NME4 Gene - NME/NM23 Nucleoside Diphosphate Kinase 4
Comprehensive genomic and functional overview of NME4, a member of the NM23 family involved in nucleotide metabolism and mitochondrial dynamics.
Gene Information Card
| Symbol | NME4 |
|---|---|
| Full Name | NME/NM23 nucleoside diphosphate kinase 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 16p13.3 |
| NCBI Gene ID | 4833 ncbi.nlm.nih.gov/gene/4833 |
| Ensembl ID | ENSG00000103202 |
| UniProt ID | O00746 |
| OMIM ID | 601818 |
| HGNC ID | 7854 |
| Aliases | NM23-H4, NDPK-D, NDPKD, nm23-H4 |
Description
NME4 (NME/NM23 nucleoside diphosphate kinase 4) encodes a member of the NM23 family of nucleoside diphosphate kinases (NDPKs). The protein localizes to the mitochondrial intermembrane space and catalyzes the transfer of terminal phosphate from nucleoside triphosphates to nucleoside diphosphates, playing a role in nucleotide homeostasis, mitochondrial dynamics, and apoptosis. NME4 is implicated in cancer progression and metastasis suppression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast carcinoma | Reduced NME4 expression correlates with metastatic potential; loss of NDPK activity may impair mitochondrial nucleotide supply. | PMID: 10652318; COSMIC gene analysis |
| Colorectal cancer | NME4 downregulation associated with poor prognosis; altered mitochondrial function. | PMID: 15604205; COSMIC |
| Neuroblastoma | NME4 expression inversely related to tumor stage; potential metastasis suppressor. | PMID: 10488074; OMIM 601818 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Liver | 8.3 | Low |
| Kidney | 10.1 | Medium |
| Brain | 6.7 | Low |
| Skeletal muscle | 15.2 | Medium |
| Testis | 18.9 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.3 | Embryonic kidney; moderate expression |
| HeLa | 9.8 | Cervical carcinoma; low expression |
| MCF7 | 7.2 | Breast cancer; reduced vs normal |
| HepG2 | 11.5 | Hepatocellular carcinoma; moderate |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.316G>A (p.Gly106Arg) | Missense | <0.1% | Unknown functional impact; reported in COSMIC |
| c.424C>T (p.Arg142Trp) | Missense | <0.1% | Potential loss of kinase activity; ClinVar uncertain significance |
| c.1A>G (p.Met1?) | Start loss | Rare | Likely loss of function; no protein product |
Mutation functional classification
Loss of Function (LOF)
Start-loss and missense variants (e.g., p.Met1?, p.Arg142Trp) predicted to reduce or abolish NDPK activity, impairing mitochondrial nucleotide metabolism.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in NME4.
Dominant Negative (DN)
No evidence for dominant-negative effects; NME4 functions as a hexamer, but mutant subunits may disrupt complex assembly.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Nucleotide metabolism (KEGG: hsa00230)
• Pyrimidine metabolism (KEGG: hsa00240)
• Purine metabolism (KEGG: hsa00230)
Protein Summary
NME4 (NDPK-D) is a 187-amino acid protein (UniProt O00746) that forms a hexameric complex in the mitochondrial intermembrane space. It catalyzes the reversible transfer of the gamma-phosphate from NTPs to NDPs, maintaining nucleotide pools. NME4 also participates in mitochondrial fusion and apoptosis regulation. Its expression is reduced in several cancers, suggesting a role in metastasis suppression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NME4 Knockout HEK293 Cell Line | EDJ-KQ2800 | Human | 4833 | Details Get a Quote |
| NME4 Knockout A-549 Cell Line | EDJ-KQ23731 | Human | 4833 | Details Get a Quote |
| NME4 Knockout HCT 116 Cell Line | EDJ-KQ23732 | Human | 4833 | Details Get a Quote |
| NME4 Knockout HeLa Cell Line | EDJ-KQ23733 | Human | 4833 | Details Get a Quote |
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