ANXA4
protein-codingannexin A4, the group of Annexins
Gene summary
Annexin IV (ANX4) belongs to the annexin family of calcium-dependent phospholipid binding proteins. Although their functions are still not clearly defined, several members of the annexin family have been implicated in membrane-related events along exocytotic and endocytotic pathways. ANX4 has 45 to 59% identity with other members of its family and shares a similar size and exon-intron organization. Isolated from human placenta, ANX4 encodes a protein that has possible interactions with ATP, and has in vitro anticoagulant activity and also inhibits phospholipase A2 activity. ANX4 is almost exclusively expressed in epithelial cells. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2016]
- ANX4
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~182.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ANXA4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001153.5. 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 | 4 | ||
| missense | 41 | 3 | 44 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 11 | 11 | ||||
| Total | 0 | 0 | 53 | 4 | 2 | 59 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001144.1 | 12 | MANE Select | |
| Ensembl | ENSP00000377833.4 | 12 | MANE Select | |
| RefSeq | NP_001307627.1 | 12 | Standard | |
| RefSeq | NP_001307629.1 | 12 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| anxa4 | Danio rerio | Structure: liver Quality: increased process quality abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Prostaglandin Synthesis and Regulation
- EGFR1
Biological Process
- regulation of transcription by RNA polymerase II
- signal transduction
- Notch signaling pathway
- epithelial cell differentiation
- negative regulation of NF-kappaB transcription factor activity
Molecular Function
- phospholipase inhibitor activity
- calcium ion binding
- protein binding
- calcium-dependent phospholipid binding
- heparin binding
Cellular Component
- nucleus
- cytoplasm
- cytosol
- plasma membrane
- cell surface
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000394295
- Coding exons
- 12
- Length
- 182040
- Individuals with no LoFs
- 125668
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 79
- Defined
- 125747
- p
- 0.000314
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.855 | 160 | 193 | 0.827 | 0.0000114 | 2093 |
| Missense (PolyPhen) | 60 | 81.844 | 0.73311 | 898 | ||
| Synonymous | 0.617 | 68 | 74.8 | 0.909 | 0.00000468 | 608 |
| Loss of Function | 1.50 | 16 | 23.9 | 0.669 | 0.00000152 | 243 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00055 | 0.00055 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00027 | 0.00027 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00025 | 0.00025 | rare |
| South Asian | 0.00075 | 0.00075 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Calcium/phospholipid-binding protein which promotes membrane fusion and is involved in exocytosis. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.196
Intolerance Scores
- LoFtool
- 0.873
- RVIS EVS
- 0.66
- RVIS percentile EVS
- 84.55
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.819
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |