ANXA1
protein-codingannexin A1, the group of Annexins|Receptor ligands
Gene summary
This gene encodes a membrane-localized protein that binds phospholipids. This protein inhibits phospholipase A2 and has anti-inflammatory activity. Loss of function or expression of this gene has been detected in multiple tumors. [provided by RefSeq, Dec 2014]
Previous symbols:
- ANX1
- LPC1
MANE transcript
NM_000700.3
Inheritance
—
ClinVar variants
U:65B:4
Top phenotype
ANXA1-related disorder
gnomAD constraint
pLI —, LoF o/e 0.66
Max pathogenic AF
—
Genomic locus
chr9:73,151,865-73,170,629
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~18.8 kbLoading mutation effect viewer...
GenCC 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 ANXA1 variants in ClinVar
not specifiedTotal: 56
not providedTotal: 8
ANXA1-related disorderTotal: 8
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000700.3. 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 | 2 | 3 | |||
| missense | 62 | 1 | 63 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 65 | 1 | 3 | 69 |
Loading ClinVar variants...
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
Showing 4 of 61 transcripts
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000691.1 | 12 | MANE Select | |
| Ensembl | ENSP00000257497.6 | 12 | MANE Select | |
| Ensembl | ENSP00000366109.1 | 12 | Standard | |
| Ensembl | ENSP00000366109.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Integrated Breast Cancer Pathway
- Spinal Cord Injury
- VEGFA-VEGFR2 Signaling Pathway
- Interleukin-4 and 13 signaling
- Prostaglandin Synthesis and Regulation
Biological Process
- neutrophil homeostasis
- adaptive immune response
- monocyte chemotaxis
- regulation of leukocyte migration
- phagocytosis
Molecular Function
- single-stranded DNA binding
- single-stranded RNA binding
- signaling receptor binding
- structural molecule activity
- calcium ion binding
Cellular Component
- cornified envelope
- phagocytic cup
- extracellular region
- extracellular space
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000376911
- Coding exons
- 12
- Length
- 18637
- Individuals with no LoFs
- 125618
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 116
- Defined
- 125734
- p
- 0.000461
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0490 | 188 | 190 | 0.990 | 0.00000988 | 2252 |
| Missense (PolyPhen) | 50 | 57.299 | 0.87261 | 739 | ||
| Synonymous | 0.227 | 63 | 65.3 | 0.964 | 0.00000351 | 637 |
| Loss of Function | 1.46 | 14 | 21.2 | 0.659 | 0.00000107 | 264 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00015 | 0.00012 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00065 | 0.00065 | rare |
| Finnish | 0.0015 | 0.0015 | notable |
| European (Non-Finnish) | 0.00037 | 0.00037 | rare |
| South Asian | 0.00069 | 0.00069 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays important roles in the innate immune response as effector of glucocorticoid-mediated responses and regulator of the inflammatory process. Has anti-inflammatory activity (PubMed:8425544). Plays a role in glucocorticoid-mediated down- regulation of the early phase of the inflammatory response (By similarity). Promotes resolution of inflammation and wound healing (PubMed:25664854). Functions at least in part by activating the formyl peptide receptors and downstream signaling cascades (PubMed:15187149, PubMed:25664854). Promotes chemotaxis of granulocytes and monocytes via activation of the formyl peptide receptors (PubMed:15187149). Contributes to the adaptive immune response by enhancing signaling cascades that are triggered by T- cell activation, regulates differentiation and proliferation of activated T-cells (PubMed:17008549). Promotes the differentiation of T-cells into Th1 cells and negatively regulates differentiation into Th2 cells (PubMed:17008549). Has no effect on unstimulated T cells (PubMed:17008549). Promotes rearrangement of the actin cytoskeleton, cell polarization and cell migration (PubMed:15187149). Negatively regulates hormone exocytosis via activation of the formyl peptide receptors and reorganization of the actin cytoskeleton (PubMed:19625660). Has high affinity for Ca(2+) and can bind up to eight Ca(2+) ions (By similarity). Displays Ca(2+)-dependent binding to phospholipid membranes (PubMed:2532504, PubMed:8557678). Plays a role in the formation of phagocytic cups and phagosomes. Plays a role in phagocytosis by mediating the Ca(2+)-dependent interaction between phagosomes and the actin cytoskeleton (By similarity). {ECO:0000250|UniProtKB:P10107, ECO:0000250|UniProtKB:P19619, ECO:0000269|PubMed:15187149, ECO:0000269|PubMed:17008549, ECO:0000269|PubMed:19625660, ECO:0000269|PubMed:2532504, ECO:0000269|PubMed:25664854, ECO:0000269|PubMed:2936963, ECO:0000269|PubMed:8425544, ECO:0000269|PubMed:8557678}.;
Recessive Scores
- pRec
- 0.520
Intolerance Scores
- LoFtool
- 0.826
- RVIS EVS
- -0.32
- RVIS percentile EVS
- 31.69
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.995
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |