SPAG4 (Sperm Associated Antigen 4)
A gene encoding a protein involved in sperm flagellar function and potential roles in cancer and male infertility.
Gene Information Card
| Symbol | SPAG4 |
|---|---|
| Full Name | Sperm Associated Antigen 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 20q11.22 |
| NCBI Gene ID | 6676 ncbi.nlm.nih.gov/gene/6676 |
| Ensembl ID | ENSG00000101204 |
| UniProt ID | Q9NPE6 |
| OMIM ID | 609171 |
| HGNC ID | 11216 |
| Aliases | SUN4, MGC126514, MGC126516 |
Description
SPAG4 (Sperm Associated Antigen 4) encodes a member of the SUN (Sad1/UNC-84) domain-containing protein family. The protein is localized to the nuclear envelope and is essential for sperm flagellar development and male fertility. It is also implicated in cancer cell migration and invasion, with altered expression observed in various malignancies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Male infertility (asthenozoospermia) | Defects in SPAG4 disrupt sperm flagellar assembly and motility, leading to reduced sperm function. | PMID: 23505308 |
| Lung cancer | Overexpression of SPAG4 promotes cell migration and invasion via cytoskeletal remodeling. | PMID: 29367606 |
| Hepatocellular carcinoma | Upregulation of SPAG4 correlates with poor prognosis and metastasis. | PMID: 31019238 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 48.2 | High |
| Lung | 6.5 | Low |
| Liver | 4.1 | Low |
| Breast | 3.8 | Low |
| Colon | 2.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung cancer) | 12.3 | Overexpressed compared to normal lung |
| HepG2 (liver cancer) | 9.7 | Moderate expression |
| MCF7 (breast cancer) | 5.1 | Low expression |
| HeLa (cervical cancer) | 7.8 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.01% | Potential loss of start codon; functional impact unknown |
| c.287C>T (p.Pro96Leu) | Missense | <0.01% | Rare variant; no disease association reported |
| c.512G>A (p.Arg171Gln) | Missense | <0.01% | Observed in cancer samples; significance unclear |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in SPAG4 are associated with impaired sperm flagellar assembly and male infertility.
Gain of Function (GOF)
Gain-of-function (overexpression) in cancer cells promotes migration and invasion.
Dominant Negative (DN)
No dominant-negative mutations have been reported for SPAG4.
View complete mutation data：
Gene Ontology (GO)
Pathways
• REACT:118779 ~ Sperm motility and flagellar assembly
• REACT:147422 ~ SUN domain protein interactions at the nuclear envelope
Protein Summary
SPAG4 (SUN4) is a 45 kDa protein containing an N-terminal SUN domain that mediates tethering of the nuclear envelope to the cytoskeleton. It is predominantly expressed in testis, where it localizes to the manchette and flagellum during spermiogenesis. In somatic cells, SPAG4 is involved in nuclear positioning and cell migration. Aberrant expression in cancers suggests a role in tumor progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SPAG4 Knockout HEK293 Cell Line | EDJ-KQ5831 | Human | 6676 | Details Get a Quote |
| SPAG4 Knockout A-549 Cell Line | EDJ-KQ29271 | Human | 6676 | Details Get a Quote |
| SPAG4 Knockout HCT 116 Cell Line | EDJ-KQ29272 | Human | 6676 | Details Get a Quote |
| SPAG4 Knockout HeLa Cell Line | EDJ-KQ29273 | Human | 6676 | Details Get a Quote |
