IFI44L

Chr 1

interferon induced protein 44 like

Also known as: C1orf29, GS3686, TLDC5B

NCBI Gene: 10964 ENSG00000137959 UniProt: Q53G44 OMIM: 613975

This interferon-stimulated gene encodes a protein that provides antiviral and antibacterial activity by promoting macrophage differentiation, facilitating inflammatory cytokine secretion, and controlling viral replication, while also serving as a feedback regulator of interferon responses. Mutations in IFI44L cause autosomal recessive immunodeficiency, with patients presenting with severe, recurrent infections affecting multiple organ systems. The gene shows very low constraint against loss-of-function variants, consistent with a recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to be involved in immune response. Predicted to act upstream of or within cellular response to virus. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.52

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.52LOEUF

pLI 0.000

Z-score -0.10

OE 1.03 (0.71–1.52)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.21Z-score

OE missense 1.22 (1.11–1.34)

299 obs / 245.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.03 (0.71–1.52)

0≤0.351.4

Missense OE?1.22 (1.11–1.34)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 18 / 17.6Missense obs/exp: 299 / 245.7Syn Z: 0.16

Background carrier burden — how many people carry a rare variant somewhere in IFI44L?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 83

686 rare PASS variants

Rare truncating (LoF)

1 in 2,000

101 rare PASS variants

Rare synonymous (reference)

1 in 260

220 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for IFI44L. 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 130	1 in 2,700
South Asian	~43k	1 in 72	1 in 1,100
Remaining (unassigned)	~30k	1 in 55	1 in 1,600
European (Finnish)	~27k	1 in 560	1 in 2,100
Admixed American	~22k	1 in 54	1 in 2,700
African / African American	~21k	1 in 46	1 in 270
East Asian	~20k	1 in 77	1 in 470
Ashkenazi Jewish	~13k	1 in 480	none seen
Middle Eastern	~2,884	1 in 55	≈ 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): 7 of 8 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 8.? see exons ↓