NME8: A Key Regulator of Ciliary Function and Spermatogenesis
Comprehensive genomic and proteomic analysis of NME8 (NM23-H8), a member of the nucleoside diphosphate kinase family involved in microtubule stability and male fertility.
Gene Information Card
| Symbol | NME8 |
|---|---|
| Full Name | NME/NM23 family member 8 |
| Gene Type | protein-coding |
| Chromosomal Location | 7p14.1 |
| NCBI Gene ID | 51314 ncbi.nlm.nih.gov/gene/51314 |
| Ensembl ID | ENSG00000106633 |
| UniProt ID | Q9Y6R4 |
| OMIM ID | 607421 |
| HGNC ID | 18273 |
| Aliases | NM23-H8, TXNDC3, SPTRX-2, CILD6 |
Description
NME8 encodes a member of the nucleoside diphosphate kinase (NDPK) family, also known as NM23-H8. The protein contains a thioredoxin domain and is localized to the axoneme of cilia and flagella. It is essential for proper ciliary motility and spermatogenesis. Mutations in NME8 cause primary ciliary dyskinesia type 6 (CILD6), characterized by respiratory tract infections, situs inversus, and male infertility due to defective sperm flagella.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Primary ciliary dyskinesia 6 (CILD6) | Loss-of-function mutations disrupt axonemal dynein assembly, impairing ciliary and flagellar motility. | OMIM #610852; ClinVar; PMID: 17999360 |
| Male infertility (asthenozoospermia) | Defective NME8 leads to abnormal sperm flagella structure and reduced motility. | OMIM #607421; PMID: 17999360 |
| Situs inversus totalis | Impaired nodal cilia function during embryonic development causes randomization of left-right asymmetry. | OMIM #610852; PMID: 17999360 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Lung | 6.8 | Low |
| Trachea | 5.2 | Low |
| Fallopian tube | 4.1 | Low |
| Brain (cerebellum) | 2.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Spermatozoa | N/A | High expression in flagella |
| Respiratory epithelial cells | N/A | Ciliated cells show moderate expression |
| HEK293 | 0.5 | Low (RNA-seq) |
| HeLa | 0.3 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.671C>T (p.Pro224Leu) | Missense | Rare | Loss of function; associated with CILD6 |
| c.1039C>T (p.Arg347*) | Nonsense | Rare | Premature stop; loss of function |
| c.1492G>A (p.Gly498Arg) | Missense | Rare | Likely damaging; disrupts thioredoxin domain |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations (e.g., p.Arg347*, p.Pro224Leu) lead to truncated or misfolded protein, impairing axonemal dynein function.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ciliary motility (Reactome: R-HSA-5620924)
• Axoneme assembly (Reactome: R-HSA-5620916)
• Nucleoside diphosphate kinase pathway (KEGG: map00230)
Protein Summary
NME8 (NM23-H8) is a 648-amino acid protein with an N-terminal thioredoxin domain and a C-terminal nucleoside diphosphate kinase domain. It localizes to the axoneme of cilia and flagella, where it participates in microtubule stabilization and dynein arm assembly. The protein is highly expressed in testis and respiratory ciliated cells. Mutations cause primary ciliary dyskinesia type 6, with symptoms including chronic respiratory infections, situs inversus, and male infertility.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NME8 Knockout HEK293 Cell Line | EDJ-KQ10339 | Human | 51314 | Details Get a Quote |
| NME8 Knockout HeLa Cell Line | EDJ-KQ56283 | Human | 51314 | Details Get a Quote |
| NME8 Knockout A-549 Cell Line | EDJ-KQ64771 | Human | 51314 | Details Get a Quote |
| NME8 Knockout HCT 116 Cell Line | EDJ-KQ73219 | Human | 51314 | Details Get a Quote |
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