NT5M

Summary

NT5M (5’,3’-nucleotidase, mitochondrial, HGNC:15769) is a protein-coding gene on chromosome 17p11.2, encoding 5’(3’)-deoxyribonucleotidase, mitochondrial (Q9NPB1). Dephosphorylates preferentially the 5’- and 2’(3’)-phosphates of uracil and thymine (deoxy)ribonucleotide monophosphates.

This gene encodes a 5’ nucleotidase that localizes to the mitochondrial matrix. This enzyme dephosphorylates the 5’- and 2’(3’)-phosphates of uracil and thymine deoxyribonucleotides. The gene is located within the Smith-Magenis syndrome region on chromosome 17.

Source: NCBI Gene 56953 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 46 total
• GTEx eGene: eQTL in 41 tissues, sQTL in 6 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.52 (unconstrained)
• MANE Select transcript: NM_020201

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15769
Approved symbol	NT5M
Name	5’,3’-nucleotidase, mitochondrial
Location	17p11.2
Locus type	gene with protein product
Status	Approved
Aliases	dNT-2, dNT2, mdN
Ensembl gene	ENSG00000205309
Ensembl biotype	protein_coding
OMIM	605292
Entrez	56953

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 12 nonsense_mediated_decay, 5 protein_coding, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000389022

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 3: 4, TSL 5: 1

ENST00000389022, ENST00000470418, ENST00000478373, ENST00000480529, ENST00000483704, ENST00000582909, ENST00000616989, ENST00000879604, ENST00000983453, ENST00000983454, ENST00000983455, ENST00000983456, ENST00001045337, ENST00001045338, ENST00001045339, ENST00001045340, ENST00001045341, ENST00001123525, ENST00001142790

RefSeq mRNA: 4 — MANE Select: NM_020201 NM_001438936, NM_001438937, NM_001438938, NM_020201

CCDS: CCDS32581

Canonical transcript exons

ENST00000389022 — 5 exons

Exon	Start	End
ENSE00001504694	17344794	17344908
ENSE00003503594	17306543	17306643
ENSE00003683043	17323185	17323245
ENSE00003846894	17303373	17303817
ENSE00004801607	17346805	17347663

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 87.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.9457 / max 110.0044, expressed in 1257 samples.

Highest expression (Bgee): monocyte, primordial germ cell in gonad, mononuclear cell, apex of heart, leukocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

NT5M is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 41 tissues and its splicing (sQTL) in 6 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 47 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	1.2e-87	+0.76	17:17270152:GTC:G
Cells Cultured fibroblasts	eqtl	2.6e-31	+0.71	17:17303887:C:G
Cells EBV-transformed lymphocytes	eqtl	7.6e-31	+1.10	17:17305651:G:A
Skin Sun Exposed Lower leg	eqtl	3.0e-24	+0.68	17:17304918:G:A
Adipose Subcutaneous	eqtl	7.0e-23	+0.81	17:17303887:C:G
Artery Tibial	eqtl	3.2e-22	+0.70	17:17304918:G:A
Skin Not Sun Exposed Suprapubic	eqtl	1.0e-19	+0.66	17:17304918:G:A
Colon Sigmoid	eqtl	2.0e-17	+0.75	17:17299383:C:G
Colon Transverse	eqtl	1.6e-16	+0.48	17:17303887:C:G
Nerve Tibial	eqtl	4.8e-16	+0.61	17:17303887:C:G
Thyroid	eqtl	9.8e-16	+0.57	17:17303887:C:G
Lung	eqtl	1.3e-15	+0.76	17:17303887:C:G
Artery Aorta	eqtl	2.6e-15	+1.42	17:17303358:G:C
Esophagus Mucosa	eqtl	4.0e-15	+0.57	17:17303887:C:G
Testis	eqtl	8.7e-15	-0.26	17:17316856:A:C
Muscle Skeletal	eqtl	2.3e-13	+0.59	17:17303358:G:C
Adipose Visceral Omentum	eqtl	1.1e-10	+0.55	17:17305651:G:A
Esophagus Gastroesophageal Junction	eqtl	9.3e-10	+0.37	17:17303887:C:G
Spleen	eqtl	1.3e-09	+0.84	17:17305651:G:A
Esophagus Muscularis	eqtl	2.6e-07	+0.27	17:17303887:C:G

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
159736	3.7158	1238
159737	0.2299	112

Top tissues by expression

showing 100 of 280 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	87.13	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.04	gold quality
mononuclear cell	CL:0000842	86.79	gold quality
apex of heart	UBERON:0002098	86.54	gold quality
leukocyte	CL:0000738	85.97	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.71	gold quality
right frontal lobe	UBERON:0002810	84.34	gold quality
anterior cingulate cortex	UBERON:0009835	83.52	gold quality
cingulate cortex	UBERON:0003027	83.46	gold quality
gastrocnemius	UBERON:0001388	83.34	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.19	gold quality
left testis	UBERON:0004533	83.12	gold quality
right testis	UBERON:0004534	82.97	gold quality
prefrontal cortex	UBERON:0000451	82.31	gold quality
muscle of leg	UBERON:0001383	82.26	gold quality
right hemisphere of cerebellum	UBERON:0014890	81.39	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.25	gold quality
testis	UBERON:0000473	80.89	gold quality
cerebellar hemisphere	UBERON:0002245	80.88	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.85	gold quality
cerebellar cortex	UBERON:0002129	80.69	gold quality
neocortex	UBERON:0001950	80.32	gold quality
heart left ventricle	UBERON:0002084	80.23	gold quality
amygdala	UBERON:0001876	79.84	gold quality
nucleus accumbens	UBERON:0001882	79.83	gold quality
frontal cortex	UBERON:0001870	79.76	gold quality
cardiac ventricle	UBERON:0002082	79.68	gold quality
primary visual cortex	UBERON:0002436	79.56	gold quality
cerebellum	UBERON:0002037	79.20	gold quality
caudate nucleus	UBERON:0001873	79.17	gold quality
muscle organ	UBERON:0001630	78.79	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	78.68	gold quality
putamen	UBERON:0001874	78.42	gold quality
blood	UBERON:0000178	78.38	gold quality
adenohypophysis	UBERON:0002196	78.38	gold quality
cerebral cortex	UBERON:0000956	78.34	gold quality
ganglionic eminence	UBERON:0004023	78.17	gold quality
ventricular zone	UBERON:0003053	78.09	gold quality
pituitary gland	UBERON:0000007	78.07	gold quality
telencephalon	UBERON:0001893	77.77	gold quality
forebrain	UBERON:0001890	77.42	gold quality
brain	UBERON:0000955	77.03	gold quality
cortical plate	UBERON:0005343	76.96	gold quality
spinal cord	UBERON:0002240	76.64	gold quality
lower esophagus muscularis layer	UBERON:0035833	76.24	gold quality
lower esophagus	UBERON:0013473	76.23	gold quality
granulocyte	CL:0000094	75.68	gold quality
heart	UBERON:0000948	75.17	gold quality
Ammon’s horn	UBERON:0001954	74.84	gold quality
temporal lobe	UBERON:0001871	74.82	gold quality
right atrium auricular region	UBERON:0006631	74.81	gold quality
muscle layer of sigmoid colon	UBERON:0035805	74.62	gold quality
Brodmann (1909) area 23	UBERON:0013554	74.47	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	74.45	gold quality
biceps brachii	UBERON:0001507	74.35	gold quality
hypothalamus	UBERON:0001898	74.35	gold quality
left uterine tube	UBERON:0001303	74.25	gold quality
occipital lobe	UBERON:0002021	74.25	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	74.03	gold quality
substantia nigra	UBERON:0002038	73.69	gold quality
right ovary	UBERON:0002118	73.67	gold quality
body of uterus	UBERON:0009853	73.33	gold quality
cardiac atrium	UBERON:0002081	73.10	gold quality
left ovary	UBERON:0002119	72.99	gold quality
ectocervix	UBERON:0012249	72.84	gold quality
endocervix	UBERON:0000458	72.69	gold quality
stromal cell of endometrium	CL:0002255	72.49	gold quality
lower esophagus mucosa	UBERON:0035834	72.36	gold quality
midbrain	UBERON:0001891	72.27	gold quality
bone marrow	UBERON:0002371	72.18	gold quality
metanephros cortex	UBERON:0010533	71.91	gold quality
skeletal muscle tissue	UBERON:0001134	70.98	gold quality
esophagus	UBERON:0001043	70.92	gold quality
tendon of biceps brachii	UBERON:0008188	69.98	gold quality
anatomical system	UBERON:0000467	69.93	gold quality
multicellular organism	UBERON:0000468	69.71	gold quality
material anatomical entity	UBERON:0000465	69.70	gold quality
trabecular bone tissue	UBERON:0002483	69.62	gold quality
superior frontal gyrus	UBERON:0002661	69.62	gold quality
ovary	UBERON:0000992	69.60	gold quality
buccal mucosa cell	CL:0002336	69.40	gold quality
gluteal muscle	UBERON:0002000	69.06	gold quality
triceps brachii	UBERON:0001509	69.04	gold quality
body of stomach	UBERON:0001161	68.96	gold quality
tibial nerve	UBERON:0001323	68.77	gold quality
muscle tissue	UBERON:0002385	68.74	gold quality
mucosa of stomach	UBERON:0001199	68.51	gold quality
omental fat pad	UBERON:0010414	68.39	gold quality
peritoneum	UBERON:0002358	68.37	gold quality
smooth muscle tissue	UBERON:0001135	68.22	gold quality
adipose tissue of abdominal region	UBERON:0007808	68.00	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	67.96	gold quality
bone marrow cell	CL:0002092	67.88	silver quality
fundus of stomach	UBERON:0001160	67.69	gold quality
right uterine tube	UBERON:0001302	67.55	gold quality
prostate gland	UBERON:0002367	67.46	gold quality
transverse colon	UBERON:0001157	67.23	gold quality
body of pancreas	UBERON:0001150	67.03	gold quality
subcutaneous adipose tissue	UBERON:0002190	66.99	gold quality
quadriceps femoris	UBERON:0001377	66.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.97

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Frontal cortex	tissue	27.2
Caudate putamen	tissue	16.6
Cerebral cortex	tissue	13.8	low
Occipital cortex	tissue	13.8
Motor cortex	tissue	13.7
Somatosensory cortex	tissue	13.7
Temporal cortex	tissue	12.7
Insular cortex	tissue	12.5
Skeletal muscle	tissue	12.4	low
Prefrontal cortex	tissue	12.3
Hippocampal formation	tissue	12.0
Entorhinal cortex	tissue	12.0
Retrosplenial and cingulate cortex	tissue	11.6
Retrosplenial cortex	tissue	11.4
Thalamus	tissue	10.8
Superior colliculi	tissue	10.6
Pons	tissue	10.0
Amygdala	tissue	10.0
Midbrain	tissue	10.0
Cerebellum	tissue	9.9	low
Putamen	tissue	9.2
Medulla oblongata	tissue	8.7
Spinal cord	tissue	8.6
Hypothalamus	tissue	8.5
Ventral forebrain	tissue	8.4
Basal ganglia	tissue	8.2	medium
Substantia nigra	tissue	8.0
Septum	tissue	7.7
Periaqueductal gray	tissue	7.6
Olfactory bulb	tissue	7.5
Postcentral gyrus	tissue	7.1
Corpus callosum	tissue	6.9
Hippocampus	tissue	5.2	low
Nucleus accumbens	tissue	5.1
Pituitary gland	tissue	4.7
Bone marrow	tissue	4.4	low
Tongue	tissue	4.2
Locus coeruleus	tissue	4.2
Choroid plexus	tissue	3.6
Testis	tissue	2.5	high
Heart muscle	tissue	2.1	medium
Parathyroid gland	tissue	1.7
Ovary	tissue	1.2	not detected
Vagina	tissue	1.2	low
Thymus	tissue	1.0
Kidney	tissue	0.9	medium
Prostate	tissue	0.9	not detected
Cervix	tissue	0.8	low
Fallopian tube	tissue	0.8	medium
Adipose tissue	tissue	0.7	medium
Esophagus	tissue	0.7	low
Salivary gland	tissue	0.7	low
Endometrium 1	tissue	0.7	low
Seminal vesicle	tissue	0.6	low
Skin 1	tissue	0.5	medium
Small intestine	tissue	0.5	medium
Breast	tissue	0.4	medium
Retina	tissue	0.4
Smooth muscle	tissue	0.4	not detected
Urinary bladder	tissue	0.4	not detected

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Ventral hippocampus (10.6), Precentral gyrus (10.5), Dorsal hippocampus (10.1), Subiculum (9.9), Ventral posterolateral thalamic nucleus (9.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting NT5M by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

28 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-128-1-5P	99.33	60.46	332
HSA-MIR-128-2-5P	99.33	60.83	311
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-4664-5P	98.17	65.07	1020
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-493-3P	97.50	66.44	731
HSA-MIR-4786-5P	97.45	67.89	924
HSA-MIR-1225-3P	97.29	64.60	876
HSA-MIR-342-5P	97.25	64.10	817
HSA-MIR-6762-5P	96.55	64.62	972
HSA-MIR-6845-5P	96.55	64.65	969
HSA-MIR-3135A	96.41	65.30	494
HSA-MIR-4772-5P	95.60	68.04	617
HSA-MIR-3174	94.63	63.64	577

Functional genomics

gnomAD constraint: pLI 5e-09, LOEUF 1.52, missense Z -0.995 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000389022 — one region, missense o/e 1.02.

Literature-anchored findings (GeneRIF, showing 4)

• Overproduction in cultured cells and functional aspects (PMID:12124385)
• structures of dNT-2 in complex with bound phosphate and beryllium trifluoride plus thymidine as model for a phosphoenzyme-product complex (PMID:12352955)
• substrate specificity analysis of the human mitochondrial deoxyribonucleotidase (PMID:16004879)
• An alternative splice variant of the mdN gene containing an 18-nucleotide insertion encoding 6 amino acids (GKWPAT) at the 3’-end of the penultimate exon 4 has been characterized. (PMID:24506201)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nt5m	ENSMUSG00000032615
rattus_norvegicus	Nt5m	ENSRNOG00000003332

Paralogs (1): NT5C (ENSG00000125458)

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bordetella parapertussis 12822	Q7WC96	98.4%	Diamond
Bordetella bronchiseptica RB50	Q7WQA0	98.4%	Diamond
Bordetella pertussis Tohama I	Q7W066	97.8%	Diamond
Acanthamoeba polyphaga mimivirus	Q5UPP9	35.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
COPS3	protein-coding	8533
FLCN	protein-coding	201163
PLD6	protein-coding	201164
MED9	protein-coding	55090

Protein

Protein identifiers

5’(3’)-deoxyribonucleotidase, mitochondrial — Q9NPB1 (reviewed: Q9NPB1)

Alternative names: Deoxy-5’-nucleotidase 2

All UniProt accessions (5): Q9NPB1, J3QLR5, J3QRN4, K7EPW8, Q2I378

UniProt curated annotations — full annotation on UniProt →

Function. Dephosphorylates preferentially the 5’- and 2’(3’)-phosphates of uracil and thymine (deoxy)ribonucleotide monophosphates. Shows low activity toward dGMP and marginal activity toward dIMP.

Subunit / interactions. Homodimer.

Subcellular location. Mitochondrion.

Tissue specificity. Highly expressed in heart, brain and skeletal muscle. Detected at very low levels in kidney and pancreas.

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

RefSeq proteins (4): NP_001425865, NP_001425866, NP_001425867, NP_064586* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010708	5’(3’)-deoxyribonucleotidase	Family
IPR023214	HAD_sf	Homologous_superfamily
IPR036412	HAD-like_sf	Homologous_superfamily

Pfam: PF06941

Catalyzed reactions (Rhea)

• dTMP + H2O = thymidine + phosphate (RHEA:11080)
• 3’-UMP + H2O = uridine + phosphate (RHEA:27890)
• dUMP + H2O = 2’-deoxyuridine + phosphate (RHEA:29355)
• UMP + H2O = uridine + phosphate (RHEA:29359)
• dGMP + H2O = 2’-deoxyguanosine + phosphate (RHEA:29379)
• thymidine 3’-phosphate + H2O = thymidine + phosphate (RHEA:37247)
• uridine 2’-phosphate + H2O = uridine + phosphate (RHEA:37355)

UniProt features (66 total): binding site 40, helix 11, strand 6, turn 4, active site 2, transit peptide 1, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

21 structures by resolution:

PDB	Title	Method	Resolution (Å)
4MUM	Crystal structure of mitochondrial 5’(3’)-deoxy ribonucleotidase alternative spliced …	X-RAY DIFFRACTION	1.27
6G2M	Crystal structure of human mitochondrial 5’(3’)-deoxyribonucleotidase in complex with the …	X-RAY DIFFRACTION	1.37
4NFL	Crystal structure of human mitochondrial 5’(3’)-deoxyribonucleotidase in complex with the …	X-RAY DIFFRACTION	1.38
1Q92	Crystal structure of human mitochondrial deoxyribonucleotidase in complex with the …	X-RAY DIFFRACTION	1.4
4L6A	Structure of human mitochondrial 5’(3’)-deoxyribonucleotidase	X-RAY DIFFRACTION	1.4
6G2L	Crystal structure of human mitochondrial 5’(3’)-deoxyribonucleotidase in complex with the …	X-RAY DIFFRACTION	1.48
4YIK	Crystal structure of human cytosolic 5’(3’)-deoxyribonucleotidase in complex with the …	X-RAY DIFFRACTION	1.48
1Q91	Crystal structure of human mitochondrial deoxyribonucleotidase in complex with the …	X-RAY DIFFRACTION	1.6
4MWO	Crystal structure of human mitochondrial 5’(3’)-deoxyribonucleotidase in complex with the …	X-RAY DIFFRACTION	1.67
1Z4M	Structure of the D41N variant of the human mitochondrial deoxyribonucleotidase in complex …	X-RAY DIFFRACTION	1.7
1Z4K	Structure of the D41N variant of the human mitochondrial deoxyribonucleotidase in complex …	X-RAY DIFFRACTION	1.75
1MH9	Crystal Structure Analysis of deoxyribonucleotidase	X-RAY DIFFRACTION	1.8
1Z4J	Structure of the D41N variant of the human mitochondrial deoxyribonucleotidase in complex …	X-RAY DIFFRACTION	1.8
1Z4L	Structure of the D41N variant of the human mitochondrial deoxyribonucleotidase in complex …	X-RAY DIFFRACTION	1.8
2JAU	Crystal structure of D41N variant of human mitochondrial 5’(3’)- deoxyribonucleotidase …	X-RAY DIFFRACTION	1.8
4L6C	Crystal structure of human mitochondrial deoxyribonucleotidase in complex with the …	X-RAY DIFFRACTION	1.8
6G22	Crystal structure of human mitochondrial 5’(3’)-deoxyribonucleotidase in complex with the …	X-RAY DIFFRACTION	1.85
2JAW	Crystal structure of D41N variant of human mitochondrial 5’(3’)- deoxyribonucleotidase …	X-RAY DIFFRACTION	1.95
1Z4I	Structure of the D41N variant of the human mitochondrial deoxyribonucleotidase in complex …	X-RAY DIFFRACTION	1.98
1Z4P	Structure of the D41N variant of the human mitochondrial deoxyribonucleotidase in complex …	X-RAY DIFFRACTION	2
1Z4Q	Structure of the D41N variant of the human mitochondrial deoxyribonucleotidase in complex …	X-RAY DIFFRACTION	2.05

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NPB1-F1	91.24	0.87

Human Protein Atlas

Protein class: Metabolic proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH uncertain

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)

Position	Role
41	nucleophile
43	proton donor

Ligand- & substrate-binding residues (40)

Position	Role
43	uridine 2’-phosphate
49	thymidine 3’-phosphate
49	uridine 2’-phosphate
77	dGMP
77	dTMP
77	dUMP
77	thymidine 3’-phosphate
77	UMP
77	uridine 2’-phosphate
78	dGMP
78	dTMP
78	dUMP
78	UMP
119	Mg(2+)
121	Mg(2+)
124	Mg(2+)
130	dUMP
130	thymidine 3’-phosphate
130	UMP
130	uridine 2’-phosphate
131	dGMP
131	dTMP
131	dUMP
131	thymidine 3’-phosphate
131	UMP
131	uridine 2’-phosphate
143	dUMP
143	thymidine 3’-phosphate
143	UMP
165	dGMP
41	Mg(2+)
165	dTMP
165	uridine 2’-phosphate
175	Mg(2+)
176	Mg(2+)
43	dGMP
43	dUMP
43	Mg(2+)
43	thymidine 3’-phosphate
43	UMP

Mutagenesis-validated functional residues (1)

Position	Phenotype
41	loss of activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-73621	Pyrimidine catabolism	curated
R-HSA-1430728	Metabolism	—
R-HSA-15869	Metabolism of nucleotides	—
R-HSA-8956319	Nucleotide catabolism	—

MSigDB gene sets: 104 (showing top): REACTOME_PYRIMIDINE_CATABOLISM, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_PYRIMIDINE_CONTAINING_COMPOUND_CATABOLIC_PROCESS, GOBP_PYRIMIDINE_NUCLEOTIDE_METABOLIC_PROCESS, GOBP_PYRIMIDINE_NUCLEOTIDE_CATABOLIC_PROCESS, GOBP_PYRIMIDINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_CATABOLIC_PROCESS, KEGG_PURINE_METABOLISM, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GOBP_NUCLEOSIDE_PHOSPHATE_CATABOLIC_PROCESS, GOBP_NUCLEOSIDE_MONOPHOSPHATE_METABOLIC_PROCESS, WONG_MITOCHONDRIA_GENE_MODULE

GO Biological Process (11): DNA replication (GO:0006260), pyrimidine deoxyribonucleotide catabolic process (GO:0009223), GMP catabolic process (GO:0046038), TMP catabolic process (GO:0046045), UMP catabolic process (GO:0046050), dGMP catabolic process (GO:0046055), dTMP catabolic process (GO:0046074), dUMP catabolic process (GO:0046079), nucleobase-containing compound metabolic process (GO:0006139), nucleotide metabolic process (GO:0009117), deoxyribonucleotide catabolic process (GO:0009264)

GO Molecular Function (6): nucleotide binding (GO:0000166), nucleotidase activity (GO:0008252), 5’-nucleotidase activity (GO:0008253), 3’-nucleotidase activity (GO:0008254), metal ion binding (GO:0046872), hydrolase activity (GO:0016787)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Nucleotide catabolism	1
Metabolism	1
Metabolism of nucleotides	1

GO top-level categories

33 GO namespaces:

Category	Terms
pyrimidine ribonucleoside monophosphate catabolic process	2
pyrimidine ribonucleotide catabolic process	2
pyrimidine deoxyribonucleoside monophosphate catabolic process	2
pyrimidine deoxyribonucleotide catabolic process	2
nucleotidase activity	2
DNA metabolic process	1
DNA biosynthetic process	1
pyrimidine nucleotide catabolic process	1
pyrimidine deoxyribonucleotide metabolic process	1
deoxyribose phosphate catabolic process	1
purine ribonucleotide catabolic process	1
purine ribonucleoside monophosphate catabolic process	1
GMP metabolic process	1
TMP metabolic process	1
UMP metabolic process	1
purine deoxyribonucleotide catabolic process	1
purine deoxyribonucleoside monophosphate catabolic process	1
dGMP metabolic process	1
dTMP metabolic process	1
dUMP metabolic process	1
primary metabolic process	1
nucleoside phosphate metabolic process	1
catabolic process	1
deoxyribonucleotide metabolic process	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
phosphatase activity	1
cation binding	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 9 of 19 annotations. The rest are phylogenetic / computational / electronic (IEA).

9 experimentally-supported GO terms:

GO term	NS	Evidence
GMP catabolic process	BP	direct assay
TMP catabolic process	BP	direct assay
UMP catabolic process	BP	direct assay
dGMP catabolic process	BP	direct assay
dTMP catabolic process	BP	direct assay
dUMP catabolic process	BP	direct assay
mitochondrion	CC	high-throughput
3’-nucleotidase activity	MF	direct assay
5’-nucleotidase activity	MF	direct assay

Protein interactions and networks

STRING

showing 16 of 552 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NT5M	COPS3	Q9UNS2	883
NT5M	TYMP	P19971	806
NT5M	NME4	O00746	792
NT5M	DGUOK	P78532	769
NT5M	NT5C3A	Q9H0P0	760
NT5M	CMPK1	P30085	742
NT5M	AK3	Q9UIJ7	736
NT5M	NT5C1A	Q9BXI3	698
NT5M	AK4	P27144	684
NT5M	LLGL1	Q15334	659
NT5M	AK2	P54819	620
NT5M	TK2	O00142	618
NT5M	NT5C1B	Q96P26	616
NT5M	POLG	P54098	615
NT5M	CMPK2	Q5EBM0	612
NT5M	TK1	P04183	612

IntAct

BioGRID (8 interactions; top human partners by supporting records): AOC1 (Positive Genetic), DAPK3 (Positive Genetic), KCNQ4 (Negative Genetic), NDUFB1 (Positive Genetic), NOS2 (Negative Genetic), PIK3CD (Negative Genetic), PTTG1 (Synthetic Growth Defect), SPPL3 (Positive Genetic)

Disease & clinical

Genetic variants

Variant evidence for NT5M: 46 ClinVar records (0 pathogenic / likely pathogenic); 2 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	4
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 938):

Position(s)	Effect	Δscore	Sites
17:17306644–17306645	donor_loss	1.0000	4
17:17344769	acceptor_gain	1.0000
17:17344792–17344793	acceptor_loss	1.0000	6
17:17306541–17306542	acceptor_loss	0.9900	6
17:17306644	donor_loss	0.9900
17:17323183–17323184	acceptor_loss	0.9900	6
17:17323246–17323247	donor_loss	0.9900	5
17:17344771	acceptor_gain	0.9900
17:17344777	acceptor_gain	0.9900
17:17344781	acceptor_gain	0.9900

AlphaMissense

616 missense substitutions predicted likely pathogenic (of 1,482 scored), across 141 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M42	9	0.911	0.982
D43	8	0.995	0.997
D176	8	0.993	0.998
D41	8	0.991	0.995
D175	8	0.989	0.996
F49	8	0.968	0.995
D164	8	0.956	0.987
N199	8	0.949	0.996
F101	8	0.937	0.993
F194	8	0.934	0.997
F75	8	0.923	0.995
F102	8	0.921	0.993
H198	8	0.917	0.990
F53	8	0.909	0.991
S131	8	0.865	0.987
H191	8	0.835	0.959
W189	7	0.991	0.998
W214	7	0.991	0.998
K165	7	0.980	0.999
C129	7	0.978	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:605292 | disease phenotypes:

GWAS associations

2 associations:

Study	Trait	p-value
GCST010396_135	Gut microbiota (bacterial taxa, hurdle binary method)	9e-7
GCST010107_15	L-selectin levels	2e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0008202	L-Selectin measurement
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3751654 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Adenosine turnover

ChEMBL bioactivities

1 potent at pChembl≥5 of 2 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.89	Ki	128	nM	CHEMBL3752084

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Tenofovir	decreases expression	1
Resveratrol	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Amiodarone	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Fluorouracil	increases expression	1
Niclosamide	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	decreases expression	1
S-Nitrosoglutathione	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3755233	Binding	Inhibition of N-terminal hexaHis-tagged human mitochondrial 5’(3’)-deoxynucleotidase using dUMP as substrate	Structure-based design of a bisphosphonate 5(3)-deoxyribonucleotidase inhibitor — *Medchemcomm*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for NT5M across ~30M SureChEMBL compounds — explore on Sugi Predict.