcript: NM_033253

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17818
Approved symbol	NT5C1B
Name	5’-nucleotidase, cytosolic IB
Location	2p24.2
Locus type	gene with protein product
Status	Approved
Aliases	AIRP, CN-IB
Ensembl gene	ENSG00000185013
Ensembl biotype	protein_coding
OMIM	610526
Entrez	93034

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000304081, ENST00000359846, ENST00000406971, ENST00000416783, ENST00000418427, ENST00000460052, ENST00000490687

RefSeq mRNA: 5 — MANE Select: NM_033253 NM_001002006, NM_001199086, NM_001199087, NM_001199088, NM_033253

CCDS: CCDS33149, CCDS33150

Canonical transcript exons

ENST00000304081 — 9 exons

Exon	Start	End
ENSE00001945896	18589439	18589569
ENSE00003467468	18587503	18587592
ENSE00003533496	18582868	18582997
ENSE00003560288	18584088	18584255
ENSE00003566800	18576184	18576368
ENSE00003677436	18584514	18584978
ENSE00003682687	18576773	18576895
ENSE00003687955	18586254	18586391
ENSE00003978121	18562871	18564119

Expression profiles

Bgee: expression breadth ubiquitous, 157 present calls, max score 99.56.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0088 / max 7.2174, expressed in 3 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27050	0.0887	3
27049	0.0088	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.56	gold quality
left testis	UBERON:0004533	91.03	gold quality
right testis	UBERON:0004534	90.83	gold quality
testis	UBERON:0000473	88.34	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.06	gold quality
adult organism	UBERON:0007023	82.64	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.01	gold quality
tibialis anterior	UBERON:0001385	71.51	silver quality
pancreatic ductal cell	CL:0002079	69.52	silver quality
right coronary artery	UBERON:0001625	68.34	gold quality
right lobe of liver	UBERON:0001114	67.83	gold quality
lower esophagus	UBERON:0013473	67.60	gold quality
lower esophagus muscularis layer	UBERON:0035833	67.54	gold quality
islet of Langerhans	UBERON:0000006	67.11	gold quality
ileal mucosa	UBERON:0000331	66.22	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	66.22	gold quality
esophagus	UBERON:0001043	65.37	gold quality
rectum	UBERON:0001052	65.33	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	64.34	gold quality
esophagus mucosa	UBERON:0002469	63.60	gold quality
lower esophagus mucosa	UBERON:0035834	63.56	gold quality
body of stomach	UBERON:0001161	63.44	gold quality
descending thoracic aorta	UBERON:0002345	62.73	gold quality
apex of heart	UBERON:0002098	62.49	gold quality
stomach	UBERON:0000945	62.10	gold quality
thoracic aorta	UBERON:0001515	61.94	gold quality
ascending aorta	UBERON:0001496	61.88	gold quality
skin of abdomen	UBERON:0001416	61.87	gold quality
tibial artery	UBERON:0007610	61.87	gold quality
popliteal artery	UBERON:0002250	61.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting NT5C1B, 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-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-4519	99.48	66.10	859
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-122B-3P	99.21	68.90	1333
HSA-MIR-21-3P	99.21	68.95	1312
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-4764-5P	98.88	65.53	894
HSA-MIR-3161	98.71	67.14	816
HSA-MIR-4274	98.59	66.10	630
HSA-MIR-548AO-5P	98.55	69.57	1362
HSA-MIR-548AX	98.55	69.58	1362
HSA-MIR-4709-5P	98.51	67.25	1335
HSA-MIR-7114-5P	98.51	67.87	1349
HSA-MIR-1182	96.41	64.89	336

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nt5c1ba	ENSDARG00000018153
danio_rerio	nt5c1bb	ENSDARG00000033742
mus_musculus	Nt5c1b	ENSMUSG00000020622
rattus_norvegicus	Nt5c1b	ENSRNOG00000004296

Paralogs (1): NT5C1A (ENSG00000116981)

Protein

Protein identifiers

Cytosolic 5’-nucleotidase 1B — Q96P26 (reviewed: Q96P26)

Alternative names: Autoimmune infertility-related protein, Cytosolic 5’-nucleotidase IB

All UniProt accessions (5): Q96P26, A0A140VJC7, C4AM88, C9JW75, H7BZQ4

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolysis of nucleotide monophosphates, releasing inorganic phosphate and the corresponding nucleoside, AMP is the major substrate.

Subcellular location. Cytoplasm.

Tissue specificity. Highly expressed in testis, placenta and pancreas. Detected at lower levels in heart, kidney, liver and lung.

Activity regulation. Activated by ADP.

Similarity. Belongs to the 5’-nucleotidase type 3 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96P26-1	1, CN-Ib alpha	yes
Q96P26-2	2
Q96P26-3	3
Q96P26-4	4

RefSeq proteins (5): NP_001002006, NP_001186015, NP_001186016, NP_001186017, NP_150278* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010394	5-nucleotidase	Family

Pfam: PF06189

Catalyzed reactions (Rhea), 2 shown:

• a ribonucleoside 5’-phosphate + H2O = a ribonucleoside + phosphate (RHEA:12484)
• AMP + H2O = adenosine + phosphate (RHEA:29375)

UniProt features (19 total): sequence conflict 7, compositionally biased region 5, splice variant 3, region of interest 2, chain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96P26-F1	63.86	0.31

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): 467 (nucleophile)

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-74259	Purine catabolism
R-HSA-1430728	Metabolism
R-HSA-15869	Metabolism of nucleotides
R-HSA-8956319	Nucleotide catabolism

MSigDB gene sets: 59 (showing top): GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, BRN2_01, GOBP_ORGANOPHOSPHATE_CATABOLIC_PROCESS, TGANTCA_AP1_C, TGACATY_UNKNOWN, KEGG_PURINE_METABOLISM, GOBP_NUCLEOSIDE_PHOSPHATE_CATABOLIC_PROCESS, AFFAR_YY1_TARGETS_DN, GOBP_PURINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_PURINE_CONTAINING_COMPOUND_CATABOLIC_PROCESS, FOX_Q2, EVI1_04, GOMF_MAGNESIUM_ION_BINDING

GO Biological Process (3): purine nucleotide catabolic process (GO:0006195), adenosine metabolic process (GO:0046085), nucleotide metabolic process (GO:0009117)

GO Molecular Function (4): nucleotide binding (GO:0000166), magnesium ion binding (GO:0000287), 5’-nucleotidase activity (GO:0008253), hydrolase activity (GO:0016787)

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

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Nucleotide catabolism	1
Metabolism	1
Metabolism of nucleotides	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
purine nucleotide metabolic process	1
nucleotide catabolic process	1
purine-containing compound catabolic process	1
purine ribonucleoside metabolic process	1
nucleoside phosphate metabolic process	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
metal ion binding	1
nucleotidase activity	1
catalytic activity	1
intracellular membrane-bounded organelle	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1741 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NT5C1B	NT5M	Q9NPB1	627
NT5C1B	NT5C3B	Q969T7	599
NT5C1B	NT5C	Q8TCD5	598
NT5C1B	NT5C2	P49902	523
NT5C1B	TMEM202	A6NGA9	516
NT5C1B	LKAAEAR1	Q8TD35	506
NT5C1B	NT5C3A	Q9H0P0	492
NT5C1B	EFCAB10	A6NFE3	471
NT5C1B	NME6	O75414	461
NT5C1B	SPEM3	A0A1B0GUW6	448
NT5C1B	SPATA31F1	Q6ZU69	447
NT5C1B	C4orf17	Q53FE4	433
NT5C1B	DUXB	A0A1W2PPF3	425
NT5C1B	PRR30	Q53SZ7	421
NT5C1B	GARIN3	Q8TC56	419

IntAct

0 interactions, top by confidence:

BioGRID (4): NT5C1B (Affinity Capture-MS), NT5C1B (Affinity Capture-MS), NT5C1B (Cross-Linking-MS (XL-MS)), NT5C1B (Reconstituted Complex)

ESM2 similar proteins: A0A2R8VHF7, A0JM23, A2QRA0, A4IIA7, A4IIV4, A6NFN9, A6NHR9, A7MBF6, F4IG73, F4JSE7, O17482, O95876, P12540, P21784, P34089, P38899, P55895, P56696, Q08AW4, Q0D2D7, Q12789, Q13829, Q28DC9, Q2WGJ8, Q3E7Y5, Q3UUE9, Q4R907, Q4VXA5, Q5BK83, Q5EA90, Q5F476, Q5HZS2, Q5M9F0, Q5RAX4, Q5RBH4, Q5RD21, Q6AYL6, Q6DGA7, Q6PIY5, Q70XZ2

Diamond homologs: A3KFX0, Q91YE9, Q96P26, Q9BXI3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	100
Likely benign	6
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1519 predictions. Top by Δscore:

Variant	Effect	Δscore
2:18584082:GAATA:G	donor_loss	1.0000
2:18584083:AATAC:A	donor_loss	1.0000
2:18584084:ATAC:A	donor_loss	1.0000
2:18584085:TAC:T	donor_loss	1.0000
2:18584087:C:A	donor_loss	1.0000
2:18587594:T:C	acceptor_gain	1.0000
2:18576179:CCTA:C	donor_loss	0.9900
2:18576180:CTA:C	donor_loss	0.9900
2:18576181:TA:T	donor_loss	0.9900
2:18576182:A:C	donor_loss	0.9900
2:18576183:C:G	donor_loss	0.9900
2:18576199:A:AC	donor_gain	0.9900
2:18576200:C:CC	donor_gain	0.9900
2:18576202:TTC:T	donor_gain	0.9900
2:18576219:A:AC	donor_gain	0.9900
2:18576220:C:CC	donor_gain	0.9900
2:18576366:TAC:T	acceptor_gain	0.9900
2:18576366:TACCT:T	acceptor_loss	0.9900
2:18576367:ACCT:A	acceptor_loss	0.9900
2:18576368:CCT:C	acceptor_loss	0.9900
2:18576369:C:A	acceptor_loss	0.9900
2:18576370:T:G	acceptor_loss	0.9900
2:18576372:A:C	acceptor_gain	0.9900
2:18576775:T:A	donor_gain	0.9900
2:18582862:ACTT:A	donor_loss	0.9900
2:18582863:CTTA:C	donor_loss	0.9900
2:18582864:TTAC:T	donor_loss	0.9900
2:18582865:TACC:T	donor_loss	0.9900
2:18582866:ACCGT:A	donor_loss	0.9900
2:18582867:C:CT	donor_loss	0.9900

AlphaMissense

3587 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:18563966:A:G	W555R	0.994
2:18563966:A:T	W555R	0.994
2:18582881:G:C	S396R	0.987
2:18582881:G:T	S396R	0.987
2:18582883:T:G	S396R	0.987
2:18563937:G:C	F564L	0.986
2:18563937:G:T	F564L	0.986
2:18563939:A:G	F564L	0.986
2:18564069:G:C	F520L	0.986
2:18564069:G:T	F520L	0.986
2:18564071:A:G	F520L	0.986
2:18576299:G:T	A465D	0.982
2:18584205:G:C	F318L	0.981
2:18584205:G:T	F318L	0.981
2:18584207:A:G	F318L	0.981
2:18563974:A:G	L552P	0.980
2:18563974:A:T	L552H	0.980
2:18564025:A:G	L535P	0.980
2:18563893:G:T	P579H	0.979
2:18563964:C:A	W555C	0.979
2:18563964:C:G	W555C	0.979
2:18576296:A:G	F466S	0.979
2:18563938:A:G	F564S	0.978
2:18564029:A:C	Y534D	0.978
2:18576295:A:C	F466L	0.976
2:18576295:A:T	F466L	0.976
2:18576297:A:G	F466L	0.976
2:18564078:T:A	Q517H	0.974
2:18564078:T:G	Q517H	0.974
2:18563983:A:G	L549P	0.973

dbSNP variants (sampled 300 via entrez): RS1000006558 (2:18570024 G>A), RS1000043575 (2:18581243 A>G), RS1000108601 (2:18562599 G>A), RS1000203703 (2:18587249 TC>T,TCC,TCCC), RS1000247039 (2:18588162 A>G,T), RS1000602565 (2:18579642 A>G), RS1000856533 (2:18577697 A>G), RS1000956543 (2:18585926 TC>T), RS1001343705 (2:18563535 A>G,T), RS1001428896 (2:18583725 G>A), RS1001608798 (2:18588398 A>G), RS1001638934 (2:18583162 T>C), RS1001708307 (2:18588710 G>A), RS1001763612 (2:18589044 G>A,T), RS1002099141 (2:18590625 G>T)

Disease associations

OMIM: gene MIM:610526 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST001958_19	Bulimia nervosa	1.000000e-07
GCST003991_8	Childhood ear infection	2.000000e-10
GCST004031_6	QT interval (sulfonylurea treatment interaction)	8.000000e-08
GCST006479_142	Diverticular disease	4.000000e-08
GCST006624_64	Systolic blood pressure	2.000000e-12
GCST007344_14	Estimated glomerular filtration rate	1.000000e-08
GCST008747_67	Estimated glomerular filtration rate	4.000000e-13
GCST009723_91	Vertical cup-disc ratio (adjusted for vertical disc diameter)	3.000000e-06
GCST009723_99	Vertical cup-disc ratio (adjusted for vertical disc diameter)	3.000000e-06
GCST009724_90	Vertical cup-disc ratio (multi-trait analysis)	1.000000e-09
GCST009724_91	Vertical cup-disc ratio (multi-trait analysis)	8.000000e-09
GCST010697_8	Cortical surface area (min-P)	9.000000e-11
GCST010698_76	Subcortical volume (min-P)	6.000000e-13
GCST010699_22	Brain morphology (min-P)	9.000000e-10
GCST010700_49	Cortical thickness (MOSTest)	2.000000e-10
GCST010701_21	Cortical surface area (MOSTest)	1.000000e-76
GCST010702_13	Subcortical volume (MOSTest)	4.000000e-08
GCST010703_331	Brain morphology (MOSTest)	2.000000e-10

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0007904	susceptibility to childhood ear infection measurement
EFO:0004682	QT interval
EFO:0007922	response to sulfonylurea
EFO:0009959	diverticular disease
EFO:0006335	systolic blood pressure
EFO:0006939	cup-to-disc ratio measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Adenosine turnover

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
bisphenol S	decreases methylation	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	increases expression	1
Catechin	affects cotreatment, decreases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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