NME4

Summary

NME4 (NME/NM23 nucleoside diphosphate kinase 4, HGNC:7852) is a protein-coding gene on chromosome 16p13.3, encoding Nucleoside diphosphate kinase D, mitochondrial (O00746). Mitochondria-specific nucleoside diphosphate kinase that catalyzes the transfer of a gamma-phosphoryl group from ATP to a nucleoside diphosphate via a ping-pong mechanism involving a phosphohistidine intermediate, participating in nucleoside triphosphate homeostasis.

The nucleoside diphosphate (NDP) kinases (EC 2.7.4.6) are ubiquitous enzymes that catalyze transfer of gamma-phosphates, via a phosphohistidine intermediate, between nucleoside and dioxynucleoside tri- and diphosphates. The enzymes are products of the nm23 gene family, which includes NME4 (Milon et al., 1997 [PubMed 9099850]).

Source: NCBI Gene 4833 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 44 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005009

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7852
Approved symbol	NME4
Name	NME/NM23 nucleoside diphosphate kinase 4
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	nm23-H4, NM23H4, NDPKD
Ensembl gene	ENSG00000103202
Ensembl biotype	protein_coding
OMIM	601818
Entrez	4833

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000219479, ENST00000382940, ENST00000397722, ENST00000433358, ENST00000444498, ENST00000448828, ENST00000450036, ENST00000454619, ENST00000460297, ENST00000468031, ENST00000620944, ENST00000621774, ENST00000920839

RefSeq mRNA: 7 — MANE Select: NM_005009 NM_001286433, NM_001286435, NM_001286436, NM_001286438, NM_001286439, NM_001286440, NM_005009

CCDS: CCDS10408, CCDS66886, CCDS73797

Canonical transcript exons

ENST00000219479 — 5 exons

Exon	Start	End
ENSE00001742917	397199	397313
ENSE00001958819	400219	400754
ENSE00003584758	399379	399480
ENSE00003633172	398990	399123
ENSE00003667146	399627	399739

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 98.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 94.6483 / max 621.1796, expressed in 1806 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151900	62.3080	1796
151901	12.7899	1686
151902	6.8864	1525
151903	3.4071	1358
151904	1.8021	1058
151910	1.6411	906
151905	1.4705	913
151907	1.2580	767
151898	0.8180	446
151909	0.7906	479

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	98.67	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.53	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.39	gold quality
right adrenal gland cortex	UBERON:0035827	98.37	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.31	gold quality
right adrenal gland	UBERON:0001233	98.30	gold quality
lower esophagus	UBERON:0013473	98.30	gold quality
mucosa of stomach	UBERON:0001199	98.27	gold quality
left adrenal gland cortex	UBERON:0035825	98.18	gold quality
adrenal cortex	UBERON:0001235	98.14	gold quality
saphenous vein	UBERON:0007318	98.09	gold quality
left adrenal gland	UBERON:0001234	98.08	gold quality
ventricular zone	UBERON:0003053	98.00	gold quality
left uterine tube	UBERON:0001303	97.98	gold quality
left coronary artery	UBERON:0001626	97.82	gold quality
right lobe of liver	UBERON:0001114	97.79	gold quality
coronary artery	UBERON:0001621	97.74	gold quality
thoracic aorta	UBERON:0001515	97.71	gold quality
ascending aorta	UBERON:0001496	97.70	gold quality
right coronary artery	UBERON:0001625	97.68	gold quality
aorta	UBERON:0000947	97.66	gold quality
popliteal artery	UBERON:0002250	97.66	gold quality
tibial artery	UBERON:0007610	97.65	gold quality
endocervix	UBERON:0000458	97.52	gold quality
apex of heart	UBERON:0002098	97.51	gold quality
right ovary	UBERON:0002118	97.49	gold quality
adrenal gland	UBERON:0002369	97.48	gold quality
ganglionic eminence	UBERON:0004023	97.41	gold quality
descending thoracic aorta	UBERON:0002345	97.40	gold quality
fundus of stomach	UBERON:0001160	97.39	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	586.64
E-HCAD-4	yes	164.10
E-GEOD-36552	yes	100.71
E-MTAB-6701	yes	54.34
E-CURD-122	yes	24.64
E-MTAB-9067	yes	20.28
E-HCAD-6	yes	19.02
E-MTAB-8271	yes	9.85
E-CURD-112	yes	9.76
E-MTAB-9388	no	10.79
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

48 targeting NME4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548AN	99.97	70.91	2817
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4498	99.47	67.42	2360

Literature-anchored findings (GeneRIF, showing 13)

• High expression of ERCC1, FLT1, NME4 and PCNA in myelodysplastic syndrome was associated with poor prognosis and disease progression along the sequence of 5q-syndrome/RCMD/RAEB/de novo AML (PMID:18604718)
• Nm23-H4 acts as a lipid-dependent mitochondrial switch with dual function in phosphotransfer serving local GTP supply and cardiolipin transfer for apoptotic signaling and putative other functions (PMID:23150663)
• 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)
• Mitochondrial NM23-H4/NDPK-D: a bifunctional nanoswitch for bioenergetics and lipid signaling (PMID:25231795)
• miR-196 performed it’s their function by inhibiting NME4 expression and further activating p-JNK, suppressing TIMP1, and augmenting MMP1/9. (PMID:25233933)
• NDPK-D has an important role in the early stages of mitophagy as induced by carbonyl cyanide m-chlorophenylhydrazone as well as by PINK1-Parkin-independent stimuli such as rotenone and 6-hydroxydopamine. (PMID:26742431)
• Nucleoside diphosphate kinase D (NME4/NDPK-D) shows intermembrane phospholipid transfer activity in vitro and in cellular systems, which relies on NME4/NDPK-D interaction with cardiolipin [Review]. (PMID:29035377)
• After knockdown of NME4 with short hairpin RNA, the cell cycle was arrest at the G1 phase, and proliferation and colony formation were inhibited in the NCIH1299 and A549 cell lines. (PMID:31257488)
• NME4 modulates PD-L1 expression via the STAT3 signaling pathway in squamous cell carcinoma. (PMID:32192776)
• Widely targeted metabolomic analyses unveil the metabolic variations after stable knock-down of NME4 in esophageal squamous cell carcinoma cells. (PMID:32504364)
• Differential Expression of NME4 in Trophoblast Stem-Like Cells and Peripheral Blood Mononuclear Cells of Normal Pregnancy and Preeclampsia. (PMID:37096311)
• NME4 suppresses NFkappaB2-CCL5 axis, restricting CD8+ T cell tumour infiltration in oesophageal squamous cell carcinoma. (PMID:39016535)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nme4	ENSDARG00000088390
mus_musculus	Nme4	ENSMUSG00000024177
rattus_norvegicus	Nme4	ENSRNOG00000075475

Paralogs (8): NME8 (ENSG00000086288), NME3 (ENSG00000103024), NME5 (ENSG00000112981), NME7 (ENSG00000143156), NME6 (ENSG00000172113), NME9 (ENSG00000181322), NME1 (ENSG00000239672), NME2 (ENSG00000243678)

Protein

Protein identifiers

Nucleoside diphosphate kinase D, mitochondrial — O00746 (reviewed: O00746)

Alternative names: Nucleoside diphosphate kinase 4, nm23-H4

All UniProt accessions (7): O00746, A0A087WVT9, A2IDC9, F2Z297, F2Z2X0, H0Y6J0, Q4TT34

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondria-specific nucleoside diphosphate kinase that catalyzes the transfer of a gamma-phosphoryl group from ATP to a nucleoside diphosphate via a ping-pong mechanism involving a phosphohistidine intermediate, participating in nucleoside triphosphate homeostasis. In vitro, purine nucleoside triphosphates are much more effective as donors and acceptors than pyrimidine nucleoside triphosphates, and ribonucleosides derivatives are superior to their deoxyribonucleosides counterparts. Associates with cardiolipin-containing mitochondrial inner membrane and locally produces ADP in the mitochondrial intermembrane space, which is directly taken up via the ADP/ATP translocase (ANT) into the matrix to stimulate respiratory ATP regeneration. Also directly provides GTP for mitochondrial GTPases, such as the dynamin-related GTPase OPA1. Additionally, catalyzes the anionic phospholipid transfer, namely cardiolipin, from the mitochondrial inner membrane (IM) to the outer membrane (OM) through the formation of contact sites between IM and OM, in a nucleoside diphosphate kinase-independent manner. The switch between the nucleoside diphosphate kinase and the phospholipid transfer activity may depend on the availability and accessibility of cardiolipin and other anionic phospholipids in the IM outer leaflet and OM inner leaflet.

Subunit / interactions. Homohexamer. Interacts with OPA1. Interacts with CAPN8.

Subcellular location. Mitochondrion intermembrane space. Mitochondrion matrix. Mitochondrion outer membrane.

Tissue specificity. Widely distributed. Found at very high levels in prostate, heart, liver, small intestine, and skeletal muscle tissues, and in low amounts in the brain and in blood leukocytes.

Activity regulation. Binding to anionic phospholipids, predominantly to cardiolipin inhibits its phosphotransfer activity.

Similarity. Belongs to the NDK family.

Isoforms (2)

UniProt ID	Names	Canonical?
O00746-1	1	yes
O00746-2	2

RefSeq proteins (7): NP_001273362, NP_001273364, NP_001273365, NP_001273367, NP_001273368, NP_001273369, NP_005000* (*=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), 9 shown:

• a ribonucleoside 5’-diphosphate + ATP = a ribonucleoside 5’-triphosphate + ADP (RHEA:18113)
• UDP + ATP = UTP + ADP (RHEA:25098)
• CDP + ATP = CTP + ADP (RHEA:25237)
• dCDP + ATP = dCTP + ADP (RHEA:27678)
• dTDP + ATP = dTTP + ADP (RHEA:27682)
• GDP + ATP = GTP + ADP (RHEA:27686)
• dGDP + ATP = dGTP + ADP (RHEA:27690)
• a cardiolipin(in) = a cardiolipin(out) (RHEA:38695)
• a 2’-deoxyribonucleoside 5’-diphosphate + ATP = a 2’-deoxyribonucleoside 5’-triphosphate + ADP (RHEA:44640)

UniProt features (38 total): binding site 17, helix 11, strand 4, mutagenesis site 2, transit peptide 1, chain 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1EHW	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00746-F1	85.65	0.75

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): 151 (pros-phosphohistidine intermediatee)

Ligand- & substrate-binding residues (17): 127; 127; 138; 138; 145; 145; 145; 148; 148; 148; 45; 45 …

Mutagenesis-validated functional residues (2):

Position	Phenotype
90	abolishes cardiolipin-containing membrane binding; decreases lipid transfer and pro-apoptotic activity; does not change
129	does not affect autophosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-499943	Interconversion of nucleotide di- and triphosphates
R-HSA-1430728	Metabolism
R-HSA-15869	Metabolism of nucleotides

MSigDB gene sets: 228 (showing top): ACTACCT_MIR196A_MIR196B, MODULE_151, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_PYRIMIDINE_NUCLEOSIDE_TRIPHOSPHATE_BIOSYNTHETIC_PROCESS, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOMF_GTPASE_BINDING, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, GTGCCTT_MIR506, SMITH_TERT_TARGETS_DN, GOBP_PYRIMIDINE_NUCLEOTIDE_METABOLIC_PROCESS

GO Biological Process (8): GTP biosynthetic process (GO:0006183), UTP biosynthetic process (GO:0006228), CTP biosynthetic process (GO:0006241), lipid transport (GO:0006869), nucleoside metabolic process (GO:0009116), protein hexamerization (GO:0034214), intermembrane phospholipid transfer (GO:0120010), nucleotide metabolic process (GO:0009117)

GO Molecular Function (14): nucleoside diphosphate kinase activity (GO:0004550), ATP binding (GO:0005524), phospholipid binding (GO:0005543), protein-containing complex binding (GO:0044877), metal ion binding (GO:0046872), GTPase binding (GO:0051020), phosphatidylglycerol transfer activity (GO:0140339), mitochondrion-mitochondrion outer membrane tether activity (GO:0160204), cardiolipin binding (GO:1901612), nucleotide binding (GO:0000166), protein binding (GO:0005515), lipid binding (GO:0008289), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (6): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), mitochondrial inner membrane (GO:0005743), mitochondrial intermembrane space (GO:0005758), mitochondrial matrix (GO:0005759), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of nucleotides	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	3
pyrimidine ribonucleoside triphosphate biosynthetic process	2
pyrimidine ribonucleotide biosynthetic process	2
mitochondrial membrane	2
purine ribonucleotide biosynthetic process	1
purine ribonucleoside triphosphate biosynthetic process	1
GTP metabolic process	1
UTP metabolic process	1
CTP metabolic process	1
transport	1
lipid localization	1
nucleobase-containing small molecule metabolic process	1
carbohydrate derivative metabolic process	1
protein complex oligomerization	1
phospholipid transport	1
intermembrane lipid transfer	1
nucleoside phosphate metabolic process	1
phosphotransferase activity, phosphate group as acceptor	1
nucleobase-containing compound kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
lipid binding	1
cation binding	1
enzyme binding	1
phospholipid transfer activity	1
membrane-membrane adaptor activity	1
phosphatidylglycerol binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle outer membrane	1
organelle inner membrane	1
mitochondrial envelope	1
organelle envelope lumen	1
mitochondrion	1
intracellular organelle lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

5780 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NME4	CKMT1B	P12532	840
NME4	NT5M	Q9NPB1	790
NME4	AK3	Q9UIJ7	787
NME4	AK4	P27144	780
NME4	DGUOK	P78532	776
NME4	CMPK1	P30085	757
NME4	CMPK2	Q5EBM0	715
NME4	AK2	P54819	706
NME4	DTYMK	P23919	651
NME4	SLC6A8	P48029	649
NME4	PLSCR3	Q9NRY6	642
NME4	TK2	O00142	588
NME4	RP2	O75695	582
NME4	SUCLG1	P53597	526
NME4	POLR3K	Q9Y2Y1	485

IntAct

256 interactions, top by confidence:

A	B	Type	Score
NME4	NME1	psi-mi:“MI:0915”(physical association)	0.900
NME1	NME4	psi-mi:“MI:0915”(physical association)	0.900
NME4	HTT	psi-mi:“MI:0915”(physical association)	0.680
NME4	TRIP13	psi-mi:“MI:0915”(physical association)	0.670
USP32	NME4	psi-mi:“MI:0914”(association)	0.560
NME4	SUFU	psi-mi:“MI:0915”(physical association)	0.560
SUFU	NME4	psi-mi:“MI:0915”(physical association)	0.560
ZBTB16	NME4	psi-mi:“MI:0915”(physical association)	0.560
TTC19	NME4	psi-mi:“MI:0915”(physical association)	0.560
NXF1	NME4	psi-mi:“MI:0915”(physical association)	0.560
CABP2	NME4	psi-mi:“MI:0915”(physical association)	0.560
CABP5	NME4	psi-mi:“MI:0915”(physical association)	0.560
TRAPPC2	NME4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (225): NME4 (Affinity Capture-MS), NME4 (Two-hybrid), NME4 (Affinity Capture-RNA), NME4 (Affinity Capture-RNA), NME4 (Affinity Capture-MS), NME4 (Affinity Capture-MS), NME4 (Two-hybrid), TRIP13 (Two-hybrid), NME4 (Two-hybrid), NME4 (Two-hybrid), NME2 (Affinity Capture-MS), NME4 (Affinity Capture-MS), NME4 (Affinity Capture-MS), MIPEP (Affinity Capture-MS), NME4 (Affinity Capture-MS)

ESM2 similar proteins: A0JNU3, A1L1F1, A2AIL4, A4IHH4, A4QP75, B3MGZ0, B4GGT6, F6ZFR0, O00746, O08776, O55137, O55171, O88202, O88267, P36776, P49753, P87355, Q28CM7, Q32LB9, Q330K2, Q3B8B2, Q3T056, Q4R816, Q4VK78, Q566Y1, Q58DL1, Q59HJ6, Q5EBA1, Q5RJV0, Q6DFN1, Q80YD1, Q810S1, Q86U10, Q8BWN8, Q8CGK3, Q8HY87, Q8NC60, Q924S5, Q96BQ1, Q99KK9

Diamond homologs: A0A3Q0KJ78, A2BNH4, A2BU01, A2CDK0, A2VD68, A4J0S4, A5D5U8, A6N0M9, A8G244, B0C4I0, B0JHT4, B0TBN6, B1I1P4, B1WQB7, B2IX22, B4FK49, B8DBZ7, B8FZD1, B8HUM7, B9E6K9, C0ZCD6, C1KWM9, O00746, O29491, O49203, O57535, O60361, O64903, O81372, P08879, P15531, P15532, P19804, P22392, P22887, P27950, P31103, P36010, P39207, P47919

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2591 predictions. Top by Δscore:

Variant	Effect	Δscore
16:397311:CGGG:C	donor_loss	1.0000
16:397312:GG:G	donor_gain	1.0000
16:397312:GGGTG:G	donor_loss	1.0000
16:397313:GG:G	donor_gain	1.0000
16:397315:T:A	donor_loss	1.0000
16:398985:T:A	acceptor_gain	1.0000
16:398986:GAA:G	acceptor_loss	1.0000
16:398987:AAGGA:A	acceptor_loss	1.0000
16:398988:A:AG	acceptor_gain	1.0000
16:398988:A:T	acceptor_loss	1.0000
16:398988:AG:A	acceptor_gain	1.0000
16:398988:AGGAG:A	acceptor_gain	1.0000
16:398989:G:GA	acceptor_gain	1.0000
16:398989:G:T	acceptor_loss	1.0000
16:398989:GG:G	acceptor_gain	1.0000
16:398989:GGA:G	acceptor_gain	1.0000
16:398989:GGAGG:G	acceptor_gain	1.0000
16:399121:CAG:C	donor_loss	1.0000
16:399122:AG:A	donor_loss	1.0000
16:399124:G:C	donor_loss	1.0000
16:399125:T:A	donor_loss	1.0000
16:399367:A:AG	acceptor_gain	1.0000
16:399367:AAT:A	acceptor_gain	1.0000
16:399369:T:TA	acceptor_gain	1.0000
16:399477:CATGG:C	donor_loss	1.0000
16:399479:TGG:T	donor_loss	1.0000
16:399480:GGTA:G	donor_loss	1.0000
16:399481:G:GC	donor_loss	1.0000
16:399481:G:GG	donor_gain	1.0000
16:399482:T:G	donor_loss	1.0000

AlphaMissense

1211 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:400277:T:C	F167L	0.995
16:400279:C:A	F167L	0.995
16:400279:C:G	F167L	0.995
16:399430:T:C	F93L	0.992
16:399432:C:A	F93L	0.992
16:399432:C:G	F93L	0.992
16:400235:A:C	S153R	0.992
16:400237:C:A	S153R	0.992
16:400237:C:G	S153R	0.992
16:399033:G:C	K45N	0.991
16:399033:G:T	K45N	0.991
16:399630:T:A	W111R	0.991
16:399630:T:C	W111R	0.991
16:399709:T:A	I137K	0.991
16:399712:G:T	R138M	0.990
16:400278:T:C	F167S	0.990
16:399095:T:C	F66S	0.989
16:399723:A:C	S142R	0.989
16:399725:C:A	S142R	0.989
16:399725:C:G	S142R	0.989
16:399649:T:A	V117D	0.985
16:399673:G:A	G125E	0.985
16:399709:T:G	I137R	0.985
16:400236:G:T	S153I	0.984
16:399080:T:C	F61S	0.983
16:399031:A:G	K45E	0.982
16:399673:G:T	G125V	0.981
16:399706:C:T	T136I	0.981
16:399094:T:C	F66L	0.980
16:399096:C:A	F66L	0.980

dbSNP variants (sampled 300 via entrez): RS1001696755 (16:399854 G>A,C), RS1002075185 (16:394820 C>G,T), RS1002077697 (16:398780 C>G,T), RS1002134927 (16:398810 G>A,C), RS1002405219 (16:398656 C>T), RS1002751879 (16:400592 C>T), RS1002916289 (16:396684 C>T), RS1003128033 (16:397989 A>C,G), RS1003310737 (16:398156 G>A), RS1004015289 (16:398579 G>A,C,T), RS1004626090 (16:396863 G>A), RS1005420289 (16:397803 G>A), RS1005450841 (16:395014 C>T), RS1005477939 (16:400585 G>A,C,T), RS1005512039 (16:400405 C>G)

Disease associations

OMIM: gene MIM:601818 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001873_5	Red blood cell traits	9.000000e-48
GCST001873_6	Red blood cell traits	2.000000e-34
GCST001873_8	Red blood cell traits	4.000000e-22
GCST005951_12	Body mass index	5.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0004527	mean corpuscular hemoglobin
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4488 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 8,319 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1201346	BALSALAZIDE	4	8,319

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs5841	DECR2, NME4		0.00	0

ChEMBL bioactivities

1 potent at pChembl≥5 of 3 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.11	EC50	7800	nM	CHEMBL5204662

PubChem BioAssay actives

1 with measured affinity, of 8 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
5-[4-[4-(2-carboxyethylcarbamoyl)phenyl]triazol-1-yl]-2-hydroxybenzoic acid	1863416: Binding affinity to NME4 in human MCF7 cell lysate by pull down assay based LC-MS/MS analysis	ec50	7.8000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	5
sodium arsenite	increases abundance, affects cotreatment, increases expression, decreases expression	4
bisphenol A	affects expression, decreases expression, decreases methylation	3
cobaltous chloride	decreases expression	3
Cyclosporine	decreases expression	3
methylmercuric chloride	decreases expression	2
Doxorubicin	decreases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Quercetin	decreases expression	2
Smoke	increases expression, decreases expression	2
lead acetate	affects cotreatment, increases expression	1
methylselenic acid	decreases expression	1
beta-lapachone	decreases expression	1
afimoxifene	decreases response to substance	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases expression, increases abundance	1
Atrazine	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5118486	Binding	Binding affinity to NME4 in human MCF7 cell lysate by pull down assay based LC-MS/MS analysis	Development of hetero-triaryls as a new chemotype for subtype-selective and potent Sirt5 inhibition. — Eur J Med Chem

Cellosaurus cell lines

7 cell lines: 5 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3CG	Abcam HEK293T NME4 KO 1	Transformed cell line	Female
CVCL_B3CH	Abcam HEK293T NME4 KO 2	Transformed cell line	Female
CVCL_D7VW	Ubigene A-549 NME4 KO	Cancer cell line	Male
CVCL_E2E5	HAP1 NME4 (-) 1	Cancer cell line	Male
CVCL_E2E6	HAP1 NME4 (-) 2	Cancer cell line	Male
CVCL_E2E7	HAP1 NME4 (-) 3	Cancer cell line	Male
CVCL_E2E8	HAP1 NME4 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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