NAPRT

Summary

NAPRT (nicotinate phosphoribosyltransferase, HGNC:30450) is a protein-coding gene on chromosome 8q24.3, encoding Nicotinate phosphoribosyltransferase (Q6XQN6). Catalyzes the first step in the biosynthesis of NAD from nicotinic acid, the ATP-dependent synthesis of beta-nicotinate D-ribonucleotide from nicotinate and 5-phospho-D-ribose 1-phosphate. In precision oncology, NAPRT Promoter Hypermethylation confers sensitivity to GNE-617 in Cancer (CIViC Level D).

Nicotinic acid (NA; niacin) is converted by nicotinic acid phosphoribosyltransferase (NAPRT; EC 2.4.2.11) to NA mononucleotide (NaMN), which is then converted to NA adenine dinucleotide (NaAD), and finally to nicotinamide adenine dinucleotide (NAD), which serves as a coenzyme in cellular redox reactions and is an essential component of a variety of processes in cellular metabolism including response to stress (Hara et al., 2007).

Source: NCBI Gene 93100 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 151 total — 1 pathogenic
• GTEx eGene: eQTL in 49 tissues, sQTL in 49 (q < 0.05)
• ChEMBL bioactivity: 11 clinical-phase molecules tested; no curated mechanism-of-action drug
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.49 (unconstrained)
• MANE Select transcript: NM_145201

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30450
Approved symbol	NAPRT
Name	nicotinate phosphoribosyltransferase
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Aliases	PP3856
Ensembl gene	ENSG00000147813
Ensembl biotype	protein_coding
OMIM	611552
Entrez	93100

Gene structure

Transcript identifiers

Ensembl transcripts: 50 — 30 protein_coding, 11 nonsense_mediated_decay, 7 retained_intron, 2 non_stop_decay

MANE Select: ENST00000449291

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

ENST00000449291, ENST00000340490, ENST00000426292, ENST00000435154, ENST00000460623, ENST00000462059, ENST00000464332, ENST00000480946, ENST00000488096, ENST00000491904, ENST00000498076, ENST00000525583, ENST00000529179, ENST00000532645, ENST00000896704, ENST00000896705, ENST00000896706, ENST00000896707, ENST00000896708, ENST00000896709, ENST00000896710, ENST00000896711, ENST00000896712, ENST00000896713, ENST00000896714, ENST00000896715, ENST00000896716, ENST00000896717, ENST00000896718, ENST00000933603, ENST00000933604, ENST00000933605, ENST00000955117, ENST00000955118, ENST00000955119, ENST00000955120, ENST00000955121, ENST00000955122, ENST00000987245, ENST00000987247, ENST00000987248, ENST00000987251, ENST00000987252, ENST00001015196, ENST00001015198, ENST00001015199, ENST00001015200, ENST00001015201, ENST00001106420, ENST00001135702

RefSeq mRNA: 4 — MANE Select: NM_145201 NM_001286829, NM_001363145, NM_001363146, NM_145201

CCDS: CCDS6403, CCDS69555

Canonical transcript exons

ENST00000449291 — 13 exons

Exon	Start	End
ENSE00002146374	143578093	143578330
ENSE00003482025	143575622	143575702
ENSE00003510338	143576646	143576842
ENSE00003542919	143575423	143575525
ENSE00003553156	143576432	143576572
ENSE00003556511	143577657	143577739
ENSE00003559413	143577062	143577177
ENSE00003618724	143576078	143576162
ENSE00003645013	143575191	143575345
ENSE00003655258	143577816	143577943
ENSE00003675092	143577269	143577399
ENSE00003678711	143574986	143575093
ENSE00003683696	143574785	143574900

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.7570 / max 1026.3619, expressed in 1633 samples.

Highest expression (Bgee): mucosa of transverse colon, lobe of liver, lower esophagus mucosa, duodenum, esophagus mucosa.

Genetic regulation across tissues (GTEx eQTL / sQTL)

NAPRT is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 49 tissues and its splicing (sQTL) in 49 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 98 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	1.3e-140	-1.04	8:143578341:C:CG
Skin Not Sun Exposed Suprapubic	sqtl	5.6e-138	+1.40	8:143575631:G:A
Skin Sun Exposed Lower leg	sqtl	1.4e-136	+1.43	8:143575631:G:A
Muscle Skeletal	sqtl	1.3e-132	+1.39	8:143575631:G:A
Nerve Tibial	eqtl	4.8e-123	-1.09	8:143578341:C:CG
Thyroid	eqtl	4.2e-121	-1.19	8:143578341:C:CG
Cells Cultured fibroblasts	eqtl	7.1e-118	+0.94	8:143581491:G:A
Skin Sun Exposed Lower leg	eqtl	4.5e-116	+0.78	8:143594692:C:T
Testis	sqtl	4.1e-115	+1.65	8:143575631:G:A
Adipose Subcutaneous	sqtl	3.0e-114	+1.38	8:143575631:G:A
Whole Blood	sqtl	3.5e-110	+1.19	8:143575631:G:A
Skin Not Sun Exposed Suprapubic	eqtl	4.8e-101	+0.80	8:143594692:C:T
Adipose Subcutaneous	eqtl	1.1e-100	+0.64	8:143580183:G:A
Whole Blood	eqtl	4.6e-98	+0.63	8:143594692:C:T
Adipose Visceral Omentum	sqtl	1.5e-95	+1.25	8:143575631:G:A
Esophagus Mucosa	sqtl	9.2e-93	+1.35	8:143575631:G:A
Artery Tibial	eqtl	1.4e-92	+0.77	8:143594692:C:T
Lung	sqtl	1.8e-91	+1.10	8:143575631:G:A
Esophagus Muscularis	sqtl	5.1e-90	+1.41	8:143575631:G:A
Artery Tibial	sqtl	2.5e-88	+1.32	8:143575631:G:A

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
95493	15.6632	1617
95494	0.7570	392
95495	0.3149	154
95492	0.0135	4
95491	0.0084	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	98.01	gold quality
right lobe of liver	UBERON:0001114	97.95	gold quality
lower esophagus mucosa	UBERON:0035834	97.73	gold quality
duodenum	UBERON:0002114	97.62	gold quality
esophagus mucosa	UBERON:0002469	96.59	gold quality
liver	UBERON:0002107	96.53	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.22	gold quality
skin of leg	UBERON:0001511	96.05	gold quality
small intestine	UBERON:0002108	96.04	gold quality
transverse colon	UBERON:0001157	95.97	gold quality
zone of skin	UBERON:0000014	95.93	gold quality
skin of abdomen	UBERON:0001416	95.91	gold quality
apex of heart	UBERON:0002098	95.85	gold quality
metanephros cortex	UBERON:0010533	95.63	gold quality
blood	UBERON:0000178	95.45	gold quality
body of stomach	UBERON:0001161	95.34	gold quality
spleen	UBERON:0002106	95.27	gold quality
fundus of stomach	UBERON:0001160	95.15	gold quality
minor salivary gland	UBERON:0001830	94.96	gold quality
saliva-secreting gland	UBERON:0001044	94.94	gold quality
monocyte	CL:0000576	94.78	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.63	gold quality
right adrenal gland cortex	UBERON:0035827	94.62	gold quality
vagina	UBERON:0000996	94.53	gold quality
right lung	UBERON:0002167	94.49	gold quality
leukocyte	CL:0000738	94.45	gold quality
ectocervix	UBERON:0012249	94.45	gold quality
adult mammalian kidney	UBERON:0000082	94.35	gold quality
mucosa of stomach	UBERON:0001199	94.21	gold quality
esophagus	UBERON:0001043	94.11	gold quality
right adrenal gland	UBERON:0001233	93.94	gold quality
subcutaneous adipose tissue	UBERON:0002190	93.94	gold quality
omental fat pad	UBERON:0010414	93.84	gold quality
left adrenal gland cortex	UBERON:0035825	93.84	gold quality
adipose tissue	UBERON:0001013	93.81	gold quality
cortex of kidney	UBERON:0001225	93.69	gold quality
colon	UBERON:0001155	93.60	gold quality
intestine	UBERON:0000160	93.56	gold quality
upper lobe of left lung	UBERON:0008952	93.25	gold quality
stomach	UBERON:0000945	93.20	gold quality
left adrenal gland	UBERON:0001234	93.10	gold quality
right ovary	UBERON:0002118	93.00	gold quality
thoracic mammary gland	UBERON:0005200	92.97	gold quality
endocervix	UBERON:0000458	92.90	gold quality
left uterine tube	UBERON:0001303	92.87	gold quality
bone marrow	UBERON:0002371	92.78	gold quality
right coronary artery	UBERON:0001625	92.66	gold quality
granulocyte	CL:0000094	92.61	gold quality
prostate gland	UBERON:0002367	92.31	gold quality
uterine cervix	UBERON:0000002	92.19	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.04	gold quality
right lobe of thyroid gland	UBERON:0001119	91.97	gold quality
left coronary artery	UBERON:0001626	91.85	gold quality
bone marrow cell	CL:0002092	91.83	gold quality
heart left ventricle	UBERON:0002084	91.74	gold quality
tibial nerve	UBERON:0001323	91.59	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.50	gold quality
right uterine tube	UBERON:0001302	91.43	gold quality
lower esophagus	UBERON:0013473	91.42	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.39	gold quality
left ovary	UBERON:0002119	91.33	gold quality
thoracic aorta	UBERON:0001515	90.99	gold quality
adrenal gland	UBERON:0002369	90.95	gold quality
ascending aorta	UBERON:0001496	90.94	gold quality
descending thoracic aorta	UBERON:0002345	90.91	gold quality
multicellular organism	UBERON:0000468	90.88	gold quality
ovary	UBERON:0000992	90.77	gold quality
left lobe of thyroid gland	UBERON:0001120	90.60	gold quality
body of uterus	UBERON:0009853	90.49	gold quality
thyroid gland	UBERON:0002046	90.48	gold quality
kidney	UBERON:0002113	90.39	gold quality
left testis	UBERON:0004533	90.34	gold quality
urinary bladder	UBERON:0001255	90.20	gold quality
heart	UBERON:0000948	90.06	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.95	gold quality
lung	UBERON:0002048	89.78	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.75	gold quality
testis	UBERON:0000473	89.73	gold quality
right atrium auricular region	UBERON:0006631	89.70	gold quality
right testis	UBERON:0004534	89.59	gold quality
cerebellar hemisphere	UBERON:0002245	89.34	gold quality
cerebellum	UBERON:0002037	89.25	gold quality
cerebellar cortex	UBERON:0002129	89.24	gold quality
body of pancreas	UBERON:0001150	89.23	gold quality
vermiform appendix	UBERON:0001154	89.06	gold quality
myometrium	UBERON:0001296	88.99	gold quality
tibial artery	UBERON:0007610	88.92	gold quality
gastrocnemius	UBERON:0001388	88.91	gold quality
tonsil	UBERON:0002372	88.91	gold quality
adenohypophysis	UBERON:0002196	88.87	gold quality
popliteal artery	UBERON:0002250	88.87	gold quality
pituitary gland	UBERON:0000007	88.49	gold quality
gall bladder	UBERON:0002110	87.88	gold quality
muscle of leg	UBERON:0001383	87.81	gold quality
putamen	UBERON:0001874	87.21	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.04	gold quality
fallopian tube	UBERON:0003889	86.87	gold quality
nucleus accumbens	UBERON:0001882	86.79	gold quality
lymph node	UBERON:0000029	86.75	gold quality
right frontal lobe	UBERON:0002810	86.72	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Duodenum	tissue	57.7	high
Small intestine	tissue	44.6	high
Vagina	tissue	29.7	not detected
Salivary gland	tissue	27.5	medium
Esophagus	tissue	23.1	not detected
Stomach 1	tissue	21.3	medium
Skin 1	tissue	21.0	low
Bone marrow	tissue	20.7	low
Liver	tissue	19.4	low
Substantia nigra	tissue	15.2
Hypothalamus	tissue	14.5
Pons	tissue	14.3
Midbrain	tissue	13.1
Thalamus	tissue	12.9
Pancreas	tissue	11.7	not detected
Colon	tissue	11.6	medium
Superior colliculi	tissue	11.6
Adrenal gland	tissue	11.0	high
Hippocampal formation	tissue	11.0
Medulla oblongata	tissue	10.7
Septum	tissue	10.6
Periaqueductal gray	tissue	10.1
Pituitary gland	tissue	10.0
Seminal vesicle	tissue	9.9	low
Spleen	tissue	9.3	not detected
Spinal cord	tissue	9.2
Kidney	tissue	8.7	high
Cerebral cortex	tissue	8.4	low
Motor cortex	tissue	8.4
Cerebellum	tissue	8.4	not detected
Basal ganglia	tissue	8.3	not detected
Ventral forebrain	tissue	8.3
Lung	tissue	8.2	not detected
Prefrontal cortex	tissue	8.1
Retrosplenial cortex	tissue	8.1
Entorhinal cortex	tissue	7.6
Insular cortex	tissue	7.4
Amygdala	tissue	7.3
Corpus callosum	tissue	7.3
Retrosplenial and cingulate cortex	tissue	7.3
Temporal cortex	tissue	7.3
Skeletal muscle	tissue	7.2	not detected
Somatosensory cortex	tissue	7.2
Urinary bladder	tissue	6.6	high
Olfactory bulb	tissue	6.6
Lymph node	tissue	6.2	not detected
Occipital cortex	tissue	6.2
Prostate	tissue	6.1	low
Putamen	tissue	6.0
Appendix	tissue	6.0	medium
Cervix	tissue	5.9	low
Heart muscle	tissue	5.7	not detected
Nucleus accumbens	tissue	5.7
Fallopian tube	tissue	5.7	not detected
Choroid plexus	tissue	5.6
Gallbladder	tissue	5.5	medium
Ovary	tissue	5.2	medium
Placenta	tissue	5.1	medium
Adipose tissue	tissue	5.0	not detected
Tonsil	tissue	4.9	low

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Blood vessel (18.4), Subiculum (11.0), Dorsal spinal cord (9.2), Ventral spinal cord (9.0), Parahippocampal cortex (white matter) (7.5).

Regulation

Is transcription factor: no

Functional genomics

gnomAD constraint: pLI 3e-27, LOEUF 1.49, missense Z -1.85 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000449291 — one region, missense o/e 1.12.

Literature-anchored findings (GeneRIF, showing 12)

• NA elevates cellular NAD levels through NAPRT function and, thus, protects the cells against stress, partly due to lack of feedback inhibition of NAPRT but not NamPRT by NAD (PMID:17604275)
• NAPRT expression was varied in lymphomas with 30-50% low expression except for Hodgkin’s lymphoma where 85% displayed low expression (PMID:21492230)
• Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) activity by small molecule GMX1778 regulates reactive oxygen species (ROS)-mediated cytotoxicity in a p53- and nicotinic acid phosphoribosyltransferase1 (NAPRT1)-dependent manner (PMID:22570471)
• Tumor-specific promoter hypermethylation of NAPRT1 inactivates one of two NAD salvage pathways, resulting in synthetic lethality with the coadministration of a NAMPT inhibitor. (PMID:24097869)
• High NAPRTase expression is associated with neoplasms. (PMID:26675378)
• Synthesis and Degradation of Adenosine 5’-Tetraphosphate by Nicotinamide and Nicotinate Phosphoribosyltransferases (PMID:28416276)
• No correlation between IDH1/2 mutation status and sensitivity for NAMPT inhibitors was observed. Strikingly, higher methylation of the NAPRT promoter was observed in high-grade versus low-grade chondrosarcomas. In conclusion, this study identified NAMPT as a potential target for treatment of chondrosarcoma (PMID:28860121)
• Association of Schizophrenia Risk With Disordered Niacin Metabolism in an Indian Genome-wide Association Study. (PMID:31268507)
• Study demonstrated that PPM1D mutant astrocytes and patient-derived PPM1D mutant diffuse intrinsic pontine glioma lines are particularly sensitive to treatment with NAMPT inhibitors. Mutant PPM1D-induced NAMPT inhibitor sensitivity is driven by hypermethylation of CpG islands throughout the genome and the epigenetic silencing of NAPRT, a key gene involved in NAD biosynthesis. (PMID:31439867)
• these data identify NAPRT as a endogenous ligand for TLR4 and a mediator of inflammation. (PMID:31511522)
• NAPRT Expression Regulation Mechanisms: Novel Functions Predicted by a Bioinformatics Approach. (PMID:34946971)
• NAPRT, but Not NAMPT, Provides Additional Support for NAD Synthesis in Esophageal Precancerous Lesions. (PMID:36432602)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	naprt	ENSDARG00000027930
mus_musculus	Naprt	ENSMUSG00000022574
rattus_norvegicus	Naprt	ENSRNOG00000007939
drosophila_melanogaster	Naprt	FBGN0031589
caenorhabditis_elegans		WBGENE00021882

Paralogs (1): NAMPT (ENSG00000105835)

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
Mycobacterium tuberculosis CDC1551	P9WJI6	100.0%	Diamond
Mycobacterium tuberculosis H37Rv	P9WJI7	100.0%	Diamond
Bos taurus	A5PK51	89.3%	Diamond
Arabidopsis thaliana	Q84WV8	88.5%	Diamond
Dictyostelium discoideum	Q55G10	54.1%	Diamond
Bacillus subtilis subsp. subtilis str. 168	O32090	42.1%	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
SNORD149	snoRNA	109623485
ZC3H3	protein-coding	23144
MROH6	protein-coding	642475
GSDMD	protein-coding	79792
EEF1D	protein-coding	1936
PYCR3	protein-coding	65263
TIGD5	protein-coding	84948
GFUS	protein-coding	7264

Protein

Protein identifiers

Nicotinate phosphoribosyltransferase — Q6XQN6 (reviewed: Q6XQN6)

Alternative names: FHA-HIT-interacting protein, Nicotinate phosphoribosyltransferase domain-containing protein 1

All UniProt accessions (6): A0A087WUT5, C9J8U2, Q6XQN6, G5E977, H0YDA6, H0YF31

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the first step in the biosynthesis of NAD from nicotinic acid, the ATP-dependent synthesis of beta-nicotinate D-ribonucleotide from nicotinate and 5-phospho-D-ribose 1-phosphate. Helps prevent cellular oxidative stress via its role in NAD biosynthesis.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm. Cytosol.

Post-translational modifications. Transiently phosphorylated on a His residue during the reaction cycle. Phosphorylation strongly increases the affinity for substrates and increases the rate of nicotinate D-ribonucleotide production. Dephosphorylation regenerates the low-affinity form of the enzyme, leading to product release.

Cofactor. Activity is highest with Mn(2+).

Pathway. Cofactor biosynthesis; NAD(+) biosynthesis; nicotinate D-ribonucleotide from nicotinate: step 1/1.

Similarity. Belongs to the NAPRTase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6XQN6-1	1	yes
Q6XQN6-2	2
Q6XQN6-3	3

RefSeq proteins (4): NP_001273758, NP_001350074, NP_001350075, NP_660202* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006405	Nic_PRibTrfase_pncB	Family
IPR007229	Nic_PRibTrfase-Fam	Family
IPR013785	Aldolase_TIM	Homologous_superfamily
IPR036068	Nicotinate_pribotase-like_C	Homologous_superfamily
IPR040727	NAPRTase_N	Domain
IPR041619	NAPRTase_C	Domain

Pfam: PF17767, PF17956

Enzyme classification (BRENDA)

• EC 6.3.4.21 — nicotinate phosphoribosyltransferase (BRENDA: 15 organisms, 35 substrates, 62 inhibitors, 38 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
5-PHOSPHO-ALPHA-D-RIBOSE 1-DIPHOSPHATE	0.0002–4.5	13
NICOTINATE	0.0005–0.3	12
ATP	0.07–0.4	5
NICOTINIC ACID	0.0127–0.0155	2
GTP	0.34	1
ITP	1.16	1

Catalyzed reactions (Rhea)

• 5-phospho-alpha-D-ribose 1-diphosphate + nicotinate + ATP + H2O = nicotinate beta-D-ribonucleotide + ADP + phosphate + diphosphate (RHEA:36163)

UniProt features (71 total): helix 25, strand 20, mutagenesis site 11, binding site 4, sequence conflict 4, modified residue 2, splice variant 2, chain 1, turn 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
4YUB	Crystal structure of human Nicotinic Acid Phosphoribosyltransferase	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6XQN6-F1	94.94	0.92

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Ligase, Metabolic proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus; cytosol; nucleoplasm

Antibody reliability (HPA): IH enhanced · IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4)

Position	Role
21	nicotinate
210	nicotinate
318	nicotinate
380	5-phospho-alpha-D-ribose 1-diphosphate

Post-translational modifications (2)

Type	Positions
Phosphohistidine	213
Phosphoserine	537

Mutagenesis-validated functional residues (11)

Position	Phenotype
19	complete loss of activity.
21	partial loss of activity in the presence of atp, complete loss in the absence of atp.
169	partial loss of activity.
209	partial loss of activity.
213	partial loss of activity.
288	partial loss of activity.
318	partial loss of activity in the presence of atp, almost complete loss in the absence of atp.
357	small loss of activity.
379	complete loss of activity.
380	partial loss of activity.
381	partial loss of activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-6798695	Neutrophil degranulation	curated
R-HSA-196807	Nicotinate metabolism	curated
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-1430728	Metabolism	—
R-HSA-196854	Metabolism of vitamins and cofactors	—
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors	—

MSigDB gene sets: 95 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PURINE_CONTAINING_COMPOUND_SALVAGE, GOBP_NADPLUS_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, GOMF_LIGASE_ACTIVITY_FORMING_CARBON_NITROGEN_BONDS, GOBP_PURINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_NUCLEOTIDE_SALVAGE, GOBP_METABOLIC_COMPOUND_SALVAGE

GO Biological Process (4): response to oxidative stress (GO:0006979), NAD+ biosynthetic process via the salvage pathway (GO:0034355), NAD+ biosynthetic process (GO:0009435), pyridine nucleotide biosynthetic process (GO:0019363)

GO Molecular Function (6): nicotinate phosphoribosyltransferase activity (GO:0004516), transferase activity (GO:0016740), metal ion binding (GO:0046872), protein binding (GO:0005515), glycosyltransferase activity (GO:0016757), ligase activity (GO:0016874)

GO Cellular Component (4): extracellular region (GO:0005576), cytosol (GO:0005829), azurophil granule lumen (GO:0035578), extracellular exosome (GO:0070062)

Reactome top-level categories

5 top-level categories:

Category	Pathways
Metabolism of water-soluble vitamins and cofactors	1
Innate Immune System	1
Immune System	1
Metabolism of vitamins and cofactors	1
Metabolism	1

GO top-level categories

20 GO namespaces:

Category	Terms
catalytic activity	2
cellular anatomical structure	2
response to stress	1
NAD+ biosynthetic process	1
pyridine nucleotide salvage	1
purine nucleotide salvage	1
purine nucleotide biosynthetic process	1
nicotinamide nucleotide biosynthetic process	1
NAD+ metabolic process	1
nucleotide biosynthetic process	1
pyridine-containing compound biosynthetic process	1
ligase activity, forming carbon-nitrogen bonds	1
cation binding	1
binding	1
transferase activity	1
cytoplasm	1
vacuolar lumen	1
secretory granule lumen	1
azurophil granule	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 14 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
NAD+ biosynthetic process via the salvage pathway	BP	mutant phenotype
response to oxidative stress	BP	mutant phenotype
cytosol	CC	direct assay
extracellular exosome	CC	high-throughput assay
nicotinate phosphoribosyltransferase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 748 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NAPRT	NAMPT	P43490	948
NAPRT	QPRT	Q15274	825
NAPRT	NMNAT1	Q9HAN9	818
NAPRT	NMRK1	Q9NWW6	806
NAPRT	A0A2R8YFG2	A0A2R8YFG2	743
NAPRT	NADSYN1	Q6IA69	735
NAPRT	NMNAT2	Q9BZQ4	731
NAPRT	HAAO	P46952	670
NAPRT	KMO	O15229	630
NAPRT	AFMID	Q63HM1	620
NAPRT	TDO2	P48775	613
NAPRT	NMRK2	Q9NPI5	607
NAPRT	BST1	Q10588	585
NAPRT	NADK	O95544	582
NAPRT	ACMSD	Q8TDX5	577

IntAct

Human interaction partners of NAPRT in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
GRAMD2B	physical association	0.560	3
RBPMS	physical association	0.560	3

BioGRID (50 interactions; top human partners by supporting records): ACLY (Co-fractionation), APEX1 (Affinity Capture-RNA), APRT (Co-fractionation), ARMC1 (Co-fractionation), C6orf211 (Co-fractionation), CCDC57 (Two-hybrid), CDK15 (Affinity Capture-MS), DHRS11 (Co-fractionation), EEF1A1 (Co-fractionation), EHMT2 (Two-hybrid), EIF2A (Co-fractionation), ETNK1 (Affinity Capture-MS), GRAMD3 (Two-hybrid), HNRNPK (Co-fractionation), HSPA8 (Co-fractionation)

Disease & clinical

Genetic variants

Variant evidence for NAPRT: 151 ClinVar records (1 pathogenic / likely pathogenic); 1 CIViC cancer variant; 3 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	104
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
3024645	GRCh37/hg19 8q23.3-24.3(chr8:113392581-146364022)x3	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore NAPRT’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 23 predictions of 1,050):

Position(s)	Effect	Δscore	Sites
8:143575421–143575422	donor_loss	1.0000	5
8:143575530	acceptor_gain	1.0000
8:143576430–143576431	donor_loss	1.0000	4
8:143576573	acceptor_loss	1.0000
8:143576577	acceptor_gain	1.0000
8:143577267–143577268	donor_loss	1.0000	4
8:143577655–143577656	donor_loss	1.0000	4
8:143577665	donor_gain	1.0000
8:143575195	donor_gain	0.9900
8:143575524	acceptor_gain	0.9900

AlphaMissense

930 missense substitutions predicted likely pathogenic (of 3,395 scored), across 282 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
D19	8	0.962	0.978
F41	8	0.928	0.994
D320	8	0.916	0.967
D436	8	0.915	0.958
M25	8	0.896	0.979
D288	8	0.895	0.950
F50	8	0.890	0.980
H213	8	0.866	0.960
F191	8	0.858	0.977
F283	8	0.821	0.948
E135	7	0.962	0.996
F45	7	0.926	0.960
F54	7	0.916	0.978
K407	7	0.914	0.974
F215	7	0.904	0.966
F92	7	0.897	0.969
N196	7	0.885	0.987
E167	7	0.884	0.956
F70	7	0.877	0.941
F272	7	0.874	0.927

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	8.67e-06
Pancreatic Adenocarcinoma (validation)	unfavorable	0.000462
Kidney Renal Papillary Cell Carcinoma (TCGA)	favorable	0.000812

Disease associations

OMIM: gene MIM:611552 | disease phenotypes:

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (1 panels, 0 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

1 panels:

Panel	Rating
Haematological malignancies cancer susceptibility	amber

GWAS associations

3 associations:

Study	Trait	p-value
GCST008459_2	Schizophrenia	1e-9
GCST008459_1	Schizophrenia	4e-8
GCST000281_7	Attention deficit hyperactivity disorder	9e-6

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523354 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,838,006 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

11 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL269644	ACETANILIDE	4	23,709
CHEMBL288470	AMINOPYRINE	4	8,309
CHEMBL25	ASPIRIN	4	696,632
CHEMBL6	INDOMETHACIN	4	157,305
CHEMBL686	MEFENAMIC ACID	4	62,458
CHEMBL1228	OXYPHENBUTAZONE ANHYDROUS	4	24,211
CHEMBL101	PHENYLBUTAZONE	4	59,810
CHEMBL424	SALICYLIC ACID	4	674,431
CHEMBL832	SULFINPYRAZONE	4	13,851
CHEMBL277474	ANTIPYRINE	3	82,267
CHEMBL23588	FLUFENAMIC ACID	2	35,023

Clinical evidence (CIViC)

Drug × variant × indication, from 1 curated evidence items. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

1 predictive associations by evidence level:

Variant	Therapy	Indication	Effect	Level	CIViC
NAPRT Promoter Hypermethylation	GNE-617	Cancer	Sensitivity/Response	CIViC D	EID897

CIViC curated variants (1)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

Promoter Hypermethylation.

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

24 potent at pChembl≥5 of 24 total, top 24 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	FLUFENAMIC ACID
10.30	Ki	0.05	nM	MEFENAMIC ACID
10.12	Ki	0.075	nM	PYRAZINOIC ACID
10.00	Ki	0.1	nM	PHENYLBUTAZONE
9.82	Ki	0.15	nM	INDOMETHACIN
9.80	Ki	0.16	nM	SALICYLIC ACID
9.64	Ki	0.23	nM	CHEMBL53297
9.55	Ki	0.28	nM	CHEMBL394308
9.52	Ki	0.3	nM	OXYPHENBUTAZONE ANHYDROUS
9.30	Ki	0.5	nM	SULFINPYRAZONE
9.30	Ki	0.5	nM	ASPIRIN
9.30	Kd	0.495	nM	CHEMBL5653589
9.30	ED50	0.495	nM	CHEMBL5653589
9.25	Ki	0.56	nM	6-CHLORONICOTINIC ACID
9.12	Ki	0.75	nM	CHEMBL4438353
9.12	Ki	0.75	nM	ISONICOTINIC ACID
9.11	Ki	0.78	nM	PYRIDINE
9.09	Ki	0.82	nM	CHEMBL3322868
9.00	Ki	1	nM	ANTIPYRINE
9.00	Ki	1	nM	AMINOPYRINE
9.00	Ki	1	nM	ACETANILIDE
8.94	Ki	1.16	nM	2-PICOLINIC ACID
8.89	Ki	1.28	nM	CHEMBL1741437
8.72	Ki	1.9	nM	BENZOIC ACID

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148823: Binding affinity to human NAPRT incubated for 45 mins by Kinobead based pull down assay	kd	0.0005	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	3
N-(4-(1-benzoylpiperidin-4-yl)butyl)-3-(pyridin-3-yl)acrylamide	decreases activity	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
Smoke	decreases expression, increases abundance, increases expression	2
Cyclosporine	decreases expression	2
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
lead acetate	decreases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	decreases methylation	1
puag-haad	increases expression	1
ICG 001	increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	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
Sunitinib	decreases expression	1
Dinitrochlorobenzene	affects binding	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Methapyrilene	decreases methylation	1
Pesticides	affects methylation	1
Thimerosal	decreases expression	1
Thiram	decreases expression	1
Aflatoxin B1	affects expression	1
Acrylamide	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

ChEMBL screening assays

16 unique, capped per target: 16 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4418184	Binding	Inhibition of NAPRT (unknown origin)	Sensitization of cancer cells to nampt inhibitors by nicotinic acid phosphoribosyltransferase neutralization

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1NX	Abcam K-562 NAPRT KO	Cancer cell line	Female
CVCL_D2KH	Abcam Raji NAPRT KO	Cancer cell line	Male
CVCL_UQ99	Abcam Jurkat NAPRT KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

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