AIF1
protein-codingallograft inflammatory factor 1, the group of EF-hand domain containing
Gene summary
This gene encodes a protein that binds actin and calcium. This gene is induced by cytokines and interferon and may promote macrophage activation and growth of vascular smooth muscle cells and T-lymphocytes. Polymorphisms in this gene may be associated with systemic sclerosis. Alternative splicing results in multiple transcript variants, but the full-length and coding nature of some of these variants is not certain. [provided by RefSeq, Jan 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1.8 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 AIF1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001623.5. 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 | 0 | |||||
| missense | 8 | 1 | 9 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 14 | 1 | 0 | 15 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001614.3 | 6 | MANE Select | |
| Ensembl | ENSP00000365227.3 | 6 | MANE Select | |
| RefSeq | NP_001305899.1 | 3 | Standard | |
| RefSeq | NP_116573.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Spinal Cord Injury
- Protein alkylation leading to liver fibrosis
Biological Process
- microglial cell activation
- positive regulation of protein phosphorylation
- phagocytosis, engulfment
- inflammatory response
- negative regulation of gene expression
Molecular Function
- molecular_function
- calcium ion binding
- actin filament binding
Cellular Component
- phagocytic cup
- nucleus
- cytoplasm
- cytosol
- actin filament
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000376059
- Coding exons
- 6
- Length
- 1838
- Individuals with no LoFs
- 125657
- Homozygous LoFs
- 3
- Heterozygous LoFs
- 88
- Defined
- 125748
- p
- 0.000362
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.216 | 72 | 77.3 | 0.931 | 0.00000371 | 969 |
| Missense (PolyPhen) | 28 | 26.31 | 1.0643 | 352 | ||
| Synonymous | 1.71 | 20 | 32.4 | 0.618 | 0.00000185 | 266 |
| Loss of Function | 0.151 | 9 | 9.50 | 0.947 | 4.99e-7 | 113 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00073 | 0.00072 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00017 | 0.00017 | rare |
| South Asian | 0.0015 | 0.0014 | notable |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Actin-binding protein that enhances membrane ruffling and RAC activation. Enhances the actin-bundling activity of LCP1. Binds calcium. Plays a role in RAC signaling and in phagocytosis. May play a role in macrophage activation and function. Promotes the proliferation of vascular smooth muscle cells and of T- lymphocytes. Enhances lymphocyte migration. Plays a role in vascular inflammation. {ECO:0000269|PubMed:15117732, ECO:0000269|PubMed:16049345, ECO:0000269|PubMed:18699778}.;
Intolerance Scores
- LoFtool
- 0.860
- RVIS EVS
- 0.15
- RVIS percentile EVS
- 64.11
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0996
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |