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IRF6 interferon regulatory factor 6 [ Homo sapiens (human) ]

Gene ID: 3664, updated on 7-Apr-2024

Summary

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Official Symbol
IRF6provided by HGNC
Official Full Name
interferon regulatory factor 6provided by HGNC
Primary source
HGNC:HGNC:6121
See related
Ensembl:ENSG00000117595 MIM:607199; AllianceGenome:HGNC:6121
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
LPS; PIT; PPS; VWS; OFC6; PPS1; VWS1
Summary
This gene encodes a member of the interferon regulatory transcription factor (IRF) family. Family members share a highly-conserved N-terminal helix-turn-helix DNA-binding domain and a less conserved C-terminal protein-binding domain. The encoded protein may be a transcriptional activator. Mutations in this gene can cause van der Woude syndrome and popliteal pterygium syndrome. Mutations in this gene are also associated with non-syndromic orofacial cleft type 6. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2011]
Expression
Broad expression in skin (RPKM 34.2), esophagus (RPKM 31.3) and 19 other tissues See more
Orthologs
mouse all
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Genomic context

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See IRF6 in Genome Data Viewer
Location:
1q32.2
Exon count:
9
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (209785617..209806142, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (209032385..209052912, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (209958962..209979487, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2470 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2471 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2472 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2473 Neighboring gene adenosine A2b receptor pseudogene 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2474 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2475 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:209944889-209945388 Neighboring gene MPRA-validated peak675 silencer Neighboring gene TRAF3 interacting protein 3 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:209957609-209958226 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:209958227-209958842 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:209979409-209979752 Neighboring gene chromosome 1 open reading frame 74 Neighboring gene VISTA enhancer hs932 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_2681 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2477 Neighboring gene Sharpr-MPRA regulatory region 1786 Neighboring gene UTP25 small subunit processome component Neighboring gene NANOG hESC enhancer GRCh37_chr1:210048900-210049401 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr1:210068740-210069939 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:210071837-210072364 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_2736 Neighboring gene Sharpr-MPRA regulatory region 13960 Neighboring gene synaptotagmin 14 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:210166703-210167203 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_2861 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_2872 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_2922 Neighboring gene NANOG hESC enhancer GRCh37_chr1:210284477-210284996 Neighboring gene MPRA-validated peak677 silencer Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_2948

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. A Variant in the IRF6 Promoter Associated with the Risk for Orofacial Clefting. Li MJ, et al. J Dent Res, 2023 Jul. PMID 37161310,
  2. A Complex Intrachromosomal Rearrangement Disrupting IRF6 in a Family with Popliteal Pterygium and Van der Woude Syndromes. Al-Kurbi AA, et al. Genes (Basel), 2023 Mar 31. PMID 37107607, Free PMC Article
  3. The IRF6 AP-2α binding site polymorphism relate to the severity of non-syndromic orofacial cleft of Indonesian patients. Nasroen SL, et al. Minerva Dent Oral Sci, 2023 Feb. PMID 36847740
  4. Association of single nucleotide polymorphisms in the IRF6 gene with nonsyndromic cleft lip with or without cleft palate in Kinh Vietnamese patients. Phan HDB, et al. Mol Biol Rep, 2023 Feb. PMID 36484949
  5. Novel de novo missense mutation in the interferon regulatory factor 6 gene in an Italian infant with IRF6-related disorder. Schierz IAM, et al. Ital J Pediatr, 2022 Jul 29. PMID 35906647, Free PMC Article

See all (192) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Review on the Role of IRF6 in the Pathogenesis of Non-syndromic Orofacial Clefts.
    Title: Review on the Role of IRF6 in the Pathogenesis of Non-syndromic Orofacial Clefts.
  2. Identification and validation of IRF6 related to ovarian cancer and biological function and prognostic value.
    Title: Identification and validation of IRF6 related to ovarian cancer and biological function and prognostic value.
  3. Biophysical and functional characterization of N-terminal domain of Human Interferon Regulatory Factor 6.
    Title: Biophysical and functional characterization of N-terminal domain of Human Interferon Regulatory Factor 6.
  4. [Correlation between methylation of interferon regulatory factor 6 gene promoter in renal tissues and overall survival of patients with Kidney renal clear cell carcinoma].
    Title: [Correlation between methylation of interferon regulatory factor 6 gene promoter in renal tissues and overall survival of patients with Kidney renal clear cell carcinoma].
  5. Association between IRF6, TP63, GREM1 Gene Polymorphisms and Non-Syndromic Orofacial Cleft Phenotypes in Vietnamese Population: A Case-Control and Family-Based Study.
    Title: Association between IRF6, TP63, GREM1 Gene Polymorphisms and Non-Syndromic Orofacial Cleft Phenotypes in Vietnamese Population: A Case-Control and Family-Based Study.
  6. A Variant in the IRF6 Promoter Associated with the Risk for Orofacial Clefting.
    Title: A Variant in the IRF6 Promoter Associated with the Risk for Orofacial Clefting.
  7. A Complex Intrachromosomal Rearrangement Disrupting IRF6 in a Family with Popliteal Pterygium and Van der Woude Syndromes.
    Title: A Complex Intrachromosomal Rearrangement Disrupting IRF6 in a Family with Popliteal Pterygium and Van der Woude Syndromes.
  8. Association between variants around IRF6 and non-syndromic orofacial cleft in Western Han Chinese.
    Title: Association between variants around IRF6 and non-syndromic orofacial cleft in Western Han Chinese.
  9. A Comprehensive Genetic Analysis of Slovenian Families with Multiple Cases of Orofacial Clefts Reveals Novel Variants in the Genes IRF6, GRHL3, and TBX22.
    Title: A Comprehensive Genetic Analysis of Slovenian Families with Multiple Cases of Orofacial Clefts Reveals Novel Variants in the Genes IRF6, GRHL3, and TBX22.
  10. The IRF6 AP-2alpha binding site polymorphism relate to the severity of non-syndromic orofacial cleft of Indonesian patients.
    Title: The IRF6 AP-2α binding site polymorphism relate to the severity of non-syndromic orofacial cleft of Indonesian patients.
Submit: New GeneRIF Correction See all GeneRIFs (167)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated 2012-07-06)

ClinGen Genome Curation Page
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated 2012-07-06)

ClinGen Genome Curation Page

EBI GWAS Catalog

Description
A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4.
EBI GWAS Catalog
Genome-wide meta-analyses of nonsyndromic cleft lip with or without cleft palate identify six new risk loci.
EBI GWAS Catalog
Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables DNA binding ISS
Inferred from Sequence or Structural Similarity
more info
  
enables DNA-binding transcription activator activity, RNA polymerase II-specific IEA
Inferred from Electronic Annotation
more info
  
enables DNA-binding transcription factor activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables DNA-binding transcription factor activity, RNA polymerase II-specific IBA
Inferred from Biological aspect of Ancestor
more info
  
enables DNA-binding transcription factor activity, RNA polymerase II-specific ISA
Inferred from Sequence Alignment
more info
  
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables sequence-specific DNA binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables sequence-specific double-stranded DNA binding IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in cell development IEA
Inferred from Electronic Annotation
more info
  
involved_in cranial skeletal system development IEA
Inferred from Electronic Annotation
more info
  
involved_in immune system process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in keratinocyte differentiation IEA
Inferred from Electronic Annotation
more info
  
involved_in keratinocyte proliferation IEA
Inferred from Electronic Annotation
more info
  
involved_in limb development IEA
Inferred from Electronic Annotation
more info
  
involved_in mammary gland epithelial cell differentiation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of cell population proliferation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of keratinocyte proliferation IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of stem cell proliferation IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of DNA-templated transcription ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of transcription by RNA polymerase II IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in roof of mouth development IEA
Inferred from Electronic Annotation
more info
  
involved_in stem cell proliferation IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
part_of chromatin ISA
Inferred from Sequence Alignment
more info
  
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in extracellular exosome HDA PubMed 
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
interferon regulatory factor 6

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_007081.2 RefSeqGene

    Range
    4993..25518
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001206696.2 → NP_001193625.1  interferon regulatory factor 6 isoform 2

    See identical proteins and their annotated locations for NP_001193625.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus, compared to isoform 1.
    Source sequence(s)
    AK296960, AL022398, DA016081
    Consensus CDS
    CCDS55681.1
    UniProtKB/Swiss-Prot
    O14896
    Related
    ENSP00000440532.1, ENST00000542854.5
    Conserved Domains (1) summary
    pfam10401
    Location:129 → 312
    IRF-3; Interferon-regulatory factor 3

  2. NM_006147.4 → NP_006138.1  interferon regulatory factor 6 isoform 1

    See identical proteins and their annotated locations for NP_006138.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AL022398, BC014852, DA016081
    Consensus CDS
    CCDS1492.1
    UniProtKB/Swiss-Prot
    B4DLE2, D3DT90, F5GWX8, G0ZTL0, O14896
    UniProtKB/TrEMBL
    B2R762, G0Z349
    Related
    ENSP00000355988.3, ENST00000367021.8
    Conserved Domains (2) summary
    pfam00605
    Location:9 → 114
    IRF; Interferon regulatory factor transcription factor
    pfam10401
    Location:224 → 407
    IRF-3; Interferon-regulatory factor 3

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    209785617..209806142 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    209032385..209052912 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O14896.1 GenPept UniProtKB/Swiss-Prot:O14896

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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