NT5DC3

Summary

NT5DC3 (5’-nucleotidase domain containing 3, HGNC:30826) is a protein-coding gene on chromosome 12q23.3, encoding 5’-nucleotidase domain-containing protein 3 (Q86UY8).

Predicted to enable 5’-nucleotidase activity. Located in mitochondrion. Part of receptor complex.

Source: NCBI Gene 51559 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 168 total
• MANE Select transcript: NM_001031701

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30826
Approved symbol	NT5DC3
Name	5’-nucleotidase domain containing 3
Location	12q23.3
Locus type	gene with protein product
Status	Approved
Aliases	TU12B1-TY, FLJ11266
Ensembl gene	ENSG00000111696
Ensembl biotype	protein_coding
OMIM	611076
Entrez	51559

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 2 protein_coding, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000392876, ENST00000415849, ENST00000447799, ENST00000465502, ENST00000474268, ENST00000933413

RefSeq mRNA: 1 — MANE Select: NM_001031701 NM_001031701

CCDS: CCDS41824

Canonical transcript exons

ENST00000392876 — 14 exons

Exon	Start	End
ENSE00000818267	103787441	103787527
ENSE00001000556	103788838	103788919
ENSE00001000557	103793410	103793512
ENSE00001000558	103793164	103793265
ENSE00001000559	103806855	103806929
ENSE00001000561	103806322	103806377
ENSE00001193946	103793937	103793997
ENSE00001193951	103796894	103797031
ENSE00001406207	103772310	103778081
ENSE00002213723	103840949	103841234
ENSE00002323762	103814937	103815121
ENSE00003521324	103785335	103785475
ENSE00003573531	103780300	103780364
ENSE00003585585	103798587	103798677

Expression profiles

Bgee: expression breadth ubiquitous, 198 present calls, max score 95.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.6228 / max 639.6168, expressed in 1709 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132976	5.4788	1473
132977	4.3207	1512
132975	2.4603	905
132974	0.2155	69
132978	0.1475	54

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
muscle layer of sigmoid colon	UBERON:0035805	95.14	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.11	gold quality
lower esophagus	UBERON:0013473	92.02	gold quality
colonic epithelium	UBERON:0000397	91.26	gold quality
popliteal artery	UBERON:0002250	89.91	gold quality
tibial artery	UBERON:0007610	89.87	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	88.83	gold quality
middle temporal gyrus	UBERON:0002771	88.69	gold quality
aorta	UBERON:0000947	88.68	gold quality
body of uterus	UBERON:0009853	88.31	gold quality
ascending aorta	UBERON:0001496	87.40	gold quality
thoracic aorta	UBERON:0001515	87.25	gold quality
blood vessel layer	UBERON:0004797	85.39	gold quality
descending thoracic aorta	UBERON:0002345	84.98	gold quality
sural nerve	UBERON:0015488	84.82	gold quality
mucosa of stomach	UBERON:0001199	84.47	gold quality
colon	UBERON:0001155	83.63	gold quality
left coronary artery	UBERON:0001626	83.61	gold quality
transverse colon	UBERON:0001157	83.07	gold quality
large intestine	UBERON:0000059	82.94	gold quality
right coronary artery	UBERON:0001625	82.56	gold quality
Brodmann (1909) area 23	UBERON:0013554	82.38	gold quality
adrenal tissue	UBERON:0018303	82.37	gold quality
coronary artery	UBERON:0001621	82.22	gold quality
esophagus	UBERON:0001043	81.53	gold quality
tibial nerve	UBERON:0001323	81.35	gold quality
rectum	UBERON:0001052	81.23	gold quality
calcaneal tendon	UBERON:0003701	81.10	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.77	gold quality
myometrium	UBERON:0001296	80.59	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.36
E-ENAD-17	no	993.31

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• TU12B1-TY may contribute to the development and/or progression of human pancreatic cancer (PMID:15547748)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	nt5dc3	ENSDARG00000062949
mus_musculus	Nt5dc3	ENSMUSG00000054027
rattus_norvegicus	Nt5dc3	ENSRNOG00000026793
drosophila_melanogaster	Nt5c	FBGN0033426
drosophila_melanogaster	Nt5b	FBGN0052549
caenorhabditis_elegans		WBGENE00022201

Paralogs (4): NT5C2 (ENSG00000076685), NT5DC4 (ENSG00000144130), NT5DC2 (ENSG00000168268), NT5DC1 (ENSG00000178425)

Protein

Protein identifiers

5’-nucleotidase domain-containing protein 3 — Q86UY8 (reviewed: Q86UY8)

Alternative names: GRP94-neighboring nucleotidase

All UniProt accessions (3): Q86UY8, H7C193, H7C3S8

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Expressed in brain, placenta, skeletal muscle, pancreas, testis, uterus, and small intestine. Reduced expression in pancreatic cancer cells.

Cofactor. Binds 1 Mg(2+) ion per subunit.

Similarity. Belongs to the 5’(3’)-deoxyribonucleotidase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86UY8-1	1	yes
Q86UY8-2	2

RefSeq proteins (1): NP_001026871* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008380	HAD-SF_hydro_IG_5-nucl	Family
IPR016695	Pur_nucleotidase	Family
IPR023214	HAD_sf	Homologous_superfamily
IPR036412	HAD-like_sf	Homologous_superfamily

Pfam: PF05761

UniProt features (11 total): binding site 4, active site 2, splice variant 2, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86UY8-F1	87.18	0.78

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): 102 (nucleophile); 104 (proton donor)

Ligand- & substrate-binding residues (4): 102; 104; 251–259; 389

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 130 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, ONKEN_UVEAL_MELANOMA_UP, GARCIA_TARGETS_OF_FLI1_AND_DAX1_DN, IVANOVA_HEMATOPOIESIS_STEM_CELL_LONG_TERM, GOCC_RECEPTOR_COMPLEX, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_NUCLEOTIDASE_ACTIVITY, GOMF_PHOSPHORIC_ESTER_HYDROLASE_ACTIVITY, chr12q23, DUTERTRE_ESTRADIOL_RESPONSE_6HR_UP, BHAT_ESR1_TARGETS_NOT_VIA_AKT1_UP, BHAT_ESR1_TARGETS_VIA_AKT1_UP, ZWANG_CLASS_1_TRANSIENTLY_INDUCED_BY_EGF, GOMF_PHOSPHATASE_ACTIVITY

GO Biological Process (0):

GO Molecular Function (3): 5’-nucleotidase activity (GO:0008253), metal ion binding (GO:0046872), hydrolase activity (GO:0016787)

GO Cellular Component (3): mitochondrion (GO:0005739), cytosol (GO:0005829), signaling receptor complex (GO:0043235)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
nucleotidase activity	1
cation binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
protein-containing complex	1

Protein interactions and networks

STRING

408 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NT5DC3	HSPB3	Q12988	649
NT5DC3	KRTAP19-5	Q3LI72	514
NT5DC3	SYT17	Q9BSW7	460
NT5DC3	TRIM11	Q96F44	448
NT5DC3	TAFA3	Q7Z5A8	434
NT5DC3	N4BP2L1	Q5TBK1	406
NT5DC3	MRPS18C	Q9Y3D5	391
NT5DC3	NCLN	Q969V3	374
NT5DC3	GOLGA8K	D6RF30	370
NT5DC3	SLC75A1	Q14728	363
NT5DC3	AIMP2	Q13155	362
NT5DC3	SPECC1	Q5M775	359
NT5DC3	TSHZ1	Q6ZSZ6	345
NT5DC3	CNFN	Q9BYD5	343
NT5DC3	FAXDC2	Q96IV6	339

IntAct

22 interactions, top by confidence:

A	B	Type	Score
ARHGEF6	PAK1	psi-mi:“MI:0914”(association)	0.800
MARVELD2	GAP43	psi-mi:“MI:0914”(association)	0.530
ARHGEF6	YWHAH	psi-mi:“MI:0914”(association)	0.530
NT5DC3	NT5DC2	psi-mi:“MI:0915”(physical association)	0.400
SIRT4	VWA8	psi-mi:“MI:0914”(association)	0.350
KIF11	ILVBL	psi-mi:“MI:0914”(association)	0.350
Gsk3b	SYNPO2	psi-mi:“MI:0914”(association)	0.350
EXOSC2	WDR46	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
ZNF211	NT5DC3	psi-mi:“MI:0914”(association)	0.350
SERBP1	UBA6	psi-mi:“MI:0914”(association)	0.350
YARS2	VWA8	psi-mi:“MI:0914”(association)	0.350
IL25	POTEF	psi-mi:“MI:0914”(association)	0.350
NDUFS7	NUDT19	psi-mi:“MI:0914”(association)	0.350
TRMT61B	PRORP	psi-mi:“MI:0914”(association)	0.350
	VWA8	psi-mi:“MI:2364”(proximity)	0.270
HSPD1	VWA8	psi-mi:“MI:2364”(proximity)	0.270
MGST3	VWA8	psi-mi:“MI:2364”(proximity)	0.270
PDK1	VWA8	psi-mi:“MI:2364”(proximity)	0.270
NT5DC3	TNF	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (53): NT5DC3 (Affinity Capture-MS), NT5DC3 (Affinity Capture-MS), NT5DC3 (Affinity Capture-MS), NT5DC3 (Affinity Capture-MS), NT5DC2 (Affinity Capture-MS), NT5DC3 (Affinity Capture-MS), NT5DC3 (Proximity Label-MS), NT5DC3 (Proximity Label-MS), NT5DC3 (Proximity Label-MS), DNAJC5 (Co-fractionation), FKBP10 (Co-fractionation), VPS35 (Co-fractionation), NT5DC3 (Affinity Capture-MS), NT5DC3 (Affinity Capture-RNA), NT5DC3 (Affinity Capture-MS)

ESM2 similar proteins: A1Z3X3, A3KFX0, A4GWN3, E9Q4Z2, O00763, P13255, P50747, P82922, Q0J035, Q14749, Q1LZ96, Q28559, Q28C34, Q29513, Q29555, Q3TFD2, Q3UHE1, Q3UX43, Q5E9L7, Q5IH13, Q5IH14, Q5ZJT0, Q60HG1, Q64311, Q68EN5, Q6NWD4, Q6NYU2, Q6Q0N3, Q6ZN16, Q80YV4, Q86UY8, Q8BJQ9, Q8C092, Q8C5H8, Q8N6S4, Q8NFZ0, Q8TDX6, Q91W86, Q91XQ2, Q91YY4

Diamond homologs: A4IHT9, Q3UHB1, Q54XC1, Q5TFE4, Q6GN91, Q6Q0N3, Q75K12, Q86UY8, Q86YG4, Q9H857, Q2TBU5, Q8C5P5, Q5EBF1, Q5ZIZ4, Q6DKB0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	126
Likely benign	11
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2815 predictions. Top by Δscore:

Variant	Effect	Δscore
12:103777845:T:TA	donor_gain	1.0000
12:103778077:TTTCT:T	acceptor_gain	1.0000
12:103778078:TTCT:T	acceptor_gain	1.0000
12:103778080:CT:C	acceptor_gain	1.0000
12:103778082:C:CC	acceptor_gain	1.0000
12:103778091:CAA:C	acceptor_gain	1.0000
12:103778092:A:T	acceptor_gain	1.0000
12:103778093:A:AC	acceptor_gain	1.0000
12:103778093:A:C	acceptor_gain	1.0000
12:103793159:CTCA:C	donor_loss	1.0000
12:103793160:TCAC:T	donor_loss	1.0000
12:103793161:CAC:C	donor_loss	1.0000
12:103793162:A:T	donor_loss	1.0000
12:103793162:ACCT:A	donor_gain	1.0000
12:103793163:CCT:C	donor_gain	1.0000
12:103793163:CCTC:C	donor_gain	1.0000
12:103793403:AACTT:A	donor_loss	1.0000
12:103793404:ACTTA:A	donor_loss	1.0000
12:103793405:CTT:C	donor_loss	1.0000
12:103793406:TTACA:T	donor_loss	1.0000
12:103793407:TA:T	donor_loss	1.0000
12:103793408:A:AC	donor_gain	1.0000
12:103793409:C:CC	donor_gain	1.0000
12:103793409:CA:C	donor_gain	1.0000
12:103793409:CACAA:C	donor_gain	1.0000
12:103793508:CTTTT:C	acceptor_gain	1.0000
12:103793511:TT:T	acceptor_gain	1.0000
12:103793512:TC:T	acceptor_loss	1.0000
12:103793513:C:CC	acceptor_gain	1.0000
12:103793513:CT:C	acceptor_loss	1.0000

AlphaMissense

3637 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:103777986:G:T	A497D	1.000
12:103778034:C:G	R481P	1.000
12:103785444:C:T	G407D	1.000
12:103785454:A:G	W404R	1.000
12:103785454:A:T	W404R	1.000
12:103787445:A:G	L395P	1.000
12:103787447:G:C	D394E	1.000
12:103787447:G:T	D394E	1.000
12:103787448:T:A	D394V	1.000
12:103787448:T:C	D394G	1.000
12:103787448:T:G	D394A	1.000
12:103787449:C:G	D394H	1.000
12:103787463:T:A	D389V	1.000
12:103787466:C:A	G388V	1.000
12:103787466:C:T	G388D	1.000
12:103793431:G:A	T299I	1.000
12:103806358:T:A	D163V	1.000
12:103806877:C:T	G149E	1.000
12:103806878:C:G	G149R	1.000
12:103806878:C:T	G149R	1.000
12:103815025:T:A	D102V	1.000
12:103777987:C:G	A497P	0.999
12:103777988:G:C	F496L	0.999
12:103777988:G:T	F496L	0.999
12:103777990:A:G	F496L	0.999
12:103777998:A:G	L493P	0.999
12:103778016:G:A	T487I	0.999
12:103778042:G:C	S478R	0.999
12:103778042:G:T	S478R	0.999
12:103778044:T:G	S478R	0.999

dbSNP variants (sampled 300 via entrez): RS1000003215 (12:103813814 G>A), RS1000057624 (12:103811959 T>A), RS1000073332 (12:103812226 T>C), RS1000103413 (12:103807574 C>T), RS1000106539 (12:103812135 T>A), RS1000156036 (12:103807836 T>A), RS1000173026 (12:103762970 C>T), RS1000220650 (12:103771110 G>T), RS1000235938 (12:103842262 G>A), RS1000247434 (12:103788488 GT>G), RS1000266065 (12:103800683 G>A), RS1000275123 (12:103758829 C>T), RS1000300567 (12:103776890 G>A), RS1000329733 (12:103782188 G>A), RS1000362936 (12:103818024 C>G)

Disease associations

OMIM: gene MIM:611076 | 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
GCST000246_7	Attention deficit hyperactivity disorder	5.000000e-06
GCST001214_1	Coronary restenosis	1.000000e-07
GCST006366_8	Central corneal thickness	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005213	central corneal thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cisplatin	increases expression, decreases expression, affects expression, affects cotreatment	3
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Estradiol	affects cotreatment, increases expression	2
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
2-methyl-4-isothiazolin-3-one	increases expression	1
sulforaphane	increases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
aflatoxin B2	decreases methylation	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
K 7174	increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Acrolein	increases abundance, affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Ozone	affects cotreatment, decreases expression, increases abundance	1
Dihydrotestosterone	increases expression	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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