ANXA5
protein-codingannexin A5, the group of Annexins
Gene summary
The Annexin 5 gene spans 29 kb containing 13 exons, and encodes a single transcript of approximately 1.6 kb and a protein product with a molecular weight of about 35 kDa.The protein encoded by this gene belongs to the annexin family of calcium-dependent phospholipid binding proteins some of which have been implicated in membrane-related events along exocytotic and endocytotic pathways. Annexin 5 is a phospholipase A2 and protein kinase C inhibitory protein with calcium channel activity and a potential role in cellular signal transduction, inflammation, growth and differentiation. Annexin 5 has also been described as placental anticoagulant protein I, vascular anticoagulant-alpha, endonexin II, lipocortin V, placental protein 4 and anchorin CII. Polymorphisms in this gene have been implicated in various obstetric complications. [provided by RefSeq, Dec 2019]
- ENX2
- ANX5
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~29.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0013729
Submitter: PanelApp Australia
Inheritance Pattern: Unknown
Disease ID:MONDO:0013729
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ANXA5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001154.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 47 | 2 | 49 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 54 | 3 | 1 | 58 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001145.1 | 12 | MANE Select | |
| Ensembl | ENSP00000296511.5 | 12 | MANE Select | |
| Ensembl | ENSP00000424106.1 | 10 | Standard | |
| Ensembl | ENSP00000424106.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Apoptosis-related network due to altered Notch3 in ovarian cancer
- Simplified Interaction Map Between LOXL4 and Oxidative Stress Pathway
- Prostaglandin Synthesis and Regulation
- Platelet degranulation
- Response to elevated platelet cytosolic Ca2+
Biological Process
- platelet degranulation
- signal transduction
- blood coagulation
- response to organic substance
- negative regulation of blood coagulation
Molecular Function
- phospholipase inhibitor activity
- calcium-transporting ATPase activity
- calcium ion binding
- protein binding
- phospholipid binding
Cellular Component
- extracellular region
- cytoplasm
- cytosol
- focal adhesion
- external side of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000296511
- Coding exons
- 12
- Length
- 29159
- Individuals with no LoFs
- 125520
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 224
- Defined
- 125745
- p
- 0.000895
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.551 | 149 | 169 | 0.881 | 0.00000847 | 2068 |
| Missense (PolyPhen) | 63 | 72.459 | 0.86946 | 891 | ||
| Synonymous | 0.258 | 55 | 57.5 | 0.957 | 0.00000257 | 611 |
| Loss of Function | -0.0562 | 22 | 21.7 | 1.01 | 0.00000117 | 254 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00075 | 0.00074 | rare |
| Latino/Admixed American | 0.00017 | 0.00017 | rare |
| Ashkenazi Jewish | 0.0067 | 0.0068 | notable |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0.00065 | 0.00065 | rare |
| European (Non-Finnish) | 0.00072 | 0.00072 | rare |
| South Asian | 0.0011 | 0.0011 | notable |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: This protein is an anticoagulant protein that acts as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation cascade.;
- Disease
- DISEASE: Pregnancy loss, recurrent, 3 (RPRGL3) [MIM:614391]: A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions. {ECO:0000269|PubMed:17339269}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.464
Intolerance Scores
- LoFtool
- 0.896
- RVIS EVS
- 0.13
- RVIS percentile EVS
- 63.2
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.801
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |