NME1 Gene: Functions, Associated Diseases, and Clinical Significance
A comprehensive overview of the NME1 gene, its protein product, expression patterns, mutations, and implications in health and disease.
Gene Information Card
| Symbol | NME1 |
|---|---|
| Full Name | NME/NM23 nucleoside diphosphate kinase 1 |
| Gene Type | protein coding |
| Chromosomal Location | 17q21.33 |
| NCBI Gene ID | 4830 ncbi.nlm.nih.gov/gene/4830 |
| Ensembl ID | ENSG00000239672 |
| UniProt ID | P15531 |
| OMIM ID | 156490 |
| HGNC ID | 7849 |
| Aliases | AWD, GAAD, NB, NDPKA, NDPK-A, NM23, NM23-H1 |
Description
The NME1 gene encodes nucleoside diphosphate kinase A (NDPKA), a multifunctional enzyme involved in nucleotide metabolism, signal transduction, and transcriptional regulation. It is well-known as a metastasis suppressor in various cancers, with reduced expression correlating with increased metastatic potential. NME1 also participates in DNA repair, apoptosis, and cellular differentiation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Reduced NME1 expression or loss of function is associated with increased metastatic potential in melanoma, breast, ovarian, and hepatocellular carcinomas. The mechanism involves altered NDPK activity, histidine kinase signaling, and regulation of transcription factors such as MYC and TP53. | Multiple studies (e.g., Steeg et al., 1988; Leone et al., 1991) and clinical data (e.g., high NME1 expression correlates with better prognosis in some cancers). |
| Neuroblastoma | NME1 mutations (e.g., P97L) have been identified in aggressive neuroblastoma, leading to loss of metastasis suppressor function and altered kinase activity. | Case reports and functional studies (e.g., Chang et al., 1994). |
| Developmental disorders | Homozygous loss-of-function mutations in NME1 have been reported in patients with a syndrome characterized by intellectual disability, microcephaly, and cardiac defects, suggesting a role in neurodevelopment. | Exome sequencing studies (e.g., OMIM entry). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Blood | 10.2 | Low |
| Bone Marrow | 8.5 | Low |
| Brain | 12.3 | Medium |
| Heart | 15.1 | Medium |
| Kidney | 13.4 | Medium |
| Liver | 11.8 | Medium |
| Lung | 14.2 | Medium |
| Pancreas | 9.7 | Low |
| Skin | 16.5 | Medium |
| Small Intestine | 12.9 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 18.2 | Cervical cancer cell line; high expression |
| MCF7 | 15.6 | Breast cancer cell line; moderate expression |
| A549 | 14.8 | Lung cancer cell line; moderate expression |
| HepG2 | 13.9 | Liver cancer cell line; moderate expression |
| K562 | 11.3 | Leukemia cell line; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| P97L | Missense | Rare (somatic in neuroblastoma) | Loss of metastasis suppressor function; altered kinase activity |
| S120G | Missense | Rare (somatic in neuroblastoma) | Impaired histidine kinase activity; affects DNA repair |
| R34C | Missense | Rare (somatic in various cancers) | Reduced NDPK activity; potential dominant-negative effect |
| c.668+1G>A | Splice site | Very rare (germline in developmental syndrome) | Loss of function due to aberrant splicing |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce or abolish NDPK activity, such as P97L and S120G, lead to loss of metastasis suppressor function and impaired DNA repair.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; some variants may exhibit altered substrate specificity but not oncogenic activation.
Dominant Negative (DN)
Some missense mutations (e.g., R34C) may interfere with oligomerization, exerting a dominant-negative effect on wild-type NME1.
View complete mutation data：
Gene Ontology (GO)
| • nucleoside diphosphate kinase activity | • ATP binding |
| • histidine kinase activity | • protein binding |
| • DNA binding | • transcription factor binding |
| • signal transducer activity | • nucleotide binding |
| • kinase activity | • magnesium ion binding |
Pathways
• Nucleotide metabolism
• Pyrimidine metabolism
• Purine metabolism
• p53 signaling pathway
• Apoptosis
• MAPK signaling pathway
• Wnt signaling pathway
• TGF-beta signaling pathway
Protein Summary
NME1 encodes a 17 kDa protein (152 amino acids) that forms hexamers and functions as a nucleoside diphosphate kinase, transferring phosphate from ATP to NDPs. It also possesses histidine kinase activity and can act as a transcription factor modulator. The protein is localized in the cytoplasm, nucleus, and membrane, and is involved in cell proliferation, differentiation, and metastasis suppression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NME1 Knockout HEK293 Cell Line | EDJ-KQ50481 | Human | 4830 | Details Get a Quote |
| NME1-NME2 Knockout HEK293 Cell Line | EDJ-KQ52395 | Human | 654364 | Details Get a Quote |
| NME1 Knockout HeLa Cell Line | EDJ-KQ53999 | Human | 4830 | Details Get a Quote |
| NME1-NME2 Knockout HeLa Cell Line | EDJ-KQ60668 | Human | 654364 | Details Get a Quote |
| NME1 Knockout A-549 Cell Line | EDJ-KQ62492 | Human | 4830 | Details Get a Quote |
| NME1-NME2 Knockout A-549 Cell Line | EDJ-KQ69142 | Human | 654364 | Details Get a Quote |
| NME1 Knockout HCT 116 Cell Line | EDJ-KQ70958 | Human | 4830 | Details Get a Quote |
| NME1-NME2 Knockout HCT 116 Cell Line | EDJ-KQ77494 | Human | 654364 | Details Get a Quote |
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