IFI16

Chr 1

interferon gamma inducible protein 16

Also known as: IFNGIP1, PYHIN2

NCBI Gene: 3428 ENSG00000163565 UniProt: Q16666 OMIM: 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]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.03

LOEUF

Multiple*

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in IFI16?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 69

932 rare PASS variants

Rare truncating (LoF)

1 in 1,500

123 rare PASS variants

Rare synonymous (reference)

1 in 170

329 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for IFI16. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 1,500
South Asian	~43k	1 in 68	1 in 1,200
Remaining (unassigned)	~30k	1 in 54	1 in 910
European (Finnish)	~27k	1 in 330	1 in 3,000
Admixed American	~22k	1 in 50	1 in 1,900
African / African American	~21k	1 in 47	1 in 1,300
East Asian	~20k	1 in 68	1 in 3,300
Ashkenazi Jewish	~13k	1 in 270	none seen
Middle Eastern	~2,884	1 in 49	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 8 of 11 coding exons well covered in gnomAD exomes; exons 8, 9, 12 marginal. Genomes: 9 of 11 (exons 8, 9 below).? see exons ↓