NME2

Summary

NME2 (NME/NM23 nucleoside diphosphate kinase 2, HGNC:7850) is a protein-coding gene on chromosome 17q21.33, encoding Nucleoside diphosphate kinase B (P22392). Catalyzes the transfer of a gamma-phosphoryl group from a nucleoside triphosphate, mainly ATP, to a nucleoside diphosphate via a ping-pong mechanism involving a phosphohistidine intermediate, therefore contributing to the nucleoside triphosphate homeostasis. It is a selective cancer dependency (DepMap: 24.4% of cell lines).

Nucleoside diphosphate kinase (NDK) exists as a hexamer composed of ‘A’ (encoded by NME1) and ‘B’ (encoded by this gene) isoforms. Multiple alternatively spliced transcript variants have been found for this gene. Read-through transcription from the neighboring upstream gene (NME1) generates naturally-occurring transcripts (NME1-NME2) that encode a fusion protein comprised of sequence sharing identity with each individual gene product.

Source: NCBI Gene 4831 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• GTEx eGene: eQTL in 49 tissues, sQTL in 50 (q < 0.05)
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Cancer dependency (DepMap): dependent in 24.4% of screened cell lines
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.49 (unconstrained)
• MANE Select transcript: NM_002512
• Interaction hub: 3,239 STRING partners (top 2% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7850
Approved symbol	NME2
Name	NME/NM23 nucleoside diphosphate kinase 2
Location	17q21.33
Locus type	gene with protein product
Status	Approved
Aliases	NM23-H2, NDPKB
Ensembl gene	ENSG00000243678
Ensembl biotype	protein_coding
OMIM	156491
Entrez	4831

Gene structure

Transcript identifiers

Ensembl transcripts: 60 — 54 protein_coding, 3 retained_intron, 3 nonsense_mediated_decay

MANE Select: ENST00000512737

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

ENST00000512737, ENST00000393183, ENST00000393190, ENST00000485076, ENST00000503064, ENST00000513177, ENST00000514264, ENST00000570801, ENST00000573262, ENST00000861527, ENST00000861528, ENST00000861529, ENST00000926696, ENST00000926697, ENST00000926698, ENST00000926699, ENST00000926700, ENST00000926701, ENST00000926702, ENST00000926703, ENST00000926704, ENST00000926705, ENST00000926706, ENST00000926707, ENST00000941167, ENST00000941168, ENST00000941169, ENST00000990976, ENST00001039742, ENST00001039743, ENST00001039744, ENST00001059192, ENST00001059193, ENST00001059196, ENST00001059214, ENST00001059221, ENST00001059222, ENST00001059223, ENST00001102842, ENST00001102843, ENST00001102844, ENST00001102845, ENST00001102846, ENST00001102847, ENST00001102848, ENST00001102849, ENST00001102850, ENST00001102851, ENST00001102852, ENST00001102853, ENST00001122027, ENST00001122028, ENST00001130334, ENST00001130335, ENST00001130336, ENST00001130337, ENST00001130338, ENST00001130339, ENST00001130340, ENST00001139922

RefSeq mRNA: 5 — MANE Select: NM_002512 NM_001018137, NM_001018138, NM_001018139, NM_001198682, NM_002512

CCDS: CCDS11580, CCDS74107

Canonical transcript exons

ENST00000512737 — 5 exons

Exon	Start	End
ENSE00003460413	51171487	51171744
ENSE00003651397	51166411	51166497
ENSE00003705710	51169937	51170049
ENSE00003721718	51166827	51166956
ENSE00003781211	51168242	51168343

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 555.0081 / max 2562.4250, expressed in 1827 samples.

Highest expression (Bgee): ovary, skin of abdomen, zone of skin, skin of leg, metanephros cortex.

Genetic regulation across tissues (GTEx eQTL / sQTL)

NME2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 49 tissues and its splicing (sQTL) in 50 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 99 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Subcutaneous	sqtl	0.0e+00	+2.90	17:51149056:G:A
Artery Tibial	sqtl	0.0e+00	+2.78	17:51149056:G:A
Muscle Skeletal	sqtl	0.0e+00	+2.82	17:51149056:G:A
Skin Sun Exposed Lower leg	sqtl	0.0e+00	+2.83	17:51149056:G:A
Whole Blood	sqtl	0.0e+00	+2.79	17:51149056:G:A
Thyroid	sqtl	6.5e-267	+2.98	17:51149056:G:A
Nerve Tibial	sqtl	6.8e-254	+2.92	17:51149056:G:A
Esophagus Mucosa	sqtl	1.6e-253	+3.03	17:51149056:G:A
Lung	sqtl	4.5e-236	+3.20	17:51149056:G:A
Cells Cultured fibroblasts	sqtl	1.3e-234	+2.91	17:51149056:G:A
Skin Not Sun Exposed Suprapubic	sqtl	2.3e-228	+2.93	17:51149056:G:A
Adipose Visceral Omentum	sqtl	5.5e-217	+2.85	17:51149056:G:A
Esophagus Muscularis	sqtl	3.0e-212	+2.83	17:51149056:G:A
Breast Mammary Tissue	sqtl	3.6e-171	+2.81	17:51149056:G:A
Artery Aorta	sqtl	1.9e-167	+2.92	17:51149056:G:A
Colon Sigmoid	sqtl	6.1e-152	+3.02	17:51149056:G:A
Colon Transverse	sqtl	7.3e-144	+3.12	17:51149056:G:A
Testis	sqtl	1.0e-143	+2.89	17:51149056:G:A
Heart Atrial Appendage	sqtl	1.2e-136	+2.75	17:51149056:G:A
Stomach	sqtl	9.7e-134	+2.73	17:51149056:G:A

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
161742	398.4006	1827
161743	155.1590	1818
161740	1.2380	446
161741	0.2105	83

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ovary	UBERON:0002119	99.56	gold quality
skin of abdomen	UBERON:0001416	99.55	gold quality
zone of skin	UBERON:0000014	99.54	gold quality
skin of leg	UBERON:0001511	99.54	gold quality
ovary	UBERON:0000992	99.53	gold quality
metanephros cortex	UBERON:0010533	99.53	gold quality
endocervix	UBERON:0000458	99.52	gold quality
left coronary artery	UBERON:0001626	99.52	gold quality
esophagus mucosa	UBERON:0002469	99.52	gold quality
mucosa of transverse colon	UBERON:0004991	99.52	gold quality
lower esophagus	UBERON:0013473	99.52	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.52	gold quality
esophagus	UBERON:0001043	99.51	gold quality
thoracic mammary gland	UBERON:0005200	99.51	gold quality
body of pancreas	UBERON:0001150	99.50	gold quality
right ovary	UBERON:0002118	99.50	gold quality
stromal cell of endometrium	CL:0002255	99.49	gold quality
vagina	UBERON:0000996	99.49	gold quality
adipose tissue	UBERON:0001013	99.49	gold quality
subcutaneous adipose tissue	UBERON:0002190	99.49	gold quality
body of uterus	UBERON:0009853	99.49	gold quality
omental fat pad	UBERON:0010414	99.49	gold quality
myometrium	UBERON:0001296	99.48	gold quality
ectocervix	UBERON:0012249	99.48	gold quality
left adrenal gland	UBERON:0001234	99.47	gold quality
left adrenal gland cortex	UBERON:0035825	99.47	gold quality
saliva-secreting gland	UBERON:0001044	99.46	gold quality
body of stomach	UBERON:0001161	99.46	gold quality
minor salivary gland	UBERON:0001830	99.46	gold quality
right lobe of thyroid gland	UBERON:0001119	99.45	gold quality
cortex of kidney	UBERON:0001225	99.45	gold quality
right adrenal gland	UBERON:0001233	99.45	gold quality
prostate gland	UBERON:0002367	99.45	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.45	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.45	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.44	gold quality
transverse colon	UBERON:0001157	99.43	gold quality
lower esophagus mucosa	UBERON:0035834	99.43	gold quality
fundus of stomach	UBERON:0001160	99.42	gold quality
mucosa of stomach	UBERON:0001199	99.42	gold quality
ascending aorta	UBERON:0001496	99.42	gold quality
thoracic aorta	UBERON:0001515	99.42	gold quality
right coronary artery	UBERON:0001625	99.42	gold quality
right adrenal gland cortex	UBERON:0035827	99.42	gold quality
descending thoracic aorta	UBERON:0002345	99.41	gold quality
left lobe of thyroid gland	UBERON:0001120	99.40	gold quality
colon	UBERON:0001155	99.40	gold quality
pancreas	UBERON:0001264	99.40	gold quality
left uterine tube	UBERON:0001303	99.40	gold quality
fallopian tube	UBERON:0003889	99.40	gold quality
uterine cervix	UBERON:0000002	99.39	gold quality
adult mammalian kidney	UBERON:0000082	99.38	gold quality
thyroid gland	UBERON:0002046	99.38	gold quality
right uterine tube	UBERON:0001302	99.37	gold quality
popliteal artery	UBERON:0002250	99.37	gold quality
tibial artery	UBERON:0007610	99.37	gold quality
adrenal gland	UBERON:0002369	99.34	gold quality
intestine	UBERON:0000160	99.33	gold quality
adenohypophysis	UBERON:0002196	99.33	gold quality
spleen	UBERON:0002106	99.32	gold quality
upper lobe of left lung	UBERON:0008952	99.32	gold quality
tibial nerve	UBERON:0001323	99.31	gold quality
pituitary gland	UBERON:0000007	99.30	gold quality
smooth muscle tissue	UBERON:0001135	99.30	gold quality
stomach	UBERON:0000945	99.29	gold quality
putamen	UBERON:0001874	99.29	gold quality
substantia nigra	UBERON:0002038	99.28	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.28	gold quality
right lung	UBERON:0002167	99.27	gold quality
tonsil	UBERON:0002372	99.27	gold quality
islet of Langerhans	UBERON:0000006	99.26	gold quality
urinary bladder	UBERON:0001255	99.26	gold quality
cortical plate	UBERON:0005343	99.26	gold quality
right atrium auricular region	UBERON:0006631	99.26	gold quality
small intestine	UBERON:0002108	99.25	gold quality
caudate nucleus	UBERON:0001873	99.24	gold quality
nucleus accumbens	UBERON:0001882	99.24	gold quality
rectum	UBERON:0001052	99.23	gold quality
lymph node	UBERON:0000029	99.22	gold quality
Ammon’s horn	UBERON:0001954	99.22	gold quality
placenta	UBERON:0001987	99.22	gold quality
gastrocnemius	UBERON:0001388	99.20	gold quality
amygdala	UBERON:0001876	99.20	gold quality
temporal lobe	UBERON:0001871	99.19	gold quality
apex of heart	UBERON:0002098	99.19	gold quality
kidney	UBERON:0002113	99.19	gold quality
anterior cingulate cortex	UBERON:0009835	99.19	gold quality
vermiform appendix	UBERON:0001154	99.18	gold quality
hypothalamus	UBERON:0001898	99.18	gold quality
duodenum	UBERON:0002114	99.18	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.17	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.17	gold quality
heart	UBERON:0000948	99.16	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.16	gold quality
prefrontal cortex	UBERON:0000451	99.15	gold quality
cerebral cortex	UBERON:0000956	99.15	gold quality
muscle of leg	UBERON:0001383	99.15	gold quality
frontal cortex	UBERON:0001870	99.12	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.12	gold quality
heart left ventricle	UBERON:0002084	99.10	gold quality

Single-cell (SCXA)

Detected in 22 experiment(s), a significant marker in 17.

Experiment	Marker?	Max mean expression
E-MTAB-6653	yes	1446.34
E-GEOD-149689	yes	1352.18
E-HCAD-4	yes	86.02
E-GEOD-125970	yes	53.64
E-MTAB-8410	yes	48.77
E-MTAB-10553	yes	35.65
E-CURD-46	yes	33.98
E-CURD-112	yes	33.77
E-CURD-122	yes	23.19
E-HCAD-9	yes	19.88
E-HCAD-1	yes	19.01
E-MTAB-10042	yes	17.45
E-ANND-3	yes	15.89
E-MTAB-9467	yes	11.69
E-MTAB-9067	yes	10.43

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Vagina	tissue	567.7	medium
Pancreas	tissue	452.2	medium
Skeletal muscle	tissue	445.7	not detected
Ovary	tissue	432.0	low
Breast	tissue	419.2	low
Choroid plexus	tissue	400.1
Salivary gland	tissue	398.1	medium
Colon	tissue	368.4	medium
Urinary bladder	tissue	338.8	high
Tongue	tissue	329.8
Esophagus	tissue	324.9	medium
Adipose tissue	tissue	318.2	not detected
Duodenum	tissue	314.7	medium
Bone marrow	tissue	310.6	medium
Rectum	tissue	309.7	high
Fallopian tube	tissue	302.5	medium
Stomach 1	tissue	289.5	high
Pituitary gland	tissue	285.8
Cervix	tissue	278.6	medium
Tonsil	tissue	270.5	medium
Lymph node	tissue	269.9	high
Adrenal gland	tissue	268.9	medium
Smooth muscle	tissue	267.0	not detected
Skin 1	tissue	265.8	medium
Small intestine	tissue	265.3	medium
Heart muscle	tissue	248.6	not detected
Appendix	tissue	244.7	medium
Seminal vesicle	tissue	232.9	medium
Liver	tissue	232.6	low
Kidney	tissue	226.4	high
Epididymis	tissue	222.7	medium
Endometrium 1	tissue	219.5	medium
Spleen	tissue	200.4	medium
Placenta	tissue	192.2	medium
Parathyroid gland	tissue	189.1	medium
Prostate	tissue	182.2	high
Thyroid gland	tissue	179.3	medium
Thymus	tissue	177.0
Frontal cortex	tissue	175.3
Gallbladder	tissue	175.3	low
Caudate putamen	tissue	169.9
Spinal cord	tissue	164.8
Pons	tissue	160.2
Locus coeruleus	tissue	156.9
Lung	tissue	156.5	low
Medulla oblongata	tissue	155.1
Substantia nigra	tissue	150.5
Cerebral cortex	tissue	145.8	medium
Motor cortex	tissue	145.8
Nucleus accumbens	tissue	139.7
Somatosensory cortex	tissue	138.2
Hippocampus	tissue	134.9	medium
Superior colliculi	tissue	134.0
Hippocampal formation	tissue	133.5
Putamen	tissue	132.9
Midbrain	tissue	132.4
Temporal cortex	tissue	131.4
Thalamus	tissue	131.1
Entorhinal cortex	tissue	130.7
Retrosplenial and cingulate cortex	tissue	126.3

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (598.2), Mammillary body (203.7), Anterior thalamic nucleus, ventral (199.4), Lateral funiculus (white matter) (193.0), Posterior thalamic nucleus (189.2).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets:

Target	Regulation
MYC	Activation

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

Targeting NME2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

6 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-4709-3P	98.88	68.04	1594
HSA-MIR-1301-5P	98.09	66.62	495
HSA-MIR-6502-5P	98.09	66.73	495
HSA-MIR-3152-5P	96.98	66.88	819
HSA-MIR-4423-5P	95.24	64.42	454

Functional genomics

gnomAD constraint: pLI 5.7e-07, LOEUF 1.49, missense Z 1.07 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000512737 — one region, missense o/e 0.82. DepMap (CRISPR cell-line fitness): dependent in 24.4% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): Onda 9 (-1.32), SNU-1544 (-1.292), SCS-214 (-1.283), LCLC-97TM1 (-1.25), HCC-15 (-1.096), LN-235 (-1.023), JVE-187 (-0.964), HCC-366 (-0.961), NCI-H2887 (-0.941), MHH-NB-11 (-0.918), T3M-3 (-0.907), LPS6 (-0.893), Caki-1 (-0.886), GI-ME-N (-0.874), HCE-4 (-0.874).

Literature-anchored findings (GeneRIF, showing 40)

• The N-myc and c-myc downstream pathways include the chromosome 17q genes nm23-H1 and nm23-H2. (PMID:11960382)
• NM23-H2 protein expression in human leukemia cell lines is related to cellular lineage and differentiation stages. (PMID:12007505)
• The nucleotide-binding site of NM23-H2 plays a critical role in not only the NDP kinase reaction but also the reactions involving covalent DNA binding and DNA cleavage catalysis. (PMID:12009894)
• expression of nucleoside diphosphate kinase in Alzheimer disease and Down syndrome brains (PMID:12200143)
• found that Nm23-H5 and NDP kinases A and B are differently distributed in spermatids and mature spermatozoa and could therefore be involved at various levels of sperm differentiation and function (PMID:14499630)
• Nm23-H2 had a cytoplasmic and nuclear localization but was induced to translocate to the plasma membrane upon stimulation of thromboxane A2 receptor beta to show extensive co-localization with the receptor. (PMID:14976202)
• Novel roles of NM23 proteins in skin homeostasis, repair and disease. (PMID:16862176)
• novel association of NM23-H2 with ERbeta and show for the first time its expression in vascular cells and demonstrate regulation of its expression and localization by estrogen (PMID:17272673)
• Thus, these results indicate the existence of a previously undiscovered mechanism by which NM23-H2 involves in the regulation of Diva-mediated apoptosis. (PMID:17532299)
• NM23-H2 as an estrogen receptor beta-associated protein may play an important role in modulating the response to endogenous and exogenous estrogens. (PMID:17964137)
• describe the identification of NM23-H2 as a novel HLA-A32-restricted TAA of CML cells and demonstrate the presence of specifically reactive T cells in a patient 5 years after transplantation (PMID:18496563)
• While hPLIC proteins are not ubiquitinated by HERC3, HERC5 plays an important role in ubiquitination of Nm23B. (PMID:18535780)
• data indicate that NM23H2 is a negative regulator of cellular proliferation stimulated by EGF- and Ras-mediated activation of the ERK pathway (PMID:19022560)
• Role of NM23-H2 in the regulation of cell shape and migration via Rho family GTPase signals is reported. (PMID:19381785)
• Data suggest that transglutaminase 2 is overexpressed in cystic fibrosis and affects nucleoside diphosphate kinase function (PMID:19619546)
• Data support the hypothesis that exogenous pDNA binds to cytoplasmic shuttle proteins NM23-H2 and Chx10, and is then translocated to the nucleus using the minimal import machinery. (PMID:19638341)
• further demonstrate that shNDPK-B is released into the circulation in immunocompromized mice carrying the human breast carcinoma cell MDA-MB- (PMID:20830314)
• Studies indicate that most of the proteins known to interact with human NME proteins were also found in starlet sea anemone. (PMID:21085602)
• NM23-H2 expression enhances tumorigenicity. (PMID:22192927)
• post-transcriptional up-regulation of the tumor antigen NME2 is a common and specific property of CML closely associated with Bcr-Abl activity (PMID:22251158)
• NME mRNA and high NME2 mRNA are strong indicator of increased event-free survival independent of FLT3-internal tandem duplication in cytogenetically normal acute myeloid leukemia (PMID:22421058)
• PuF may regulate the APP gene promoter (PMID:23368879)
• nucleoside diphosphate kinase B (NDPK-B), activates TRPV5 channel activity and Ca(2+) flux, and this activation requires histidine 711 in the carboxy-terminal tail of TRPV5. (PMID:24523290)
• findings show NDPKs (NM23-H1/H2/H4) interact with and provide GTP to dynamins, allowing these motor proteins to work with high thermodynamic efficiency for membrane remodeling (PMID:24970086)
• NDPK-B and NDPK-D were shown to bind efficiently to liposomes mimicking plasma membrane and mitochondrial inner membrane (PMID:25010650)
• NDPKB is required for VEGF-induced angiogenesis and contributes to the correct localization of VEGF receptor type 2 and VE-cadherin at the endothelial adherens junctions. (PMID:25147336)
• PIWIL2 modulates tumor cell proliferation and F-actin filaments by interacting with NME2 and regulating c-Myc expression. (PMID:25193865)
• The results demonstrate that reduced NME2 levels lead to transcriptional de-repression of vinculin and regulate lung cancer metastasis. (PMID:25249619)
• Regulatory functions of Nm23-H2 in tumorigenesis: insights from biochemical to clinical perspectives (PMID:25413836)
• Recent findings demonstrate NME2 presence at telomere ends, association with telomerase, and NME2’s role in inhibition of telomerase activity in cancer cells (PMID:25547372)
• NME2 may have an inhibitory activity on the propagation and invasion of gastric cancer cells. (PMID:25700270)
• Overexpression of Nm23H1 did not affect tumorigenesis in nude mice assays, while overexpression of Nm23H2 enhanced tumor growth with elevated expression of the c-Myc proto-oncogene. (PMID:25748386)
• Patients whose MPM tissues expressed elevated mRNA levels of BIRC5, DSP, NME2, and THBS2 showed a statistically significant shorter overall survival. (PMID:25771974)
• A novel mechanism of CARMA3 in lung cancer stemness and metastasis through the negative regulation of NME2 was identified. (PMID:25906011)
• Role of Interaction and Nucleoside Diphosphate Kinase B in Regulation of the Cystic Fibrosis Transmembrane Conductance Regulator Function by cAMP-Dependent Protein Kinase A (PMID:26950439)
• Data suggest that NME2 participates in epigenetic repression of TERT expression via a mechanism that is dependent on interactions with G-quadruplex DNA; NME2 appears to interact with TERT promoter as NME2/REST/LSD1 complex. (NME2 = metastasis suppressor protein 2; TERT = telomerase reverse transcriptase; REST = RE1-silencing transcription factor; LSD1 = lysine specific demethylase 1) (PMID:28717007)
• The data presented suggest an important role for cytoplasmic IRF6 in regulating the availability or localization of the NME1/2 complex and thus the dynamic behavior of epithelia during lip/palate development. (PMID:28767310)
• interacts with nucleotide-binding site NBD1 in CFTR via a motif involving amino acid residues 36-56 on the surface of NDPK-B [review] (PMID:29251738)
• NME2 mediates chemoresistance to 5-FU in CRC (PMID:29475390)
• Study reports that NME2 is an oncogene in osteosarcoma (OS) that is associated with its clinicopathologic features. Downregulation of NME2 could reduce the proliferation of OS cells and arrest the OS cell cycle in the G2/M phase. The deregulation of NME2 enhanced the expression of c-Myc and affected the proliferation of osteosarcoma. (PMID:29630434)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nme2	ENSMUSG00000020857
rattus_norvegicus	Nme2	ENSRNOG00000001226
rattus_norvegicus	Nme2	ENSRNOG00000002671

Paralogs (8): NME8 (ENSG00000086288), NME3 (ENSG00000103024), NME4 (ENSG00000103202), NME5 (ENSG00000112981), NME7 (ENSG00000143156), NME6 (ENSG00000172113), NME9 (ENSG00000181322), NME1 (ENSG00000239672)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97356) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 13 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal stomach morphology	1
abnormal liver morphology	1
abnormal uterus morphology	1
abnormal kidney morphology	1
enlarged kidney	1
enlarged uterus	1
abnormal CD4-positive, alpha-beta T cell physiology	1
abnormal T-helper 1 physiology	1
abnormal T-helper 2 physiology	1
decreased tumor necrosis factor secretion	1
decreased interferon-gamma secretion	1
decreased interleukin-13 secretion	1
decreased interleukin-2 secretion	1

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
Streptococcus pneumoniae Hungary19A-6	B1I8R2	100.0%	Diamond
Streptococcus pneumoniae CGSP14	B2IM38	100.0%	Diamond
Streptococcus pneumoniae JJA	C1CGP2	100.0%	Diamond
Streptococcus pneumoniae Taiwan19F-14	C1CTL2	100.0%	Diamond
Drosophila melanogaster	P08879	100.0%	Diamond
Synechococcus elongatus PCC 7942 = FACHB-805	P50590	100.0%	Diamond
Streptococcus pneumoniae TIGR4	P65536	100.0%	Diamond
Streptococcus pneumoniae R6	P65537	100.0%	Diamond
Merluccius merluccius	P85280	100.0%	Diamond
Merluccius capensis	P85281	100.0%	Diamond
Merluccius senegalensis	P85282	100.0%	Diamond
Merluccius polli	P85283	100.0%	Diamond
Merluccius paradoxus	P85284	100.0%	Diamond
Merluccius hubbsi	P85285	100.0%	Diamond
Merluccius gayi	P85286	100.0%	Diamond
Merluccius polylepis	P85287	100.0%	Diamond
Merluccius australis australis	P85288	100.0%	Diamond
Merluccius productus	P85289	100.0%	Diamond
Macruronus novaezelandiae	P85291	100.0%	Diamond
Macruronus magellanicus	P85292	100.0%	Diamond
Streptococcus pneumoniae D39	Q04IK8	100.0%	Diamond
Streptococcus agalactiae A909	Q3K1G0	100.0%	Diamond
Trichormus variabilis ATCC 29413	Q3M7K5	100.0%	Diamond
Streptococcus thermophilus CNRZ1066	Q5M011	100.0%	Diamond
Streptococcus thermophilus LMG 18311	Q5M4M4	100.0%	Diamond
Synechococcus elongatus PCC 6301	Q5N1M1	100.0%	Diamond
Pongo abelii	Q5RC56	100.0%	Diamond
Bacillus cereus E33L	Q63DL7	100.0%	Diamond
[Bacillus thuringiensis] serovar konkukian str. 97-27	Q6HL40	100.0%	Diamond
Drosophila yakuba	Q6XI71	100.0%	Diamond
Bacillus anthracis	Q81SV8	100.0%	Diamond
Streptococcus agalactiae 2603V/R	Q8E031	100.0%	Diamond
Nostoc sp. PCC 7120 = FACHB-418	Q8YRP2	100.0%	Diamond
Prochlorococcus marinus str. NATL1A	A2BZG4	99.3%	Diamond
Oryza sativa Indica Group	A6N0M9	99.3%	Diamond
Desulfitobacterium hafniense DCB-2	B8FZD1	99.3%	Diamond
Streptococcus pneumoniae P1031	C1CMQ6	99.3%	Diamond
Oryza sativa Japonica Group	Q07661	99.3%	Diamond
Desulfitobacterium hafniense Y51	Q251Q1	99.3%	Diamond
Prochlorococcus marinus str. NATL2A	Q46I11	99.3%	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
LINC02073	ncRNA	105371828
LINC02072	ncRNA	440446
UTP18	protein-coding	51096
MBTD1	protein-coding	54799
NME1-NME2	protein-coding	654364
NME1	protein-coding	4830
SPAG9	protein-coding	9043
LINC02071	ncRNA	101927274

Protein

Protein identifiers

Nucleoside diphosphate kinase B — P22392 (reviewed: P22392)

Alternative names: C-myc purine-binding transcription factor PUF, Histidine protein kinase NDKB, Nucleoside diphoshate kinase 2, nm23-H2

All UniProt accessions (3): P22392, F6XY72, Q6FHN3

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the transfer of a gamma-phosphoryl group from a nucleoside triphosphate, mainly ATP, to a nucleoside diphosphate via a ping-pong mechanism involving a phosphohistidine intermediate, therefore contributing to the nucleoside triphosphate homeostasis. Also functions as a histidine protein kinase by transferring the phosphoryl group from the phosphohistidine intermediate to a histidine residue in target proteins. Phosphorylates the GNB1 subunit of heterotrimeric G proteins at ‘His-266’, generating a high-energy phosphate group that promotes GTP formation and enables receptor-independent activation of heterotrimeric G proteins. Also phosphorylates KCNN4 at ‘His-358’, leading to activation of its intermediate conductance calcium-activated potassium channel activity, Ca(2+) influx, and subsequent activation of B and T cells. Additionally involved in transcriptional regulation through direct DNA binding and chromatin remodeling. In this context, functions as a single-stranded DNA binding protein that binds and stabilizes the G-quadruplex (G4) structures within the nuclease hypersensitive element (NHE) III(1) region of the MYC gene promoter, facilitating recruitment of additional single-strand DNA binding proteins and activation of MYC transcription. G4 DNA-binding activity is independent of its nucleoside diphosphate kinase function and recognizes both folded and unfolded G4 structures. With NME1, may regulate acetyl-CoA (AcCoA) usage between histone acetylation and fatty acid synthesis by targeting AcCoA release at ATP-rich, HAT-associated chromatin regions. Also negatively regulates Rho activity by interacting with AKAP13/LBC.

Subunit / interactions. Homohexamer. Heterohexamer of two different chains: A/NME1 and B/NME2 (A5B or A4B2 or A3B3 or A2B4 or AB5). Interacts with CAPN8. Interacts with AKAP13. Interacts with ITGB1BP1 (via C-terminal domain region); this interaction leads to their recruitment to ITGB1-rich cell adhesion sites in cell spreading on FN1. Interacts with BCL2L10.

Subcellular location. Cytoplasm. Nucleus. Cell projection. Lamellipodium. Ruffle Cytoplasm. Perinuclear region. Nucleus Cytoplasm.

Tissue specificity. Ubiquitously expressed. Ubiquitously expressed.

Post-translational modifications. Autophosphorylated.

Miscellaneous. Involved in the activation pathway of bemnifosbuvir (AT-527) and its epimer, AT-752. AT-527 and AT-752 are two guanosine analogs tested in clinical trials against several RNA viruses, which are activated into their common 5’-triphosphate AT-9010 in human cells. Mediates the last activation step by catalyzing transformation of AT-8500 into AT-9010. Based on a naturally occurring readthrough transcript which produces an NME1-NME2 fusion protein.

Similarity. Belongs to the NDK family.

Isoforms (2)

UniProt ID	Names	Canonical?
P22392-1	1, NM23-H2	yes
P22392-2	3, NM23-LV

RefSeq proteins (5): NP_001018147, NP_001018148, NP_001018149, NP_001185611, NP_002503* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001564	Nucleoside_diP_kinase	Family
IPR023005	Nucleoside_diP_kinase_AS	Active_site
IPR034907	NDK-like_dom	Domain
IPR036850	NDK-like_dom_sf	Homologous_superfamily

Pfam: PF00334

Enzyme classification (BRENDA)

• EC 2.7.4.6 — nucleoside-diphosphate kinase (BRENDA: 102 organisms, 269 substrates, 41 inhibitors, 131 Km, 29 kcat entries)

Substrate kinetics (BRENDA)

20 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GTP	0.07–5.5	22
ADP	0.024–1.26	17
ATP	0.005–4.6	14
DTDP	0.001–1.1	11
CTP	0.04–12	8
UTP	0.11–27	8
DCDP	0.01–0.56	6
GDP	0.02–0.049	5
UDP	0.1–0.28	5
TTP	0.89–5.28	4
8-BROMO-IDP	0.033–0.06	2
CDP	0.05–0.69	2
DGDP	0.14–0.25	2
DCTP	0.02	1
DGTP	0.041	1

Catalyzed reactions (Rhea)

• a ribonucleoside 5’-diphosphate + ATP = a ribonucleoside 5’-triphosphate + ADP (RHEA:18113)
• UDP + ATP = UTP + ADP (RHEA:25098)
• CDP + ATP = CTP + ADP (RHEA:25237)
• dTDP + ATP = dTTP + ADP (RHEA:27682)
• GDP + ATP = GTP + ADP (RHEA:27686)
• IDP + ATP = ITP + ADP (RHEA:30347)
• a 2’-deoxyribonucleoside 5’-diphosphate + ATP = a 2’-deoxyribonucleoside 5’-triphosphate + ADP (RHEA:44640)
• ADP + ATP = ADP + ATP (RHEA:84315)

UniProt features (33 total): helix 13, binding site 10, strand 4, mutagenesis site 2, chain 1, region of interest 1, splice variant 1, active site 1

Structure

Experimental structures (PDB)

8 structures by resolution:

PDB	Title	Method	Resolution (Å)
3BBB	Crystal structure of the NM23-H2 transcription factor complex with dinucleotide d(AG)	X-RAY DIFFRACTION	1.3
8PYW	Crystal structure of the human Nucleoside-diphosphate kinase B domain bound to compound …	X-RAY DIFFRACTION	1.55
3BBC	Crystal structure of R88A mutant of the NM23-H2 transcription factor	X-RAY DIFFRACTION	1.7
3BBF	Crystal structure of the NM23-H2 transcription factor complex with GDP	X-RAY DIFFRACTION	1.7
8PIE	Crystal structure of the human nucleoside diphosphate kinase B domain in complex with the …	X-RAY DIFFRACTION	1.9
1NUE	X-RAY STRUCTURE OF NM23 HUMAN NUCLEOSIDE DIPHOSPHATE KINASE B COMPLEXED WITH GDP AT 2 …	X-RAY DIFFRACTION	2
7KPF	NME2 bound to myristoyl-CoA	X-RAY DIFFRACTION	2.23
1NSK	THE CRYSTAL STRUCTURE OF A HUMAN NUCLEOSIDE DIPHOSPHATE KINASE, NM23-H2	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22392-F1	97.65	0.99

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins, Cancer-related genes, Candidate cancer biomarkers, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol

Antibody reliability (HPA): IH approved · IF supported

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)

Position	Role
118	pros-phosphohistidine intermediate

Ligand- & substrate-binding residues (10)

Position	Role
115	GDP
118	DNA
152	GDP
12	DNA
12	GDP
52	DNA
88	GDP
94	DNA
94	GDP
115	DNA

Mutagenesis-validated functional residues (2)

Position	Phenotype
88	decreased single-stranded dna-binding and nucleotide-binding activity. no effect on 3d-structure.
118	loss of histidine kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 curated (TAS) of 9; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

9 pathways:

ID	Pathway	Evidence
R-HSA-9748787	Azathioprine ADME	curated
R-HSA-499943	Interconversion of nucleotide di- and triphosphates	curated
R-HSA-6798695	Neutrophil degranulation	curated
R-HSA-9755088	Ribavirin ADME	curated
R-HSA-9748784	Drug ADME	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-1430728	Metabolism	—
R-HSA-15869	Metabolism of nucleotides	—

MSigDB gene sets: 256 (showing top): GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_INNATE_IMMUNE_SYSTEM, KAAB_FAILED_HEART_ATRIUM_DN, GOBP_POSITIVE_REGULATION_OF_KERATINOCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_EPIDERMIS_DEVELOPMENT, GOCC_SECRETORY_GRANULE, GOMF_NUCLEASE_ACTIVITY, MODULE_151, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_POSITIVE_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MORF_UBE2I, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_PYRIMIDINE_NUCLEOSIDE_TRIPHOSPHATE_BIOSYNTHETIC_PROCESS

GO Biological Process (18): GTP biosynthetic process (GO:0006183), UTP biosynthetic process (GO:0006228), CTP biosynthetic process (GO:0006241), DNA-templated transcription (GO:0006351), cell adhesion (GO:0007155), integrin-mediated signaling pathway (GO:0007229), nucleoside triphosphate biosynthetic process (GO:0009142), regulation of fatty acid biosynthetic process (GO:0042304), regulation of apoptotic process (GO:0042981), negative regulation of apoptotic process (GO:0043066), positive regulation of keratinocyte differentiation (GO:0045618), regulation of epidermis development (GO:0045682), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), ITP biosynthetic process (GO:0046042), positive regulation of epithelial cell proliferation (GO:0050679), positive regulation of DNA-templated transcription initiation (GO:2000144), nucleotide metabolic process (GO:0009117)

GO Molecular Function (14): DNA-binding transcription activator activity (GO:0001216), DNA binding (GO:0003677), nucleoside diphosphate kinase activity (GO:0004550), protein histidine kinase activity (GO:0004673), kinase activity (GO:0016301), GDP binding (GO:0019003), identical protein binding (GO:0042802), metal ion binding (GO:0046872), G-quadruplex DNA binding (GO:0051880), coenzyme A binding (GO:0120225), nucleotide binding (GO:0000166), protein binding (GO:0005515), ATP binding (GO:0005524), transferase activity (GO:0016740)

GO Cellular Component (12): ruffle (GO:0001726), extracellular region (GO:0005576), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), lamellipodium (GO:0030027), secretory granule lumen (GO:0034774), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), cell periphery (GO:0071944), ficolin-1-rich granule lumen (GO:1904813), mitochondrion (GO:0005739)

Reactome top-level categories

5 top-level categories:

Category	Pathways
Drug ADME	2
Metabolism of nucleotides	1
Innate Immune System	1
Metabolism	1
Immune System	1

GO top-level categories

showing 60 of 71 GO namespaces:

Category	Terms
cellular anatomical structure	5
nucleoside triphosphate biosynthetic process	4
positive regulation of DNA-templated transcription	3
anion binding	3
cytoplasm	3
purine ribonucleotide biosynthetic process	2
purine ribonucleoside triphosphate biosynthetic process	2
pyrimidine ribonucleoside triphosphate biosynthetic process	2
pyrimidine ribonucleotide biosynthetic process	2
apoptotic process	2
nucleoside phosphate binding	2
heterocyclic compound binding	2
cell leading edge	2
plasma membrane bounded cell projection	2
intracellular membrane-bounded organelle	2
GTP metabolic process	1
UTP metabolic process	1
CTP metabolic process	1
gene expression	1
RNA biosynthetic process	1
cellular process	1
cell surface receptor signaling pathway	1
biosynthetic process	1
nucleoside triphosphate metabolic process	1
fatty acid biosynthetic process	1
regulation of fatty acid metabolic process	1
regulation of lipid biosynthetic process	1
regulation of programmed cell death	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
keratinocyte differentiation	1
positive regulation of epidermal cell differentiation	1
regulation of keratinocyte differentiation	1
positive regulation of multicellular organismal process	1
epidermis development	1
regulation of developmental process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
ITP metabolic process	1
positive regulation of cell population proliferation	1
epithelial cell proliferation	1
regulation of epithelial cell proliferation	1
DNA-templated transcription initiation	1
regulation of DNA-templated transcription initiation	1
nucleoside phosphate metabolic process	1
transcription cis-regulatory region binding	1
DNA-binding transcription factor activity	1
nucleic acid binding	1
phosphotransferase activity, phosphate group as acceptor	1
nucleobase-containing compound kinase activity	1
protein kinase activity	1
phosphotransferase activity, nitrogenous group as acceptor	1
transferase activity, transferring phosphorus-containing groups	1
guanyl ribonucleotide binding	1
protein binding	1
cation binding	1
DNA binding	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 25 of 44 annotations. The rest are phylogenetic / computational / electronic (IEA).

25 experimentally-supported GO terms:

GO term	NS	Evidence
ITP biosynthetic process	BP	direct assay
integrin-mediated signaling pathway	BP	direct assay
negative regulation of apoptotic process	BP	mutant phenotype
nucleoside triphosphate biosynthetic process	BP	direct assay
positive regulation of DNA-templated transcription	BP	direct assay
positive regulation of DNA-templated transcription initiation	BP	direct assay
positive regulation of epithelial cell proliferation	BP	mutant phenotype
positive regulation of keratinocyte differentiation	BP	mutant phenotype
positive regulation of transcription by RNA polymerase II	BP	direct assay
regulation of epidermis development	BP	mutant phenotype
cell periphery	CC	direct assay
cytoplasm	CC	direct assay
cytosol	CC	direct assay
extracellular exosome	CC	high-throughput assay
lamellipodium	CC	direct assay
nucleus	CC	high-throughput assay
ruffle	CC	direct assay
DNA binding	MF	direct assay
DNA-binding transcription activator activity	MF	direct assay
G-quadruplex DNA binding	MF	direct assay
GDP binding	MF	mutant phenotype
identical protein binding	MF	physical interaction
kinase activity	MF	direct assay
nucleoside diphosphate kinase activity	MF	direct assay
protein histidine kinase activity	MF	direct assay

Protein interactions and networks

STRING

showing 16 of 3,239 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NME2	KCNN4	O15554	877
NME2	DTYMK	P23919	791
NME2	CSN3	P07498	720
NME2	MYC	P01106	720
NME2	PHPT1	Q9NRX4	664
NME2	TOMM40	O96008	630
NME2	PUM3	Q15397	577
NME2	RP2	O75695	497
NME2	KCNN3	Q9UGI6	476
NME2	NF1	P21359	443
NME2	NUCLEOLIN	P19338	441
NME2	PUM2	Q8TB72	441
NME2	CNBP	P20694	440
NME2	PUM1	Q14671	430
NME2	LEF1	Q9UJU2	427
NME2	MTMR6	Q9Y217	427

IntAct

Human interaction partners of NME2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 73 partners by confidence:

Partner	Interaction type	MIscore	Records
NME1	physical association	0.750	2
ITGB1BP1	physical association	0.670	7
NME4	association	0.660	2
DNM2	direct interaction	0.520	1
CEP135	physical association	0.400	1
OR10H3	physical association	0.400	1
ORF42	physical association	0.400	1
SLC48A1	physical association	0.400	1
YWHAZ	physical association	0.400	1
BNIPL	physical association	0.370	1
CTBP1	physical association	0.370	1
FXR1	physical association	0.370	1
GIT2	physical association	0.370	1
RAB5A	physical association	0.370	1
RHOB	physical association	0.370	1
SVIL	physical association	0.370	1
ACTN2	association	0.350	1
CCNG2	association	0.350	1
CSRP3	association	0.350	1
FKBP3	association	0.350	1
LRG1	association	0.350	1
NME2P1	association	0.350	1
PREX1	association	0.350	1
TRAIP	association	0.350	1
WDR47	association	0.350	1
ACLY	physical association	0.000	1
AK2	physical association	0.000	1
ATIC	physical association	0.000	1
CACYBP	physical association	0.000	1
CBR1	physical association	0.000	1

BioGRID (389 interactions; top human partners by supporting records): NME1 (Affinity Capture-MS; 14 records), NME3 (Affinity Capture-MS; 5 records), MDM2 (Reconstituted Complex; 3 records), NME1-NME2 (Affinity Capture-MS; 3 records), TBXA2R (Affinity Capture-Western; 3 records), TRABD (Affinity Capture-MS; 3 records), ACLY (Affinity Capture-MS; 2 records), APP (Affinity Capture-MS; 2 records), CCNG2 (Affinity Capture-MS; 2 records), DSTN (Co-fractionation; 2 records), ESR1 (Affinity Capture-MS; 2 records), FGB (Affinity Capture-MS; 2 records), HERC5 (Affinity Capture-Western; 2 records), HSF1 (Affinity Capture-Luminescence; 2 records), LDHB (Co-fractionation; 2 records)

SIGNOR signaling

showing 3 of 5 signaling interactions:

A	Effect	B	Mechanism
NME2	up-regulates	KCNN4	phosphorylation
NME2	“up-regulates activity”	NME2	phosphorylation
HERC5	“up-regulates quantity by stabilization”	NME2	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Negative regulation of NOTCH4 signaling	6	24.6×	4e-05
Regulation of activated PAK-2p34 by proteasome mediated degradation	5	24.0×	1e-04
Regulation of ornithine decarboxylase (ODC)	5	23.4×	1e-04
Vpu mediated degradation of CD4	5	22.9×	1e-04
Autodegradation of the E3 ubiquitin ligase COP1	5	22.9×	1e-04
Ubiquitin-dependent degradation of Cyclin D	5	22.9×	1e-04
Cross-presentation of soluble exogenous antigens (endosomes)	5	21.9×	1e-04
Vif-mediated degradation of APOBEC3G	5	21.9×	1e-04

Disease & clinical

Genetic variants

Variant evidence for NME2: 3 GWAS associations.

ClinVar

No ClinVar records for this gene.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 29 predictions of 191):

Position(s)	Effect	Δscore	Sites
17:51166825–51166826	acceptor_loss	1.0000	5
17:51166958	donor_loss	1.0000
17:51168236	acceptor_gain	1.0000
17:51168240–51168241	acceptor_loss	1.0000	4
17:51168241	acceptor_gain	1.0000
17:51168344–51168345	donor_loss	1.0000	5
17:51169935–51169936	acceptor_loss	1.0000	2
17:51170050–51170051	donor_loss	1.0000	5
17:51166498–51166499	donor_loss	0.9900	4
17:51166826	acceptor_loss	0.9900

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

5 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (validation)	unfavorable	3.29e-05
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	5.08e-05
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000423
Kidney Renal Clear Cell Carcinoma (validation)	unfavorable	0.000434
Lung Adenocarcinoma (validation)	unfavorable	0.000825

Disease associations

OMIM: gene MIM:156491 | disease phenotypes:

GWAS associations

3 associations:

Study	Trait	p-value
GCST006585_604	Blood protein levels	7e-30
GCST000817_172	Height	3e-8
GCST008103_41	Bipolar disorder	4e-7

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2160 (SINGLE PROTEIN), CHEMBL4296074 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,246 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL598797	CUDC-101	1	2,246

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

42 measured of 42 human assays (42 total across all organisms); most potent 42 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL4105151	KD	1800 nM
CHEMBL4104243	KD	2000 nM
CHEMBL4063228	KD	3400 nM
CHEMBL4102519	KD	6400 nM
CHEMBL4095292	KD	7600 nM
CHEMBL4074606	KD	10100 nM
CHEMBL4079924	KD	10400 nM
CHEMBL4077960	KD	10700 nM
CHEMBL4078248	KD	10800 nM
CHEMBL4101313	KD	10800 nM
CHEMBL4103917	KD	11700 nM
CHEMBL4090566	KD	12200 nM
CHEMBL4065975	KD	12400 nM
CHEMBL4086337	KD	13200 nM
CHEMBL4096008	KD	13300 nM
CHEMBL4076101	KD	13800 nM
CHEMBL4098152	KD	14300 nM
CHEMBL4077352	KD	14600 nM
CHEMBL4085831	KD	15400 nM
CHEMBL4073986	KD	15400 nM
CHEMBL4066570	KD	15800 nM
CHEMBL4071264	KD	16300 nM
CHEMBL4084873	KD	16700 nM
CHEMBL4094111	KD	16800 nM
CHEMBL4092067	KD	17100 nM
CHEMBL4070857	KD	18000 nM
CHEMBL4079211	KD	18400 nM
CHEMBL4097029	KD	18500 nM
CHEMBL4093578	KD	20600 nM
CHEMBL4103750	KD	25600 nM
CHEMBL4092696	KD	25600 nM
CHEMBL4060902	KD	27500 nM
CHEMBL4068364	KD	38000 nM
CHEMBL4096516	KD	44200 nM
CHEMBL4088340	KD	45700 nM
CHEMBL4093039	KD	48500 nM
CHEMBL4079549	KD	55300 nM
CHEMBL4069549	KD	56000 nM
CHEMBL4103811	KD	59400 nM
CHEMBL4091727	KD	61600 nM
CHEMBL4076899	KD	68000 nM
CHEMBL4103438	KD	72800 nM

ChEMBL bioactivities

17 potent at pChembl≥5 of 79 total, top 17 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.85	Kd	142	nM	CUDC-101
5.75	Kd	1800	nM	CHEMBL4105151
5.70	Kd	2000	nM	CHEMBL4104243
5.51	Kd	3100	nM	CHEMBL4104243
5.47	Kd	3400	nM	CHEMBL4063228
5.34	Kd	4600	nM	CHEMBL4104243
5.34	Kd	4600	nM	CHEMBL4063228
5.19	Kd	6400	nM	CHEMBL4102519
5.12	Kd	7600	nM	CHEMBL4090566
5.12	Kd	7600	nM	CHEMBL4095292
5.11	Kd	7700	nM	CHEMBL4104243
5.09	Kd	8100	nM	CHEMBL4102519
5.07	Kd	8500	nM	CHEMBL4101313
5.05	Kd	8900	nM	CHEMBL4103750
5.04	Kd	9200	nM	CHEMBL4077960
5.02	Kd	9600	nM	CHEMBL4085831
5.00	Kd	1.01e+04	nM	CHEMBL4074606

PubChem BioAssay actives

32 with measured affinity, of 310 total; 11 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
7-[4-(3-ethynylanilino)-7-methoxyquinazolin-6-yl]oxy-N-hydroxyheptanamide	1425091: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1420	uM
N-[4-[(E)-[7-fluoro-6-(4-methylpiperazin-1-yl)-9-oxo-1,2-dihydropyrrolo[2,1-b]quinazolin-3-ylidene]methyl]phenyl]-3-[4-(2-hydroxyethyl)piperazin-1-yl]propanamide	1432002: Binding affinity to NT647-labeled His-tagged NM23-H2 (unknown origin) expressed in Escherichia coli BL21(DE3) after 30 mins by microscale thermophoresis method	kd	1.8000	uM
(3E)-6-[3-(dimethylamino)propylamino]-7-fluoro-3-[(2-hydroxy-4-phenylmethoxyphenyl)methylidene]-1,2-dihydropyrrolo[2,1-b]quinazolin-9-one	1450617: Binding affinity to N-terminal NT-647-NHS labeled NM23-H2 (unknown origin) after 30 mins by MST analysis	kd	2.0000	uM
(3E)-6-[3-(diethylamino)propylamino]-7-fluoro-3-[(2-hydroxy-4-phenylmethoxyphenyl)methylidene]-1,2-dihydropyrrolo[2,1-b]quinazolin-9-one	1450617: Binding affinity to N-terminal NT-647-NHS labeled NM23-H2 (unknown origin) after 30 mins by MST analysis	kd	3.4000	uM
(3E)-6-[2-(dimethylamino)ethylamino]-7-fluoro-3-[(2-hydroxy-4-phenylmethoxyphenyl)methylidene]-1,2-dihydropyrrolo[2,1-b]quinazolin-9-one	1450617: Binding affinity to N-terminal NT-647-NHS labeled NM23-H2 (unknown origin) after 30 mins by MST analysis	kd	6.4000	uM
(3E)-7-fluoro-3-[(2-hydroxy-4-phenylmethoxyphenyl)methylidene]-6-(2-piperidin-1-ylethylamino)-1,2-dihydropyrrolo[2,1-b]quinazolin-9-one	1450617: Binding affinity to N-terminal NT-647-NHS labeled NM23-H2 (unknown origin) after 30 mins by MST analysis	kd	7.6000	uM
N-[3-(diethylamino)propyl]-4-[(E)-[7-fluoro-9-oxo-6-(2-pyrrolidin-1-ylethylamino)-1,2-dihydropyrrolo[2,1-b]quinazolin-3-ylidene]methyl]benzamide	1450616: Binding affinity to NM23-H2 (unknown origin) by SPR analysis	kd	7.6000	uM
(3E)-6-[3-(dimethylamino)propylamino]-7-fluoro-3-[[4-[(E)-2-pyridin-2-ylethenyl]phenyl]methylidene]-1,2-dihydropyrrolo[2,1-b]quinazolin-9-one	1450616: Binding affinity to NM23-H2 (unknown origin) by SPR analysis	kd	8.5000	uM
(3E)-6-[3-(dimethylamino)propylamino]-7-fluoro-3-[(4-prop-2-ynoxyphenyl)methylidene]-1,2-dihydropyrrolo[2,1-b]quinazolin-9-one	1450617: Binding affinity to N-terminal NT-647-NHS labeled NM23-H2 (unknown origin) after 30 mins by MST analysis	kd	8.9000	uM
(3E)-3-[(3,4-dihydroxyphenyl)methylidene]-6-[3-(dimethylamino)propylamino]-7-fluoro-1,2-dihydropyrrolo[2,1-b]quinazolin-9-one	1450616: Binding affinity to NM23-H2 (unknown origin) by SPR analysis	kd	9.2000	uM
(3E)-6-[3-(dimethylamino)propylamino]-7-fluoro-3-[(4-propan-2-yloxyphenyl)methylidene]-1,2-dihydropyrrolo[2,1-b]quinazolin-9-one	1450616: Binding affinity to NM23-H2 (unknown origin) by SPR analysis	kd	9.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Calcitriol	decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	decreases expression, increases reaction	2
2,4,6-tribromophenol	increases expression	1
methylmercuric chloride	increases expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	decreases expression	1
tributyltin	increases reaction, decreases expression	1
triphenyltin chloride	decreases expression, increases reaction	1
arsenite	affects binding, increases reaction	1
tetrabromobisphenol A	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
ochratoxin A	decreases expression	1
4-hydroxy-2-nonenal	decreases expression	1
triphenyltin	decreases expression	1
quinoline	increases expression	1
tributyltinisothiocyanate	decreases expression	1
JP8 aviation fuel	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
pyrimidifen	increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
abrine	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
hexabrominated diphenyl ether 153	increases expression	1
N’-(10H-indolo(3,2-b)quinolin-11-yl)-N,N-dimethylpropane-1,3-diamine	affects binding, decreases reaction	1
(+)-JQ1 compound	decreases expression	1
Decitabine	affects methylation	1
Alitretinoin	decreases expression	1

ChEMBL screening assays

34 unique, capped per target: 34 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3991804	Binding	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by ma	The target landscape of clinical kinase drugs. — *Science*

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for NME2 across ~30M SureChEMBL compounds — explore on Sugi Predict.