IFIH1

Chr 2

interferon induced with helicase C domain 1

Also known as: AGS7, Hlcd, IDDM19, IMD95, MDA-5, MDA5, RLR-2, SGMRT1

NCBI Gene: 64135ENSG00000115267UniProt: Q9BYX4

IFIH1 encodes MDA5 which is an intracellular sensor of viral RNA that triggers the innate immune response. Sensing RNA length and secondary structure, MDA5 binds dsRNA oligonucleotides with a modified DExD/H-box helicase core and a C-terminal domain, thus leading to a proinflammatory response that includes interferons. It has been shown that Coronaviruses (CoVs) as well as various other virus families, are capable of evading the MDA5-dependent interferon response, thus impeding the activation of the innate immune response to infection. MDA5 has also been shown to play an important role in enhancing natural killer cell function in malaria infection. In addition to its protective role in antiviral responses, MDA5 has been implicated in autoimmune and autoinflammatory diseases such as type 1 diabetes, systemic lupus erythematosus, and Aicardi-Goutieres syndrome[provided by RefSeq, Jul 2020]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtType 1 diabetes mellitus 19
UniProtAicardi-Goutieres syndrome 7
UniProtSingleton-Merten syndrome 1
UniProtImmunodeficiency 95

Clinical highlights

Gene-disease validity (ClinGen)
IFIH1-related type 1 interferonopathy · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.
4
Active trials
111
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
1.55
LOEUF
GOF
Mechanism· G2P
📖
GeneReview available — IFIH1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
1.55LOEUF
pLI 0.000
Z-score -1.57
OE 1.25 (1.01–1.55)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-0.79Z-score
OE missense 1.10 (1.02–1.17)
586 obs / 534.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?1.25 (1.01–1.55)
0≤0.351.4
Missense OE?1.10 (1.02–1.17)
0≤0.61.4
Synonymous OE?1.12
0≤1.21.6
LoF obs/exp: 59 / 47.3Missense obs/exp: 586 / 534.7Syn Z: -1.33

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

IFIH1 · 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