IFI44L
Chr 1interferon induced protein 44 like
Also known as: C1orf29, GS3686, TLDC5B
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.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
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
119 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 14 | 0 | 14 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 1 | 65 | 11 | 0 | 77 |
Likely Benign | 0 | 5 | 1 | 1 | 7 |
Benign | 0 | 2 | 0 | 1 | 3 |
| Total | 1 | 72 | 27 | 2 | 102 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
IFI44L · 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
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Host Response to Infection by Direct Analysis of Leukocyte Single Cell-type Gene Expression/transcript Abundance, Direct LS-TA. a Prospective Study Will Evaluate the Performance of Direct LS-TA in Triage Febrile Patients Into Major Categories of Infections: Viral, Bacterial or Active Tuberculosis.
NOT YET RECRUITINGHost Response to Infection by Direct Analysis of Leukocyte Single Cell-type Gene Expression/transcript Abundance, Direct LS-TA
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools