IRF6

Protein identityUniProt · HPA

UniProt accession

O14896

Gene

IRF6

Ensembl

ENSG00000117595

Chromosome

1

Canonical length

467 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors

Subcellular location

Nucleoplasm,Cytosol

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

467 residues, UniProt reviewed canonical sequence.

>O14896|IRF6
     1  MALHPRRVRL KPWLVAQVDS GLYPGLIWLH RDSKRFQIPW KHATRHSPQQ EEENTIFKAW
    61  AVETGKYQEG VDDPDPAKWK AQLRCALNKS REFNLMYDGT KEVPMNPVKI YQVCDIPQPQ
   121  GSIINPGSTG SAPWDEKDND VDEEDEEDEL DQSQHHVPIQ DTFPFLNING SPMAPASVGN
   181  CSVGNCSPEA VWPKTEPLEM EVPQAPIQPF YSSPELWISS LPMTDLDIKF QYRGKEYGQT
   241  MTVSNPQGCR LFYGDLGPMP DQEELFGPVS LEQVKFPGPE HITNEKQKLF TSKLLDVMDR
   301  GLILEVSGHA IYAIRLCQCK VYWSGPCAPS LVAPNLIERQ KKVKLFCLET FLSDLIAHQK
   361  GQIEKQPPFE IYLCFGEEWP DGKPLERKLI LVQVIPVVAR MIYEMFSGDF TRSFDSGSVR
   421  LQISTPDIKD NIVAQLKQLY RILQTQESWQ PMQPTPSMQL PPALPPQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against IRF6 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.43

Highest tissue expression

104 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about IRF6.

Disease | AllUniProt

Conditions IRF6 is implicated in, by any mechanism.

• Van der Woude syndrome 1 (VWS1) MIM:119300
• Popliteal pterygium syndrome (PPS) MIM:119500
• Non-syndromic orofacial cleft 6 (OFC6) MIM:608864

Disease | GeneticClinVar

131 pathogenic / likely-pathogenic of 388 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Van der Woude syndrome
• Popliteal pterygium syndrome
• Orofacial cleft 6, susceptibility to
• Van der Woude syndrome 1
• IRF6-related condition

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.13

gnomAD pLI

1

gnomAD missense Z

2.74

DepMap mean gene effect

-0.05

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell development
• cranial skeletal system development
• immune system process
• keratinocyte differentiation
• keratinocyte proliferation
• limb development
• mammary gland epithelial cell differentiation
• negative regulation of cell population proliferation
• negative regulation of keratinocyte proliferation
• negative regulation of stem cell proliferation
• positive regulation of DNA-templated transcription
• positive regulation of transcription by RNA polymerase II
• regulation of transcription by RNA polymerase II
• roof of mouth development
• stem cell proliferation

Molecular functions

• DNA binding
• DNA-binding transcription activator activity, RNA polymerase II-specific
• DNA-binding transcription factor activity
• DNA-binding transcription factor activity, RNA polymerase II-specific
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• sequence-specific DNA binding
• sequence-specific double-stranded DNA binding

Cellular components

• chromatin
• cytoplasm
• cytosol
• extracellular exosome
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Interferon regulatory factor, DNA-binding domain
• SMAD/FHA domain superfamily
• SMAD-like domain superfamily
• Interferon regulatory factor-3
• Interferon regulatory factor, conserved site
• Winged helix-like DNA-binding domain superfamily
• Winged helix DNA-binding domain superfamily
• Interferon regulatory factor transcription factor
• Interferon-regulatory factor 3

KeywordsUniProt

• Cytoplasm
• Differentiation
• DNA-binding
• Nucleus
• Transcription
• Transcription regulation
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of IRF6 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SERPINB5
• IRF8