IFI16
Gamma-interferon-inducible protein 16
Also known as: IF16_HUMAN, IFNGIP1, PYHIN2
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q16666
- Gene
- IFI16
- Ensembl
- ENSG00000163565
- Chromosome
- 1
- Canonical length
- 785 aa
- Protein class
- Plasma proteins, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm,Nucleoli,Cytosol
- Quaternary structure
- Homooligomer
OverviewNCBI Gene
This gene encodes a member of the HIN-200 (hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats) family of cytokines. The encoded protein contains domains involved in DNA binding, transcriptional regulation, and protein-protein interactions. The protein localizes to the nucleoplasm and nucleoli, and interacts with p53 and retinoblastoma-1. It modulates p53 function, and inhibits cell growth in the Ras/Raf signaling pathway. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2011]
Canonical amino-acid sequenceUniProt
785 residues, UniProt reviewed canonical sequence.
>Q16666|IFI16
1 MGKKYKNIVL LKGLEVINDY HFRMVKSLLS NDLKLNLKMR EEYDKIQIAD LMEEKFRGDA
61 GLGKLIKIFE DIPTLEDLAE TLKKEKLKVK GPALSRKRKK EVDATSPAPS TSSTVKTEGA
121 EATPGAQKRK KSTKEKAGPK GSKVSEEQTQ PPSPAGAGMS TAMGRSPSPK TSLSAPPNSS
181 STENPKTVAK CQVTPRRNVL QKRPVIVKVL STTKPFEYET PEMEKKIMFH ATVATQTQFF
241 HVKVLNTSLK EKFNGKKIII ISDYLEYDSL LEVNEESTVS EAGPNQTFEV PNKIINRAKE
301 TLKIDILHKQ ASGNIVYGVF MLHKKTVNQK TTIYEIQDDR GKMDVVGTGQ CHNIPCEEGD
361 KLQLFCFRLR KKNQMSKLIS EMHSFIQIKK KTNPRNNDPK SMKLPQEQRQ LPYPSEASTT
421 FPESHLRTPQ MPPTTPSSSF FTKKSEDTIS KMNDFMRMQI LKEGSHFPGP FMTSIGPAES
481 HPHTPQMPPS TPSSSFLTTK SEDTISKMND FMRMQILKEG SHFPGPFMTS IGPAESHPHT
541 PQMPPSTPSS SFLTTLKPRL KTEPEEVSIE DSAQSDLKEV MVLNATESFV YEPKEQKKMF
601 HATVATENEV FRVKVFNIDL KEKFTPKKII AIANYVCRNG FLEVYPFTLV ADVNADRNME
661 IPKGLIRSAS VTPKINQLCS QTKGSFVNGV FEVHKKNVRG EFTYYEIQDN TGKMEVVVHG
721 RLTTINCEEG DKLKLTCFEL APKSGNTGEL RSVIHSHIKV IKTRKNKKDI LNPDSSMETS
781 PDFFFLocalizationUniProt · AlphaFold · HPA
Whether an antibody against IFI16 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.45
- Highest tissue expression
- 131 nTPM
Expression across tissuesHPA
Tissue
- lymph node: 131 nTPM
- tonsil: 125 nTPM
- thymus: 109 nTPM
- appendix: 108 nTPM
- urinary bladder: 106 nTPM
- spleen: 102 nTPM
Single-cell type
- neutrophils: 683 nCPM
- breast lactating cells: 601 nCPM
- vascular endothelial cells: 470 nCPM
- hofbauer cells: 413 nCPM
- microglia: 411 nCPM
- ocular epithelial cells: 402 nCPM
Immune cell
- neutrophil: 165 nTPM
- naive B-cell: 95 nTPM
- NK-cell: 92 nTPM
- memory B-cell: 89 nTPM
- T-reg: 82 nTPM
- myeloid DC: 68 nTPM
Brain region
- medulla oblongata: 61 nTPM
- white matter: 54 nTPM
- thalamus: 51 nTPM
- spinal cord: 49 nTPM
- pons: 47 nTPM
- hypothalamus: 43 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about IFI16.
Disease | AutoantibodyPubMed
Conditions in which antibodies against IFI16 are reported. Each links to that disease's full target list.
ReferencesPubMed · IEDB
Publications for IFI16 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
20 publications
- The DNA sensors AIM2 and IFI16 are SLE autoantigens that bind neutrophil extracellular traps.
2022 · Elife · RCR 3.7 · 53 citations - Association of Antibodies to Interferon-Inducible Protein-16 With Markers of More Severe Disease in Primary Sjögren's Syndrome.
2016 · Arthritis Care Res (Hoboken) · RCR 1.5 · 44 citations - A novel autoantigen to differentiate limited cutaneous systemic sclerosis from diffuse cutaneous systemic sclerosis: the interferon-inducible gene IFI16.
2006 · Arthritis Rheum · RCR 1.4 · 66 citations - Role of the interferon-inducible gene IFI16 in the etiopathogenesis of systemic autoimmune disorders.
2007 · Ann N Y Acad Sci · RCR 1.4 · 74 citations - Redistribution of the nuclear protein IFI16 into the cytoplasm of ultraviolet B-exposed keratinocytes as a mechanism of autoantigen processing.
2011 · Br J Dermatol · RCR 1.4 · 57 citations
Show 15 more
- Identification of specific autoantigens in Sjögren's syndrome by SEREX.
2005 · Immunology · RCR 1.2 · 61 citations - Serum IFI16 and anti-IFI16 antibodies in psoriatic arthritis.
2020 · Clin Exp Immunol · RCR 1.1 · 21 citations - Circulating Interferon-Inducible Protein IFI16 Correlates With Clinical and Serological Features in Rheumatoid Arthritis.
2016 · Arthritis Care Res (Hoboken) · RCR 1 · 30 citations - Distinct Anti-IFI16 and Anti-GP2 Antibodies in Inflammatory Bowel Disease and Their Variation with Infliximab Therapy.
2016 · Inflamm Bowel Dis · RCR 1 · 30 citations - Anti-IFI16 antibodies and their relation to disease characteristics in systemic lupus erythematosus.
2013 · Lupus · RCR 0.9 · 35 citations - IFI16 filament formation in salivary epithelial cells shapes the anti-IFI16 immune response in Sjögren's syndrome.
2018 · JCI Insight · RCR 0.8 · 26 citations - Prognostic value of anti-IFI16 autoantibodies in pulmonary arterial hypertension and mortality in patients with systemic sclerosis.
2024 · Med Clin (Barc) · RCR 0.8 · 3 citations - Mislocalization of the interferon inducible protein IFI16 by environmental insults: implications in autoimmunity.
2015 · Cytokine Growth Factor Rev · RCR 0.6 · 21 citations - Anti-Interferon-Inducible Protein 16 Antibodies Associate With Digital Gangrene in Patients With Scleroderma.
2016 · Arthritis Rheumatol · RCR 0.6 · 16 citations - Detection of anti-IFI16 antibodies by ELISA: clinical and serological associations in systemic sclerosis.
2011 · Rheumatology (Oxford) · RCR 0.6 · 22 citations - Risk of Digital Vascular Events in Scleroderma Patients Who Have Both Anticentromere and Anti-Interferon-Inducible Protein 16 Antibodies.
2017 · Arthritis Care Res (Hoboken) · RCR 0.6 · 12 citations - Interferon gamma-inducible protein 16 (IFI16) and anti-IFI16 antibodies in primary Sjögren's syndrome: findings in serum and minor salivary glands.
2015 · Reumatismo · RCR 0.4 · 11 citations - Anti-interferon gamma-inducible protein 16 antibodies: Identification of a novel autoantigen in idiopathic interstitial pneumonia and its clinical characteristics based on a multicenter cohort study.
2024 · Clin Immunol · RCR 0.3 · 2 citations - The predictive value of anti-IFI16 antibodies for the development or persistence of digital ulcers in systemic sclerosis.
2025 · Clin Rheumatol · 3 citations - Plasma autoantibodies as novel risk markers for stroke: A nested case-control study of the JPHC study.
2026 · Clin Chim Acta
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.03
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.57
- DepMap mean gene effect
- 0.01
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- activation of innate immune response
- autophagy
- cellular response to glucose starvation
- cellular response to interferon-beta
- cellular response to ionizing radiation
- defense response to virus
- inflammatory response
- innate immune response
- intrinsic apoptotic signaling pathway by p53 class mediator
- intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
- monocyte differentiation
- myeloid cell differentiation
- negative regulation of AIM2 inflammasome complex assembly
- negative regulation of DNA binding
- negative regulation of DNA-templated transcription
- negative regulation of gene expression, epigenetic
- negative regulation of innate immune response
- negative regulation of transcription by RNA polymerase II
- negative regulation of viral genome replication
- positive regulation of cytokine production
- positive regulation of interleukin-1 beta production
- positive regulation of transcription by RNA polymerase II
- regulation of autophagy
- regulation of inflammatory response
Molecular functions
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of IFI16 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads IFI16 as an antibody target. Whether an autoantibody or antibody against IFI16 could matter depends on whether native IFI16 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
IFI16 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label IFI16 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
Loading the interactive Seroatlas protein explorer...