IFI16

Chr 1

interferon gamma inducible protein 16

Also known as: IFNGIP1, PYHIN2

NCBI Gene: 3428ENSG00000163565UniProt: Q16666OMIM: 147586

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]

OMIMResearchGenerating clinical summary…
MultiplemechanismLOEUF 1.03
Clinical Summary— IFI16
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
97 VUS of 137 total submissions
💊
Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
1.03LOEUF
pLI 0.000
Z-score 1.43
OE 0.72 (0.51–1.03)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
0.57Z-score
OE missense 0.92 (0.84–1.00)
351 obs / 382.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.72 (0.51–1.03)
0≤0.351.4
Missense OE?0.92 (0.84–1.00)
0≤0.61.4
Synonymous OE?1.02
0≤1.21.6
LoF obs/exp: 21 / 29.3Missense obs/exp: 351 / 382.1Syn Z: -0.21

This gene — mechanism propensity

DN
0.77top 25%
GOF
0.7127th %ile
LOF
0.2190th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

137 submitted variants in ClinVar

ClinVar

Classification Summary

VUS97
Likely Benign15
Benign2
97
VUS
15
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
97
0
0
97
Likely Benign
0
15
0
0
15
Benign
0
2
0
0
2
Total011400114

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

10 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap IFI16 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

IFI16 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients