IFI6
protein-codinginterferon alpha inducible protein 6
Gene summary
This gene was first identified as one of the many genes induced by interferon. The encoded protein may play a critical role in the regulation of apoptosis. A minisatellite that consists of 26 repeats of a 12 nucleotide repeating element resembling the mammalian splice donor consensus sequence begins near the end of the second exon. Alternatively spliced transcript variants that encode different isoforms by using the two downstream repeat units as splice donor sites have been described. [provided by RefSeq, Jul 2008]
- G1P3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.1 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 IFI6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002038.4. 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 | ||||
| missense | 17 | 17 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 20 | 0 | 0 | 20 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002029.3 | 4 | MANE Select | |
| Ensembl | ENSP00000354736.6 | 4 | MANE Select | |
| RefSeq | NP_075010.1 | 4 | Standard | |
| RefSeq | NP_075011.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Type II interferon signaling (IFNG)
- Cytokine Signaling in Immune system
- Immune System
- Interferon alpha/beta signaling
- Interferon Signaling
Biological Process
- release of cytochrome c from mitochondria
- apoptotic process
- immune response
- regulation of epidermal growth factor receptor signaling pathway
- negative regulation of apoptotic process
Molecular Function
- protein binding
Cellular Component
- mitochondrion
- mitochondrial inner membrane
- plasma membrane
- integral component of membrane
- mitochondrial membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000339145
- Coding exons
- 4
- Length
- 6158
- Individuals with no LoFs
- 119541
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 119542
- p
- 0.00000418
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.32 | 49 | 82.7 | 0.592 | 0.00000517 | 847 |
| Missense (PolyPhen) | 17 | 30.012 | 0.56644 | 315 | ||
| Synonymous | 0.465 | 39 | 42.9 | 0.910 | 0.00000335 | 279 |
| Loss of Function | 0.587 | 3 | 4.32 | 0.695 | 1.82e-7 | 56 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role in apoptosis, negatively regulating the intrinsinc apoptotic signaling pathway and TNFSF10-induced apoptosis (PubMed:15685448, PubMed:17823654, PubMed:26244642). However, it has also been shown to have a pro-apoptotic activity (PubMed:27673746). Has an antiviral activity towards hepatitis C virus/HCV by inhibiting the EGFR signaling pathway, which activation is required for entry of the virus into cells (PubMed:25757571). {ECO:0000269|PubMed:15685448, ECO:0000269|PubMed:17823654, ECO:0000269|PubMed:25757571, ECO:0000269|PubMed:26244642, ECO:0000269|PubMed:27673746}.;
Recessive Scores
- pRec
- 0.160
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.829
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Low | Low | Low |
| Cancer | Low | Low | Low |