IFI27

protein-coding

interferon alpha inducible protein 27

Gene summary

Enables several functions, including RNA polymerase II-specific DNA-binding transcription factor binding activity; identical protein binding activity; and lamin binding activity. Involved in several processes, including cell surface receptor signaling pathway; host-mediated perturbation of viral genome replication; and protein K48-linked ubiquitination. Acts upstream of or within negative regulation of transcription by RNA polymerase II and regulation of protein export from nucleus. Located in mitochondrial membrane and nuclear inner membrane. Is active in mitochondrion. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001130080.3

Inheritance

—

ClinVar variants

U:24B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.78

Max pathogenic AF

—

Genomic locus

chr14:94,104,836-94,116,695

External References & Databases

Ensembl (ENSG00000165949)

Transcript & Mutation Effects

hg38 • Region Span ~11.9 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 IFI27 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 14

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001130080.3. 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						0
missense			13 clinvar	2 clinvar		15
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			11 clinvar			11
Total	0	0	24	2	0	26

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 60 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001130080.3	RefSeq	NP_001123552.1	4	MANE Select
ENST00000621160.5	Ensembl	ENSP00000483498.1	4	MANE Select
NM_001288952.2	RefSeq	NP_001275881.1	4	Standard
NM_001288956.2	RefSeq	NP_001275885.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cytokine Signaling in Immune system
Immune System
Interferon alpha/beta signaling
Interferon Signaling

Biological Process

negative regulation of transcription by RNA polymerase II
apoptotic process
viral process
proteasome-mediated ubiquitin-dependent protein catabolic process
modulation by host of viral genome replication

Molecular Function

RNA polymerase II activating transcription factor binding
molecular_function
protein binding
lamin binding
identical protein binding

Cellular Component

nuclear envelope
nuclear inner membrane
mitochondrion
mitochondrial outer membrane
endoplasmic reticulum membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000555744
Coding exons: 4
Length: 11852
Individuals with no LoFs: 114914
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 114915
p: 0.00000435

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.414	60	69.7	0.861	0.00000390	708
Missense (PolyPhen)		7	10.173	0.68812		98
Synonymous	0.00613	32	32.0	0.999	0.00000229	280
Loss of Function	0.405	3	3.86	0.778	1.63e-7	48

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000097	0.0000097	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable adapter protein involved in different biological processes (PubMed:22427340, PubMed:27194766). Part of the signaling pathways that lead to apoptosis (PubMed:18330707, PubMed:27673746, PubMed:24970806). Involved in type-I interferon- induced apoptosis characterized by a rapid and robust release of cytochrome C from the mitochondria and activation of BAX and caspases 2, 3, 6, 8 and 9 (PubMed:18330707, PubMed:27673746). Also functions in TNFSF10-induced apoptosis (PubMed:24970806). May also have a function in the nucleus, where it may be involved in the interferon-induced negative regulation of the transcriptional activity of NR4A1, NR4A2 and NR4A3 through the enhancement of XPO1-mediated nuclear export of these nuclear receptors (PubMed:22427340). May thereby play a role in the vascular response to injury (By similarity). In the innate immune response, has an antiviral activity towards hepatitis C virus/HCV (PubMed:27194766, PubMed:27777077). May prevent the replication of the virus by recruiting both the hepatitis C virus non-structural protein 5A/NS5A and the ubiquitination machinery via SKP2, promoting the ubiquitin-mediated proteasomal degradation of NS5A (PubMed:27194766, PubMed:27777077). {ECO:0000250|UniProtKB:Q8R412, ECO:0000269|PubMed:18330707, ECO:0000269|PubMed:22427340, ECO:0000269|PubMed:24970806, ECO:0000269|PubMed:27194766, ECO:0000269|PubMed:27673746, ECO:0000269|PubMed:27777077}.;

Recessive Scores

pRec: 0.0647

Intolerance Scores

LoFtool: 0.621
RVIS EVS: 0.37
RVIS percentile EVS: 74.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.146

Gene Damage Prediction

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