IFI16

interferon gamma inducible protein 16, the group of Pyrin domain containing|Pyrin and HIN domain family

Basic information

Region (hg38): 1:158999967-159055155

Links

ENSG00000163565 ∙ NCBI:3428 ∙ OMIM:147586 ∙ HGNC:5395 ∙ Uniprot:Q16666 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IFI16 gene.

• Inborn genetic diseases (36 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IFI16 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			31	7	2	40
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	31	7	2

Variants in IFI16

This is a list of pathogenic ClinVar variants found in the IFI16 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-159014843-A-G		not specified	Uncertain significance (Jan 06, 2023)
1-159014892-A-G		not specified	Uncertain significance (Sep 26, 2023)
1-159015883-G-A			Likely benign (Mar 01, 2023)
1-159015928-G-T		not specified	Uncertain significance (Feb 14, 2023)
1-159015931-C-G		not specified	Uncertain significance (Mar 06, 2023)
1-159015935-C-T		not specified	Uncertain significance (Oct 03, 2022)
1-159015947-C-T		not specified	Uncertain significance (Aug 29, 2022)
1-159016560-G-C		not specified	Uncertain significance (Dec 15, 2023)
1-159016608-T-G		not specified	Uncertain significance (Feb 10, 2022)
1-159016623-G-A		not specified	Likely benign (Feb 07, 2023)
1-159016640-G-A		not specified	Uncertain significance (Jun 21, 2023)
1-159018233-C-T		not specified	Uncertain significance (Mar 06, 2023)
1-159018286-C-T		not specified	Uncertain significance (Jun 29, 2023)
1-159018484-A-G		not specified	Likely benign (Nov 10, 2022)
1-159018504-A-T		not specified	Uncertain significance (Dec 14, 2021)
1-159018514-G-A		not specified	Uncertain significance (May 27, 2022)
1-159018529-C-A		not specified	Uncertain significance (Jan 17, 2024)
1-159018529-C-T			Likely benign (Nov 01, 2022)
1-159018547-G-A		not specified	Uncertain significance (Dec 21, 2023)
1-159018555-T-G		not specified	Uncertain significance (Jun 29, 2023)
1-159018601-C-T		not specified	Uncertain significance (Dec 12, 2023)
1-159018623-T-C		not specified	Uncertain significance (Feb 28, 2024)
1-159020358-G-T		not specified	Uncertain significance (Dec 15, 2023)
1-159020419-T-C		not specified	Uncertain significance (Nov 10, 2022)
1-159020480-A-T		not specified	Uncertain significance (Aug 26, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IFI16	protein_coding	protein_coding	ENST00000368131	10	55188

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.78e-11	0.600	125680	0	9	125689	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.566	351	382	0.919	0.0000186	4835
Missense in Polyphen		64	73.261	0.87359		975
Synonymous	-0.210	135	132	1.02	0.00000673	1343
Loss of Function	1.43	21	29.3	0.716	0.00000165	391

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000190	0.000183
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000471	0.0000462
European (Non-Finnish)	0.0000361	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds double-stranded DNA. Binds preferentially to supercoiled DNA and cruciform DNA structures. Seems to be involved in transcriptional regulation. May function as a transcriptional repressor. Could have a role in the regulation of hematopoietic differentiation through activation of unknown target genes. Controls cellular proliferation by modulating the functions of cell cycle regulatory factors including p53/TP53 and the retinoblastoma protein. May be involved in TP53-mediated transcriptional activation by enhancing TP53 sequence-specific DNA binding and modulating TP53 phosphorylation status. Seems to be involved in energy-level-dependent activation of the ATM/ AMPK/TP53 pathway coupled to regulation of autophagy. May be involved in regulation of TP53-mediated cell death also involving BRCA1. May be involved in the senescence of prostate epithelial cells. Involved in innate immune response by recognizing viral dsDNA in the cytosol and probably in the nucleus. After binding to viral DNA in the cytoplasm recruits TMEM173/STING and mediates the induction of IFN-beta. Has anti-inflammatory activity and inhibits the activation of the AIM2 inflammasome, probably via association with AIM2. Proposed to bind viral DNA in the nucleus, such as of Kaposi's sarcoma-associated herpesvirus, and to induce the formation of nuclear caspase-1-activating inflammasome formation via association with PYCARD. Inhibits replication of herpesviruses such as human cytomegalovirus (HCMV) probably by interfering with promoter recruitment of members of the Sp1 family of transcription factors. Necessary to activate the IRF3 signaling cascade during human herpes simplex virus 1 (HHV-1) infection and promotes the assembly of heterochromatin on herpesviral DNA and inhibition of viral immediate-early gene expression and replication. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer. {ECO:0000269|PubMed:11146555, ECO:0000269|PubMed:12894224, ECO:0000269|PubMed:14654789, ECO:0000269|PubMed:20890285, ECO:0000269|PubMed:21573174, ECO:0000269|PubMed:21575908, ECO:0000269|PubMed:22046441, ECO:0000269|PubMed:22291595, ECO:0000269|PubMed:23027953, ECO:0000269|PubMed:24198334, ECO:0000269|PubMed:24413532, ECO:0000269|PubMed:9642285}.
• Pathway: NOD-like receptor signaling pathway - Homo sapiens (human);Senescence and Autophagy in Cancer;STING mediated induction of host immune responses;Innate Immune System;Immune System;IRF3-mediated induction of type I IFN;Cytosolic sensors of pathogen-associated DNA (Consensus)

Recessive Scores

• pRec: 0.105

Intolerance Scores

• loftool: 0.779
• rvis_EVS: 1.4
• rvis_percentile_EVS: 94.75

Haploinsufficiency Scores

• pHI: 0.128
• hipred: Y
• hipred_score: 0.633
• ghis: 0.417

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.504

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mndal

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;positive regulation of cytokine production;activation of innate immune response;autophagy;inflammatory response;cell population proliferation;regulation of autophagy;hemopoiesis;myeloid cell differentiation;monocyte differentiation;positive regulation of type I interferon production;positive regulation of interleukin-1 beta production;cellular response to interferon-beta;regulation of gene expression, epigenetic;cellular response to glucose starvation;intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator;negative regulation of DNA binding;negative regulation of viral genome replication;innate immune response;negative regulation of innate immune response;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;defense response to virus;cellular response to ionizing radiation;intrinsic apoptotic signaling pathway by p53 class mediator;activation of cysteine-type endopeptidase activity;negative regulation of cysteine-type endopeptidase activity
• Cellular component: nucleus;nucleoplasm;nucleolus;cytosol;membrane;nuclear speck
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription repressor activity, RNA polymerase II-specific;double-stranded DNA binding;RNA binding;protein binding;transcription factor binding