IFIT5

protein-coding

interferon induced protein with tetratricopeptide repeats 5, the group of Tetratricopeptide repeat domain containing

Gene summary

Enables RNA binding activity and double-stranded DNA binding activity. Involved in defense response to virus; negative regulation of viral genome replication; and positive regulation of canonical NF-kappaB signal transduction. Located in several cellular components, including IkappaB kinase complex; actin cytoskeleton; and ruffle membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_012420.3

Inheritance

—

ClinVar variants

U:49B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.52

Max pathogenic AF

—

Genomic locus

chr10:89,414,568-89,421,605

External References & Databases

Ensembl (ENSG00000152778)

Transcript & Mutation Effects

hg38 • Region Span ~7.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IFIT5 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 51

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012420.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous					1 clinvar	1
missense			49 clinvar	2 clinvar	1 clinvar	52
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	49	2	2	53

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012420.3	RefSeq	NP_036552.1	2	MANE Select
ENST00000371795.5	Ensembl	ENSP00000360860.4	2	MANE Select
ENST00000679632.1	Ensembl	ENSP00000506256.1	2	Standard
ENST00000680591.1	Ensembl	ENSP00000505914.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

positive regulation of I-kappaB kinase/NF-kappaB signaling
negative regulation of viral genome replication
innate immune response
defense response to virus

Molecular Function

tRNA binding
RNA cap binding
double-stranded DNA binding
RNA binding
single-stranded RNA binding

Cellular Component

cytosol
plasma membrane
IkappaB kinase complex
actin cytoskeleton
ruffle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000371795
Coding exons: 2
Length: 6416
Individuals with no LoFs: 125677
Homozygous LoFs: 1
Heterozygous LoFs: 70
Defined: 125748
p: 0.000282

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.353	238	254	0.938	0.0000129	3172
Missense (PolyPhen)		72	71.687	1.0044		982
Synonymous	0.725	85	93.9	0.905	0.00000459	904
Loss of Function	1.83	9	17.2	0.524	9.18e-7	240

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00033	0.00033	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.0015	0.0014	notable
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Interferon-induced RNA-binding protein involved in the human innate immune response. Has a broad and adaptable RNA structure recognition important for RNA recognition specificity in antiviral defense. Binds precursor and processed tRNAs as well as poly-U-tailed tRNA fragments (PubMed:25092312, PubMed:23317505, PubMed:23774268). Specifically binds single-stranded RNA bearing a 5'-triphosphate group (PPP-RNA), thereby acting as a sensor of viral single-stranded RNAs. Single-stranded PPP-RNAs, which lack 2'-O-methylation of the 5' cap and bear a 5'-triphosphate group instead, are specific from viruses, providing a molecular signature to distinguish between self and non-self mRNAs by the host during viral infection. Directly binds PPP-RNA in a non- sequence-specific manner (PubMed:23334420). Also recognizes and selectively binds AT-rich dsDNA (PubMed:23774268). Additionally, as a mediator in innate immunity, regulates positively IKK-NFKB signaling by sinergizing the recruitment of IKK to MAP3K7 (PubMed:26334375). {ECO:0000269|PubMed:23317505, ECO:0000269|PubMed:23334420, ECO:0000269|PubMed:23774268, ECO:0000269|PubMed:25092312, ECO:0000269|PubMed:26334375}.;

Recessive Scores

pRec: 0.112

Intolerance Scores

LoFtool: 0.441
RVIS EVS: 0
RVIS percentile EVS: 53.73

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.776

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium