ANXA5 (Annexin A5) Gene: Structure, Function, and Clinical Significance
Comprehensive biomedical overview of the ANXA5 gene, including genomic data, protein function, expression, mutations, and associated diseases.
Gene Information Card
| Symbol | ANXA5 |
|---|---|
| Full Name | Annexin A5 |
| Gene Type | protein-coding |
| Chromosomal Location | 4q27 |
| NCBI Gene ID | 308 ncbi.nlm.nih.gov/gene/308 |
| Ensembl ID | ENSG00000164111 |
| UniProt ID | P08758 |
| OMIM ID | 131230 |
| HGNC ID | 543 |
| Aliases | ANX5, ENX2, PP4, RPRL1, anchorin CII, annexin V, placental anticoagulant protein I (PAP-I), thromboplastin inhibitor, vascular anticoagulant-alpha (VAC-alpha) |
Description
ANXA5 encodes annexin A5, a calcium-dependent phospholipid-binding protein that forms a protective shield on cell membranes. It exhibits anticoagulant properties by competing with prothrombin for binding to phosphatidylserine. The protein is highly expressed in placenta, endothelial cells, and various epithelia. ANXA5 is involved in membrane organization, vesicle trafficking, signal transduction, and apoptosis. Reduced ANXA5 expression is linked to placental thrombosis and recurrent pregnancy loss. The gene spans approximately 28 kb on chromosome 4q27 and contains 13 exons.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Recurrent pregnancy loss (RPL) | Reduced ANXA5 expression on placental syncytiotrophoblast leads to loss of anticoagulant shield, promoting microthrombi and impaired placental perfusion. | ClinVar, OMIM #131230 |
| Antiphospholipid syndrome (APS) | Anti-annexin A5 antibodies disrupt the annexin A5 shield, increasing thrombotic risk. | ClinVar, OMIM #131230 |
| Thrombophilia | ANXA5 promoter polymorphisms (e.g., M2 haplotype) reduce gene expression, increasing venous thromboembolism risk. | NCBI Gene, OMIM #131230 |
| Systemic lupus erythematosus (SLE) | Autoantibodies against annexin A5 contribute to thrombotic complications. | ClinVar |
| Myocardial infarction | Reduced annexin A5 levels associated with increased thrombotic risk. | NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Placenta | 112.5 | High |
| Adrenal gland | 45.2 | Medium |
| Thyroid | 38.7 | Medium |
| Kidney | 32.1 | Medium |
| Liver | 28.4 | Medium |
| Heart | 22.6 | Medium |
| Lung | 18.3 | Medium |
| Skeletal muscle | 12.1 | Low |
| Brain | 8.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HUVEC (umbilical vein endothelial) | 45.0 | High expression |
| HeLa (cervical carcinoma) | 38.2 | High expression |
| A549 (lung carcinoma) | 30.5 | Medium expression |
| MCF7 (breast carcinoma) | 25.1 | Medium expression |
| HEK293 (embryonic kidney) | 22.0 | Medium expression |
| K562 (leukemia) | 15.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1Val) | missense | <0.01% | Loss of start codon; reduced protein expression |
| c.76C>T (p.Arg26Cys) | missense | <0.01% | Altered calcium binding; reduced anticoagulant activity |
| c.229G>A (p.Gly77Ser) | missense | <0.01% | Impaired phospholipid binding |
| c.388C>T (p.Arg130Trp) | missense | <0.01% | Reduced membrane affinity |
| c.487G>A (p.Gly163Arg) | missense | <0.01% | Unknown functional effect |
| M2 haplotype (promoter) | regulatory | 5-15% in European populations | Reduced transcription; associated with RPL and thrombosis |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce ANXA5 expression or phospholipid binding (e.g., M2 haplotype, p.Met1Val, p.Arg26Cys) lead to loss of anticoagulant shield, promoting thrombosis.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations described; haploinsufficiency is the proposed mechanism.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Annexin pathway (Reactome: R-HSA-1474244)
• Formation of annular gap junctions (Reactome: R-HSA-190828)
• Phospholipid binding and coagulation cascade (KEGG: hsa04610)
• Apoptosis (KEGG: hsa04210)
Protein Summary
Annexin A5 is a 35.7 kDa protein (320 amino acids) composed of four homologous repeats, each containing a calcium-binding site. It binds preferentially to phosphatidylserine in a calcium-dependent manner. The protein forms a two-dimensional crystal lattice on membrane surfaces, acting as an anticoagulant shield that prevents prothrombinase complex assembly. It is widely expressed, with highest levels in placenta, endothelial cells, and epithelia. Annexin A5 is also involved in apoptosis, where it binds to exposed phosphatidylserine on apoptotic cells, and in membrane repair, vesicle trafficking, and signal transduction. Reduced expression or function is associated with thrombotic disorders and recurrent pregnancy loss.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ANXA5 Knockout HEK293 Cell Line | EDJ-KQ1920 | Human | 308 | Details Get a Quote |
| ANXA5 Knockout A-549 Cell Line | EDJ-KQ21838 | Human | 308 | Details Get a Quote |
| ANXA5 Knockout HCT 116 Cell Line | EDJ-KQ21839 | Human | 308 | Details Get a Quote |
| ANXA5 Knockout HeLa Cell Line | EDJ-KQ21840 | Human | 308 | Details Get a Quote |
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